EMULSION PHASE MATCHING (EPM) TECHNIQUE FOR PREDICTING OPTIMAL EMULSIFERS

Transcription

1 EMULSION PHASE MATCHING (EPM) TECHNIQUE FOR PREDICTING OPTIMAL EMULSIFERS By Teresa J. Harding A thesis submitted in fulfilment of the requirements for the award of Doctor of Philosophy 2006 Centre for Applied Colloid and Biocolloid Science School of Chemical Engineering and Science Swinburne University of Technology Melbourne, Australia

2 ACKNOWLEDGEMENTS Perplexed by the trial and error approach that emulsifier selection usually required before a stable emulsion system could be formed, I had an idea for an alternative approach to emulsifier selection which I wanted to investigate. A special thank-you to Dr. Ian Harding for supporting the idea and giving me the opportunity to undertake this work. I would like to thank all three supervisors, Dr. Ian Harding, Dr. Russell Crawford and Dr. Ian Bowater for their time, guidance and contributions throughout the study. Thank-you to my employer Cognis Australia, who offered me the flexibility in my role to carry out this work. Finally, to my husband, Ron, whose unyielding support, makes absolutely anything possible. Thank-you for being there as always! i

3 PREFACE I hearby declare that, to the best of my knowledge, this thesis contains no material previously written or published by another person, except where reference is made in the text. I also declare that none of this work has been previously submitted for a degree or similar award at another institution. Teresa Harding ii

4 TABLE OF CONTENTS ACKNOWLEDGEMENTS PREFACE TABLE OF CONTENTS LIST OF TABLES LIST OF FIGURES ABBREVIATIONS AND SYMBOLS CHEMICAL FORMULAS OF MATERIALS USED ABSTRACT i ii iii viii xi xiii xv xvii CHAPTER 1 LITERATURE REVIEW AND INTRODUCTION 1.1 SURFACTANT OVERVIEW History and Development Classification of Surfactant Types EMULSIONS Formation Nonionic Surfactants in Emulsions Stability Considerations for Cosmetic Emulsions TECHNIQUES TO PREDICT AND MEASURE EMULSION STABILITY Particle Size Determination Visual Assessment 21 iii

5 1.4 THEORIES TO AID SURFACTANT SELECTION Hydrophile-Lipophile Balance (HLB) Limitations of the HLB System Solubility Parameter Component Solubility Parameters Phase Inversion Temperature New Method Introduction Emulsion Phase Matching (EPM) Summary and Comparison of Theories TECHNIQUES TO CLASSIFY EMULSIFIER MOIETIES Surface Tension Interfacial Tension Application of the Solubility Parameter 41 CHAPTER 2 EPM TECHNIQUE FOR EMULSIFIER SELECTION 2.1 DEVELOPMENT OF EPM THEORY Hydrophobic and Hydrophilic Moieties of Emulsifiers Example of the Splitting Process as applied to Laureth EPM Database EPM Theory Benefits of EPM Technique 52 CHAPTER 3 MATERIALS AND METHODS 3.1 MATERIALS Emulsifiers Selected for EPM Technique Evaluation Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers Oils Selected for EPM Technique 55 iv

6 3.1.3 Auxiliary Materials Selected for EPM Technique METHODS The First Ten Angstroms (FTÅ) 200 Instrument Instrument Standardisation and Calibration Interfacial Tension Measurement Emulsion Preparation Oil Concentration Order of Mixing Degree of Mixing Emulsifier Concentration (Theoretical Determination) Temperature of Emulsification Summary of Emulsion Preparation Parameters Emulsion Evaluation Visual Determination Malvern Mastersizer Instrument Validation Commercial Emulsion Evaluation 79 CHAPTER 4 MATERIALS CHARACTERISATION 4.1 CHARACTERISATION OF EMULSIFIERS Interfacial Tension Data Determination for EPM Technique Measured Interfacial Tension Data for Selected Emulsifier Moieties FTÅ 200 Droplet Contrast Data Extrapolation Classical HLB and Solubility Parameter Classification Alternative Solubility Parameter Classification using EPM Concept CHARACTERISATION OF OILS Interfacial Tension Data HLB and Solubility Parameter Classification of Oils 97 v

7 CHAPTER 5 EMULSION PREPARATION EMULSIFIER CONCENTRATION EFFECTS ON EMULSION FORMATION AND STABILITY Effect of Emulsifier Concentration on Interfacial Tension Effect on Emulsifier Concentration on Particle Size Effect on Emulsion Stability DEGREE AND TIME OF MIXING Effect on Particle Size and Stability 106 CHAPTER 6 CHARACTERISATION OF EMULSIONS 6.1 DESIGN AND STABILITY OF TEST EMULSION SYSTEMS Ideal Emulsion System Design EPM vs HLB Comparison: Test Emulsion EPM and EPM vs HLB: Test Emulsion Stability of Commercially Representative Emulsion Systems Stability Comparison of HLB and EPM Derived Emulsion Systems Confirmation of Optimal Oil Blends for EPM Technique 117 CHAPTER 7 PREDICTING OPTIMAL EMULSIFIERS 7.1 USING THE EPM TECHNIQUE FOR EMULSIFIER PREDICTION DESIGN AND DEVELOPMENT OF MODEL EMULSION Product Requirements and Design Application of the EPM Technique 122 vi

8 7.2.3 Emulsion Stability Model Emulsion System Using Alternative EPM Emulsifier Second Model Emulsion System Using Alternative EPM Emulsifier 127 CHAPTER 8 CONCLUSIONS AND RECOMMENDATIONS FOR ADVANCEMENT OF EPM TECHNIQUE 8.1 OUTLINE SUMMARY OF EXPERIMENTATION POSITIVE ATTRIBUTES OF THE EPM TECHNIQUE Discussion of Positive Attributes NEGATIVE ATTRIBUTES OF THE EPM TECHNIQUE Discussion of Negative Attributes FUTURE REQUIREMENTS TO VALIDATE EPM THEORY FUTURE REQUIREMENTS OF COSMETIC EMULSIONS RECOMMENDATIONS FOR FURTHER WORK 139 REFERENCES 140 APPENDICES Appendix 1 Examples of Ethoxylated Surfactant Types (ICI) 152 Appendix 2 Mastersizer Standard Analysis Results 155 vii

9 LIST OF TABLES Chapter 1 Table 1.1 Table 1.2 Table 1.3 Table 1.4 Chemical Classification of Surfactants Typical Cosmetic Emulsion Ingredients Group HLB Numbers HLB Values Related to Surfactant Application Chapter 3 Table 3.1 Table 3.2 Table 3.3 Table 3.4 Table 3.5 Table 3.6 Table 3.7 Table 3.8 Table 3.9 Table 3.10 Table 3.11 Emulsifiers Selected for EPM Technique Evaluation Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers Selected Oils - Simple Esters Selected Oils - from other Chemical Groups Auxiliary Ingredients Selected for EPM Technique Evaluation FTÅ 200 Instrument Repeatability Calibration Results for Diethylene Glycol and Hexane Surface Tension Validation Cloud Points of Selected Emulsifiers Emulsion Preparation Parameters Droplet Size Evaluation of Commercial Emulsion Products Chapter 4 Table 4.1 Table 4.2 Table 4.3 Table 4.4 Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers Interfacial Tension Data (mn m 20 C) Between Ranges of Alkanes and Glycol Materials (Selected Emulsifier Moieties) Interfacial Tension Results (mn m 20 C) with Dye Added Interfacial Tension Data (mn m 20 C) Between Ranges of Alkanes and Glycol Materials (Selected Emulsifier Moieties) Summary Data with Extrapolated Data Included viii

10 Table 4.5 Table 4.6 Table 4.7 Table 4.8 Table 4.9 EPM Values (Expressed and Measured as Interfacial Tension) for Selected Emulsifiers HLB and Solubility Parameter Values for Selected Emulsifiers Solubility Parameter Values as Applied to the Hydrophobic and Hydrophilic Moieties of the Selected Emulsifiers and to EPM Technique Interfacial Tension Results for Selected Oils against Purified Water Summary of Interfacial Tension, Required HLB and Solubility Parameter Values for the Selected Oils Chapter 5 Table 5.1 Table 5.2 Table 5.3 Table 5.4 Effect of Emulsifier Concentration on Droplet Size Effect of Emulsifier Concentration on Emulsion Stability Summary of Optimal Emulsifier Concentration Determination Shear Time vs Emulsifier Concentration to Achieve 2.5 µm Droplet Size Chapter 6 Table 6.1 Proposed Ideal Test Emulsion Systems Table 6.2 EPM / HLB Comparison: Test Emulsion 4 Table 6.3 Results and Stability of Test Emulsion 4 Table 6.4 EPM Test Series 5 Table 6.5 Test Series 5 Emulsion Systems Matched with HLB Values Table 6.6 Results and Stability of Test Emulsion 5 Table 6.7 HLB and EPM Emulsion Comparison Table 6.8 Ceteareth Emulsifier Systems Emulsified at 75ºC Table 6.9 EPM Emulsion Screening 1 Table 6.10 EPM Emulsion Screening 2 ix

11 Chapter 7 Table 7.1 Model Formulation Ingredients Table 7.2 Model Emulsion Stability Results at 20ºC and 40ºC Table 7.3 Model Emulsion (Using Ceteareth-12) Stability Results at 20ºC and 40ºC Table 7.4 Second Model Formulation Ingredients Table 7.5 Second Model Emulsion Stability Results at 20ºC and 40ºC x

12 LIST OF FIGURES Chapter 1 Figure 1.1 Figure 1.2 Figure 1.3 Figure 1.4 Figure 1.5 Simplified Diagram of a Surfactant Acting as a Detergent Schematic Diagrams of O/W and W/O Emulsion Types Laser Particle Size: System Overview Schematic Diagram of the EPM Technique Surface Tension Derived from Hanging Pendant Drop Chapter 2 Figure 2.1 Example of Emulsifier Splitting in EPM Technique Chapter 3 Figure 3.1 Figure 3.2 Figure 3.3 Photograph of the FTÅ Instrument Set-up Malvern Mastersizer Histogram and Graphical Standard Results Histogram and Graphical Results for Mixed 5 μm and 14 μm Standards Chapter 4 Figure 4.1 Figure 4.2 Figure 4.3 Figure 4.4 Figure 4.5 Diagrammatic Outline of the EPM Technique Example of Emulsifier Splitting in EPM Technique Effect of Alkane Chain Length on Interfacial Tension Interfacial Tension Values for Selected Emulsifier Moieties Interfacial Tension Data for Selected Emulsifier Hydrophiles with MW > 150 g mol -1 xi

13 Chapter 5 Figure 5.1 Effect of Laureth-4 Concentration on Interfacial Tension Water + Laureth-4: Capric / Caprylic Triglyceride System Chapter 7 Figure 7.1 Marketing Brief for a New Product Development Chapter 8 Figure 8.1 Example of a Polymer Displaying Self-Emulsifying Properties xii

14 ABBREVIATIONS AND SYMBOLS Abbreviations DPD EIP EO EPM FTÅ HLB HLB E INCI O/W PEG PIT POE TGA W/O Dissipative Particle Dynamics Emulsion Inversion Point Ethylene Oxide Emulsion Phase Matching First Ten Ångstroms Hydrophile-Lipophile Balance Extended HLB Scale International Nomenclature Cosmetic Ingredients Oil-in-water Polyethylene Glycol Phase Inversion Temperature Polyoxyethylenated Therapeutic Goods Administration Water-in-oil Symbols ΔA ΔH v δ δ a δ b δ d δ h δ o δ p Change in Interfacial Area Heat of Vaporisation Solubility Parameter Solubility Parameter due to Lewis Acid Interactions Solubility Parameter due to Lewis Base Interactions Solubility Parameter due to Dispersion Forces Solubility Parameter due to Hydrogen Bonding Solubility Parameter due to Orientation Effects Solubility Parameter due to Polarity Effects xiii

15 δ t η ρ γ a c D d i g H H L p r R R O SA S E S W V V i [ V ] Molar Volume W Work Total Solubility Parameter Viscosity Density Surface Tension/Interfacial Tension Radius of Droplet Cohesion Parameter Statistically determined Diameter value Diameter of particle size class i Local acceleration due to gravity Drop Height Hydrophile Lipophile Capillary Pressure Radius Alkyl Group Cohesive Energy Ratio Surface Area Equatorial Diameter Drop Width at Height H Rate of Sedimentation (Velocity) Relative Volume for particle size class i xiv

16 CHEMICAL FORMULAS OF MATERIALS USED INCI Name Chemical Formula Laureth-2 Laureth-3 Laureth-4 CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 2 OH CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 3 OH CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH Ceteareth-12 Ceteareth-20 Ceteareth-30 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 12 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 12 OH 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 20 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 20 OH 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 30 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 30 OH Dodecane Hexadecane Octadecane Diethylene Glycol Triethylene Glycol PEG 200 PEG 300 PEG 400 PEG 600 PEG 1000 PEG 1500 CH 3 (CH 2 ) 10 CH 3 CH 3 (CH 2 ) 14 CH 3 CH 3 (CH 2 ) 16 CH 3 H(OCH 2 CH 2 ) 2 OH H(OCH 2 CH 2 ) 3 OH H(OCH 2 CH 2 ) 4 OH H(OCH 2 CH 2 ) 6 OH H(OCH 2 CH 2 ) 8 OH H(OCH 2 CH 2 ) 12 OH H(OCH 2 CH 2 ) 20 OH H(OCH 2 CH 2 ) 30 OH xv

17 INCI Name Chemical Formula Ethyl Hexyl Palmitate Hexyl Laurate Decyl Oleate Ethyl Hexyl Stearate Iso-Propyl Myristate Iso-Propyl Palmitate CH 3 (CH 2 ) 14 COO CH 2 CH(CH 2 CH 3 )(CH 2 ) 3 CH 3 CH 3 (CH 2 ) 10 COO(CH 2 ) 5 CH 3 CH 3 (CH 2 ) 7 CHCH(CH 2 ) 7 COO CH 2 (CH 2 ) 8 CH 3 CH 3 (CH 2 ) 16 COO CH 2 CH(CH 2 CH 3 )(CH 2 ) 3 CH 3 CH 3 (CH 2 ) 12 COO CH(CH 3 ) 2 CH 3 (CH 2 ) 14 COO CH(CH 3 ) 2 Dibutyl Adipate Capric/Caprylic Triglyceride Cocoglycerides Octyl dodecanol CH 3 (CH 2 ) 3 OOC(CH 2 ) 4 COO(CH 2 ) 3 CH 3 CH 2 (OCOR)CH(OCOR)CH 2 (OCOR) R = C 7 H 15 and C 9 H 19 (present in all possible combinations) General formula as capric / caprylic triglyceride with also mono- and di- glycerides from- C 8 C 16 CH 3 (CH 2 ) 9 CH(CH 2 (CH 2 ) 6 CH 3 )CH 2 OH Dioctyl cyclohexane Mineral Oil Dicapryl Ether 1,3 di-c 8 H 17 C 6 H 4 CH 3 (CH 2 ) X CH 3 X = CH 3 (CH 2 ) 6 CH 2 OCH 2 (CH 2 ) 6 CH 3 xvi

18 ABSTRACT The formation of a stable emulsion is more of an art than a science. Emulsions are inherently unstable heterogenous systems such that a truly stable emulsion is not feasible. However, commercial emulsions are very common indicating that it is possible to achieve a commercially stable emulsion. A commercially stable emulsion can be defined as one that remains homogenous throughout its commercial life. Emulsions provide an aesthetically pleasing and practical method of forming a homogenous mixture of oil and water. This type of product is very common with examples including milk, mayonnaise, cosmetic creams and paints. Despite the very many emulsion products available and the considerable time and effort spent on research, there is still no definitive technique available that can pinpoint an emulsifier or emulsifier combination that will form a guaranteed commercially stable emulsion. Trial and error is still required in emulsion formulation. The techniques that are available to help reduce the number of emulsifier options that should be considered have been outlined in this thesis. One, the Hydrophile-Lipophile Balance (HLB) is well known to the emulsification industry and very popular. The benefits and the limitations of this technique are reviewed along with the modifications and extensions of the technique that have been proposed throughout its 50 year life. It is important to note that the HLB technique is over 50 years old. The commercial demands of emulsion products have developed considerably in this time and emulsion systems tend to be somewhat more complex with more ingredients required than when this technique was first formulated. A fresh approach to emulsifier selection is desirable and this work proposes a new concept called the Emulsion Phase Matching or EPM technique. The name arises from the fact that, in this technique, each phase of the emulsion is considered independently of the other, although with all auxiliary ingredients included. A quantitative measure of the difference between the two phases to be emulsified (in this case interfacial tension) is matched to the xvii

19 difference between the hydrophobic and hydrophilic moieties of the emulsifier to be used. A good match should correlate to a stable emulsion. The data should ultimately be listed in a database to make this task simpler. However, the scope of the current work was to test the concept, in general, and the use of interfacial tension, in specific, as the measure of difference. Interfacial tension was, indeed, found to be linked to emulsion stability. Test emulsions were designed to test the proposed EPM technique and to compare the results with those emulsions that would be achieved if the HLB technique was used. Results for both ideal and commercial emulsions (refer Chapter 6) did show superior results for the EPM proposed emulsion, both in terms of initial droplet size of the emulsion as well as its longer term stability. Although the work completed in this thesis only touches the surface of a full validation of the proposed method, it does show encouraging signs and raises some interesting questions regarding emulsion formation, resulting stability and the mechanisms involved with each process. This is an area where further work is justified in the quest to remove the trial and error approach to emulsifier selection. xviii

20 Chapter 1 CHAPTER 1 LITERATURE REVIEW AND INTRODUCTION 1.1 SURFACTANT OVERVIEW Materials that we now know by the relatively recent term surfactant have actually been in use for thousands of years. For example, the use of the alkali metal soaps as articles of trade by the Phoenicians has been documented as early as 600 BC (Markoe, 2000). A soap like material was found in clay pots during excavation of ancient Babylon giving evidence that soap making was known even as early as 2800 BC (Unilever, 2002). Alkali metal soaps function as cleaning and foaming agents and are still used today. Essential to their efficiency as detergents is their ability to act as surfactants. This is only one of many possible surfactant applications, but the most commonly known. Surfactants obtain their special properties due to the molecular structure of their component molecules. This is composed of two distinct parts, or moieties. Each of the two parts possess opposing properties: one part is water loving (hydrophilic) and the other is water hating (hydrophobic), thus overall the surfactant is ampiphilic. Schematically, surfactants are typically displayed as being tadpole like with a small hydrophilic head group and a long non-polar hydrophobic tail: Hydrophilic head group Hydrophobic tail Because of this dual personality surfactants prefer to position themselves at surfaces or interfaces, since it is only here that each part can be in contact with its preferred environment. At higher concentrations, they may additionally self-assemble into aggregrates which form distinct aqueous and oil-like phases

21 Chapter 1 Figure 1.1 demonstrates one way in which surfactants are able to function as detergents; the long hydrophobic tails of the alkali metal soap are soluble in the non-polar grease or dirt, and the polar, hydrophilic head group is soluble in water. The result is that the surfactant lies at the interface as shown, lowering the interfacial tension between these materials. This reduces the work of adhesion between the dirt and the substrate and increases the ease with which the dirt particle lifts off by agitation, usually mechanical. Figure 1.1 Simplified Diagram of a Surfactant Acting as a Detergent This detergent application is so well known, both in the home and in industry, that almost everybody has some appreciation for surfactants, although they may not know the product by this name. Without surfactants, all cleaning processes would be significantly more difficult, less efficient and more time consuming. Detergency covers many different aspects of cleaning from liquid laundry, high acid or alkaline hard surface cleaners and also automated process cleaners which require different surfactants again to optimize performance. Several texts are available that are dedicated to the various aspects of detergency (Showell, 1998, Broze, 1999, Friedli, 2001). The comprehensive detail of this area, although of considerable interest, is outside the scope of this work. A less well known mechanism of detergency is through the formation of mesomorphic phases, into which grease can be solubilised. Nonionic surfactants are generally required and the mechanism involves the formation of a liquid crystal type phase which, in turn, requires a low temperature. Although less well known, this mechanism is considered very important and is the basis behind cold power laundry detergents (Kirk-Othmer, 1993)

22 Chapter 1 The term surfactant is very much a general term for all products that possess surfaceactive properties and is, in fact, a contraction of the term surface active agent. Because there are so many surfactant types they are often further sub-divided according to their most suitable application(s). Classifications include detergents, wetting agents, solubilisers and emulsifiers. It is the subgroup known as emulsifiers that is the focus of this work. Emulsifiers are surfactants that have found specific application in the formation and more importantly, in the stabilisation of emulsions. It is interesting to note that many surfactants (including soap) can have application in many areas and can occur in more than one of the above classification areas. Detergents interact at the surface to dislodge the dirt or grease, but they must also be able to emulsify or solubilise that dirt ensuring that it stays in solution and does not become redeposited. Soap can contribute to the whole detergency process but is a relatively poor emulsifier compared to other materials. Consequently, most detergent products (i.e., laundry, dishwashing etc) sold commercially are made up of a mixture of several surfactants each offering different surface active properties History and Development Soap is the oldest known surfactant and has been in use for more than 4500 years (Sellington, 1998). Soap is formed when natural fats and oils are heated with an alkali; a process known as saponification. Although there is no documented evidence, soap is believed to have been discovered as a result of fat from an altar, on which burnt sacrifices were made, running into a nearby stream and causing foam formation. The alkali used would have been potash (potassium carbonate) which is formed when wood and plants are burned. The ashes from the firewood would have partly saponified the sacrificial animal s fat

23 Chapter 1 By the nineteenth century the making of soap had become a major industry (Sellington, 1998). Soap was cheap, readily available, highly effective, and was the only widely known cleaning agent. The first non-soap material specifically used for its surface active properties was a sulphonated castor oil, which was first introduced in the late nineteenth century as a dyeing aid, and is still used today in the textile and leather industries (Schick, 1980). In Germany during World War I, a shortage of available animal and vegetable fats forced companies to investigate the use of synthetic materials. The broad range of possibilities and performance benefits for synthetic surfactants was quickly realised and this initiated rapid and thorough development in the area of surfactant technology. Initially this was driven around the development of synthetic anionic surfactants. A major disadvantage of soap is evident when used in hard water. Water insoluble salts are formed (calcium or magnesium stearate) which are responsible for a ring around the bathtub or surface being cleaned and this renders the product ineffective as a detergent. This ring is caused by the carboxylate end group of the soap which complexes with metal ions, such as calcium found in hard water, forming a precipitate. Synthetic anionic surfactants could be created to largely overcome this problem by using materials whose calcium and magnesium salts possess a small degree of water solubility. One example is sodium lauryl sulphate (SLS) which forms calcium sulphate in hard water. The water solubility of calcium sulphate is small, at only 0.2% at 18 C (Merck, 2001), but this is sufficient to almost eliminate the formation of the visible ring. This was the start of major development in this area which has meant that today, anionic surfactants still make up the largest proportion of surfactants produced (around 49% of all surfactants made according to the Key Centre for Polymer Colloids (KCPC, (Anionic Surfactants), 2003) and 60% according to Holmberg et al ( 2003)). Anionic surfactants were not the only major class of synthetic detergent to be developed in the early 20 th Century. Schoeller & Wittwer (1930), in the mid to late 1930 s, synthesised the entire range of ethoxylated surfactants and launched a new area of - 4 -

24 Chapter 1 nonionic surfactant science. For a man who had created what is at least a multi-billion dollar industry, he remains virtually unknown (Sellington, 1998)! These surfactants were relatively simple to vary in composition making it easy to systematically study the effect of different hydrophobic and hydrophilic compositions. The range and use of nonionic surfactants grew from this point onwards making them now the largest class used in the area of surface science (KCPC (Nonionic Surfactants), 2003). Nonionic surfactants differ from anionic (and cationic) surfactants in that the molecules are uncharged. Traditionally, polyethylene oxide chains are used as the hydrophilic group. Polyethylene oxide is a water soluble polymer and the polymers used in emulsion technology are typically 3 30 units long. Alcohol ethoxylates and alkylphenol ethoxylates are the two most common classes of nonionic surfactants. Because of the importance of these surfactant classes in emulsion technology, further detail on the scope of the emulsifiers available and the properties they can offer will be covered in section More recently a newer class of nonionic surfactant, the alkyl polyglucosides (APGs), has been introduced. For the last 20 years surfactants within this group have been dubbed new generation nonionic surfactants (KCPC (Nonionic Surfactants), 2003). In these molecules the hydrophilic group is a glucose derivative, generally with only one or two glucose molecules in the chain. These surfactants can challenge the anionics in terms of detergency and foamability and the high chain APGs (C12 to C18) do possess emulsification properties. In terms of emulsion formation, however, APGs do not offer the flexibility of the nonionic ethoxylates and so have a more limited application in this area. APGs possess excellent mildness for personal care cleansing applications as well as improving biodegradability for home and industrial applications (Hill et al, 1997). There is good reason to believe that in the future these materials will take a considerable portion of the anionic surfactant market share, particularly if dermatological and environmental factors continue to grow in importance at the current rate

25 Chapter Classification of Surfactant Types The hydrophobic part of a surfactant is generally a long-chain hydrocarbon moiety. The hydrophilic part is a polar or ionic group that imparts some water solubility to the molecule. The most useful chemical classification of surfactants, for aqueous systems, is primarily based upon the nature of the hydrophile and is outlined in Table 1.1. Although the major surfactant classification is determined by the hydrophile, the hydrophobe can also vary considerably in composition. Most commonly, it is simply a long chain alkyl group which can range from C 8 to C 20 with either a straight or branched chain. This alone provides hundreds of potential surfactant possibilities. In addition, many other hydrophobic groups are available, including alkylbenzenes, alkylnaphthalenes and polydimethylsiloxanes. Table 1.1 Chemical Classification of Surfactants Classification Hydrophile Properties / Uses Anionic Negatively charged. e.g., sulphate (ROSO - 3 M + ), carboxyl (COO - M + ). Largest used surfactant class; mainly for detergents and cleansing products. Minor application in emulsification. Cationic Amphoteric Nonionic Positively charged. e.g., quarternary ammonium halides (R 4 N + X - ). The molecule contains, or can potentially contain, both a negative and a positive charge e.g., sulphobetaines (RN + (CH 3 ) 2 CH 2 CH 2 SO - 3 ). No charge. Water solubility derived from polar groups such as polyoxyethylene (-OCH 2 CH 2 O-) n Bacteriocide and conditioning agent in textiles and personal care. Incompatible with anionic surfactants. Rarely used in emulsions. Possess good synergies with anionic and cationic surfactants and are commonly used as co-surfactants in detergent and cleansing preparations. Rarely used in emulsion applications. Largest surfactant class used in emulsification. High compatibility with ionics. Low sensitivity to electrolytes and ph.

26 Chapter 1 From the wide range of surfactants available, the choice of an optimal surfactant for a given application can become a tedious and lengthy process. It is the aim of this work to provide a summary of the currently available techniques to aid surfactant selection and then to postulate a new, potentially more suitable, technique for the selection of today s emulsifiers. 1.2 EMULSIONS The classic definition of an emulsion was originally advanced by Becher, (1965): a heterogeneous system, consisting of at least one immiscible liquid dispersed in another in the form of droplets, whose diameters, in general, exceed 0.1 μm. Such systems possess a minimal stability, which may be accentuated by such additives as surface active agents, finely divided solids, etc. Emulsions generally consist of water, or an aqueous solution, as one immiscible phase and an insoluble oil as the other immiscible phase. Two emulsion types dominate: 1. Oil-in-water (O/W) emulsion, where the oil phase is dispersed in the aqueous phase. 2. Water-in-oil (W/O) emulsion, where the aqueous phase is dispersed in the oil phase. These emulsion types are shown diagrammatically in Figure 1.1 along with an illustration of the terms dispersed and continuous phases which are also commonly used in emulsion terminology (Poly, 2002). There are many practical examples of emulsions in everyday life that use both natural and synthetic surfactants. Milk and mayonnaise are naturally formed emulsions with lecithin present as the natural surfactant. Paint and cosmetic creams or lotions are examples of products made using essentially synthetic emulsifiers

27 Chapter 1 O/W and W/O Emulsification Hydrophilic Micelle Formation Continuous aqueous phase: O/W emulsion Continuous Aqueous Phase Dispersed Oily Lipophilic Emulsifier Inverse Micelle Continuous oil phase: W/O emulsion Dispersed Aqueous Phase Continuous Oily Phase Figure 1.2 Schematic Diagrams of O/W and W/O Emulsion Types Formation If oil is tipped into water, the two phases will separate almost immediately. If the two phases are shaken vigorously the mixture becomes more opaque in appearance and droplets can be seen. On standing the two phases will quickly re-separate into two distinct layers once again. If enough energy is used, however, smaller droplets will form, slightly prolonging the separation process. The separation of the two phases even when small droplets have been formed, show that the emulsion is not yet stable. This indicates the importance of stabilisation, as well as formation mechanisms. The work required, W, to generate one square centimetre of new interface is given by: W = γ ΔA where γ is the interfacial tension between the two liquid phases and ΔA is the change (increase) in the interfacial area

28 Chapter 1 The formation of the small droplets generates a large amount of surface area, which is why a large amount of work is required. For example, if 15 ml of mineral oil is emulsified in water giving an average droplet diameter of 2.5 µm then the interfacial area would have increased to just under 10 m 2 (see for a detailed calculation to determine the number of droplets formed). The interfacial tension between mineral oil and water is 44 mn m -1, and so the work required to disperse this oil in water is of the order of 400 J. Since this amount of work remains in the emulsion system as potential energy, the system will be thermodynamically unstable and will rapidly undergo whatever transformations are possible to attain minimum potential energy (e.g., minimise interfacial area). This is why the oil and water phases quickly separate again following mixing. If a material can be added that reduces the interfacial tension to, say, below 10 mn m -1, then there is a substantial reduction in the work required to form the emulsion and subsequent reduction in potential energy of the system. The result is that a significantly more stable system can be achieved. This is the function of the surfactant. Surfactants have lower energy at an interface than they do in either the oil or the water phase and act to lower the overall energy of the emulsion. In the case detailed in the calculation above, the remaining energy in the emulsion system would be reduced from ~400 J to <10 J if a surfactant was utilised which reduced the interfacial tension to < 1 mn m -1. Surfactants aid the initial mixing of an emulsion system as discussed (by lowering the work required) and also contribute to emulsion stability (by providing a kinetic barrier to emulsion coalescence). The emulsifying agent forms an adsorbed film around the dispersed droplets which helps to prevent coagulation and coalescence. The actual stabilisation mechanism is usually very complex and varies from system to system. Many texts are available that cover this area in the detail it warrants (e.g., Sjoeblom, 2001, Hunter, 2001, Becher, 2001, Morrison & Ross, 2002, Rosen, 2004) and, indeed, it is an area still under development. The important point with regard to this work is that - 9 -

29 Chapter 1 surfactants serve two purposes: to aid in the formation of the emulsion and to help stabilise that emulsion Nonionic Surfactants in Emulsions Nonionic emulsifiers have advantages over ionic emulsifiers, which make them the emulsifier of choice in many applications. Nonionic systems are substantially free of affects arising from the insolubility of specific salts e.g., water hardness, and therefore more latitude is possible in formulations (Becher & Schick, 1987). This is of great importance in agricultural formulations, where the water hardness varies significantly with location (Becher, 1985). They are, however, not free from all affect arising from the presence of electrolyte in the formulation, despite popular belief to the contrary. The cloud points and micellar properties of nonionic surfactants are affected by electrolyte. In general, high electrolyte concentration makes nonionics less water soluble with increasing temperature (Meguro et al, 1997, Mackay, 1997) reducing their efficiency. The newer sugar based nonionic surfactants (i.e., APG s) are an exception. Like anionic surfactants, their solubility increases with temperature (Holmberg et al, 2003). The most striking advantage of nonionic emulsifiers (ethoxylated) is that they allow the formulator to systematically control the polarity of the emulsifier. Ethoxylated surfactants can be tailor made with high precision with regard to the average number of oxyethylene units added to a specific hydrophobe (e.g., a fatty alcohol). The vast arrays of sequential nonionic surfactants have led to the systematic study of emulsion stability and were used to develop the well known HLB approach (covered in greater depth in Section 1.4.1). The development of these nonionic surfactants must, in some part, be also responsible for the detailed knowledge now available in most areas of surface science including solubilisation, emulsion technology and wettability

30 Chapter 1 The chemical company ICI produced the most comprehensive range of ethoxylated surfactants on a global basis and Appendix 1 displays details and properties of the vast range of Teric nonionic surfactants (alcohol ethoxylates) that were available from ICI before they were disbanded in Australia in the late 1990s. Similar ranges of surfactants are now available from many of the surfactant suppliers (i.e., Huntsman, Cognis, Orica etc) although the range available is now a little less extensive Stability Emulsions undergo several destabilising mechanisms which are covered in detail in numerous surface and colloidal chemistry texts including Hunter (2001) and Rosen (2004). However, in brief, the major destabilising mechanisms include; i) coagulation, where droplets form close-packed aggregates which are difficult to re-disperse, ii) flocculation, where droplets form loose-packed aggregates which are relatively easy to re-disperse, and iii) coalescence, where droplets merge to form larger droplets of greater total volume but lesser total surface area. Random Brownian motion is sometimes all that is required for coagulation to occur. Coalescence often follows coagulation and eventually the dispersed phase can become a continuous phase, separated from the dispersion medium by a single interface. The time taken for such phase separation may be anything from seconds to centuries, depending on the emulsion formulation and manufacturing conditions. It is this length of time that is used to define emulsion stability and varies according to the application. For example, cosmetic lotion products usually require a two year shelf life (Therapeutic Goods Administration (TGA), 1994) and so anything that shows signs of separation within two years is considered unstable. Pesticide emulsion concentrates, on the other hand, are designed to be added directly to the farmer s spray tank to form the emulsion

31 Chapter 1 immediately prior to spraying. The so-formed emulsion is only usually tested for stability for up to 24 hours only because these product types are recommended by the manufacturers for immediate spraying only. Good selection of emulsifiers and stabilisers enables them to adsorb strongly at the interface between the continuous and disperse phases. By their presence, such materials can reduce the energetic driving force to coalescence by forming a mechanical or chemical barrier between drops. This is a key factor to achieving emulsion stability. Emulsifiers have been mentioned already but stabilizers are typically polymers which form a steric barrier to coalescence. Other examples are hydrophobic solid particles which stabilize W/O emulsions or hydrophilic solid particles which stabilize O/W emulsions ( Aveyard & Clint, 2003). As interfacial tension values fall, the ease of emulsion formation increases and the droplet size achievable decreases (Everett, 1988). Systems in which the interfacial tension falls to near zero (<10-3 mn m -1 ) may emulsify spontaneously under the influence of thermal energy and produce droplets so small (<100 nm diameter) that they scatter little light and give rise to clear dispersions. The microemulsions so formed occupy a place between macroemulsions and micelles and are thermodynamically stable. The interfacial tension is so low that only thermal energy is required for emulsification (the main driving force is the configurational entropy gain in having so many droplets). Microemulsions are extensively used for low viscosity emulsions like commercial spray emulsion products. Macroemulsions generally do not provide sufficient stability for the desired life of such a low viscosity product. Microemulsions were first reported by Hoar and Schulman (Hoar and Schulman, 1943), who described transparent or translucent systems that formed spontaneously when oil and water are mixed with relatively large amounts of an ionic surfactant combined with a cosurfactant. The systems described have been shown to be dispersions of very small drops (radius ~100 nm) of water in oil

32 Chapter 1 The formation of a microemulsion is, like that of conventional emulsions, still rather an art. Science has not advanced to the point where one can predict with accuracy what is going to happen in the beaker or reaction vessel with all mixtures of ingredients, let alone what is going to happen in large scale manufacture. As previously stated, microemulsions (which form spontaneously), can only be formed if the interfacial tension is so low that the remaining free energy of the interface can be overcompensated by the configurational entropy of the dispersion process. Although a single surfactant lowers the interfacial tension, this is usually insufficient to enable microemulsion formation even when using a high shear mixer and processing at elevated temperatures. The addition of a second surfactant of a different chemical nature is usually necessary to lower the interfacial tension still further (Luckham, 1986). This second surfactant is termed a co-surfactant, is commonly an alcohol (Everett, 1988) and need not be, by itself, a powerful surfactant. Although microemulsions are undoubtedly the most stable emulsion type, three to ten times the level of total surfactant is required in their formation as compared to a standard macroemulsion. When cost and, in the case of cosmetic emulsions, dermatological compatibility, are considered, these emulsion types are often unsuitable for commercial preparations Considerations for Cosmetic Emulsions Materials used for cosmetic application must demonstrate excellent skin compatibility as well as superior aesthetic properties. Specific marketing claims are frequently a major driving force behind the materials selected and these claims often require the addition of many more auxiliary ingredients than would commonly be found in other emulsion applications

33 Chapter 1 Table 1.2 provides an overview of typical raw materials listed in cosmetic emulsion formulations (Cognis GmbH, Care Chemicals Division CD-Rom, 1999). Table 1.2 Typical Cosmetic Emulsion Ingredients Emulsion Phase Oil Phase Ingredients Emollients Hydrophilic, oil soluble consistency factors Lipid soluble emulsifiers Oil soluble additives / active ingredients Aqueous Phase Water Water soluble moisturisers Water soluble emulsifiers (e.g., solubilisers) Polymer stabilisers and thickeners Water soluble additives /active ingredients It is not uncommon for a cosmetic formulation to include ten to fifteen separate ingredients. Frequently several emollients are used, for example to achieve the desired sensory properties; or several herbal active ingredients are used to increase marketability. All of these materials may need to be formulated into a stable product. Any auxiliary ingredient that possesses surface activity itself, or can affect the solubility, polarity or hydrophobicity of either phase, can influence emulsion formation and stability. There is no current technique for surfactant selection that satisfactorily considers all the auxiliary ingredients in the selection process. In fact, it is often the practise to formulate a stable emulsion in the absence of crucial additives (particularly colour, fragrance and preservatives). When these are then added, much of the initial research and development is rendered invalid. It is common practice to carry out very little further development leading to a product which is no longer at is optimum. With the complexity of today s emulsion systems, particularly in the cosmetic area, this is an area that needs to be addressed

34 Chapter 1 The use of polymers in cosmetic formulations continues to grow. Sodium polyacrylate and acrylate co-polymers are commonly used to regulate viscosity and provide additional stability to the emulsion. Even in sprayable emulsion systems, a small amount of polymer provides some steric stabilisation to improve the shelf-life of commercial formulations. Self-emulsifying polymers are also now on the market to act as co-emulsifiers or even to offer an alternative to conventional emulsifiers (by trapping the oil phase within voids of polymer gel matrix offering excellent stability (see Chapter 8)). As long chain materials that sit on, but do not penetrate into, the dermal layers polymers have an additional benefit in that they are a milder option for skincare. A so called emulsifier-free marketing concept is beginning to appear in advertisements ( It is very possible that these products may become important in terms of future direction of cosmetic emulsions and so are of interest to this work. The possible part polymers can play in cosmetic emulsion technology will be discussed further in Chapter 8 where the future directions of the Emulsion Phase Matching Technique, the topic of this study, are put forward

35 Chapter TECHNIQUES TO PREDICT AND MEASURE EMULSION STABILITY At the formulation development stage it is important to be able to predict the life of a test emulsion, ahead of its usual shelf life. The usual technique to measure this (Therapeutic Goods Administration (TGA), 2003 and 2004) is by means of ageing samples by storing them at a range of different temperatures (known as accelerated storage tests). The Arrhenius equation (Arrhenius, 1889) is often used to calculate the factor for increased ageing (Turner, 2002). The Arrhenius equation states that a rise in temperature of 10 C will cause approximately a doubling of the rate of chemical reaction. It is assumed that doubling the rate of chemical reaction doubles the rate of decay of packaging and product (Turner, 2002). Therefore, 6 months stability storage at 40 C is assumed to indicate the equivalent chemical stability of a product stored for 2 years at 20 C (and 1 year at 30 C although this storage condition is rarely used). In terms of the product itself, this decay as far as the TGA is concerned, applies to the chemical stability of actives i.e., sunscreen or pharmaceutical actives, and not necessarily the physical condition of the emulsion itself. However, if the emulsion has destabilized then there is no doubt that this will be evident in the analysis of the actives. The accelerated storage tests at elevated temperatures make use of a lower viscosity component (from Stokes Law (see section 1.3.4), which increases the rate of sedimentation. Higher temperatures also speed up the rate of Brownian motion and the consequent number of droplet collisions. The higher temperatures give particles more energy such that, when they collide, they are more likely to coagulate and/or coalesce. This, in turn, increases their particle size and thus their rate of sedimentation. Any tendency for the formulation to undergo flocculation and/or creaming effects will usually show up more quickly under accelerated storage testing. However, depending on the stabilization mechanism, increasing temperatures sometimes (not often) increases stability. This may occur, for example, when the increased energy allows a partially flocculated system to de-flocculate, giving rise to a more stable emulsion. Thus stability tests should also be carried out at lower temperatures

36 Chapter 1 Storage temperatures typically used include: 4 C Room temperature (RT) which can be 20 or 25 C 40 or 45 C 50 or 54 C A continuous cycling temperature, where the temperature covers a cycle from - 5ºC to + 40ºC over each 24 hour period - 10, - 15 or even - 20ºC is sometimes also used when the product is destined for colder climates These temperatures are the most common temperatures but others can be used, providing a justification for the use of the temperature employed is submitted to the regulatory body. Depending on the product s final application and selected storage temperatures, the test samples are evaluated at designated time periods. Typically these can include 2 and 24 hours, 1 week and 3, 6, 12 and 24 months. One, or more, of the many techniques available to identify the first signs of emulsion instability caused by accelerated ageing can be used. These methods include particle (or droplet) size analysis and the convenient and effective method of visual examination. Both techniques were used in the current work and are described below. Conductance, centrifuge and ultrasound evaluations are other common techniques that could have been used as an alternative to droplet size analysis. Development of new and alternative techniques to speed up the analysis of emulsion stability continues. Currently, 3 and 6 month successful accelerated storage test results are the minimum required to obtain approval for a product to be commercialised within TGA guidelines (TGA, 2003 and 2004). If a technique was approved that could more quickly predict emulsion stability and product shelf life, then product commercialisation could be sped up by several months. This is an attractive proposition for manufacturers

37 Chapter 1 and drives the quest to find a new technique that can shorten the stability requirements before approval is given. Recent work includes the techniques of differential scanning calorimetry (DSC), (Yamamoto, 1994), high frequency spectroscopy (Kageshima et al, 2003) and continued developments of existing ultrasound techniques (Daniels, 2002). Fairhurst et al, (2002) have combined acoustic spectroscopy with electro-acoustics to measure both particle size and zeta potential on O/W and W/O emulsions without the need for dilution. It has been the requirement for dilution in many techniques that has thus far prevented them gaining widespread approval with regulatory bodies. Dilution of the system changes it in an irreversible manner and so there can never be full confidence that the results are sufficiently representative to accurately predict stability. It should also be noted that assumptions are frequently used in instrumental data analysis e.g., many particle size instruments assume that the test material is spherical. When measuring emulsion stability, an instrumental technique is preferably backed up by a visual technique which provides different but complimentary information (e.g., can differentiate between flocculation and coalescence). Two such techniques used in conjunction can provide a more comprehensive picture of the material under test and this is the reason why two techniques were selected in the current work Particle Size Determination Comparison of the particle size distributions of fresh and aged emulsion samples is a very good way of determining information on the stability of an emulsion system. For example, both Ostwald Ripening (Hunter, 2001) and droplet coalescence reduces the number of droplets observed and increases the average particle size. An increase in particle size is, of course, expected since all emulsions are inherently unstable. It is the rate of this increase which is of importance. Frequently, the rate is sufficiently fast to be a problem to medium term stability, but sufficiently slow to be undetected by the human eye. Under these conditions, particle sizing is an effective means for early detection of emulsion instability

38 Chapter 1 The particle size instrument used in this project was a laser light scattering device (Malvern Mastersizer S). A schematic diagrammatic representation is given in Figure 1.3. All light scattering based particle sizers are comprised of an optical measurement unit which forms the basic part of the sensor, and a computer which manages the measurement and performs result analysis and presentation. Spatial Filter Collimating Flow Cell Focussing Lens Lens Laser Detector Interlace Electronics Sample Dispersion Unit Computer Figure 1.3 Laser Particle Size: System Overview The light scattered by the particles, as they pass through the flow cell, and the unscattered remainder, are incident on a receiver lens known as the focussing lens. This operates as a Fourier transform lens forming the far field diffraction pattern of the scattered light at its focal plane. Here, the detector gathers the scattered light over the range of angles of scatter. The unscattered light is brought to a focus on the detector and passes through a small aperture in the detector and out of the optical system. The total laser power passing out of the system in this way is monitored, allowing the sample volume concentration to be determined

39 Chapter 1 Laser light scattering can be used to measure the size distribution of any one material phase dispersed in another. The only qualification of the technique is that each phase must be optically distinct and the medium must be transparent to the laser wavelength. This means that the refractive index of the test material must be different from the medium in which it is supported. For laser light scattering particle sizers, the range of scattering angles measured is typically º. The size ranges covered are typically from 1 μm upwards in such cases. For these types of size and angle ranges, the scattering properties are largely independent of the internal optical properties of the sample material. The theory used to model the scattering in such an instrument is the Fraunhofer scattering theory (Woodruff and Delchar, 1994), which requires no assumptions of the particles optical properties. When interpreting results from laser light scattering instruments a few key points must be considered: The result is volume based. This means that when the instrument reports, for example, 11% of the total distribution in the size category μm this means that the total volume of all particles with diameters in this range represents 11% of the total volume of all particles in the distribution. A simplistic example can be used to show the importance of defining whether the distribution is number or weight (or other) averaged. Consider a sample consisting of only two sizes of particle - 50% by number having diameter 1 μm and 50% by number 10 μm. Assuming spherical particles, the volume of each of the larger particles is 1000 times the volume of one of the smaller ones. Thus, as a volume distribution, the larger particles represent 99.9% of the total volume. The result is often expressed in terms of equivalent spheres. The instrument does not consider the shape of the particle being measured (i.e., cuboid, cylindrical etc). The results are measured as a volume and the diameter values quoted are calculated based on the particle being completely spherical (or some other limited geometrics)

40 Chapter 1 The result is derived from particle size classes, optimised to match the detector geometry and optical configuration that gives the best distribution. When analysing particulate matter, the particle shape is rarely, if ever, spherical. Information on the particle shape cannot be gained and is not considered in this technique. For this reason, visual microscopic analysis, is recommended in parallel with instrumental particle size analysis. Emulsion droplets, on the other hand, are spherical and well represented by this technique Visual Assessment Although this method is a simple technique not requiring sophisticated equipment, visual assessment of emulsions following accelerated ageing is a highly effective method to evaluate emulsion stability. An aged, stable emulsion looks exactly as it did immediately after preparation - a homogenous dispersion throughout the cylinder. An emulsion showing signs of instability displays a distinct layer, either at the top or bottom of the cylinder. This is caused by separation between the dispersed and continuous phases of the emulsion and it depends on the density of the two phases whether the layer appears at the bottom (termed sedimentation) or the top (termed creaming ) of the cylinder. At this stage the separate layer appears whiter (more concentrated) than the body of the emulsion. The phenomenon of creaming receives its name from its most common instance: the separation of unhomogenised milk. What occurs in this case, and in all cases of true creaming, is not so much a breaking of the emulsion as a separation into two emulsions, one of which is richer in the disperse phase, the other poorer, than the original emulsion. The emulsion which is more concentrated is the cream. In the case of milk, the cream represents an emulsion much richer in the dispersed butter fat phase than the depleted milk phase. This is why the cream phase is often removed to provide milk that has a lower fat content

41 Chapter 1 It should be noted that while creaming may be undesirable in many cases, it does not represent a breaking of the emulsion where free oil or water can be seen as distinct, clear layers. On the other hand, since creaming is favoured by large droplet sizes, it may well be a manifestation of processes that will eventually lead to breakdown of the emulsion and phase separation. The process followed for visual assessment testing is commonly as follows: 1. A quantity of the emulsion is prepared and transferred into a graduated cylinder (e.g., 100 ml). Its appearance is examined and recorded, and the cylinder is left to stand at room temperature or in water baths or ovens at the required test temperature. Common storage test temperatures used include 4 C, RT (20 or 25 C), 40 C, 45 C and 50 or 54 C, depending on the climatic conditions of the country where the product will be sold. 2. After a defined time period, which may be hours, days, weeks or months, the cylinder is carefully removed (without agitation) from the water bath or oven and examined with the aid of a bright light (placed behind the cylinder). 3. The physical appearance of the emulsion is recorded as a percentage of free oil, cream or sediment. The presence of any of these layers is an indication of instability. Decisions have to be made as to the significance of the results achieved in terms of the shelf life of the product. For example, 0.5% cream after 1 month at 50 C may be considered tolerable but 0.5% cream after 24 hrs at room temperature might not. This visual technique is especially useful when optimising emulsifier ratios because the effect of several emulsions can easily be compared at one time. The effect of increasing or decreasing emulsifier content, or ratios of different emulsifiers, can be clearly observed. In many emulsion systems, creaming, although undesirable, is allowable to some extent. Adjustments in manufacturing technique (e.g., shear rate or duration) or formulation

42 Chapter 1 (e.g., emulsifier content or concentration of thickener) can reduce the rate of creaming to a point where it can be considered to have a negligible effect. This may be understood from a consideration of sedimentation phenomenon using Stokes Law (Sjoeblom, 1996): V = 2 2 g a (ρ2 ρ) 9 η where V = rate of sedimentation g = local acceleration due to gravity a = radius of droplet ρ = density of continuous phase ρ 2 = density of droplet (dispersed phase) η = viscosity The value of V may be positive or negative depending on the direction the particles / droplets will move. This depends on the relative values of the densities of each phase. In an O/W emulsion, for example, the oil density (ρ 2 ) is usually the smaller, hence upward sedimentation (creaming) will occur. Examination of Stokes Law leads to the conclusion that emulsion stability (with respect to creaming) is favoured by small droplet size, small density differences between the disperse and continuous phases, and by high viscosity of the continuous phase. Therefore, if a formula is changed to increase the level of thickener in a formula then stability will be improved. In the same manner if a smaller droplet size is achieved by increasing the rate or duration of shear or increasing the emulsifier then again improved stability should be expected. The accelerated storage tests at elevated temperatures make use of a lower viscosity component, which increases the rate of sedimentation and will thus show any instabilities sooner than would appear at room temperature

43 Chapter THEORIES TO AID SURFACTANT SELECTION The formulating chemist has an array of surfactants available to choose from and the selection of a suitable surfactant for a given application can, as already stated, become a tedious and lengthy process. Assistance is required to make this process easier and there is one, widely used, theory that formulation chemists use when developing emulsions. This is the Hydrophile-Lipophile Balance (HLB) theory described below (Griffin, 1949 and 1954). The system was a breakthrough in its time although it has its limitations. These limitations have prompted further theories to be developed and are a major driving force behind the proposal of the Emulsion Phase Matching theory, which is the basis of this project Hydrophile-Lipophile Balance (HLB) Whilst working in the laboratories of Atlas Powder Company (which became ICI) in the late 1940 s William C. Griffin was studying the emulsification properties of the newly synthesized, ethoxylated surface-active agents. In this work, Griffin noted the striking relationship between emulsion stability and ethylene oxide content. He correlated emulsion stability to the weight percent of ethylene oxide in the molecule and founded the HLB (Hydrophile-Lipophile Balance) system (Griffin, 1949 and 1954). The HLB of an emulsifier is an expression of the balance of the polar (water-loving) and non-polar (water-hating) groups of the emulsifier. Griffin defined HLB as: HLB = weight percent hydrophile 5 which for nonionic, ethoxylated surfactants is simply: HLB = weight percent ethylene oxide (EO)

44 Chapter 1 For example, laureth-4 has a molecular weight of 362 g mol -1. It has four moles of ethylene oxide per molecule giving 48% EO on a weight basis. The HLB of laureth-4 is: 48 5 = 9.6 The divisor was used for convenience only - values then range from 0 to 20 on an arbitrary scale. HLB is related to solubility; an emulsifier with a low HLB number has a low proportion of hydrophilic groups and tends to be oil soluble while an emulsifier with a high HLB number has a high proportion of hydrophilic group and tends to be water soluble. Following Griffin s work the HLB theory was developed by Davies & Rideal (1961), who proposed the following equation: HLB = 7 + (hydrophobic group numbers) - (hydrophilic group numbers) The group numbers are given in Table 1.3 with Table 1.4 illustrating how the HLB number relates to solubility and also to surfactant application. Table 1.3 Group HLB Numbers Hydrophilic Groups -SO 4 Na -COOK -COONa Sulfonate -N (tertiary amine) Ester (sorbitan ring) Ester (free) -COOH -OH (free) -O- -OH (sorbitan ring) HLB Lipophilic Groups HLB ~ CH- -CH 2 - -CH 3 - -CH= -(CH 2 -CH 2 -CH 2 -O-)

45 Chapter 1 Ever since the introduction of the HLB technique, there has been research into alternate methods to accurately determine the HLB number. Some are equations to link other techniques for emulsifier selection to the HLB number which will be covered in more depth in sections and Others include the determination of HLB number by the use of the phenol index (Leszak et al, 1981) or by utilizing reversed phase thin layer chromatography (Trapani et al, 1995). This continued development reflects the need for more accuracy in determining the HLB number. In more general terms, table 1.4 illustrates how the HLB number relates to solubility and also to surfactant application. This is a useful guide which is widely known and reported in almost all texts relating to the HLB technique. TABLE 1.4 HLB Value Related to Surfactant Application HLB RANGE USE SOLUBILITY W/O Emulsifiers Wetting Agents O/W Emulsifiers Detergents Solubilisers Oil soluble Water Soluble In addition to the HLB of the emulsifiers themselves, data tables are also available for the materials that are to be emulsified. These are characterised by an individual Required HLB value which are based on emulsification experience (method to determine Required HLB is given in Becher, 1973) rather than structural considerations. The Required HLB is a number which should be matched to the HLB of an emulsifier or emulsifier blend for optimal emulsion stability. For example, iso-propyl myristate (IPM) has a Required HLB of 11 and so a nonionic emulsifier, or blend of nonionic emulsifiers, having an HLB of 11 will generally make a more stable O/W emulsion than emulsifiers of any other HLB value within the same

46 Chapter 1 chemical class. To determine the optimal emulsifier combination, however, various mixtures of other types of emulsifying agents with the same weighted average HLB number must then be screened (as explained in section 1.3.2) to determine which structural types of emulsifiers give the best restuls for the particular system to be emulsified. The HLB number is indicative only of the type of emulsion to be expected, not the efficiency or effectiveness with which it will be accomplished (Rosen, 2004, Griffin, 1954, Becher 1973). This should be noted because formulators expectations of the HLB system are often greater than this. It has been pointed out (Shinoda, 1968, Boyd et al, 1972, Kloet & Schramm, 2002) that a single surfactant can produce either an O/W or a W/O emulsion, depending on the temperature at which the emulsion is prepared, the shear rate, or, at high oil concentrations, on the ratio of surfactant to oil. O/W emulsions can be prepared with certain surfactants over the entire range of HLB numbers from 2 to 17 (Rosen, 2004) HLB and Required HLB values are available for both O/W and W/O emulsions, although the data available for W/O systems is limited. Neither HLB nor Required HLB give any indication of the quantities or chemical nature of emulsifier or oil required these are left largely up to the formulator to determine. Application of the principles of the HLB concept greatly aids the formulation chemist by vastly reducing the number of candidate emulsifiers to be screened in a particular system. It cannot guarantee that the emulsifier(s) selected will give a stable emulsion but there is no system currently available that can offer this assurance. There are situations where the HLB system is over-extended and these should be known to avoid inaccurate results

47 Chapter Limitations of the HLB System 1. Temperature and HLB play a prominent role, particularly in the case of nonionic emulsifiers, in determining the partitioning of the emulsifier between phases. Raising the temperature reduces the HLB of the emulsifier while decreasing the temperature raises it. Tables of HLB values, however, rarely involve more than one temperature. 2. Any specific, chemical interactions of the emulsifier with the oil (as well as interactions with any other formulated raw material) are disregarded; only water and/or oil solubility and the physical properties of surfactants at interfaces are accounted for. With the increased number of materials now included in formulations this has become more important than when this method was first developed. 3. The matching of the emulsifier chemical type to that of the oil is left open to trial and error, albeit on a much less extensive basis. 4. A fundamental tenet of Griffin s definition of HLB (Griffin 1949 and 1954) is that the HLB of a mixture of nonionic emulsifiers is the weight average of the HLB of each of its components. This rule does successfully predict trends in stability, but only when the chemical types are similar and the dissimilarity in HLB between the emulsifiers is not too large (<5 HLB units). Solubility differences can have a major effect when the HLB difference between the emulsifiers is too large. 5. The HLB value is assumed to be the arithmetic mean of the surfactant components. This is not the case for other important parameters for nonionic surfactants e.g., the critical micelle concentration (cmc), and this may contribute to the limitations of this system. Furthermore, it is frequently not true for ionic surfactants (Shaw, 1993)

48 Chapter 1 6. Commercial nonionic surfactants are rarely single components. For instance, commercial ethoxylated surfactant laureth-4 possesses a range in the number of ethylene oxide moles present. This range is typically from 1 7 moles of ethylene oxide (Tesmann, 1988). Lower molecular weight components of the surfactant (i.e., components with 1 3 moles ethylene oxide) tend to partition into the oil phase, and raise the required HLB by effectively changing the oil phase composition. Despite its shortcomings, the HLB system remains very well accepted as an aid to emulsifier selection, particularly for simple nonionic emulsifier systems. Provided its limitations are known, the HLB system is a valuable tool for the formulation chemist. Complex nonionic or ionic emulsifiers are not within the scope of Griffin s system and should not be used. The HLB of ionic surfactants, for example, are not fully additive and are concentration dependent. Nevertheless, the system is commonly used for all emulsifier types Solubility Parameter The solubility parameter theory (Hildebrand, 1915, 1916 and Hildebrand & Scott, 1950) is based on the premise that when the solubility parameters of two materials are equal, the materials are infinitely soluble (Burke, 1984). The solubility parameter is a numerical value that indicates the relative solvency behaviour of a specific solvent. It is derived from the heat of vapourisation. The intermolecular forces that cause materials to dissolve are the same forces that prevent those materials from boiling away until a specific temperature is reached (Vaughan, 1985). The sum of all these intermolecular attractive forces has been defined by Hildebrand (1915, 1916 and Hildebrand & Scott, 1950) as the solubility parameter (δ). The concept was originally postulated by Scatchard in 1915 and greatly extended by Hildebrand (1915, 1916 and Hildebrand & Scott, 1950) who used his own earlier work

49 Chapter 1 combined with Scatchard s concept to mathematically define the solubility parameter, and showed it to be empirically related to the extent of mutual solubility of many chemical species. The character of chemicals is related to the way they interact. Interaction energy increases when character is similar, regardless of strength (Martin et al. 1985), i.e., like attracts like. The solubility parameter has many applications. It indicates to an analytical chemist what order the test materials will come through the HPLC column (Alessi et al. 1975). To biochemists, it is a value related to membrane penetration and binding (Sloan et al. 1986). For coatings chemists, it indicates which materials will readily adhere and to formulators it indicates which materials will mix, and which will separate. In mathematical terms, Hildebrand originally defined the solubility parameter as: δ = ( ΔH v / [ V ] ) 1/2 where ΔH v is the heat of vaporisation, and [ V ] is the molar volume. The energy of vaporisation forms the foundation of the expression because when the material vapourises it is no longer held together by its intermolecular forces Component Solubility Parameters (or Cohesion Parameters) Originally Hildebrand (1950) was only concerned with non-polar materials, i.e., those in which only dispersion forces act between the molecules. To be of universal use the theory had to be extended to include polar materials. This was first achieved by Hansen (1967) who included molecules interacting by dipolar and hydrogen bonding forces (as well as dispersion forces), by making the assumption that the solubility parameter could be represented by an additive function of the three components, giving a squared form of the solubility parameter which became known as the cohesion parameter (c): δ t 2 = (c) = δ d 2 + δ p 2 + δ h

50 Chapter 1 where the subscripts t, d, p and h refer to the total, dispersion, polar, and hydrogen bonding contributions respectively. For complete miscibility, two liquids need each of these parameters to be similar. Other researchers found that even Hansen s expanded parameter was insufficient for their applications and further expansion was necessary. The Hansen expression did not take into account the unsymmetrical nature of the hydrogen-bonding interactions. Beerbower, Martin & Wu (1984) developed an alternative equation, which is becoming a generally accepted improvement (in the polymer and paint industries) to the Hansen expression: δ 2 t = δ 2 d + δ 2 o + 2 δ a δ b where the subsript o refers to contributions due to orientation effects and a and b refer to contributions to Lewis acid and Lewis base interactions respectively. The solubility parameter offers a far more comprehensive system than the HLB system but has the disadvantage of being very complex with several alternative expressions available. This has been sufficient to deter formulators from applying the solubility parameter in emulsion development. In order to overcome this, some researchers (e.g., Vaughan, 1991) have put forward simpler methods to achieve estimates of solubility parameter values, which are sufficient in some cases for initial experiments. One such method is the quick and easy Drop Weight test; Ten or twenty drops (dispensed from the same pipette) of a pure non-volatile liquid with unknown drop weight are weighed and an average value for a single drop calculated. This average weight is then bracketed against the average drop weight for two nonvolatile reference liquids with known solubility parameters. Although crude, this method has been reported by Vaughan (1991) to show both linear and reproducible results. Results are completely dependent on the type of dropper used and the method is suitable for comparative testing only

51 Chapter 1 The solubility parameter is quite widely known in some industries, e.g., polymer technology, but it has not gained wide acceptance in the field of emulsion technology. Presumably, this is due to difficulties in its interpretation and use compared to the HLB system. The solubility parameter theory is based on the premise that when the solubility parameters of two materials are equal, the materials are infinitely soluble. By definition this does not apply to emulsifiers, which cannot be fully soluble in either component if they are to function as emulsifiers. It was shown (see Table 1.4) that the solubility of surfactants and their HLB values are inter-related. The activity of a surfactant is greatly affected by its bulk solubility so it is quite logical to develop the solubility parameter further to determine its relationship to the HLB system. An expression for a Cohesive Energy Ratio was defined by Beerbower (1972) which did link the solubility parameter and HLB. However, it did not achieve any simple method to determine the solubility parameter of a surfactant from its HLB number. Thus the full potential of the solubility parameter to emulsification has not yet been realised Phase Inversion Temperature One major limitation of the HLB method for selecting emulsifiers is that it makes no allowance for the change in HLB value with changes in the conditions for emulsification (temperature, nature of the oil and water phases, presence of co-surfactants or other additives). For example, the degree of hydration of an ethoxylated nonionic surfactant decreases as the temperature is raised and the surfactant becomes less hydrophilic. Consequently, its HLB must decrease. An O/W emulsion made with ethoxylated surfactant may invert when the temperature is raised and a W/O emulsion may invert to an O/W emulsion when the temperature is lowered. Shinoda and Arai (1964, 1967) recognised the importance of temperature on surfactant properties (particularly nonionic surfactants) and introduced the concept of the Phase

52 Chapter 1 Inversion Temperature (PIT) as a quantitative approach to the evaluation of surfactants in emulsion systems. The temperature at which a test emulsion (consisting of oil, aqueous phase, and 3-5% surfactant prepared by shaking at various temperatures) inverted from O/W emulsion to W/O emulsion was defined as the PIT of that particular emulsion system. This temperature (usually a range rather than a specific temperature) occurs when the interfacial properties of the system are balanced and generally emulsions of very fine droplet size are produced. The PIT temperature (or temperature range) is often easy to identify because the emulsion becomes clear due to the formation of a microemulsion. The sensitivity of emulsions, particularly nonionic emulsions, to temperature led (Shinoda & Saito, 1969) to suggest that the PIT method be used as a possible method for emulsion preparation. In such a procedure, an emulsion would be prepared near the PIT of that particular system (± 4ºC), where minimum droplet sizes can be achieved and then cooled to its normal storage or use temperature. Droplet sizes of the final, cooled emulsion are not as small as the microemulsion formed at the PIT itself but are significantly smaller (of the order of μm (Ansmann et al. 1995)) than if the same emulsion was prepared using Becher s traditional method described in Section (in the order of 1 to 10 μm). The phase inversion temperature depends on the concentration of the emulsifier mixture (Kunieda & Ishikawa, 1985) and the nature of the emulsified oils (Kunieda & Miyajima, 1989), as well as on the HLB of the emulsifier. The PIT appears to reach a constant value at 3-5% w/w surfactant concentration when an ethoxylated surfactant containing a single POE (polyoxyethoxylated) chain is used. When there is a distribution of POE chain lengths in the surfactant, the PIT decreases very sharply with increase in the surfactant concentration when the degree of ethoxylation is low. As the oil to water ratio increases in an emulsion with a fixed surfactant concentration, the PIT increases. Additives such as mineral oil, that decrease the polarity of the oil phase, increase the PIT; whereas those that increase the polarity, such as triglycerides, esters or oleic acid, lower the PIT. The addition of salts to the

53 Chapter 1 aqueous phase decreases the PIT of emulsions made with POE nonionics (Shinoda & Takeda, 1970). By varying the composition of these ingredients it is possible to alter the PIT to suit manufacturing conditions (Foerster et al. 1990). Two options for the formation of PIT emulsions are as follows: 1. hot/hot process: as with conventional emulsions both the oil and the water phases are separately heated to the temperature at which they will be mixed (~85-90 C). They are then mixed at this temperature, which is in the PIT range, and the resulting emulsion is cooled rapidly to room temperature. 2. hot/cold process: the oil phase and a portion of the water phase are heated to the PIT temperature where they are mixed to form a microemulsion. The remaining cold water is then added to aid rapid cooling to room temperature. The second method is favoured because there is less volume of liquid to be heated, which saves time and energy usage for manufacturers and the microemulsion phase enables easy visualisation of the required phase inversion. PIT technology for the manufacture of emulsions is known but not commonly used. As low viscosity emulsion products gain commercial popularity (e.g., sprayable emulsions), then it is expected that this theory will become more frequently utilised. Marketers are continually requesting lighter feeling products and the PIT technology meets this need perfectly although marketing trends for EO-free products from the growing natural products area (Aubrey Organics, Purist Company) may limit its use to a degree. Gasic et al (1998 a & b) researched the possibility of using PIT as a parameter for the selection of an appropriate nonionic emulsifier. Some linear dependence between the PIT and HLB value of the emulsifier was found for lower ethoxylates but when placing the corresponding values into an empirical equation connecting these values, the expected results were not obtained

54 Chapter New Method Introduction Emulsion Phase Matching (EPM) Despite the very many methods detailed in Chapter 1.4 to aid emulsifier selection when formulating emulsions, there is still no definitive technique available that can pinpoint an emulsifier or emulsifier combination that will form a guaranteed commercially stable emulsion. Trial and error is still required in emulsion formulation and this remains a source of frustration to formulation chemists. The idea behind this current work was to investigate a different approach that perhaps may take us a step nearer to finding a more comprehensive method for emulsifier selection. To the best knowledge of this student, and her supervisors, a new method called EPM is introduced, in this thesis, for the first time. The Emulsion Phase Matching method involves an alternative approach to surfactant selection; the surfactants, which possess two separate parts (or entities) and situate themselves between two different phases, are evaluated as two individual entities. For a required emulsion system, the separate surfactant entities are selected based upon their comparison with the two phases that are to be emulsified. Consider Figure 1.4 which displays a diagrammatic summary of the EPM technique. Emulsifier Emulsion Value 1 Value 2 Value 3 Value 4 Value 2 Value 1 = ΔValue Surfactant Value 4 Value 3 = ΔValue Emulsion Figure 1.4 Schemetic Diagram of the EPM Technique

55 Chapter 1 A given physical property is chosen and measured for each of the two surfactant entities as well as for each of the emulsion phases. The difference (ΔValue) between each pair is measured and compared. Where ΔValue Surfactant and ΔValue Emulsion are matched, then the emulsion will be the most stable according to the EPM technique. It should be noted that the EPM technique does not rely on a causal link between the selected physical parameter and emulsion stability. It does rely, however, on a correlation to exist. A low interfacial tension, for example, is thought not to directly result in emulsion stability; in fact, it should result in easier breaking of that emulsion. A low interfacial tension may, however, correlate to emulsion stability because both result from a high packing density of emulsifier at the interface Summary and Comparison of Theories The HLB technique is quite simple to use but has a large number of limitations for today s emulsions. The solubility parameter addresses several of these limitations but is too complex for everyday use and has not achieved widespread acceptance in the area of emulsion development. PIT technology is viewed by many manufacturers as requiring a change in both processing procedures and equipment and has also not been widely embraced. The EPM technique may provide a more practical approach. In this thesis, the Emulsion Phase Matching (EPM) technique is being proposed to offer a different approach to the current systems. It is designed to be more encompassing than the HLB system but just as easy to use. There is, deliberately, no attempt to inter-relate the proposed EPM technique to the existing HLB technique. It was felt that the HLB system has too many limitations to meet today s emulsion requirements (particularly in the cosmetic area) and that a completely fresh approach is required. It is believed that the Emulsion Phase Matching technique is the first technique designed to select an emulsifier based on the individual properties of both the hydrophilic and

56 Chapter 1 lipophilic moieties. As already described, surfactants are made up of two completely distinct parts, or moieties, and yet traditionally, the emulsifier is treated as a whole. The EPM technique requires the formulator to determine a measure of difference between the oil and water phases to be emulsified. An available database then enables the formulator to match their difference value to the same value for an emulsifier. It is possible that experimentation may show that a scaling factor is required to provide this match. If the difference in properties between the hydrophobic and hydrophilic moieties of the emulsifier is the same as those between the oil and water phases of the emulsion, the emulsifier is ideally balanced between the two phases at the interface and does not favour one phase over the other (i.e., is not more soluble in one phase than the other). There is, therefore, a reduced tendency for phase migration and a high possibility of maintaining a strong emulsifier layer at the interface. This will aid emulsion stability. The EPM offers two key differences from the other systems so far described: 1. It allows for consideration of the separate emulsion phases, in their entirety, to gain and utilise information about the system as a whole, including any effects of auxiliary materials. 2. It splits emulsifiers into their corresponding hydrophobic and hydrophilic entities and considers the individual effects each will have on its relevant phase of an emulsion. Full details of the EPM technique, including the theory behind it, are given in Chapter 2. The aim of this current work is to evaluate the concepts behind the EPM technique and assess its feasibility and usefulness in practical terms

57 Chapter TECHNIQUES TO CLASSIFY EMULSIFIER MOIETIES The emulsifier moieties and oil phase ingredients used in the EPM method need to be systematically measured in order to build up an EPM database. The main techniques used to obtain such measurements in this study are surface and interfacial tension. The short range intermolecular forces which are responsible for surface/interfacial tensions include van der Waals forces (particularly London dispersion forces) and also hydrogen bonding for aqueous systems as well as metal bonding for metallic surfaces. The relatively high value of the surface tension of water (72.8 mn m 20 C) reflects the contribution of hydrogen bonding. The forces represented by surface and interfacial tension are, according to Shaw (1993), assumed to be additive and are not appreciably influenced by one another. The surface tension of water can be considered as the sum of its dispersion forces and its hydrogen bonding forces. In the case of hydrocarbons, the surface tension is entirely the result of its dispersion forces. Surface and interfacial tension values, therefore, provide valuable information about the different intermolecular forces possessed by different materials and the way they interact, which is important in assessing how materials mix when forming an emulsion. The ease of emulsion formation increases, and the droplet size achievable decreases, as the interfacial tension falls (Everett, 1988) An EPM classification based on solubility parameter was also considered. A review of literature relating HLB to solubility parameters is given in section Surface Tension Molecules located at the surface of a liquid are not completely surrounded by other molecules like they are in the bulk solution. This causes a net inward force of attraction exerted on a molecule at the surface from the molecules in the bulk solution, which results in a tendency for the surface to contract. This contraction is spontaneous i.e., it is

58 Chapter 1 accompanied by a decrease in free energy and explains why droplets of liquid and bubbles of gas tend to naturally form a spherical shape. Surface tension (γ) is defined as the force acting at right angles to any line of unit length at the liquid surface (Shaw, 1993). A more favoured and clearer definition is the work required to increase the area of a surface isothermally and reversibly by a unit amount (Shaw, 1993). The unit commonly used is mn m -1 although many older texts give surface tension values in dynes cm -1. The two units are equivalent. The tension of a surface must be balanced by an equal and opposite force. For an isolated droplet the balancing force must come from stresses generated within the droplet by the surface tension itself. The stresses so generated (known as capillary pressure) depend, for liquids, on the surface tension and on the curvature of the surface. This simple experimental fact was discovered in 1709 (Hawksbee, 1709) but nearly a century passed before Young (1805) deduced the correct theoretical relationship between capillary pressure and surface curvature. Working independently from Young, Laplace (Greene, 1964) defined the first algebraic equation linking capillary pressure (p) and curvature: p = γ[(1/r 1 ) + (1/r 2 )] where γ is surface tension, and r 1 and r 2 are the radii of curvature of any two normal sections of the surface perpendicular to one another. This equation is now known as the Young-Laplace equation and describes the shape of a fluid drop under equilibrium conditions. A hanging pendant drop can be analysed more reliably than can a sitting sessile drop, since axial symmetry can be safely assumed for the pendant drop. Unfortunately, the Young-Laplace equation cannot be solved analytically and solutions rely on numerical techniques and interpolations. The classic solution was provided by Bashforth and Adams (1883) although today, the more modern recalculated tables of Padday (1969) are used

59 Chapter 1 Figure 1.5 illustrates a pendant drop and the Bashforth-Adams technique for solving the Laplace-Young equation to determine surface tension values. S W S E = Equatorial diameter (maximum) H = Distance S E from lowest point of drop shape S W = line parallel to S E at top point of H S E H = S E Given fluid density, the value of S W /S E is an entry into a reference table (Padday, 1969), which yields surface tension. Figure 1.5 Surface Tension Derived from a Hanging Pendant Drop Interfacial Tension There is no fundamental distinction between the terms surface and interface, although it is customary to describe the boundary between two phases, one of which is gaseous as a surface and the boundary between two non-gaseous phases as an interface. At the interface between two liquids there is, like that with surface tension, an imbalance of intermolecular forces. This imbalance is generally of a lesser magnitude than between a liquid and a gas. Consequently, interfacial tension (γ) values are considerably lower than surface tension values for similar materials. Interfacial tension is measured according to the same pendant drop technique as described for surface tension

60 Chapter Application of the Solubility Parameter A criticism levelled against the HLB concept has been that it disregards the effect of the chemical nature of the hydrocarbon moiety of the surfactant (Vaughan, 1993). Schott (1984) investigated the application of the solubility parameter concept to nonionic surfactants. He compared solubility parameters determined from heat of vaporisation, as well as using a calculated method derived by Small (1953), with relevant HLB values. He initially found a poor comparison between the methods but after correction for the hydrogen-bonding component he found that plots of HLB versus solubility parameter were nearly linear and parallel for the three series of polyethoxylated nonionic surfactants studied (based on dodecanol, octyl phenol and sorbitan). According to Vaughan (1993), Schott (1984) also appears to be the first person to utilise the different solubility parameters of the nonpolar and polar ends of surfactants to increase their efficiency in emulsions. He suggested altering oil or water phase ingredients to make them better match the emulsifier tails. Schott s approach has some similarity to the concept of the EPM technique whilst not quite treating the emulsifier moieties as separate entities. It appears sensible to use the solubility parameter values for the separate emulsifier moieties if they are available. Therefore, alongside the characterisation of materials for the EPM technique (in Chapter 4) the solubility parameter values of the separate entities will also be evaluated. The EPM technique is developed throughout the course of this work. The following Chapter (Chapter 2) outlines the philosophy behind the technique and how it might work in practice

61 Chapter 2 CHAPTER 2 EPM TECHNIQUE FOR EMULSIFIER SELECTION 2.1 DEVELOPMENT OF EPM THEORY The EPM technique is an emulsifier selection technique suitable to meet the emulsion formulation requirements of the current day. It is designed to be a more encompassing and accurate method for the prediction of optimal emulsifiers than the popular HLB technique but one that is just as easy to use. Cosmetic formulations have increased in complexity over recent years: Increased competition in the marketing of cosmetic formulations has meant that many more materials must be included to satisfy consumer demands or offer a product that has a perceived edge over the competition products. These additives are not easily accounted for (with regard to their effect on emulsion systems) using the HLB system. It is rare to include just one oil (emollient) ingredient in the formulation; mixtures of three or four oils are not uncommon, to meet sensorial needs or for better solubility of an active ingredient, making it more difficult to predict the most suitable emulsifier. Safety considerations of raw materials, including their impurities, are more prominent in the public domain. This is forcing some restriction in the use of some materials. Recent publications (Koopman, 2004, Begoun, 2002, Sittig, 2002) and numerous 2006 websites ( have resulted in chain letters or newspaper advertisements discussing the dangers of sodium lauryl sulfate (SLS), paraben preservatives, ethylene oxide surfactants or nitrosamines as potential carcinogens. Although there are many other articles where SLS is

62 Chapter 2 defended (NICNAS, 2002) and the information on the dangers of these materials is somewhat limited, from a marketing perspective the damage is done and SLS and parabens, at the very least, are rarely used in current cosmetic and toiletry developments. Unfortunately, this list of labelled potentially harmful materials continues to grow resulting in limitations of the use of some traditionally very commonly used raw materials. This further makes the job harder for the formulating chemist. The importance of being able to evaluate the oil and water phases, with all of their additives, cannot be over-stressed. It is common practice, for example, for a formulating chemist to select (on the basis of HLB numbers) a suitable surfactant for a given O/W emulsion, and this can often result in the preparation of a suitably stable emulsion. However, it is also common practice, after the emulsion has been stabilised, for the chemist to be required to add, for example, a herbal extract, a fragrance, preservative or dye. Not surprisingly, these additional components often destabilise the emulsion and hence their addition becomes a limiting factor in the resulting commercial viability of that product. It is difficult (although not impossible) to account for such additives using the HLB procedure. Gasic et al (2002) were able to prove that it is possible to account for additives using the HLB procedure by studying the influence of three additives (ethanol, ethylene glycol and glycerol) on the HLB values of nonionic emulsifiers. This work made the conclusions that ethanol and ethylene glycol could contribute to an increase in the stability of emulsions whilst glycerol has the opposite effect. Glycerol is a common additive in cosmetic emulsions as a humectant / moisturising agent and so this work is very relevant. Unfortunately, there are a very large number of other additives used and to do this work on each additive for each series of emulsifiers is not really feasible. The EPM procedure, to be developed here, adopts a slightly different approach. In this process, a suitable property is directly measured by the formulating chemist. The

63 Chapter 2 property is a particular measure of difference of intermolecular forces between the oil and water phases to be emulsified. An available database then enables the formulator to match their difference value to the same value for an emulsifier. Only a simple measurement of a physical property is required making the system quick and easy to use. Each moiety of a surfactant does posess very different physical and performance properties. The EPM technique is aimed to promote consideration of how these individual moieties influence the stability at the interface of a specified emulsion system Hydrophobic and Hydrophilic Moieties of Emulsifiers Within the EPM technique each of the surfactant moieties are considered as individual entities, rather than a whole molecule. Here, an emulsifier can be split into its corresponding hydrophobic and hydrophilic moieties before any further characterisation. The properties of the separate sections are then assumed to be identical to analogous compounds which have genuine physical existence and can be tested. The analogous compounds are chemically identical to the above-mentioned moieties except that they possess an additional hydrogen atom Example of the Splitting Process as applied to Laureth-4 Figure 2.1 displays diagrammatically an example of splitting the emulsifier Laureth-4. This splitting process is an important part of the EPM Technique so more detailed explanation is also given below

64 Chapter 2 Example of splitting the emulsifier laureth-4 Hydrophobic tail Hydrophilic head group CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH Add one Hydrogen to make stable materials CH 3 (CH 2 ) 10 CH 3 =C 12 H 26 H(OCH 2 CH 2 ) 4 OH Dodecane PEG 200 Figure 2.1 Example of Emulsifier Splitting in EPM Technique The emulsifier laureth-4 has the molecular formula: CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH The hydrophobic portion of the emulsifier laureth-4 is its lauryl (C 12 ) chain, CH 3 (CH 2 ) 10 CH 2 but this is not a stable material on its own. The addition of one hydrogen atom forms the stable C 12 alkane - dodecane C 12 H 26. Thus dodecane is the hydrophobic moiety for this emulsifier and for all ethoxylated, laureth emulsifiers. The hydrophilic portion of the emulsifier laureth-4 is -(OCH 2 CH 2 ) 4 OH, which again is not a stable material. The addition of a hydrogen atom forms the stable entity polyethylene glycol (PEG) 200, and this is the hydrophilic moiety for this emulsifier. The addition of a hydrogen atom (H), in this case, is likely to render the moiety slightly more hydrophobic than it really is. An alterative would be to add a hydroxyl (OH) group resulting in a diol. However, this would only serve to render the moiety more hydrophilic than it really is, and would probably be a greater deviation from reality than the addition of an H atom. It would also be problematic in terms of synthesizing the resulting compounds, particularly with the other surfactants used later in this thesis. The

65 Chapter 2 use of H to complete the molecule, rather than OH, will be used for the sake of conformity in all future compounds. It should be noted that the number that appears in the PEG 200 name, as is the case for all the PEG materials, indicates the approximate molecular weight of the substance. For example, commercial grade PEG 200 has a molecular weight range of g mol -1 (Merck, 2001). The chemical formula states 4 moles of ethylene oxide for this substance but in reality the number 4 is an average value and commercial samples will have a value around this number. Commercial grade materials were used in this work because this average number of moles of ethylene oxide also applies to the commercial emulsifiers used here, and the EPM technique is designed for commercial use. The broader distribution in EO numbers actually produce more stable O/W emulsions than those with a narrower distribution due to improved packing at the interface. They are also more stable over a larger temperature range (Saito, 1990) EPM Database An EPM database must contain data characterising a comprehensive range of commercial emulsifiers. This is an essential requirement of any technique if it is to obtain widespread acceptance and use. For the purposes of this project, where the feasibility and use of the technique is being investigated, six nonionic emulsifiers were studied. Nonionic emulsifiers are the dominant surfactant type used in emulsification and this emulsifier group would also provide the best comparison to the HLB technique. To obtain a range of values, emulsifiers were selected to be two sets of three emulsifiers: Three laureth series emulsifiers and three ceteareth series emulsifiers. The two sets of emulsifiers allow for a variation in the hydrophobic groups whilst, within each set, the hydrophilic group is varied. Many more emulsifiers will need to be added to the database as the next stage in the development of the technique

66 Chapter 2 The ultimate goal of the EPM technique is that the formulating chemist will determine the EPM value for their emulsion system (prior to emulsification) and then be able to match their value to the emulsifier EPM value in the database. In this case, there is no need for a second database comprising the required values for the oil phase, or to adjust the value to account for additives. Indeed a potentially helpful by-product to the EPM Technique is that a complimentary section in the database could very easily, with time, be put together to list auxiliary materials that generally do not alter the interfacial tension of the emulsion system. This would provide the formulator with options that have historically been added to a system without influencing the interfacial tension and resulting emulsion stability. Previous experience with other selection systems has shown that formulators want to have the data available for the other materials before they will fully use the system (the solubility parameter system is an example where insufficient data is readily available and is therefore under utilized in industry). Data for a system similar to the one they are using gives the formulator confidence and encourages them to use the system. It also shows that the system has been thoroughly tested and utilised. Unfortunately, to build up a database for all the possible oils and auxiliary materials that could be used in an emulsion is beyond the scope of this thesis. The aim here is to evaluate the feasibility of the proposed EPM technique and to put forward the next steps to advance the technique further in the future. It is recognized that further work will be required before any recommendations of the use of the EPM technique can be implemented. Interfacial tension has been selected as the parameter to classify the emulsifiers, oils and auxiliary materials to build up the EPM database. As explained in Chapter 1.5, interfacial tension values give a large amount of information about the intermolecular forces in a system which, in some circumstances, can be very different when considering the phase boundaries rather than bulk properties. Emulsions display one such circumstance where the phase boundary area is so large compared to the volume of the system that a substantial fraction of the total mass of the system is present at boundaries. In this case, surfactants can always be expected to play a

67 Chapter 2 major role in the system (Rosen, 2004) and interfacial tension is an important measure to attempt to understand what is going on in a particular system. Most significantly, interfacial tension is a technique that can be carried out using the entire oil and the entire water phases (i.e., including all the auxiliary materials). Many auxiliary materials do have an effect on surface activity whether it is an effect on micelle formation, or to consume surfactant by adsorption on their own surfaces. This important point is not covered by any current emulsifier selection technique, but is implicit in the use of the entire aqueous (or oil) phase when measuring its characteristic property (interfacial tension). Common auxiliary materials include essential oils for natural fragrance or aromatherapy claims, starches and polymers for sensorial adjustment, oil based vitamins or amino acids and peptides for skincare claims. All of these ingredients can impact on the adsorption and consequent availability of emulsifier at the emulsion interface. Interfacial tension has not been chosen on the basis of any currently recognised emulsion stability theory. Indeed, whilst it is known that lowering the interfacial chemistry makes it easier to form an emulsion, it is also known that under many conditions it also makes it easier to break that emulsion. However, a correlation between interfacial tension and surfactant concentration at the interface may be found. Indeed, work by Evans et al, (2002) proposes a model for surfactant adsorption kinetics using dynamic interfacial tension (also using the pendant drop technique). This work will be described in a little more detail in the next section (2.1.3). There is considerable work ongoing on the effect of surfactant structure on interfacial properties. Due to the large number and types of surfactants available it is a very complex area to make generalisations. Rekvig et al (2003) found that for a given interfacial tension, a double-tail surfactant is more efficient than a single-tail isomer only if the head repulsion is sufficiently strong. For a given concentration in the bulk water phase, the single tail surfactants are more efficient in both cases. In general, since highly purified surfactants produce interfacial films that are not close packed and hence not mechanically strong, good emulsifying agents are usually a mixture of two or more

68 Chapter 2 surfactants rather than an individual surfactant. A commonly used combination consists of a water soluble surfactant and an oil soluble one to increase the lateral interaction between the surface active molecules in the interfacial film and condenses it to one that is mechanically stronger than where a single surfactant only is used (Rosen, 2004). More recent work by Li et al (2005), states that there is a close correlation between the interfacial activity and the adsorption of the surfactant at the interface. This work also found a beneficial decrease in interfacial tension value if the hydrophobic chains of the surfactant and the oil have a similar structure which supports to a degree the idea behind the EPM technique. If the conditions are achieved that are the most energetically favourable for a surfactant to be at the interface between the oil and water droplets, then the highest possible concentration of emulsifier will be at the interface. A strong interfacial film should be achieved. This, coupled with the fact that cosmetic emulsions are thickened, thus reducing the number of droplet collisions that occur, should provide systems with enhanced stability. Interfacial tension measurement is also a widely known technique that is relatively simple to perform EPM Theory The principle behind the EPM technique is to create an environment where it is much more energetically favourable for the emulsifier to be at the oil/water droplet interface than anywhere else in the emulsion system. The emulsifiers selected using the EPM technique should result in a maximum concentration of emulsifier molecules at the interface, thus providing a strong defence against droplet collisions, thinning, coagulation and coalescence. The interfacial tension measurements taken for the specific oil and aqueous phases against one another provide a measure of the imbalance of attractive forces that exists at the interface between them. Similar measurements between the hydrophobic and

69 Chapter 2 hydrophilic moieties of the emulsifier, provides a measure of imbalance for the emulsifier. If these two levels of imbalance are matched then the belief is that it should be energetically more favourable for the emulsifier to go to, and remain, at the droplet interface. This would reduce the tendency for phase migration and maintain a strong emulsifier layer at the interface. Newton s Third Law of Motion states that for every action there is an equal and opposite reaction. The relevance to cosmetic chemistry is clearly seen in dermatology when soap is applied to the skin during the cleansing process. Soap possesses a high ph and the surfactant cleansing effects also results in a removal of the natural sebum required to maintain the condition of the epidermis. The sebaceous glands immediately act to counteract the condition left by the soap and restore the correct balance (the reaction to the action of the high ph on the skin). The higher the ph of the soap and the more aggressive the surfactant on the skin (the action ), the greater the potential damage to the skin and the stronger the reaction of the sebaceous glands to compensate the effect. However, as stronger re-actions are required, it is more difficult for the sebaceous glands to produce the correct amount of sebum. This can then lead to skin disorders until the system can once again be stabilised. It is always the case that the greater the imbalance or change to any system, the harder it is to judge the appropriate re-action and the longer the system takes to stabilise. The proposal of the EPM technique is that by measuring an imbalance of the two phases to be emulsified and matching this to an emulsifier whose moieties possess the same level of imbalance, then the emulsifier is balanced at the emulsion interface. If a good balance can be achieved then there should be a lower tendency for disturbance effects at the interface which therefore, requires less reaction of the emulsifier at the surface and a stronger interfacial film at the emulsion interface. No other emulsifier prediction technique has attempted to achieve a balance between the produced emulsion and the emulsifier which is situated at the interface. If the situation is

70 Chapter 2 not balanced, this must promote activity to attain a balance which may well weaken the emulsion system. The emulsifier needs to be strongly attracted to the interface upon initial mixing of the emulsion phases in order to promote a small initial droplet size. It is also very important for the emulsifier to form a strong elastic barrier to resist droplet coalescence when the droplets collide. A continually high concentration of emulsifier at the interface is one such condition that supports both of these criteria the high packing of emulsifier at the interface providing an increase in surface viscosity, as well as providing a steric barrier to coalescence. Theories to explain surfactant adsorption, resulting surface concentration at the interface and the strength of the resulting interfacial layer are only known to a limited degree in colloid science and this remains an area of future development. Sjoeblom, 2001 and Rosen, 2004 provide a comprehensive summary of the dynamics of surfactant adsorption currently known. According to Sjoeblom, the most popular surfactant adsorption isotherms are those of Langmuir (1917 & 1918), Volmer (1925), Frumkin (1925) and van der Waals (Brunauer et al., 1940). There are also expressions for the Gibbs (1928) elasticity of adsorption monolayers which correspond to these isotherms. Because of the complexity of the adsorption processes, the proposed theories are based around monolayer formation. This may or may not be the true case. Evans et al., (2002), proposed a model for surfactant adsorption kinetics which incorporated random sequential adsorption (to account for difficulty associated with packing at the interface) and mass transfer theory (to calculate the concentration of surfactant near the interface). The associated adsorption isotherm, when combined with the Gibbs equation and some micellisation equilibria, gave good agreement between the equilibrium values of the interfacial tension versus the total surfactant concentration. The agreement was not so good at concentration levels above the critical micelle concentration and Evens suggested that the micelles near the interface collapse to provide free surfactant for rapid adsorption at the interface

71 Chapter 2 The work by Evans highlights the difficulty in understanding the adsorption process at the interface, even in a single surfactant system. Considering that in cosmetic emulsions the surfactant level would most definitely be above the critical micelle concentration and there may also be two emulsifiers, it would be a very complex exercise to understand the mechanism for the formation of interfacial layer using the EPM technique. Instead, for the current work, the focus has been on forming the emulsion and measuring the resulting stability to establish the merit of the technique and identify any obvious improvements which can be made. If the correlation proves fruitful, then the next steps for advancement of the technique should include an understanding of the actual mechanisms involved. Computer simulation is becoming an effective tool for the study of interfacial systems on a detailed molecular level. The work by Li et al., (2005) used a mesoscopic level simulation named dissipative particle dynamics (DPD) to investigate the behaviour of surfactants at the water/oil interface. This technique has now been used by many researchers (Rekvig et al., 2004, Dominguez, (2002 & 2004), Dong (2004)) and is gaining credence, showing good agreement with experimentation. It is hoped that as this method, or ones like this develop, they can be used to understand, or perhaps prove, that the EPM technique can provide a strong emulsifier barrier at the interface Benefits of the EPM Technique The benefits of the EPM technique, as discussed in this Chapter, can be listed as follows: All ingredients to be included in the emulsion can be taken into consideration before the emulsifier selection is made. Method is all encompassing Even the newest materials can be considered One simple measurement only is required to be carried out by the formulator to determine the EPM value of that system. Little work required from formulator

72 Chapter 2 The value measured by the formulator is matched to a corresponding value in the EPM database to identify the optimum emulsifier(s) to be selected. Quick, easy reference system will be available Where materials are changed or added as the formula develops, a repeat of the same simple measurement only is required to see if modification to the emulsifier system is required. Offers flexibility to the formulator

73 Chapter 3 CHAPTER 3 MATERIALS AND METHODS 3.1 MATERIALS Materials were selected to prepare emulsions in both ideal and commercial systems. Emulsifiers, oils and other auxiliary materials were used to form the foundations of an EPM database Emulsifiers Selected for EPM Technique Evaluation The emulsifiers selected were from the broad ranging group of ethoxylated fatty alcohol surfactants, which have the general chemical formula: R(OCH 2 CH 2 ) n OH where R = alkyl and n = 2 to 60 Table 3.1 provides a summary of the emulsifiers selected for use in this study. The International Nomenclature Cosmetic Ingredient (INCI) name, chemical formula, tradename and supplier details are given along with HLB value (explained in Section 1.4.1) to give an indication of the range of emulsifier properties covered. Table 3.1 Emulsifiers Selected for EPM Technique Evaluation Emulsifier (INCI Name) Chemical Formula Tradename & Supplier HLB Value Laureth-2 CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 2 OH Dehydol LS2 (Cognis) 7 Laureth-3 CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 3 OH Dehydol LS3 (Cognis) 8 Laureth-4 CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH Dehydol LS4 (Cognis) 9.6 Ceteareth-12 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 12 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 12 OH Eumulgin B1 (Cognis) 13 Ceteareth-20 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 20 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 20 OH Eumulgin B2 (Cognis) 15 Ceteareth-30 50% CH 3 (CH 2 ) 14 CH 2 (OCH 2 CH 2 ) 30 OH 50% CH 3 (CH 2 ) 16 CH 2 (OCH 2 CH 2 ) 30 OH Eumulgin B3 (Cognis)

74 Chapter Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers To apply the EPM concept, the selected emulsifiers were first split into their hydrophobic and hydrophilic segments as explained in Chapter 2. The hydrophobic and hydrophilic segments for each of the selected emulsifiers are summarised in Table 3.2 along with the supplier and grade used. TABLE 3.2 Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers Emulsifier (INCI Name) Hydrophobic Moiety Grade and Supplier Hydrophilic Moiety Supplier Laureth-2 Laureth-3 Laureth-4 Dodecane Dodecane Dodecane Analar (BDH) Analar (BDH) Analar (BDH) Diethylene Glycol Triethylene Glycol PEG 200 ICI (Huntsman) ICI (Huntsman) ICI (Huntsman) Ceteareth-12 50% Octadecane 50% Hexadecane Analar (BDH) Analar (BDH) PEG 600 ICI (Huntsman) Ceteareth-20 50% Octadecane 50% Hexadecane Analar (BDH) Analar (BDH) PEG 1000 ICI (Huntsman) Ceteareth-30 50% Octadecane 50% Hexadecane Analar (BDH) Analar (BDH) PEG 1500 ICI (Huntsman) Oils Selected for EPM Technique Evaluation Oils commonly used in commercial applications were required that would display a wide range of interfacial tension values, when measured against water. A range of oils from the same chemical type was preferred in the first instance, to avoid the probability of specific and variable chemical interactions affecting the stability of the emulsion. Esters are the largest single family of cosmetic oils commercially available and those selected are detailed in Table 3.3. All oils were supplied by Cognis (formerly Henkel)

75 Chapter 3 TABLE 3.3 Selected Oils - Simple Esters Simple Esters (INCI Name) Tradename General Chemical Formula R 1 COOR 2 R 1 R 2 Ethyl Hexyl Palmitate Cegesoft C24 Palmityl C16 2-Ethyl hexyl C8 Hexyl Laurate Cetiol A Lauryl C12 Hexyl C6 Decyl Oleate Cetiol V Oleyl C18 1 Decyl C10 Ethyl Hexyl Stearate Cetiol 868 Stearyl C18 2-Ethyl hexyl C8 Iso-Propyl Myristate IPM Myristyl C14 Iso-propyl C3 Iso-Propyl Palmitate IPP Palmityl C16 Iso-propyl C3 It is a requirement by law (Federal Bureau of Consumer Affairs, 1991) that all ingredients present in a commercial formulation are listed on the label of these products for information to the consumer. If time is taken to look at the ingredients of several cream and lotion products available, it can be seen that although the most common oil is an ester, it is rarely the only oil present. The majority of products contain oils from more than one different chemical group. For example, Dove Hand Lotion contains mineral oil in combination with an ester whilst Nivea Hand Cream contains octyldodecanol and capric/caprylic triglyceride in combination with an ester It is therefore appropriate to consider a second set of oils from other classes in the scope of this project. Oils covering a much wider range of polarities are needed. A second group of oils of different polarity were, thus, also tested. Their details are given in Table

76 Chapter 3 TABLE 3.4 Selected Oils - from other Chemical Groups Name of Oil (INCI Name) Tradename Chemical Type Chemical Formula Dibutyl Adipate Cetiol B di-ester CH 3 (CH 2 ) 3 OOC(CH 2 ) 4 COO(CH 2 ) 3 CH 3 Capric/Caprylic Triglyceride Myritol 318 mixed tri-ester CH 2 (OCOR)CH(OCOR)CH 2 (OCOR) R = C 7 H 15 and C 9 H 19 Cocoglycerides Myritol 331 mixed glyceryl ester (mono-, di-, and tri-esters) General formula as above with also mono- and di- glycerides from C 8 - C 16 Octyl dodecanol Eutanol G alcohol (Guerbert) CH 3 (CH 2 ) 9 CH(CH 2 (CH 2 ) 6 CH 3 )CH 2 OH Dioctyl cyclohexane Cetiol S cycloalkane (aromatic) 1,3 di-c 8 H 17 C 6 H 4 Mineral Oil OP6A mixed aliphatic alkanes CH 3 (CH 2 ) X CH 3 X = Dicapryl Ether Cetiol OE ether CH 3 (CH 2 ) 6 CH 2 OCH 2 (CH 2 ) 6 CH Auxiliary Ingredients Selected for EPM Technique Evaluation In addition to emulsifiers and oils, commercial formulations also contain a large number of water-soluble additives. For example, aqueous systems require preservation to ensure they have a useful shelf-life. Fragrances and viscosity regulating materials are added for consumer acceptance and other active materials (e.g. herbal extracts, sunscreen filters etc) are also often included to make a marketable, desirable product. For the purposes of this work, just a few of these auxiliary materials were selected for study and these are listed in Table

77 Chapter 3 Table 3.5 Auxiliary Ingredients Selected for EPM Technique Evaluation Material (INCI Name) Water Glycerine Carbomer Cetostearyl Alcohol Tocopherol Acetate (Vitamin E) 5-Chloro-2-methyl- 4- isothiazolin-3-one Tradename and Supplier Purified Glycerine USP Carbopol ETD 2001 (BF Goodrich) Lanette MY (Cognis) Copherol 1250 (Cognis) Kathon CG (Rohm & Haas) Function Aqueous phase solvent Humectant and solvent Consistency giving agent Consistency giving agent Moisturising Agent Preservative Arginine (and) Disodium Adenosine Triphosphate (and) Mannitol (and) Pyridoxine HCl (and) RNA (and) Histidine HCl (and) Phenylalanine (and) Tyrosine Santalum Album Photonyl LS (Laboratoires Serobiologiques) Sandalwood Oil (Dragoco) Active ingredients for protection against photoageing Fragrance, essential oil active The function that these raw materials perform in the formulation is given as well as the tradename and supplier. All these suppliers listed provide their own technical supporting data and guide formulations to help the formulation chemist achieve the desired performance. All emulsifiers, oils and auxiliary materials used throughout this project have been summarised within Chapter 3.1. The next section details the main methods used to characterise these materials

78 Chapter METHODS The methods used and the accuracy of the instruments employed during this project, were vital to determine the validity of the EPM technique. Hence, a detailed description is given below The First Ten Ångstroms (FTÅ) 200 Instrument The FTÅ 200 is an instrument that uses rapid video capture of images and automatic image analysis to accurately determine properties such as surface tension, interfacial tension and contact angle. Surface and interfacial tension can be measured from a drop s shape using the Bashforth-Adams technique as explained in Chapter 1.5. The FTÅ s efficient video imaging system is capable of measuring many separate images per second, which can be used to statistically improve the precision of the results. The manufacturer (First Ten Ångstroms) recommends a minimum of 10 image analyses be used. For optimum results, First Ten Ångstroms also suggest that the image of the drop, as viewed on the computer screen, occupies at least one half of the screen. This also helps the user to determine the best definition of the image and provide a clear, sharp image necessary for analysis. The FTÅ optimally fits curves to the regions of interest in the pendant drop image to minimise noise effects and to provide accurate measurements. This has previously been difficult to achieve with any other method without large associated errors. An image is taken to check that the conditions are suitable for analysis. Error messages are displayed if the image is not sufficiently defined to enable accurate measurements to be taken. If this is the case the following adjustment options are available: a) focal length (by physical movement of the camera) b) focus (on the camera lens) c) brightness scale d) contrast scale

79 Chapter 3 A picture of the FTÅ 200 instrument is given in Figure 3.1. Computer Image of Droplet Figure 3.1 Instrument Photograph of the FTÅ 200 Instrument Set-up Once an image has been successfully taken and analysed, a series of images of the drop (a movie ) can then be taken for the actual measurement. Throughout the project, for both instrument calibration and sample measurement, 25 images were taken to enable a measurement to be recorded. The FTÅ 200 software package reduces the grey-scale computer image to a set of equations describing the drop s edges. Resolution to less than the size of one pixel is available and a least-squares fit is used to derive the curve equation. The least-squares fit effectively averages many data points into one equation, smoothing the inevitable noise in the video image. The image analysis software is next utilised to solve the analytical equations applied to the images and determine the result of the analysis. In the case of surface and interfacial

80 Chapter 3 tension, this equation was the Laplace-Young equation which is solved using the classical Bashforth-Adams technique with the more modern recalculated tables of Padday (1969). Extensive statistical analysis of the result was provided by the FTÅ 200 software package. The output values that were of most interest for the project include the average (arithmetic mean - ξ), minimum and maximum values as well as the standard deviation (σ). Surface and interfacial tension values were all reported by the FTÅ in the units of dynes which is equivalent to the more modern unit of mn m -1. The surface and interfacial tension results are reported throughout this study as the mean value with its 95% confidence limit, calculated according to basic statistical analysis Instrument Standardisation and Calibration Before making any interfacial tension measurements, it was necessary to standardise the FTÅ 200 using surface tension measurements. The standardisation was required prior to each use of the instrument and again during use if the focus control, or focal length was adjusted at any point during the analysis. Purified water was the standard material for the standardisation procedure, which was carried out in the Calibration mode of the software. On completion of the analysis, verification of the calibration was made using a fresh, purified water droplet. The FTÅ s syringe pump (driven by a stepper motor to dispense the test drops) was used to pump one millilitre of water through the syringe. The slow pump control was then used to deliver a large sized drop as portrayed on the computer screen. An analysis of this drop was made to confirm that the instrument was correctly prepared for the measurement of unknown materials. It should be noted that the purity of the water used was not validated using this technique, so an alternative technique (Du Noüy Ring) was used to carry out the validation. Only one source of purified water was used throughout the project and each time, water was taken from this source, it was tested using the Du Noüy Ring apparatus. The water was tested and only used when the measured result agreed (to ± 0.1 which is limit of instrument) with the CRC Handbook (Lide, 1994) literature value of 72.8 mn m -1 at 25ºC

81 Chapter 3 One syringe and needle type only was used throughout the project. These were a 10 ml B-D plastic disposable, sterile, single use syringe with a lock tip and a 1 inch length, grey collar, 27 guage needle. Both were supplied from Livingstone International, Laboratory Supplies. An example of purified water standardisation analysis, taken on different days over a period of several months, is given in Table 3.6, to demonstrate typical variations given by the FTÅ 200 instrument. TABLE 3.6 Analysis No. of measure -ments FTÅ Instrument Repeatability Temp C Lit. Value* (mn m -1 ) Mean of Data (mn m -1 ) 95 % Confidence Limit (±) Standard Deviation (large drop) 72.7 (small drop) (small drop) (large drop) 72.4 (small drop) * Barton, A., Handbook of Solubility Parameters and Other Cohesion Parameters, CRC Press, Boca Raton, Florida (1990) Included in the data set are results taken on the same date, within a few minutes of each other, where the influence of the size of the droplet was investigated. The recommended droplet size was a minimum of one half of the screen, as viewed by the user. However, it was observed that with some liquids this was not possible only a small, circular drop could be formed. If droplet size had an influence on the results then this required identification. Analyses 3 and 4 represent an example of data where the size of the drop was varied. It was clear that the results for the smaller drop size were farther from the literature value than with the larger drop. However, if more measurements were taken of the smaller drop this did appear to give more consistency between larger and smaller drop

82 Chapter 3 size measurements. The recommended larger drop size was used wherever possible. If only a small droplet was achievable then close to 100 measurements were made to improve the accuracy of the result. To calibrate and validate the instrument over the expected range of use, surface tensions of other materials were required. Materials were selected whose surface tension literature values fell towards the two extremes of the expected values for test materials, i.e. those of diethylene glycol and hexane. A selection of the results obtained is given in Table 3.7. Table 3.7 Calibration results for Diethylene Glycol and Hexane Temp. C Lit. Value* (mn m -1 ) Diethylene Glycol Mean of Data (mn m -1 ) 95 % Confidence Limit (±) Standard Deviation Hexane * Barton, A., Handbook of Solubility Parameters and Other Cohesion Parameters, CRC Press, Boca Raton, Florida (1990) The FTÅ 200 is a relatively new technique and even though its accuracy of pure test substances show good agreement with literature values, the instrument and its method required validation against an alternative proven instrument. The Du Noüy Ring method of surface tension measurement is widely recognised as a suitable method for determining surface tension (Hunter, 2001). Identical samples of both purified water and hexane, were measured (as sample analyses) on the two instruments. Results are given in Table

83 Chapter 3 Table 3.8 Surface Tension Validation Temp. C Lit. Value (mn m -1 ) (Hunter 2001) Du Noüy Ring Result (mn m -1 ) 95 % Confidence Limit (±) FTÅ Result (mn m -1 ) 95 % Confidence Limit (±) High Quality Distilled Water Hexane Both sets of results compare well with the literature values. The FTÅ 200 has advantages over the Du Noüy Ring instrument in that it has a sophisticated software package for analysis, provides a statistical analysis, and can measure many values in a very short period of time. The Du Noüy Ring instrument used, in this case an Analite Surface Tension Meter, displays its results to one decimal place only. This is a considerable disadvantage when measuring low surface tension values where 0.1 mn m -1 is a significant portion of the result Interfacial Tension Measurement Interfacial tension measurements between two immiscible liquids, at least one of which is clear enough to transmit light, is determined using the FTÅ 200 by exactly the same Pendant Drop technique as that used to determine surface tension. In this technique, one of the immiscible liquids is formed into a drop, via a syringe (as for surface tension determination), into a cell or bath containing the liquid against which the interfacial tension is to be tested. The interfacial tension cell attachment has two parallel windows: one to allow light to shine on the as-formed droplet (from behind) and the other to allow the camera to view the image (from the front). The liquid with the highest density (generally the hydrophilic material) was dropped into the lower density liquid (generally the hydrophobic material). This ensured that the

84 Chapter 3 resulting drop was naturally hanging from the needle, as required for the analysis, and not malformed as it attempted to rise to the surface, as would be the case if the less dense material was placed in the syringe. The resulting drop was viewed through the second liquid and consequently the resulting image was optically different to that of a drop viewed alone (e.g. when formed in air). The image tended to be less clear than those achieved for surface tension measurement and so the Contrast and Brightness controls of the instrument were adjusted to obtain an image that was suitably defined for analysis. Throughout the project, a check surface tension analysis was made between each analysis using distilled water. This ensured that there had been no drift during the test measurement, which was an effect that had been observed during early measurements. If drift was apparent, then the previous measurement was discarded and the sample retested Emulsion Preparation There are many variables involved in the preparation of emulsions. In fact, this area has been developed into a graduate degree course, and postgraduate studies on optimising and controlling the many variables involved in Emulsion Formulation Engineering are now published i.e., Salager et al, 2002 and Perez et al, For the purposes of this thesis, consistency of the emulsion preparation is of paramount importance to provide accurate, comparative results. Standard procedures as described and outlined in the following paragraphs were employed to ensure this consistency. The choice of the emulsifier was the parameter under investigation in this thesis. The remaining variables, which are listed below, only require standardisation before any testing can be commenced. 1. Oil Concentration 2. Order of Mixing

85 Chapter 3 3. Degree of Mixing 4. Emulsifier Concentration 5. Emulsification Temperature Oil Concentration The best oil concentration to use in emulsion testing is arguably a value typical of those used in commercial formulations. O/W cream and lotion formulas can, and do, cover a wide range of oil concentrations and there is no single, definitive value which is used as a standard. The oil concentration of a cosmetic cream or lotion determines the degree of moisturisation offered by the product and can be required as a carrier for pigments, sunscreens or other oil soluble actives. As a guide, the oil concentrations from twenty O/W body or hand lotion recipes, featured in the Cognis Personal Care Formulation CD- ROM (Cognis GmbH, Care Chemicals Division, 1999) and shown in appendix 3, were evaluated. The oil concentration ranged from 8 to 20% with an arithmetic mean value (to the nearest integer) of 15% and so this was the concentration of oil chosen for use throughout this thesis Order of Mixing There are two distinct phases in an emulsion; the oil phase and the aqueous phase. The emulsifier is premixed with one of the phases before mixing. Becher (1965) researched this area to show which pre-mix option is preferable: a) Emulsifier-in-water method In this method, the emulsifying agent is dissolved directly in the water, and the oil is then added, with considerable agitation. This procedure prepares O/W emulsions directly. b) Emulsifier-in-oil method

86 Chapter 3 Here, the emulsifying agent is dissolved in the oil phase. The emulsion may then be formed in two ways: i) By adding the mixture directly to the water. In this case, an O/W emulsion forms. ii) By adding water directly to the mixture. In this case, a W/O emulsion is formed but if the volume of the water phase becomes high enough it is possible to spontaneously invert the emulsion to an O/W emulsion. According to Becher (1965), the emulsifying agent-in-water technique usually results in quite coarse emulsions, with a wide range of particle size. These emulsions tend to be unstable and homogenisation is essential to produce a reasonable emulsion. For the emulsifying agent-in-oil method, Becher s findings were that this results in uniform emulsions, with a small particle size range. This technique usually results in the most stable form of emulsion. Where the water concentration is above 50%, as is usual for O/W emulsions, the addition of water directly to the mixture is preferred because the process of inverting the emulsion forms a smaller droplet size. The emulsifier in oil option (ii), adding water directly to the oil, was selected for use in this work Degree of Mixing The amount of shear applied affects the mechanical energy input into the system and so can influence the initial droplet size formed. Shear applied to emulsion systems can range from 30 rpm for a traditional paddle stirrer mixer (used in traditional hot process emulsion manufacture) to 30,000 rpm for a high shear mixer (used in lower temperature emulsion preparations). In the case of this work many emulsions were prepared at room temperature and due to the absence of heat energy a high shear mixer was required rpm was selected for 90 second duration

87 Chapter Emulsifier Concentration (Theoretical Determination) In terms of interfacial tension reduction, the emulsifier concentration should be sufficient to saturate all the available interfaces. The actual particle size distribution of the emulsion is never known prior to mixing so formulators tend to act conservatively and add a slight excess. This allows for possible higher interface availability (smaller particle size distribution) and additionally for rapid repair or broken or stretched interfaces, or to account for any unexpected loss of surfactant. A large excess would be wasteful however, and also inefficient. Furthermore, the excess forms micelles in solution, which can alter the apparent stability of the emulsion by causing solubilisation of lipophilic components. There are several interfaces in the case of an O/W emulsion that are available for surfactant adsorption. The most significant interface is that between the dispersed oil droplets and the aqueous media (i.e. the emulsion interface). Its area varies depending on the droplet size and number. Other minor interfaces include those between the aqueous phase and air and between the vessel and solution surfaces. The emulsifier will position itself at all these interfaces and will also be present free in solution as well as in micelles and/or other self-assembly aggregates. It is possible to calculate the theoretical level of emulsifier required to saturate all the interfacial area between the oil droplets and the solution. It is also possible to estimate the free surfactant level in solution from its critical micelle concentration (cmc). The sum of these two values, plus a small excess to allow for loss of surfactant at, for example, the air/solution interfaces, would be a close approximation for the minimum level of emulsifier required to saturate all surfaces. This may then be equated with the minimum level of emulsifier required to give reasonable degree of emulsion stability. In practice, of course, emulsion stability may require more than a single monolayer so this value is strictly a minimum required value. Laureth-4 is an emulsifier that is used throughout this work, with the chemical formula CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH. It can be used as an example to calculate the theoretical emulsifier concentration required to ensure surface saturation is achieved

88 Chapter 3 The following information is required: 1. Average droplet size of test emulsion in this case the aim is 2.5 µm which falls inside the typical droplet size range for macroemulsions of μm (Shaw, 1993) and was the average value for three commercial body lotions (Nivea, Vaseline Intensive Care and Dove brands, see Section ). 2. Surface area of the surfactant molecule plus its molecular weight (for laureth-4, Schick (1962) measured a value of 40 Å 2 (40 x m 2 )). Laureth-4 has a molecular weight of 360 g mol -1. Note: The surface area taken up by the surfactant molecule is dependent on the chemical nature of the oil and the presence of other competing materials. It will vary with different emulsion systems. Thus 40 Å 2 can only be taken as an indicative figure and is one reason why the following calculation should be treated as an approximation only. The calculation is carried out in the following steps: Step 1: Determination of the amount of laureth-4 per average emulsion droplet. If an average emulsion droplet is assumed to possess a diameter of 2.5 μm then its surface area (SA) is calculated as follows: SA = 4πr 2 and since r = 1.25 x 10-6 m, SA = 1.96 x m 2 (1) Given that the SA of each laureth-4 molecule is 40 x m 2 (Schick, 1962), (2) 1.96 x x = 4.9 x 10 7 laureth-4 molecules (3) that can be packed per average emulsion droplet or, 8.13 x moles of emulsifier per droplet (4) Given the molecular weight of laureth-4 is 362 g mol -1, there are: 362 x (8.13 x ) = x g emulsifier per droplet (5)

89 Chapter 3 Step 2: Emulsifier required to saturate emulsion droplet surfaces As discussed in Section , a typical oil phase concentration used in O/W emulsions is 15%. Hence for the calculation, 15 ml (15 x 10-6 m 3 ) of oil phase were used per 100 ml of final emulsion. The volume of one droplet of oil V = (4/3)πr 3 and since r = 1.25 x 10-6 m V = 8.18 x m 3 (6) Therefore, per 15 ml there are: 1.83 x droplets (7) With 2.93 x g emulsifier per droplet (from equation (5)), this gives: g emulsifier per 100 ml of emulsion (0.054%) (8) It would be expected that the emulsifier required to adequately cover the dispersed oil droplets would be, by far, the most significant portion of the total concentration of emulsifier required. Step 3: Total emulsifier required to cover all available surfaces The next portion would be expected to be any micelles formed. This figure is the cmc, which is according to Rosen (1987) and Meguro (1982), for laureth-4 is 0.03 g L -1 or %. Even with a slight excess to allow for the remaining interfaces as well as errors in the assumptions made (i.e. radius of emulsion droplet and SA of emulsifier molecules), the above combined results give a concentration of less than 0.1% emulsifier. In conclusion, for an emulsion formed using laureth-4, with an average droplet size of 2.5 μm, the theoretical level of emulsifier required to guarantee interface saturation has been calculated to be less than the order of: 0.1 % laureth-4 (9)

90 Chapter 3 An emulsifier concentration of 0.1 % is, in practice, very low. In commercial emulsion preparations the figure is commonly 2 4 %. As already explained, commercial cosmetic emulsions frequently contain a number of additives, many of which can be oil soluble. A large excess of emulsifier is often added to allow a high enough concentration to rapidly supply surfactant to the interface to promote stability. In addition micelles, formed by the excess emulsifier, help solubilise any oil soluble additives and keep these additives from separating from the emulsion. No currently available technique that assists with surfactant selection allows the formulator to easily consider the effects of auxiliary materials. The formulator, therefore, errs on the side of caution and uses more surfactant to keep the material in solution. This deficiency is one that is addressed in the proposed new technique for surfactant selection covered in this thesis. Many emulsifiers are quite large and bulky molecules so they can also contribute to steric stabilisation and to the rheological properties of the overall emulsion. The excess emulsifier utilised may provide a more viscous and congested system, which could serve to aid emulsion stability by retarding the rate of droplet collisions. It should be noted, however, that there are many, cheaper materials that can fulfill exactly the same function. Using excess emulsifier is not the most efficient method to sterically stabilise an emulsion or to control its rheology. Taking all the above factors into consideration, as well as the experiments carried out in Chapter 5, an emulsifier concentration of 0.5% w/v was selected as the standard for this work. This is still an excess over the theoretical value but significantly less than the quantity frequently found in today s emulsions to try to test the proposed technique and at the same time offer a commercial advantage to its use Temperature of Emulsification As discussed in Chapter 1.2, heat is often employed to aid the initial mixing of the emulsion phases

91 Chapter 3 Heat cannot be used in every surfactant system. Ethoxylated nonionic surfactants, for example, possess a cloud point which needs to be considered. The cloud point is the temperature (or temperature range) at which the surfactant begins to lose sufficient water solubility to affect its normal function as a surfactant. Cloud points for the laureth and ceteareth emulsifiers used in this work are given as examples in Table 1.3. TABLE 3.9 Cloud Points of Selected Emulsifiers Emulsifier Laureth-2 Laureth-3 Laureth-4 Ceteareth-10 Ceteareth-20 Ceteareth-30 Cloud Point ( C) Emulsions can be prepared using the ceteareth emulsifiers at the usual processing temperatures (typically 70-80ºC). The laureth emulsifiers, however, are only truly effective in cold processable preparations. Forming emulsions at cold temperatures is, of course, quite advantageous as it eliminates the heating step altogether, saving both time and energy costs. Usually however, it is more difficult to achieve a stable emulsion when processing cold and the selection of the emulsifier, as well as high shear mixing, are very important. Due to their low cloud point, the laureth series of emulsifiers could not be processed efficiently at high temperatures. All mixing involving these emulsifiers was carried out at 20 C. The ceteareth series of emulsifiers, however, were solid at room temperature and hence, required heating to around 50 C to melt. Since it was preferred to have a single processing temperature, (to limit the number of variables involved), the emulsifier was dissolved in the oil phase at 50 C and the oil product cooled to 20 C before mixing

92 Chapter 3 with the water phase to form the emulsion. Since 20 C was selected as the temperature of emulsification, there was no need to cool the emulsions prior to their analysis Summary of Emulsion Preparation Parameters The emulsion preparation conditions so far explained can be summarised in Table 3.10 Table 3.10 Emulsion Preparation Parameters Parameter Oil Concentration Order of Mixing Degree of Mixing Emulsifier Concentration Emulsification Temperature Value used throughout Project 15% (w/v) Emulsifier in Oil Method rpm shear (IKA) 0.5% (w/v) 20 C Emulsion Evaluation The emulsions prepared were analysed using two techniques; particle size analysis using the Malvern Mastersizer and visual assessment as discussed in Chapter 1.4. Particle size analysis was carried out on the freshly homogenised emulsion to determine how effectively the emulsifier system had emulsified the oil droplets and as a reference point to later determine if there is growth / coalescence with ageing. At this initial stage all emulsions appeared as white, homogenous liquids and visual determination could not differentiate between them

93 Chapter 3 For aged samples, where the visual indicators of cream and free oil were easily observed, the visual assessment method was preferred. When these visual indicators are apparent, visual analysis gives more information on the stability, or more particularly, instability of the product. Particle size analysis was carried out alongside, if required, but where differences in the emulsions could be clearly observed, the visual method was a clearer indicator of emulsion stability Visual Determination Once the emulsions were prepared, they were stored in 100 ml graduated stoppered cylinders 40 C. An incubator was used to maintain the temperature. The emulsions were inspected after defined time periods of 24 hours, 72 hours and 1 week and their characteristics were recorded as described in Section Tests were continued until there was a clear differentiation between the emulsions under investigation. Not all emulsions were tested for the full week of the trial because, in some cases, the emulsions had broken well before this time Malvern Mastersizer The Mastersizer is based on the principle of laser light scattering. It falls into the category of non-imaging optical systems due to the fact that the sizing is accomplished without forming an image of the particle/droplet onto a detector. In addition to using the Fraunhofer scattering theory, the Mastersizer has the option of extending its range of detection up to 135º in order to measure sizes down to 0.05 μm. The scattering from such small particles at such large angles becomes dependent on the optical properties of the material to a degree that should not be ignored. For such an extended performance it is necessary to use the Mie Theory (Schramm, 2001) model of light scattering. This theory is a complete description of the light scattering from optically homogenous spheres and requires assumptions regarding the optical nature of

94 Chapter 3 the particles. Interestingly, the Fraunhofer scattering model is fully encompassed within the Mie Theory by appropriate optical constant settings and fully agrees with it over its applicable range. The statistics of the distribution for the Malvern Mastersizer are calculated from the raw result using the derived diameters D[m,n] an internationally agreed method of defining the mean of particle size (British Standard BS2955:1993). The derived diameters are defined (Malvern, 1997): 1 D[m,n] Σ V i d i m-3 m - n = Σ V i d i n-3 where V i is the relative volume in class i with mean class diameter d i. m and n are integer values which describe the type of derived diameter. The more common of which are: D[4,3] the volume averaged mean diameter D[3,2] - the surface averaged mean diameter D[1,0] - the arithmetic mean diameter Instrument Validation Emulsion systems can be quite broad ranging in terms of their particle size distribution. For the purposes of this project, commercially viable emulsion systems were being evaluated, i.e. those that could be used for creams or lotions. Generally, a particle size range from ~1 μm to 60 μm would fully encompass the majority of these commercial systems (actual analysis examples are given in section ). Three standards were used to validate the Malvern Mastersizer: 0.9 μm - monodisperse polystyrene (Polysciences Incorporated) 5 μm - silica (ex Phase Sep (distributed by Alltech)) μm glass beads (ex Polysciences Incorporated)

95 Chapter 3 Particle size distributions for the individual standards, pairs of the standards, and all three standards in the one sample were measured to ensure instrument validity. The data is shown in Appendix 2 where it can be seen that all standards and mixtures thereof gave results within the appropriate specification (± 0.1 µm). The results for the three standards in one sample are also shown in Figure 3.2 where it can be seen that all three are clearly differentiated. Evaluation of a range of standards, using the Malvern Mastersizer and displayed in Figure 3.2, has shown that accurate measurement of the average particle size of monodisperse standards ranging from 0.9 μm to ~60 μm could be obtained. Even when all three standards were mixed together, the instrument could successfully isolate the trimodal system. To determine if the Mastersizer could separate standards that are even closer than a 5-fold difference in average particle size, an additional monodisperse standard (14 μm) was introduced. Figure 3.3 show the results, both in graphical and tabulated form, from mixed 5 µm and 14 μm standards. A bi-modal distribution was obtained for the mixed standards with a split peak showing that the instrument could just distinguish between them. The high degree of overlap suggests that this ~3-fold particle size difference between standards is the limit of differentiation for this instrument

96 Chapter 3 Result: Histogram Table ID: mixed stds 0.9/5/55 Run No: 8 Measured: 30/8/ :23 File: STDS Rec. No: 7 Analy sed: 30/8/ :23 Path: A:\ Source: Analy sed Sampler: Internal Measured Beam Obscuration: 14.1 % Presentation: 5OHD Analy sis: Poly disperse Residual: % Modif ications: None Conc. = %Vol Density = g/cm^3 S.S.A.= m^2/g Distribution: Volume D[4, 3] = um D[3, 2] = 3.73 um D(v, 0.1) = 0.98 um D(v, 0.5) = um D(v, 0.9) = um Span = 2.646E+00 Unif ormity = 1.032E+00 Size (um) Volume Under % Size (um) Volume Under % Size (um) Volume Under % Size (um) Volume Under % Volume (%) Figure 3.2 Particle Diameter (µm.) Malvern Mastersizer Histogram and Graphical Standards Results

97 Chapter 3 Result: Histogram Table ID: 5/14 stds Run No: 10 Measured: 3/9/ :58 File: STDS Rec. No: 9 Analysed: 3/9/ :58 Path: A:\ Source: Analy sed Sampler: Internal Measured Beam Obscuration: 15.6 % Presentation: 5OHD Analy sis: Poly disperse Residual: % Modif ications: None Conc. = %Vol Density = g/cm^3 S.S.A.= m^2/g Distribution: Volume D[4, 3] = 9.76 um D[3, 2] = 4.03 um D(v, 0.1) = 2.60 um D(v, 0.5) = 7.74 um D(v, 0.9) = um Span = 2.253E+00 Unif ormity = 7.150E Size (um) Volume Under % Size (um) Volume Under % Volume (%) Size (um) Volume Under % Size (um) Volume Under % Particle Diameter (µm.) Figure 3.3 Histogram and Graphical Results for Mixed 5 µm and 14 µm Standards

98 Chapter Commercial Emulsion Evaluation The EPM Technique is being evolved around today s commercial emulsion requirements. The determination of the average droplet size found in commercial emulsions is therefore necessary to provide a droplet size value to aim for when the emulsions are prepared. Three commercial lotion products where analysed for droplet size using the Malvern Mastersizer. The products, used and the corresponding results, are given in Table Table 3.11 Droplet Size Evaluation of Commercial Emulsion Products Commercial Emulsion Average Droplet Size Droplet Distribution Range (μm) (μm) Nivea Body Lotion Vaseline Intensive Care Body Lotion Dove Body Lotion Redwin Sorbolene Lotion The first three systems gave very similar results for both the average droplet size and the distribution range. The results for the Redwin product showed a wider distribution and consequent larger average droplet size. It was decided to use the results from the first three emulsions as a tighter distribution and smaller particle size generally favours overall emulsion stability. The desired droplet size selected for use in this project was 2.5 μm. This Chapter has detailed the important materials, methods and instrumentation necessary to continue with this study. The basis has now been set to investigate the EPM concept and this will be outlined in the following chapters

99 Chapter 4 CHAPTER 4 MATERIALS CHARACTERISATION 4.1 CHARACTERISATION OF EMULSIFIERS This section details the characterisation of the selected emulsifiers according to the EPM technique. For comparison, the classical HLB characterisation scale and the solubility parameter technique are also given Interfacial Tension Data Determination for EPM Technique Figure 4.1 displays a diagrammatic summary of the EPM technique, which was detailed in Chapter Emulsifier Emulsion Value 1 Value 2 Value 3 Value 4 Value 2 Value 1 = ΔValue Surfactant Value 4 Value 3 = ΔValue Emulsion Figure 4.1 Diagrammatic Outline of the EPM Technique Once each selected emulsifier (from the laureth and ceteareth emulsifier series) had been split into its corresponding hydrophobic and hydrophilic entities, the interfacial tension between the hydrophilic and hydrophobic entities was measured. By way of reminder of the emulsifier splitting process, the example given in Chapter 2 is shown again as 80

100 Chapter 4 Figure 4.2 and the tabulated hydrophobic and hydrophilic entities of the selected emulsifiers shown in Table 4.1. EPM Technique Swinburne University of Technology Example of splitting the emulsifier laureth-4 Hydrophobic tail Hydrophilic head group CH 3 (CH 2 ) 10 CH 2 (OCH 2 CH 2 ) 4 OH Add one Hydrogen to make stable materials CH 3 (CH 2 ) 10 CH 3 H(OCH 2 CH 2 ) 4 OH Dodecane PEG th ACSSSC, SA, 2-6 February 2004 Figure 4.2 Example of Emulsifier Splitting in EPM Technique Table 4.1 Hydrophobic and Hydrophilic Moieties of Selected Emulsifiers Emulsifier (INCI Name) Laureth-2 Laureth-3 Laureth-4 Hydrophobic Moiety Dodecane Hydrophilic Moiety Diethylene Glycol Triethylene Glycol PEG 200 Ceteareth-12 Ceteareth-20 Ceteareth-30 50% Octadecane 50% Hexadecane PEG 600 PEG 1000 PEG

101 Chapter Measured Interfacial Tension Data for Selected Emulsifier Moieties The split emulsifier moieties, from the laureth emulsifier series, were liquid at room temperature but the ceteareth emulsifier moieties were waxy solids and consequently, much more difficult to use. Neither the room nor unit housing the FTÅ 200, were fully temperature controllable. To eliminate the need for numerous data adjustments when measurements were taken at different temperatures, care was taken to measure all data at a room (and consequent FTÅ unit) temperature of 20 C (± 0.5ºC) by judicious choice of which days to carry out experimentation and reliance on the air conditioning of the building. Two of the three hydrophilic moieties and the hydrophobic moiety of the ceteareth emulsifiers selected (PEG 1000, PEG 1500 and the 50:50 mix of C 16 and C 18 alkanes), were solid at 20 C, and hence their interfacial tensions could not be directly measured. The interfacial tension of the C 12, C 14 and C 16 alkanes and all PEG materials up to a molecular weight of 600 (PEG 600 has a melting point of 18ºC (Lide, 1994)) could be measured directly, so experimental data was obtained for these materials and the remaining required results for the ceteareth emulsifiers were then determined by extrapolation. Additional PEG materials (PEG 300 and PEG 400), with intermediate molecular weights, were tested to extend the number of data points for the extrapolation. The interfacial tension of a 50:50 mix of C 12 /C 14 alkanes was measured to confirm that the alkanes could be mixed without any anomolous effects. To complete the data set for the alkanes, a 50:50 mix of C 14 /C 16 alkanes was also included. For commercial emulsifiers, the alkane moiety is rarely, if ever, a pure material. Mixed chain lengths are usual and for the tests to be realistic it is important to include mixed alkane moieties within the data. Table 4.2 provides a concise summary of the emulsifier moieties tested and the results that were obtained by experimentation. 82

102 Chapter 4 Table 4.2 Interfacial Tension Data (mn m 20 C) Between Ranges of Alkanes and Glycol Materials (Selected Emulsifier Moieties) Chemical Name DEG TEG PEG 200 PEG 300 PEG 400 PEG 600 Molecular Weight (g mol -1 ) Dodecane (C 12 ) Mixed System (50:50 C 12 :C 14 ) Tetradecane (C 14 ) Mixed System (50:50 C 14 :C 16 ) RI too close to see drop - Refer Table Hexadecane (C 16 ) RI too close to see drop - Refer Table 4.3 RI too close to see drop - Refer Table Notes: 1 The molecular weights of the PEG materials are given as average, approximate values because these materials are not manufactured commercially as pure components. The number of moles of ethoxyl groups present is an average value (Merck, 1999). Although it is possible to purchase these particular materials in a pure form, they are representing moieties of emulsifiers which are only commercially available as average number of moles of ethoxyl groups only. Diethylene glycol and triethylene glycol are both commercially available as pure materials. Average values in bold indicate arithmetic mean values of measured data. The remaining data was obtained using the dye test explained in the next section. For reference, interfacial tension values for many of these alkanes against water can be found in Table

103 Chapter FTÅ 200 Droplet Contrast The refractive indices of the two substances under analysis need to be sufficiently different to observe a contrast between the drop itself and the liquid in the bath. When the refractive indices of the two test materials were very similar (i.e difference) it took considerable optimisation of FTÅ 200 settings to obtain a clearly defined image suitable for analysis and was sometimes impossible. For example when attempting to measure hexadecane (R.I. of 1.434) against diethylene glycol (R.I. of 1.447) or triethylene glycol (R.I. of 1.453), it was not possible for a droplet image to be clearly observed. These data points were needed however, so a method to deal with this problem was required. The addition of a dye to the material forming the droplet to be viewed was used to overcome the difficulty. A water soluble dye (Sicovit Patent Blue 85 ex BASF) was added to the test materials. Diethylene glycol and triethylene glycol were the test materials with PEG 200 included as a known reference to show whether or not the dye would influence the resulting interfacial tension. Interfacial tensions of the three systems, with dye added, are shown in Table 4.3. The results for PEG 200 were comparable to those obtained previously (Table 4.2) and it was therefore assumed that the results for diethylene glycol and triethylene glycol were reliable. Although a faint droplet could just be made out for the interfacial tension of the mixed alkane system with diethylene glycol, the definition was not such that the FTÅ 200 could utilise more than 80% of the datapoints to generate the result. It was decided to use the addition of the dye in this case also as the accuracy of the result was much higher due to the higher droplet definition achieved. 84

104 Chapter 4 Table 4.3 Interfacial Tension Results (mn m 20 C) with Dye Added Diethylene Glycol Triethylene Glycol PEG 200 Hexadecane (C16) Av Av Av :50 C14:C16 Alkane Av Confirmation test % dye % dye % dye 14.2 As a final test to check that the dye was not influencing the interfacial tension; three different levels of dye (0.05%, 0.1% and 0.5%) were added to triethylene glycol. The interfacial tensions of these dye solutions were measured against hexadecane to determine if a difference could be observed. All average results obtained were the same (14.2 mn m -1 ), indicating the absence of interference in the measurement upon the addition of dye. These results are also displayed in Table 4.3. All results determined using the dye addition are displayed in Table 4.1 in non-bold format Data Extrapolation To determine the remaining values for the ceteareth emulsifier moieties (those which could not be measured under experimental conditions) it was necessary to extrapolate the data that had been measured. 85

105 Chapter 4 In the first instance, interfacial tension values from Table 4.2 were plotted against alkane chain length for each of the PEG hydrophiles. This is displayed in Figure 4.3. Extrapolation of these simple regression lines of best fit resulted in the relevant data point for the mixed C 16 /C 18 alkane (displayed as the point where each series line meets the green vertical line) Diethylene Glycol Series 15.2 Interfacial Tension Value (mn m -1 ) Triethylene Glycol Series 13.6 PEG 200 Series 12.8 PEG 300 Series 11.6 PEG 400 Series 11.0 PEG 600 Series 10 9 C12 C14 C16 D o d e c a n e M I x e d C C 1 4 T e t r a d e c a n e M I x e d C C 1 6 H e x a d e c a n e P r e d I c t e d C C 1 8 Alkane Chain Length Figure 4.3 Effect of Alkane Chain Length on Interfacial Tension Linear plots of alkane chain length versus interfacial tension are expected when the second phase is water (Schoenfeldt, 1969, Drelich & Miller, 2000), but could not be assumed in this case, where the second phase was a glycol. The data points from all the PEG series plots shown in Figure 4.3, however, do form a near straight line, thus giving confidence in the use of linear extrapolation to derive the C 16 /C 18 alkane values required to continue the work. The data points for the diethylene glycol and triethylene glycol however, deviate more from the line of best fit giving less confidence as discussed in coming pages. 86

106 Chapter 4 The interfacial tension data shown in Table 4.2 is summarized in Table 4.4 along with the extrapolated results for the C 16 /C 18 system. This table (Table 4.4) now shows all hydrophobic components of the selected emulsifiers (Table 4.1) but not yet all the hydrophilic components. Again, data for the remaining hydrophilic components can be obtained by extrapolation (Figure 4.4). Table 4.4 Interfacial Tension Data (mn m 20 C) Between Ranges of Alkanes and Glycol Materials (Selected Emulsifier Moieties) SUMMARY DATA WITH EXTRAPOLATED RESULTS INCLUDED Chemical Name DEG TEG PEG 200 PEG 300 PEG 400 PEG 600 Molecular Weight (g mol -1 ) Dodecane (C 12 ) Mixed System (50:50 C 12 :C 14 ) Tetradecane (C 14 ) Mixed System (50:50 C 14 :C 16 ) Hexadecane (C 16 ) Mixed System (50:50 C 16 :C 18 ) Extrapolated results In the first instance, all data in Table 4.4 was used to plot interfacial tension as a function of the molecular weight of the hydrophile, but not yet extrapolated to higher molecular weight. 87

107 Chapter 4 Using a log scale of the molecular weights, lines of best fit were added for each data set. However, upon viewing these curves it was evident that the first two points for most data sets (to the left of the red (bold), vertical line) were higher than the line of best fit, whilst the remaining points (to the right of the red, vertical line) were below it. Whilst this may indicate curvature, in this case it probably indicates two separate trends (separated by the red, bold line). The effect is more pronounced for the lower chain length alkanes but still quite obvious for the hexadecane results. An explanation for this effect was required before the results could be validated and used for a meaningful extrapolation plot. D o d e c a n e M I x e d C C 1 4 T e t r a d e c a n e 16 M I x e d C C 1 6 H e x a d e c a n e Log. (P r e d I c t e d C C 1 8 ) 15 Interfacial Tension Value (mn m -1 ) DEG TEG PEG 200 PEG 300 PEG 400 PEG Molecular Weight of Hydrophile (g mol -1 ) Log Scale Figure 4.4 Interfacial Tension Values for Selected Emulsifier Moieties Diethylene glycol (MW = 106) and triethylene glycol (MW = 150), whose points are to the left of the red (bold) line, are pure components. The PEG materials, on the other hand, are not. They are mixtures of similar polymer homologous members in the PEG series (Huntsman Literature, 2001). The molecular weight distribution of PEGs corresponds to the Poisson distribution (Flory, 1940) that demonstrates an 88

108 Chapter 4 increasing polydispersity of the molecular weight distribution with increasing mean molecular weight. The polydispersity of the PEGs probably results in different surface activity of these materials as compared with pure materials. High molecular weight material dominates any adsorption process because it has a disproportionately greater hydrophobic affect (its desire to leave the water phase). If two surfactants having the same molecular weight, but different degrees of polydispersity are compared, the more polydisperse surfactant will have more, high molecular weight material, and thus will absorb into the oil phase more strongly. Indeed, there is a large amount of experimental evidence to support similar phenomena for a host of physical properties when comparing a polydisperse and a monodisperse material possessing the same molecular weight; these include for a polydisperse system, a lower cmc (Warr et al., 1983), greater partitioning into the oil phase (Cowell et al., 2000) and lower surface tension between microemulsions and air (Kegel, 1997). The materials tested are meant to represent moieties of commercial surfactants. Commercial ethoxylated surfactants are, like the PEG materials, comprised of a mixture of polymer homologues. Indeed, PEGs are one of the starting materials in the manufacture of ethoxylated surfactants. It is, therefore, logical to use the data points from the PEGs to extrapolate to the higher molecular weight PEG s, rather than to use the data points for diethylene and triethylene glycol which have less relevance to commercial, highly ethoxylated surfactants. The data for diethylene and triethylene glycol interfacial tension were therefore not used during the extrapolation process to obtain data for high molecular weight PEGs. The data (Figure 4.4) obtained for each of the alkanes shows a general trend of reducing interfacial tension value as the molecular weight of the hydrophile increases. This is due to an effective decrease in the influence of the polar hydroxyl functionality as the number of ethylene oxide units increases. The result is that the hydrophilic entity becomes more 89

109 Chapter 4 oil-like with increasing molecular weight and so the interfacial tension between the two moieties becomes less. This, general trend, of reducing interfacial tension with increasing molecular weight of the hydrophilic entity, has been observed by many authors (Schick, 1980 and Jasper, 1972). All data sets, however, need to be extended up to a hydrophile molecular weight of 1500 g mol -1 (to yield the data required for the emulsifier ceteareth-30), which is a significantly higher molecular weight than the values actually measured. The lines displayed in Figure 4.4 are lines of best fit and were extended to a molecular weight of 1500 g mol -1 as shown in Figure D o d e c a n e M I x e d C C 1 4 T e t r a d e c a n e M I x e d C C 1 6 H e x a d e c a n e Log. Predicted (P r e d C16-C18 i c t e d C C 1 8 ) 13 Interfacial Tension Value (mn.m-1) y = Ln(x) Molecular Weight of Hydrophile (g.mol-1) Natural Log (Ln) Scale Figure 4.5 Interfacial Tension Data for Selected Emulsifier Hydrophiles with MW > 150 g mol -1 The data, as shown in Figure 4.4 to the right of the red line, results in lines that all follow a similar trend but the lines for each data set, as shown in Figure 4.5, do not form a similar, simple pattern. 90

110 Chapter 4 All lines do show the same trend of a linear decrease in interfacial tension with hydrophile molecular weight, but have increasingly steeper gradients with increasing hydrophobe molecular weight such that a point of convergence is reached. At the point of the highest molecular weight under consideration, 1500 g mol -1, the order of the curves has fully reversed, and this must cast some doubt on the extrapolation at this molecular weight. However, it is true to say that the trend of all lines is to converge at a point very near to the molecular weight of 1000 g mol -1 and at this molecular weight, the potential for error in interfacial tension is not large. The points required to continue the project are the hydrophile (or PEG) values for 600, 1000 and 1500 g mol -1 for the C 16 /C 18 alkane mixture. These are indicated by the arrowed boxes with values 10.9, 9.6 and 8.6 respectively in Figure 4.6. These figures, (from Figure 4.6 boxed arrows), complete the data required to give the EPM values (in terms of interfacial tension) for the selected emulsifier moieties. Table 4.5 shows a summary of the data points taken from Figure 4.6 as well as the relevant data values from Table 4.4. Table 4.5 EPM Values (Expressed and Measured as Interfacial Tension) for Selected Emulsifiers Emulsifier Hydrophobic Entity Density (ρ) g cm -3 (20 C) Hydrophilic Entity Density (ρ) g cm -3 (20 C) Interfacial Tension (mn m -1 ) Laureth-2 Diethylene Glycol Laureth-3 Dodecane Triethylene Glycol Laureth-4 PEG Ceteareth-12 PEG Ceteareth-20 Ceteareth-30 50% Octadecane 50%Hexadecane 0.775* PEG 1000 PEG

111 Chapter 4 *Arithmetic mean of density values for Octadecane and Hexadecane. These values in Table 4.5 are those used in the practical evaluation of the EPM technique detailed in the following chapters. The density value (Lide, 1994) for each component is also given, as this is a required input for the FTÅ 200 instrument Classical HLB and Solubility Parameter Classification From Table 4.5 the EPM values for laureth-4 and ceteareth-12 are the same (10.9 mn m -1 ). These emulsifiers have quite different HLB values as shown in Table 3.1 and so will be a good choice of emulsifier to test and compare the EPM and HLB techniques. The HLB and Solubility Parameter theories were discussed in Chapter 1.4. Values for these theories, where available, for the selected emulsifiers are given in Table 4.6 below. The EPM values (from Table 4.5) are also included for comparison. Table 4.6 HLB and Solubility Parameter Values for Selected Emulsifiers Emulsifier HLB Value Solubility Parameter (MPa) EPM Value (based on Interfacial Tension (mn m -1 )) Laureth-2 Laureth-3 Laureth * 8.1* Ceteareth-12 Ceteareth-20 Ceteareth (8.9*) 9.1 (9.3*) * Denotes Solubility Parameter determination carried out using Drop Weight Technique (refer 1.4.2) HLB values were obtained from the manufacturer and solubility parameter figures from Vaughan (1988). For surfactants that fall into the emulsifier category HLB values are 92

112 Chapter 4 widely available but solubility parameter values are not. Although solubility parameters of these emulsifiers can be calculated, it is a complex process and for the reasons explained in Section cannot be justified within the scope of this project. However, estimates in the form of drop weight measurements (as described in Section 1.4.2) were measured and results for laureth-2 and laureth-3 have been added to Table 4.6 in italics. Due to the fact that ceteareth-12 and ceteareth-30 are solid at room temperature; these materials had to be heated to 50 C to conduct the drop weight test. Because no literature support is available for the accuracy of this method at elevated temperatures the figures obtained are shown in brackets. The two theories show opposite trends with increasing molecular weight; increasing solubility parameter figures but decreasing EPM values with increasing molecular weight Alternative Solubility Parameter Classification using EPM Concept The solubility parameter is a measure of likeness of one material to another and is an excellent technique when comparing simple molecules (refer Section for further detail). When applied to emulsifiers, however, it is reasonable to assume that the hydrophobic and hydrophilic entities each have component solubility parameter values which would be considerably different to each other. Literature values listed in texts offer only one value for each emulsifier. This lies between the two values that would be achieved if each entity was measured separately. Moreover, it is possible to have a solute with the correct solubility parameter for a solvent but not be soluble because its component (see Section ) solubility parameter terms are too disparate. The EPM concept of applying values to the separate emulsifier entities may be a suitable tool to apply to solubility parameter values. Table 4.7 gives the split emulsifier moieties with their relevant solubility parameter values. Data was again obtained again from Vaughan (1988) and Barton (1990). Values for PEG 600 and PEG 1500 were not 93

113 Chapter 4 available, so were measured using the Drop Weight method described in Section and are marked with an asterisk to indicate the difference. The data for the hydrophilic entity in Table 4.7 show a clear trend for the solubility parameter, reducing as the material becomes more non-polar. As the material increases in carbon chain length it becomes less like water and less water soluble for this reason. Consequently the solubility parameter value decreases (for reference, water has a value of ~24 MPa). The interfacial tension values in Table 4.5 also show the same trend. Table 4.7: Solubility Parameter Values as Applied to the Hydrophobic and Hydrophilic Moieties of the Selected Emulsifiers and to EPM Technique Emulsifier Hydrophobic Entity Solubility Parameter (MPa) Hydrophilic Entity Solubility Parameter (MPa) EPM Value (from Sol. Parameter Data) EPM Value (from Interfacial Tension Data) Laureth-2 Diethylene Glycol Laureth-3 Dodecane 7.59 Triethylene Glycol Laureth-4 PEG Ceteareth-12 Ceteareth-20 Ceteareth-30 50% Octadecane 50% Hexadecane 7.29 PEG 600 PEG 1000 PEG * * * Denotes Solubility Parameter determination carried out using Drop Weight Technique (refer 1.4.2) If applying the EPM concept to the solubility parameter, then it would take the form of the difference between the hydrophilic and the hydrophobic entity solubility parameter values (i.e. one value subtracted from the other). The values for the EPM from the solubility parameter of the hydrophobic entity subtracted from the solubility parameter of the hydrophilic entity are shown in bold in Table

114 Chapter 4 It is clear from Table 4.7, that there is a strong similarity in the pattern of the EPM values derived from both interfacial tension and solubility parameter. With further data, a scaling factor could be calculated and confirmed to link the EPM values determined from these different methods. A scaling factor may also be required when matching the surfactant data with the oil/water data. Even with the limited results shown in Table 4.7, it can be seen that the EPM value from interfacial tension is very approximately 2.5 times the solubility parameter derived value. 4.2 CHARACTERISATION OF OILS Interfacial Tension Data Interfacial tension values between possible oil and aqueous phases are also required to prepare the EPM database and to compare these with the emulsifier data. Average interfacial tension results (arithmetic mean of three measurements) of the selected oils, were measured against purified water, and the data is given in Table 4.8 on the following page. Table 4.8 displays a clear, known trend (Shaw, 1993) in that the interfacial tension data reduces with increasing oil polarity. The trend is most easily observed when comparing materials from the same family where only the chain length differs (e.g. hexadecane compared with dodecane and IPP compared with IPM). For reference purposes, structures of all the chemicals used in this thesis are displayed on page xv. Dioctylcyclohexane (Cetiol S) has a low value for an alkane due to its cyclic structure and two octyl sidegroups. Octyl dodecanol (Eutanol G) has a high value for an alcohol. This material is a branched alcohol made according to the Guerbet reaction (Clayden et al. 2000). Steric factors result in a higher interfacial tension value. 95

115 Chapter 4 Table 4.8 Interfacial Tension Results for Selected Oils against Purified Water Trade Name or Grade Chemical Name Density (g cm -3 ) 20 C Average Interfacial Tension / mn m -1 (γ I ) (+/- 0.2 mn m -1 ) Analar Grade Hexadecane Analar Grade Dodecane OP61A Mineral Oil Cetiol OE Dicaprylyl Ether Cetiol S Dioctylcyclohexane IPP Iso-Propyl Palmitate IPM Iso-Propyl Myristate Eutanol G Octyl Dodecanol Cegesoft C24 Octyl Palmitate Cetiol 868 Octyl Stearate Cetiol A Hexyl Laurate Myritol 318 Caprylic/Capric Triglyceride Cetiol V Decyl Oleate Cetiol B Dibutyl Adipate Myritol 331 Cocoglycerides The most non-polar oil used in cosmetic formulation is mineral oil; hexadecane or dodecane are not used and interfacial tension values are included for reference only. The use of mineral oil, although is used less these days, does creates a challenge for the EPM technique in that emulsifiers will be required to have an EPM value (using absolute interfacial tension) of ~44. Table 4.4 showed EPM values for the selected nonionic emulsifiers to be in the order of By the nature of the ethoxylated nonionic surfactants, it will not be possible to achieve EPM values of ~40 using this surfactant type alone (unless a scaling factor can be applied). However, if anionic surfactants are considered then higher emulsifier EPM values can be achieved. These have a water 96

116 Chapter 4 soluble hydrophile and in the case of Sodium Lauryl Sulphate (SLS), dodecane as the hydrophobe. EPM values in the order of 40 are possible if the hydrophile is allowed to be measured in solution because the actual hydrophilic entity for SLS would be a solid salt (sodium hydrogen sulphate). The fact that there are surfactants available that could emulsify the most non-polar oil is as far as this direction will be taken in the present work. An investigation of anionic surfactants on their own or blended with nonionic surfactants is a significant amount of work which would need to be carried out in the future development of the EPM technique. The current work will concentrate on the use of the most commonly used materials in cosmetic emulsions; polar oils and nonionic emulsifiers. The possibility of the use of scaling factor for EPM values derived by interfacial tension is, however, investigated a little more in the current work in Chapter HLB and Solubility Parameter Classification of Oils For comparison, Table 4.9 on the following page, lists the measured interfacial tension (against water) data of many materials from Table 4.8 together with literature values for required HLB and classical solubility parameter data values, where available (Vaughan, 1991). The trend observed with the interfacial tension data is not followed with either the solubility parameter or the Required HLB values of the oils. However, as shown in Section 1.5 the two systems (solubility parameter and HLB) are related and do exhibit a correlation in the data in Table 4.9. Presumably, the trends seen only apply to oils of a similar class. This has already been identified as a major weakness in the application of HLB values and may or may not prove to be a similar weakness in the EPM approach. 97

117 Chapter 4 Table 4.9 Trade Name or Grade Summary of Interfacial Tension, Required HLB and Solubility Parameter Values for the Selected Oils Chemical Name Interfacial Tension (mn m -1 ) Required HLB Value Solubility Parameter Analar Grade Dodecane OP 61A Mineral Oil Cetiol OE Dicaprylyl Ether IPP Iso-Propyl Palmitate IPM Iso-Propyl Myristate Eutanol G Octyl Dodecanol Cegesoft C24 Octyl Palmitate Cetiol 868 Octyl Stearate Myritol 318 Caprylic/Capric Triglyceride Cetiol V Decyl Oleate Myritol 331 Cocoglycerides * - *Myritol 331 is a relatively new material (1999). The HLB result was supplied by the supplier Cognis. The preceding tables conclude the characterisation of the materials used throughout this work. Considerably more data would be required for a meaningful database to be constructed. However, the materials that have been evaluated can provide the feasibility tests required to decide on the usefulness of the proposed EPM technique. 98

118 Chapter 5 CHAPTER 5 EMULSION PREPARATION The aim of the EPM technique is to select the optimal emulsifier (or emulsifier combination) to achieve the best emulsion stability. A further benefit of the EPM technique is that by measuring the interfacial tension of the phases to be emulsified, the emulsion system as a whole is being considered and this could also be utilized be used to help determine the correct level of the optimal emulsifier(s) to be used. This is the subject for investigation in this Chapter. The HLB technique makes no attempt to predict emulsifier concentration. An added advantage of utilising interfacial tension is that prediction of the minimum concentration of emulsifier required to achieve the lowest interfacial tension can be obtained (by plotting interfacial tension versus concentration using the particular surfactant / surfactant blend). No current emulsifier prediction technique offers any guidance on emulsifier concentration to use. Although, invariably an excess will be used, it is useful (from a cost, solubility as well as skin compatibility perspective) to ensure that this excess is not too large and only enough to ensure adequate stability. In Section a theoretical level of laureth-4 emulsifier of 0.1% was shown to be all that would be required to emulsify 15% of oil into water. In practice, however, considerably more is required. This chapter begins to investigate the effect of emulsifier concentration on emulsion formation and stability in practice. It provides background, practical data on some elements of the emulsion preparation used in this work, as well as determining the feasibility of the EPM technique to predict emulsifier concentration. For consistency, laureth-4 was chosen as the emulsifier to be used in these experiments - to fully investigate these effects for all emulsifiers being studied was beyond the scope of this study. The parameters to be used in the preparation of the emulsions in this chapter

119 Chapter 5 were summarized in Table In this chapter, concentration, the effect of shear on initial droplet size and emulsion stability is also investigated. 5.1 EMULSIFIER CONCENTRATION EFFECTS ON EMULSION FORMATION AND STABILITY This section investigates the influence of laureth-4 concentration on interfacial tension, initial emulsifier droplet size and resulting emulsion stability Effect of Emulsifier Concentration on Interfacial Tension Solutions of varying emulsifier concentrations were prepared using laureth-4. Using the interfacial cell of the FTÅ instrument, a drop from each emulsifier solution was formed, via a syringe, into a bath of oil (capric/caprylic triglyceride). The interfacial tension for the two materials could then be measured using the methods described in Chapter 3.2. Capric/caprylic triglyceride was the oil selected because it is a common emollient in the cosmetic and pharmaceutical areas. A hanging drop was only achievable with the water phase dropped into the oil phase due to the higher density of the water. The concentrations used and the interfacial tension results obtained are summarised in Figure 5.1 in both graphical and tabulated formats. Note: with the low emulsifier dilutions used the x-axis scale of Emulsifier Concentration % m/m is the same as % w/w

120 Chapter 5 Interfacial Tension mn m Series1 Emulsifier Concentration in water (% m/m) Interfacial Tension (mn m -1 ) Emulsifier Concentration (%m/m) Figure 5.1 Effect of Laureth-4 Concentration on Interfacial Tension Water + Laureth-4 : Capric/Caprylic Triglyceride System There are two clear effects on the interfacial tension as the emulsifier concentration increases; 1) The interfacial tension values decrease strongly with initial increasing concentration. 2) A plateau is reached, which in this case is between 0.5 to 1.0%, where no further significant reduction in interfacial tension can be measured, even when two or three times the emulsifier concentration is reached. For this particular case many more data points would be required to accurately determine this point of inflexion in the results curve but for the scope of this work an approximate figure is sufficient

121 Chapter 5 This data now gives us three identifiable methods that can be useful in predicting emulsifier concentration as follows: 1. Theoretical quantity (for laureth-4 ~0.1% required to emulsify 15 mls of oil into water (Section )). 2. Cmc value (for laureth-4 ~0.003% (Section )) 3. Interfacial tension cmc value (for laureth-4 solutions into capric / caprylic triglyceride ~0.6%) The interfacial tension cmc value for emulsifier concentration (~0.6%) is very high compared to the other values. The experiment above in this Section was repeated and values were again achieved within +/- 0.1 mn m -1. The high value must be due to the fact that laureth-4 is soluble in the oil phase as well as the water phase and some emulsifier must be diffusing into the oil phase prior to the interfacial tension value stabilizing Effect of Emulsifier Concentration on Particle Size If the lowest interfacial tension value is achieved then the smallest droplet sizes should be formed. By measuring resulting droplet size formed using different emulsifier concentration it may be possible to correlate smallest droplet size to lowest interfacial tension and use this to help identify an optimal concentration. In order to verify this, emulsions were prepared using the conditions defined in Chapter 3.2. The emulsifier and oil materials, as well as the emulsifier concentrations are as in section Particle size measurements were taken on emulsions prepared both with and without shear. Results are given in Table

122 Chapter 5 Table 5.1 Emulsifer Conc n % (m/m) Effect of Emulsifier Concentration on Droplet Size Emulsion Appearance and/or Droplet size No Mechanical Shear Initial Coarse not spontaneous (free oil after 5 min) Spontaneous (57 μm) Spontaneous (34 μm) Spontaneous (18 μm) Spontaneous (18 µm) Spontaneous (18 µm) Emulsion Appearance and/or Droplet size Shear ( rpm) Initial Not determined # 3.3 μm 2.7 μm 2.1 μm 2.2 µm 2.2 µm Note: The initial droplet size measurement was taken immediately after emulsification of the system. For the case where no shear was applied the measurement was taken after 30 seconds inverting the cylinder to sufficiently homogenise. For the samples where shear was applied, the measurement was taken immediately after the 90 seconds of shear had been applied. # The droplet size for the 0.1% concentration with shear applied was not measured because the emulsion was already breaking (clearly visible) during the 30 seconds after emulsification. It was not possible to measure an accurate value for the droplet size due to this high instability. It is evident that the particle size data confirms the trend found from interfacial tension results. Also, despite the fact that the initial droplet sizes measured were very different between the shear and no shear cases, the overall trend is the same for both sets of data. In section 1.3.4, the theoretical level of emulsifier required to achieve a droplet size of 2.5 μm was determined. The result indicated that 0.1% emulsifier would be sufficient. This is clearly not the case in practice. From the data presented in Table 5.1 it can be seen that an emulsifier concentration of between 0.5 and 1 % was required to achieve 2.5 μm droplets

123 Chapter 5 The theoretical calculation for emulsifier concentration assumed that only a monolayer of emulsifier is required a fact that is not necessarily correct. The calculation also used a specific value for the surface area of an emulsifier molecule a value determined experimentally by Schick (1980). It is known that this surface area can vary quite considerably depending on the conditions and emulsifier concentration used so was only taken as an indication. It should be stressed, however, that one reason for the use of interfacial tension measurement in the development of the EPM technique was that it should correlate with surfactant concentration at the interface. The lower the interfacial tension value, the greater the tendency for the surfactant molecules to go to the interface and the more efficient the surfactant packing at the interface Effect on Emulsion Stability To conclude this set of experiments, the stability of the test emulsions (from Table 5.1) was examined visually using the method defined in Section and the results are given in Table 5.2. The 24-hour results show emulsions with both no shear and shear applied. The no shear samples (with considerably less energy input into the systems) had all separated after 24 hours and so these tests were not continued for the later time periods. Note: * Phased out indicates that the emulsion displayed two distinct phases an aqueous emulsion phase as well as > 5 ml clear, free oil. Where the previous time point clearly displayed distinct separation, this sample was not tested at the following time point. The term cream indicates first signs of instability with a higher density layer appearing at the top of the emulsion

124 Chapter 5 Table 5.2 Emulsifier Conc (%) Effect of Emulsifier Concentration on Emulsion Stability Emulsion Appearance Emulsion Appearance Emulsion Appearance After 72 hours After 1 Week After 24 hours Emulsion with shear Emulsion with shear No Shear Shear 0.1 Phased out* Phased out* Phased out* Not determined 0.3 Phased out* 5 ml cream 1 ml free oil /8 ml cream Not determined 0.5 Phased out * 2 ml cream trace free oil /4 ml cream 2 ml free oil/10 ml cream 1 Phased out* homogenous 0.5 ml cream 68 ml cream 2 Phased out* homogenous trace cream 5 ml cream 3 Phased out* homogenous trace cream 5 ml cream The stability of the emulsions increases with increasing emulsifier concentration. Again, as with the earlier interfacial tension and particle size results, only minimal improvement was observed after approximately 1% emulsifier concentration was reached. The optimal concentration in this case, was slightly higher at between 1 and 2%. At emulsifier levels of 2% or higher, there is no improvement in the stability. It should be noted that laureth- 4 does have a slight thickening effect on aqueous media so it is likely that any stability improvement as concentration increases is due to viscosity increases only. Increasing viscosity causes a slowdown in the occurrence of droplet collisions and thus shows an increase in emulsion stability but via a different mechanism to that under consideration. The three results determined in this chapter for the optimal emulsifier concentration when using laureth-4 as the emulsifier can now be easily compared alongside the theoretical determination in Section This data is summarized in Table 5.3. Table 5.3 Summary of Optimal Emulsifier Concentration Dermination Method Used Optimal Emulsifier Concentration (% m/m) Theoretical Determination 0.1 Interfacial Tension Particle Size 1.0 Observation (Visual Determination)

125 Chapter 5 Clearly, a value well in excess of 1% is required. However, studying systems that fail often tell us more than those which are stable so a level at the lower end of the requirement should be used to continue this work. It was decided to use an emulsifier concentration of 0.5%. This level is sufficient to form an adequate emulsion close to 2.5 µm but not so much emulsifier as to hide signs of initial separation. This should also avoid viscosity effects becoming significant and influencing the result. 5.2 DEGREE AND TIME OF MIXING Effect on Initial Particle Size The effect that applied shear had on the initial particle size has been so far in this study determined by applying 9000 rpm shear for 90 seconds. It was felt that it may be possible to achieve a specific, average droplet size of 2.5 μm with lower levels of emulsifier so long as shear is applied for longer. To test this, further shear was applied for varying times in an attempt to achieve an average droplet size of 2.5 μm. The time required, keeping a constant rate of shear (9000 rpm), to achieve 2.5 μm droplet size is given in Table 5.3. The resulting stability of the emulsions is also given. The particle size was measured as soon as possible after the stirrer was turned off. In practice this was approximately 2 minutes after shear was applied. The results in Table 5.3 show that it is possible to achieve an emulsion droplet size of 2.5 μm using an emulsifier concentration as little as 0.3 %, but using considerable shear. At lower concentrations it is not possible to achieve such a small droplet size, even when several minutes of additional shear is applied

126 Chapter 5 Table 5.3 Shear Time vs Emulsifier Concentration to Achieve 2.5 µm Droplet Size Emulsifier Conc n (%) Shear Time (seconds) Particle Size (μm) Appearance After 72 hours 0.1 Not determined Not determined 15 ml free oil ml free oil ml free oil ml free oil ml cream + 2 ml free oil ml cream ml free oil ml cream + trace free oil ml cream ml cream Although an initial droplet size of ~2.5 μm could be achieved using 0.3% emulsifier, the resulting emulsion was not as stable as those made from a higher concentration of emulsifier. This is despite a similar initial particle size in both cases, demonstrating the importance of more than one technique for monitoring emulsion performance. Furthermore, increasing the time of shear does not fully compensate for using less emulsifier. It was concluded that for the purposes of this study, emulsions would be prepared using an emulsifier concentration of 0.5 % w/v and using 90 seconds of a high shear rate of 9000 rpm

127 Chapter 6 CHAPTER 6 CHARACTERISATION OF EMULSIONS 6.1 DESIGN AND STABILITY OF TEST EMULSION SYSTEMS At last an evaluation of the EPM technique itself can now be carried out and this is the basis for this chapter. Using the materials detailed in Chapter 3 and the characterization results presented in Chapter 4, two series of test emulsions were designed based on phase matching emulsion components. These designed emulsions were themselves evaluated for stability and also compared to the traditional HLB system. Although it would be normal practice for emulsifiers to be selected based on the oils chosen, in this work the range of surfactants evaluated is somewhat limited. Therefore, for these initial tests we vary the oil to match the emulsifier. The emulsifier is varied, in the normal way, in the next chapter. Please note that at this stage only oil(s), water and emulsifier(s) are included in the emulsion. The expected emulsion stability of these systems is comparable to an agrochemical emulsion, for example, where ~ 8 hours (once made up) good stability is expected. Without structuring the system it is not realistic to achieve much greater stability than this without forming a more thermally stable microemulsion Ideal Emulsion System Design To begin with, it was felt necessary to at least try an ideal emulsion system in addition to commercially representative systems which would be more thoroughly evaluated for the EPM Technique

128 Chapter 6 An ideal system would be to create an emulsion where the oil and water phases are comprised of the hydrophobic and hydrophilic moieties of the emulsifier itself. This is feasible for the laureth series of emulsifiers but not for the ceteareth series, where a solid emulsion would be formed. The composition of proposed ideal systems is shown as Test Emulsions 1 3, in Table 6.1. The emulsion systems shown are described as ideal because the oil phase is perfectly matched with the hydrophobic entity of the emulsifier and the aqueous phase is perfectly matched with the hydrophilic portion of the emulsifier. Table 6.1 Proposed Ideal Test Emulsion Systems Test Lipophilic Phase Hydrophilic Phase Emulsifier 1 Dodecane Diethylene Glycol Laureth-2 2 Dodecane Triethylene Glycol Laureth-3 3 Dodecane PEG 200 Laureth-4 Although these systems are feasible for the preparation of emulsions, they differ significantly from standard commercially available emulsion systems, which use water as the main constituent of the hydrophilic phase. Without water making up the aqueous phase it is not possible to compare an equivalent HLB recommendation for this system. Another more significant problem with these systems was discovered as soon as they were prepared; the glycols and PEG 200 were each able to partially solubilise the dodecane to give one homogenous clear solution. A fundamental requirement of forming emulsions phases is that they be immiscible. Since this was not met in the proposed ideal system, no useful information could be gleaned by continuing with their study. To achieve useful and realistic emulsions for this work the glycols were replaced by water as the aqueous phase. This also enables comparison against the HLB system

129 Chapter EPM vs HLB Comparison: Test Emulsion 4 Test Emulsion 3 from Table 6.1 was again selected, this time with water replacing the glycol as the aqueous phase. This is labelled as Test 4 in Table 6.2 below. A variant of Test 4 could also be used to test the HLB theory for this dodecane / water system. HLB tables (Vaughan, 1988) show a required HLB value of for dodecane. Laureth-4 has an HLB of 9.6 and ceteareth-12 has an HLB of 13. According to the principals of the HLB system these two emulsifiers (laureth-4 and ceteareth-12) can be blended in the ratio that would achieve a match to the required HLB. In this case a ratio of 55:45 laureth-4: ceteareth-12 gave the emulsifier ratio to match the HLB of Table 6.2 shows the composition of emulsions Test 4 (using EPM Technique) and 4HLB (using HLB Technique) which were prepared and examined for direct comparison of the two techniques. The interfacial tension of the dodecane / water interface was measured as 52.8 mn m -1 which agrees with the literature value given in Table 4.9. Table 6.2 EPM / HLB Comparison: Test Emulsion 4 Test Oil Phase Aqueous Phase Emulsifier 4 Dodecane Water Laureth-4 (100%) 4HLB Dodecane Water Laureth-4 / Ceteareth-12 (55%:45%) Both emulsions formed spontaneously to give homogenous, white emulsions. The initial particle size of the emulsions as well as their visual appearance after 24 hours is given in Table 6.3. Table 6.3 Results and Stability of Test Emulsion 4 Test Emulsion Initial Droplet Size (µm) Visual Appearance After 24 hours 4 4 HLB ml cream 2 ml cream

130 Chapter 6 Results showed that the emulsifier selected under the EPM method performed marginally better than the emulsifier system selected under the HLB system. A smaller initial droplet size was achieved as well as less separation in the 24 hour visual test (Section tabulates further time point comparisons between HLB and EPM selected emulsifiers). Although this indicates a weakness in the HLB system rather than proving the strength of the EPM system, it is nevertheless, an encouraging result EPM and EPM vs HLB: Test Emulsion 5 The next series of test emulsions used oil phases that are found in commercial emulsions. For the EPM method, using the absolute interfacial tension data previously measured, it was clear that blends of oils would be required. None of the oils alone were an exact match for the emulsifiers tested. The cocoglyceride oil, Myritol 331 (interfacial tension against water of 8.3 mn m -1 ) was included in every oil blend, as required, to achieve an interfacial tension match. Interfacial tension data was previously recorded in Table 4.1 for both pure oils and also one blended ratio of the glycerides. This demonstrates the additive effect of interfacial tension in blending at least for these simple chemical combinations of oils. Later, in Section 6.1.6, there is a study to investigate whether a scaling factor might be required to accurately give the EPM value based on interfacial tension. The assumption in this section is that absolute values must be used but this is not proven at this point in time. In order to keep these initial systems in Test Emulsion 5 to one chemical family (and avoid any other chemical interactions), cocoglyceride was used in combination with the other triglyceride (capric/caprylic triglyceride, Myritol 318, which has an interfacial tension value against water measured at 20.2 mn m -1 ). Using the interfacial tension data recorded in Table 4.1 the appropriate oil blends were calculated and are detailed in Table 6.4. This Table 6.4 also outlines the corresponding emulsifier along with a summary of

131 Chapter 6 the EPM value for that emulsifier and required HLB for the oil ratio derived for that emulsifier. Example: for test emulsion 5a, a 64:36 ratio of Myritol 331 (cocoglyceride) : Myritol 318 (capric/caprylic triglyceride) gives a calculated interfacial tension value (against water) of 12.6 mn m -1. This value matches the 12.6 mn m -1 interfacial tension value measured for diethylene glycol against dodecane the separate entities of the emulsifier Laureth-2. Table 6.4 EPM Test Emulsion 5 Test Oil Phase and Ratio HLB (Required for Oil) Emulsifier HLB (Emulsifier) EPM (matching oil & emulsifier) 5a Myritol 331/ Myritol 318 (64:36) 13.4 Laureth b Myritol 331/ Myritol 318 (70:30) 13.4 Laureth c Myritol 331/ Myritol 318 (78:22) 13.4 Laureth d Myritol 331/ Myritol 318 (78:22) 13.4 Ceteareth e Myritol 331/ Myritol 318 (87:13) 13.4 Ceteareth f Myritol 331/ Myritol 318 (97:3) 13.4 Ceteareth Note: the aqueous phase in all Test 5 Emulsions was water The required HLB values of the Myritol 318 and Myritol 331 (both glycerides) are almost the same (13.3 and 13.4). This highlights one major difference between the HLB and EPM techniques because all of the Required HLB values are the same but the EPM values are different in the above emulsions. The summary of properties for commercial oils was listed in Table 4.7; no relationship was observed between required HLB and interfacial tension. It is true to say that, for these particular sets of emulsifiers, a trend can clearly be seen in the HLB values of the emulsifier and the EPM values achieved. This trend is increasing from Test 5a to 5f in HLB and decreasing in the EPM values

132 Chapter 6 Comparison of the emulsions in Table 6.4 with some which were derived on the basis of the HLB technique is again beneficial. Test emulsions 5c and 5e were selected and given the codes 5cHLB and 5eHLB. Again, the emulsifier ratio was altered in order to obtain a good HLB match. Details are given in Table 6.5. Table 6.5 Test Test Series 5 Emulsion Systems Matched with HLB Values Oil Phase and Ratio Aqueous Phase Emulsifier 5c HLB Myritol 331/ Myritol 318 (78:22) Water Laureth-4 / Ceteareth-20 (30:70) 5e HLB Myritol 331/ Myritol 318 (87:13) Water Ceteareth-12 / Ceteareth-20 (85:15) Stability of Commercially Representative Emulsion Systems The initial droplet size and resulting stability information for the test emulsion systems are tabulated in Table 6.6. Table 6.6 Results and Stability of Test Emulsion Series 5 Test 5a 5b 5c 5cHLB 5d 5e 5eHLB 5f Initial Particle Size (µm) Appearance After 24 hours 2 ml cream 1 ml cream trace cream 0.5 ml cream 1 ml cream 1 ml cream 1 ml cream 3 ml cream Appearance After 72 hours 8 ml cream + 2 ml oil 6 ml cream + 2 ml oil 4 ml cream + trace oil 5 ml cream + 1 ml free oil 6 ml cream + 1 ml free oil 6 ml cream + 2 ml oil 6 ml cream + 3 ml oil 8 ml cream + 3 ml free oil Ranking 1 = best The stability of all these systems were unacceptable after 72 hours storage at 40 C, however, cosmetic emulsion products have considerably higher viscosity than those used

133 Chapter 6 here, which reduces the number of droplet collisions and markedly increases product stability. Where emulsions of low viscosity are required for commercial products, they are usually made as PIT (Phase Inversion Temperature) emulsions which possess greater stability (refer section 1.5.3). Testing standard emulsions at low viscosity however, as in Table 6.6, allows very fast determination of emulsion stability at the early stages of formulation development and is a very useful tool, for later development of commercial emulsions. Although the stability of all emulsions was poor (after 72 hours), this was due to the lack of other stabilisers (thickeners / polymers) and certainly not so poor as to abandon product development in a real formulation exercise. Moreover, the EPM emulsions were better or, at least as good as the HLB emulsions in terms of both initial droplet size and visual stability. The EPM technique should enhance the packing and so strength of the interfacial layer offering improved (lower) initial particle size and improved stability (lower creaming and free oil). There is initial, albeit limited, support of this in these early experiments. For reference, an example of an unmatched emulsion was made simply by emulsifying 15 ml Myritol 318 with Laureth-3. This is a poor match from both a HLB and EPM point of view. The resulting emulsion had an initial particle size of 11 µm and showed 12 ml cream and a trace of oil after 2 hours. This example of a bad emulsion demonstrates the benefit of both the HLB and EPM techniques Stability Comparison of HLB and EPM Derived Emulsion System Three emulsion systems have so far been prepared where a direct comparison of the HLB and EPM selected emulsifiers was possible. However, stability has only been assessed at the initial time points. Table 6.7 provides a summary for the extension of the stability trial. It shows stability results for test emulsions 4 and 4HLB, 5c and 5cHLB, 5e and 5eHLB from 1 week to

134 Chapter 6 months. Initial particle size is also included for reference. Particle size was not measured once visible signs of destabilization were apparent because the emulsion was no longer homogenous enough to be able to obtain a representative sample. Re-mixing of the emulsion to obtain a representative sample compromises the integrity of that sample in further time points. Table 6.7 Test Emulsion 4 4HLB 5c 5cHLB 5e 5eHLB HLB and EPM Emulsion Comparison Initial Particle Size (µm) Appearance After 1 week 4 ml cream 7 ml cream 6 ml cream + tr oil 8 ml cream + 2 ml oil 9 ml cream + 4 ml oil 9 ml cream + 5 ml oil Appearance After 1 month 6 ml cream + trace oil 9 ml cream + 2 ml oil 8 ml cream + 2 ml oil 9 ml cream + 5 ml oil 9 ml cream + 5 ml oil 9 ml cream + 6 ml oil Appearance After 3 months 8 ml cream + 1 ml oil 9 ml cream + 3 ml oil 9 ml cream + 3 ml oil 9 ml cream + 6 ml oil 9 ml cream + 6 ml oil 9 ml cream + 7 ml oil A difference in terms of levels of creaming and free oil can be observed between test emulsions 4 and 4HLB and also between 5c and 5cHLB; each displaying improved stability with the EPM selected emulsifiers. The amount of free oil is the most important data to consider because this comparison indicates the relative degrees that each emulsion has broken. Test emulsions 5e and 5eHLB both performed quite poorly with a high percentage of free oil occuring after 72 hours (Table 6.6) and 1 week. There is little observable difference between the two emulsions; they both would be removed from stability at an early date as failed formulations. Ceteareth-20, the emulsifier used solely in test emulsion 5e, is a very common emulsifier used in cosmetic and pharmaceutical formulations and so the fact that it performed poorly was something of a surprise

135 Chapter 6 Because ceteareth-20 is usually emulsified at degrees C (along with ceteareth-12 in test emulsion 5cHLB and 5eHLB) it had to be confirmed whether it was the emulsification temperature that was affecting the results. Test emulsions 5cHLB, 5e and 5eHLB were repeated emulsifying at 75 degrees C. Test emulsion 7 could not be prepared at this temperature because this temperature is above the cloud point of this emulsifier. Initial particle size and visual stability results for these emulsions are tabulated in Table 6.8. Rate of duration of shear remained as previously defined. The results obtained for test emulsion 5c emulsified at 20 degrees C are included in the table for reference only. Table 6.8 Ceteareth Emulsifier Systems Emulsified at 75ºC Test Emulsion Initial Particle Size (µm) Appearance After 24 Hours Appearance After 1 week Appearance After 1 month Appearance After 3 months 5c (at 20 C) 2.7 trace cream 6 ml cream + 8 ml cream + 9 ml cream ml oil 2 ml oil 3 ml oil 5cHLB ml cream 6 ml cream + 8 ml cream + 9 ml cream + (at 75 C) 1 ml oil 3 ml oil 4 ml free oil 5e (at 75 C) 2.9 trace cream 5 ml cream + 1 ml oil 6 ml cream + 2 ml oil 8 ml cream + 3 ml oil 5eHLB (at 75 C) ml cream 7 ml cream + 2 ml oil 8 ml cream + 4 ml oil 9 ml cream + 5 ml oil Emulsifying at the higher temperature has produced improved initial droplet size and emulsion stability. This would be expected and is the reason why the vast majority of commercial emulsions are prepared at high temperature. However, the trend that the EPM selected emulsifiers have given emulsions with improved stability as compared to HLB selected emulsifiers, remains. Emulsification will continue to be carried out at 20º C for the reminder of the work for consistency with all emulsifiers under evaluation. However, some selected emulsion

136 Chapter 6 systems, where the ceteareth emulsifiers are the major emulsifier, may be re-checked with emulsification carried out at 75º C. All EPM emulsion tests have been carried out using a single emulsifier only whereas the HLB matched systems have used emulsifier combinations. As explained in Chapter 2, surfactant combinations do tend to show better stability than single systems so, if tested, may show a further advantage over the HLB matched systems. However, the commercial EO emulsifiers, as covered in Chapters 1 &2, are actually mixtures of different EO number surfactants and not pure surfactants. For this reason and considering only EO emulsifiers are being tested, it was not deemed necessary, at this stage, to repeat any of the tests using multiple EO emulsifier combinations as little, if any, improvement would be expected Confirmation of Optimal Oil Blends for EPM Technique Even when screening for optimal emulsifiers using the HLB technique, it is common to run a simple visual emulsion test exactly as outlined in Section using different oil ratios, a range of emulsifiers or to test emulsifier concentration. The HLB technique will narrow the range down for the formulator but testing is still carried out to confirm the prediction. A similar screening test can easily be carried out to demonstrate the EPM technique is predicting the correct emulsifier for different ratios of oil and would be useful to confirm a value in this technique. An aim of the EPM technique would be to provide sufficient accuracy of prediction of the emulsifiers that a screening process would not be necessary. However, at this stage the method is not yet proven and the screening exercise can help to show the effectiveness of the EPM technique. Table 6.9 and 6.10 provides a summary of the oil ratios screened with the respective results. All emulsions were prepared in the same way and with Laureth-4 again as the

137 Chapter 6 emulsifier at 0.5% to provide a tough test. All emulsions formed were initially white and homogenous. A difference could be clearly seen after 24 hours in the first screening but the test had to be continued for 72 hours in the second (narrower) screening. Table 6.9 EPM Emulsion Screening 1 Myritol 318 composition (%) Myritol 331 composition (%) EPM Value Appearance After 2 Hours 1 ml cream 1 ml cream 1 ml cream 0.5 ml cream trace cream 0.5 ml cream Appearance After 24 hours 8 ml cream 8 ml cream 7 ml cream 4 ml cream 1.5 ml cream 5 ml cream The optimum oil ratio from screening 1 is close to the 80:20 ratio of Myritol 331:Myritol 318. This can then be further screened as desired to pinpoint the exact ratio. Table 6.10 shows the next possible screening ratios. Table 6.10 EPM Emulsion Screening 2 Myritol 318 composition (%) Myritol 331 composition (%) Appearance After 2 Hours 0.5 ml cream trace cream trace cream trace cream trace cream trace cream Appearance After 24 hours 2 ml cream 1 ml cream 1 ml cream 1 ml cream 1 ml cream 1.5 ml cream Appearance After 72 hours 3 ml cream + tr oil 2 ml cream 2 ml cream 2 ml cream 2 ml cream 2.5 ml cream + tr oil

138 Chapter 6 As the oil ratios tested become narrower it becomes harder to distinguish visually, the optimum emulsion. A more sensitive technique (like Turbiscan - transmission and light backscattering measuring equipment) might be required to pick up smaller indications of instaiblity. However, it can clearly be seen that the optimum ratio calculated from the interfacial tension blends of 78% Myritol 331 and 22% Myritol 318 (EPM value of 10.9) correlates with the practical optimum ratio as shown in Table It is not possible to distinguish the best level of Myritol 331 between 76 and 79% from the practical test results with only small differences between the results of all of Screening 2. These results also indicate that when the EPM values are determined using interfacial tension, that a scaling factor is not required. All of the emulsions produced were white initially and the cream layer was, unfortunately, not dense enough, during the period of the test to be easily distinguishable using photography. It is true to say that with almost all of the screened emulsions, useable cosmetic creams could be achieved with sufficient viscosity modifiers but that there is a ratio range that does offer optimal stability for that particular system. Of course, these screening tests are time consuming and quite tedious test to carry out so if proven to not be required using the EPM Technique it would give greater impetus for the new technique to be taken on board

139 Chapter 7 CHAPTER 7 PREDICTING OPTIMAL EMULSIFIERS 7.1 USING THE EPM TECHNIQUE FOR EMULSIFIER PREDICTION A major driving force to begin this work was the need for a simple technique for emulsion development which eliminates, or at least reduces, the trial and error approach and consistently achieves reliable results. The EPM technique has taken the first steps to achieving this goal. The following steps again outline the procedure required to effectively utilise the EPM technique: 1. The formulator establishes the materials that will make up the emulsion oil and water phases. Marketing, sensory, viscosity, compatibility, and preservation requirements should all be considered at this stage. 2. Interfacial tension is measured for the water phase versus the oil phase at room temperature (20ºC). For simple cases (where no surface active components are included and the oil and water phases are single components) this could be determined from the EPM raw material database. Only limited materials have been evaluated so far and these were summarised in Table 4.4. Otherwise, a single measurement of interfacial tension is all that is required. 3. From the resulting interfacial tension value an emulsifier is selected by matching with the EPM emulsifier database. Again only limited emulsifiers have so far been characterised for the EPM technique and these materials were summarised in Table 4.1. Until an extensive database is available, further measurements of interfacial tension are required

140 Chapter MODEL EMULSION DEVELOPMENT This section provides an example, step by step guide, to a formulation development example and demonstrates how the EPM technique is applied. It begins with a fairly typical marketing brief which the formulator needs to develop a product to meet. Marketing personnel are well known in the personal care industry for changing their minds and putting pressure on the development chemist to modify the formula at short notice (and consequent reduced stability) on the basis of a promise of improved sales. The EPM technique could also be used as a basis of deciding whether the changes are allowed. If the change to the formula changes the EPM value then development and full stability should be re-started completely from the beginning. If the change has not resulted in a different EPM value then the change may be possible with a few confirmatory tests. If the chemist has a non-subjective method of making this decision then a lot of arguments will be avoided Product Requirements The marketing brief provided for a new product as given in Figure 7.1. Figure 7.1 Marketing Brief for a New Product Development The latest cosmetic magazines have focused on the damaging effects caused by long wavelength sun radiation and how this can contribute to skin damage and premature ageing. There is an opportunity for our company to launch a high quality skin protection cream, which offers protection for the active skin cells. The product should be light, elegant and be rapidly absorbed into the skin. The following claims are to be made: Cyto-immuno-photo-protector Helps to prevent skin ageing caused by visible light -121-

141 Chapter 7 Once the formulator has received the marketing brief the next step is the selection of the materials that will meet the requirements. The active ingredient around which the claims can be made is called Photonly LS, based on natural cellular components (full composition is listed in Chapter 3, Table 3.5). A usage level of 2 % is required to use the efficacy data generated by the manufacturer. The light feel of the product is mainly attributed to the nature of the oil phase materials that are incorporated. It is common to use at least one, fast spreading oil, at a low enough level to give an initial feeling of smoothness, together with one or two medium spreading oils to give a longer lasting smooth feeling on the skin. For this product, hexyl laurate (Cetiol A) will be used as the fast spreading oil and a cocoglyceride (Myritol 331) as the medium spreading oil. The requirement for the product to rapidly absorb into the skin can be achieved by using a gel-structured emulsion. High viscosities can still be reached but the product immediately absorbs into the skin on application. A carbomer based gel can be used to obtain this effect. Other auxiliary materials include sodium hydroxide (to neutralise the carbomer), Kathon CG as the preservative and Sandalwood oil to provide the fragrance Application of the EPM Technique The ingredients outlined so far make up the separate emulsion phases as shown in Table 7.1 (step 1 of EPM process)

142 Chapter 7 Table 7.1 Model Formulation Ingredients Emulsion Phase Raw Material % w/w Oil Cetiol A Myritol 331 Sandalwood Oil (fragrance) Aqueous Water Photonyl LS Carbopol ETD 2001 Kathon CG (preservative) Sodium Hydroxide (including emulsifier) This is now the complete formulation excluding the emulsifier. The interfacial tension of the two phases is next determined (step 2 of the EPM process). The two phases were prepared in the lab simply by adding all the ingredients of each phase into separate beakers at room temperature and mixing until homogenous. The interfacial tension was then measured as described in Section The average of three independent measurements was 10.9 mn m -1. From the data presented in Table 4.5 it can be seen that both Laureth-4 and Ceteareth-12 possess an EPM interfacial tension value of 10.9 mn m -1 and match the proposed emulsion phase interfacial tension value (step 3 of the EPM process). Either (or both) emulsifier(s) could be used. The advantage of gel-based emulsions is that no heating is required to form them. On this basis laureth-4 was selected for this emulsion system. A usage level of 1.0 % laureth-4 was selected. This level has been shown to produce an average droplet size of 2.5 μm when 90 s of 9000 rpm shear is applied (from Table 5.4). Too high an emulsifier level may affect both the solubility and interfacial tension of the system under investigation, and hence this should be avoided for these early tests of the EPM technique

143 Chapter % laureth-4 was added to the oil phase and the water phase (minus the sodium hydroxide) added to this mixture. An emulsion formed spontaneously but, consistent with the work in this project, 90 seconds of 9000 rpm shear was applied to ensure adequate mixing and to promote a smaller initial droplet size. The sodium hydroxide was added after homogenisation. This neutralises the carbomer and causes it to form a gel Emulsion Stability The emulsified product had a viscosity of 2,000 cps, which was thicker than the previous, basic emulsion systems tested. It would be expected, therefore, that phase separation would be observed after a longer storage period and/or higher storage temperatures. The storage tests on this product needed to be continued for longer with a focus on higher temperature storage tests. It should be noted, however, that 2,000 cps is at the lower end of a viscosity specification for a lotion (usually 2,000 8,000 cps). This viscosity was specifically selected to help pick up initial signs of instability more quickly and to be a tough test for the EPM technique. A summary of droplet size and emulsion stability results is given in Table 7.1. Due to the high stability of this formulation there was very little to report for the early storage test conditions. Consequently, only major time points are tabulated. The test sample after 6 months at 40 C (TGA, 1994) still displayed no signs of phase separation. This stability condition is used by the Therapeutic Goods Administration (TGA) to indicate stability of the product after two years at room temperature, which is the standard shelf-life for commercial products. This product would be considered to have passed its stability trial and be released for commercialisation. The 20ºC test would usually be continued for the two years to complete the stability trial

144 Chapter 7 Table 7.2 Model Emulsion Stability Results at 20ºC and 40ºC Test Condition Visual Appearance Particle Size (μm) Initial Homogenous, viscous emulsion 2.7 After 24 20ºC & 40 ºC After 1 20ºC & 40 ºC After 1 20ºC After 1 40 ºC After 3 20ºC After 3 40ºC After 6 20ºC After 6 40ºC Homogenous, viscous emulsion 2.7 Homogenous, viscous emulsion 2.7 Homogenous, viscous emulsion. No sign of separation 2.7 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 For comparison the same emulsion was prepared using laureth-2 as the emulsifier instead of laureth-4. A homogenous, viscous emulsion was initially formed but with a particle size of 11 µm. It is not possible to see cream in such a thick product but free oil was clearly evident after 24 hours. Free oil so soon in the stability test is an immediate failure and so testing was abandoned

145 Chapter Model Emulsion System Using Alternative EPM Emulsifier The EPM technique identified two possible emulsifiers as being suitable for the test emulsion detailed in Table 7.1. These emulsifiers were laureth-4 and ceteareth-12. Laureth-4 was used to form the emulsion and produced a product with very good stability. According to the HLB system laureth-4 and ceteareth-12 have very different values (9.6 for laureth-4 and 13 for ceteareth-12) and would not be selected to emulsify the same oil component. It would, therefore, be a useful exercise to test the stability of the emulsion described in Table 7.1 using ceteareth-12 as the emulsifier. This would further test the EPM technique and also highlight the differences between the EPM and HLB techniques. As before, 1.0 % of the emulsifer - this time ceteareth-12, was added to the oil phase and the water phase (minus the sodium hydroxide) was added to this mixture. Again an emulsion formed spontaneously and for consistency 90 seconds of 9000 rpm shear was applied. The sodium hydroxide was added after homogenisation to form the gel. The viscosity of the emulsion formed was this time slightly higher at 2300 cps. The stability results for this emulsion are summarised below in Table 7.3. The emulsion droplets initially formed using ceteareth-12 were marginally larger than those formed in the emulsion produced using laureth-4 as the emulsifier. This may be due to the smaller size of the laureth-4, allowing better packing at the interface but may also be due to the low temperature processing of the ceteareth-12. However, the overall stability of the emulsions were very similar. Both formulas provided very stable products. For the sake of completion and to follow the lead set in Chapter 6, this last emulsion was repeated with the emulsification carried out at 75ºC. The initial droplet size was slightly improved at 2.8 μm with again excellent stability throughout the 6 month life of the stability tests (final emulsion droplet size was 3.0 μm after the 6 month period)

146 Chapter 7 Table 7.3 Model Emulsion (Using Ceteareth-12) Stability Results at 20ºC and 40ºC Test Condition Visual Appearance Particle Size (μm) Initial Homogenous, viscous emulsion 3.0 After 24 20ºC & 40 ºC Homogenous, viscous emulsion 3.0 After 1 20ºC & 40 ºC After 1 20ºC Homogenous, viscous emulsion 3.0 Homogenous, viscous emulsion. No sign of separation 3.0 After 1 40ºC After 3 20ºC After 3 40ºC After 6 20ºC After 6 40ºC Homogenous, viscous emulsion. No sign of separation Homogenous, viscous emulsion. No sign of separation Homogenous, viscous emulsion. No sign of separation Homogenous, viscous emulsion. No sign of separation Homogenous, viscous emulsion. No sign of separation Second Model Emulsion System Using Alternative EPM Emulsifier The first model emulsion system was an example of the newer type of emulsion systems which are cold processable with their viscosity controlled by a polymer. It was also thought useful to give an example of the more traditional emulsion type which is processed at 75 80ºC and thickened with fatty alcohol

147 Chapter 7 The product brief was for a traditional moisturising handcream with Vitamin E and glycerine as the actives. Because both actives are quite heavy and sticky on the skin, only a low quantity and lighter oils (IPM and Myritol 331) were required to achieve a nice skin feel. The fragrance and preservative were kept the same as the previous system. The individual components of each emulsion phase are detailed in Table 7.4. Table 7.4 Second Model Formulation Ingredients Emulsion Phase Raw Material % w/w Oil IPM Myritol 331 Vitamin E Lanette MY Sandalwood Oil (fragrance) Aqueous Water Glycerine Kathon CG (preservative) (including emulsifier) The interfacial tension between the two phases to be emulsified was measured (at 20ºC) to be 9.4 mn m -1. Refering to Table 4.5, this interfacial tension value equates to an emulsifier requirement of 0.8 % Ceteareth-20 (0.8 x 9.6 = 7.68) and 0.2% Ceteareth-30 (0.2 x 8.6 = 1.72) to make up the 1% emulsifier level selected to match the 9.4 mn m -1 value of the two phases to be emulsified. These two emulsifiers were the ones closest (immediately above and below) the figure to be matched; at a later stage it could be determined if the emulsifiers closest to the value to be matched should preferentially be used to make up the emulsifier concentration used, or if any combination that matches the required figure will suffice

148 Chapter 7 Although it has been stressed that a full database is traditionally required by formulators before any new technique would be accepted, the above example demonstrates that it may not be necessary to have all materials tabulated in an EPM database. This example shows how simple it is to take the measurement for the interfacial tension of each phase and so individual measurements in a database are not necessarily informative. It is the value for the system in it s entirety that is the only relevant data. 0.8 % ceteareth-20 and 0.2% ceteareth-30 were added to the oil phase (minus fragrance) which was heated to 75ºC and the water phase (also at 75ºC) added to this mixture. An emulsion formed spontaneously but, consistent with the work in this project, 90 seconds of 9000 rpm shear was applied to ensure adequate mixing and to promote a smaller initial droplet size. The product was cooled with slow stirring (magnetic stirrer on a hotplate). The Sandalwood oil was added to the product below 40ºC to avoid evaporation. Once the product had cooled to 20ºC it had a viscosity of 2,500 cps, which is again a lower viscosity than a standard commercial emulsion, but serves to help test the EPM selected emulsifier system. Although an attempt was made to achieve a similar viscosity to the first model emulsion it was not possible to achieve this exactly. Cetearyl alcohol controlled viscosities do tend to be a little bit harder to accurately control than the polymer systems due to influences of stirring and rate of cooling. A summary of droplet size and emulsion stability results (major time points only) for this emulsion is given in Table

149 Chapter 7 Table 7.5 Second Model Emulsion Stability Results at 20ºC and 40ºC Test Condition Visual Appearance Particle Size (μm) Initial Homogenous, viscous emulsion 2.8 After 24 20ºC & 40 ºC After 1 20ºC & 40 ºC After 1 20ºC After 1 40 ºC After 3 20ºC After 3 40ºC After 6 20ºC After 6 40ºC Homogenous, viscous emulsion 2.8 Homogenous, viscous emulsion 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.8 Homogenous, viscous emulsion. No sign of separation 2.9 Homogenous, viscous emulsion. No sign of separation 2.9 Homogenous, viscous emulsion. No sign of separation 2.9 Once again this product would be considered to have passed its stability trial and be released for commercialisation. Two examples (the first with 2 emulsifier types) of different model emulsion formulations have shown how the EPM technique would be used in practice by the formulating chemist and that very stable commercial style emulsions can be achieved

150 Chapter 8 CHAPTER 8 CONCLUSIONS AND RECOMMENDATIONS FOR ADVANCEMENT OF EPM TECHNIQUE The research and practical studies outlined in this thesis has attempted to examine the many proposed methods for optimal emulsifier selection and to suggest a new technique with a different approach. The HLB technique is by far the most widely used method of those studied but even since this work was begun new, alternate methods have been put forward. The fact that new methods are continually being offered reflects the amount of trial and error that is still required to find an optimum emulsifier system for each new formulation developed. There is no definitive method currently in the public forum and this was the initial driver to carry out this study. New methods proposed in the last 8 years or so include using the PIT parameter or Emulsion Inversion Point (EIP), both proposed by Gasic et al. in 1998, or using colour difference (Koga et al., 2002). One common theme of most of the emulsifier selection methods proposed post HLB system is that they try to link their method to the HLB system. This is where the current work takes a different approach with the author strongly believing that all elements of the emulsion must be considered prior to selecting an emulsifier system and both moieties of the emulsifier must also be considered. 8.1 OUTLINE SUMMARY OF EXPERIMENTATION Following the detailed literature search and background research relevant for this work it is in Chapter 4, that the first splitting of the selected emulsifiers took place to yield alkanes (from the hydrophobic chain of the emulsifier) and different molecular weight glycols (from the hydrophile). From here the whole evaluation process could begin

151 Chapter 8 The interfacial tension data was initially measured between the range of alkanes and glycols that made up the selected emulsifiers. These values would derive a so-called EPM value for a particular emulsifier and be used to match oil and aqueous phases to be emulsified. Due to the physical nature of the higher molecular weight materials (PEG 1000, PEG 1500 and C16:C18 alkane) some extrapolation from the data measured for the lower molecular weight materials was required but finally EPM values, expressed and measured as interfacial tension, were determined for the selected emulsifiers. Collated, or measured interfacial tension data for the selected oils was also complied in this chapter giving the full set of initial data that could then be used to test out the EPM technique. Chapter 5 selected and standardized the optimal emulsifier concentration and the degree and time of mixing that would be used throughout the work. This was very important to ensure that the effect of the emulsifier only was evaluated throughout the work. In Chapter 6 we could, at last, begin to test out the EPM technique by making a range of emulsions. Although the number of materials that could be used was limited, eleven emulsions were prepared with six allowing direct comparison between the HLB and EPM selected emulsifiers (3 emulsions of each). The initial particle size and visual stability of the so formed emulsions were monitored for up to 72 hours to assess stability. The visual method to measure stability although basic, remains the method of choice throughout the formulation industry due to its proven reliability. The intial results achieved in Chapter 6 were encouraging with, in all cases the EPM emulsions showing better or at least as good particle size and stability than the HLB emulsions to emulsify the same oil which will be discussed later in this chapter. In Chapter 7, the final step to produce commercially acceptable cosmetic emulsions was carried out using the EPM technique to fully demonstrate how it would be used. Stable emulsion systems, suitable for commercial cosmetic products were produced. The work so far has shown the technique to be simple to use and the initial results obtained in this study have been very promising. The remainder of this chapter summarises the positive and negative findings of the EPM technique as a result of this work and outlines the ways in which the technique can be further advanced

152 Chapter POSITIVE ATTRIBUTES OF THE EPM TECHNIQUE The positive attributes of the EPM technique can be summarised as follows (with further explanation given in Section 8.2.1): All ingredients to be included in the emulsion can be taken into consideration before the emulsifier selection is made. Only one simple measurement is required to be carried out by the formulator. Where materials are changed or added as the formula develops, a repeat of the same simple measurement is all that is required to see if modification to the emulsifier system is required. Interfacial tension has been shown to be a useful method to characterise the raw materials and emulsion phases for the emulsifiers and emulsions tested. Emulsions with good stability have been able to be produced using the EPM technique. With additional tests required by the formulator, the EPM technique can offer guidance on the optimal emulsifier concentration to be used Discussion of Positive Attributes The EPM technique has addressed the issue of complex auxiliary ingredients that may effect the initial mixing and formation of the emulsion as well as effecting prolonged emulsion stability. The technique purposely utilises all formulation ingredients in its selection process

153 Chapter 8 The choice of interfacial tension to characterise the raw materials for the EPM database has been proven to have some credence. The preliminary work, in Chapter 5, as well as the emulsifiers used in the test emulsions have all given a smaller initial droplet size (relative to alternative emulsifiers) and more importantly, have been shown to give systems with greater stability than those formed with a slightly larger, initial droplet size. Interfacial tension is, in addition, quite a quick and easy test to perform. As already discussed, it is known that lowering the interfacial tension makes it easier to form an emulsion but also makes it easier to break that emulsion. Nevertheless, it was hoped to use the expected correlation between low interfacial tension and high surfactant adsorption to promote emusion stability. Matching exactly the difference between the two phases to be matched and the difference between the two moieties of the emulsifier may have achieved conditions that are the most energetically favourable for a surfactant to be at the interface between the oil and water droplets. This would then result in the highest possible concentration of emulsifier present at the interface. A strong interfacial film should be achieved and good stability would result. The emulsions tested have shown excellent long-term stability and with only 1% emulsifier being utilised. This is very unusual for commercial products, which often have 3 5 % emulsifier. It is possible, though not proven, that the favourable energetical conditions for higher surfactant concentration at the interface has been achieved. One further advantage the EPM technique has over the HLB system is that there is scope within the EPM method to measure optimal surfactant concentration. For example, this could be done by measurement of interfacial tension at varying emulsifier concentration to pinpoint the optimal concentration

154 Chapter NEGATIVE ATTRIBUTES OF THE EPM TECHNIQUE The negative attributes of the EPM technique can be summarised as follows: The use of interfacial tension as the method to characterise the system has shown some limitations with the nonionic emulsifiers that can be selected when using standard oil selection. Refer below. Interfacial tension of some high melting point emulsifiers cannot be carried out on the pure material. Extrapolation can be done here but is not ideal. An EPM database has been started but considerable work will be required to build up data for the wide range of emulsifiers that would be required to make this a viable technique for everyday use Discussion of Negative Attributes Although only a limited number of emulsifiers have been tested it appears that the EPM technique is somewhat limited in terms of the oils that will be suitable with nonionic emulsifier systems or else that a blend of oils will always be required. From Table 4.6 in Chapter 4, it is clear that the majority of oils possess interfacial tension values greater than 20 whereas the EPM values of the emulsifiers tested where all well below 20. With the use of anionic surfactants it is expected that EPM values of over 20 will be achieved, however, nonionics are by far the most commonly used surfactants used in emulsifiers so it is important that all nonionic surfactants can be used. More highly polar oils can be used to bring down the interfacial tension value to make the EPM technique viable but it should be confirmed that this blending to match interfacial tension is beneficial. Alternatively, or additionally, some time could be devoted to evaluate the possible benefits in using a scaling factor

155 Chapter FUTURE REQUIREMENTS TO VALIDATE EPM THEORY The results so far have been very promising. However, there is still a lot of work required and questions to be answered before the technique can be either properly validated or effectively used. The major points are detailed below: 1. Initial results have shown smaller initial droplet size and improved emulsion stability (greater time or higher temperature) before separation has occurred. This is believed to be due to optimal emulsifier packing of the interface resulting in higher emulsifier concentrations than usual. This needs to be proven so that the mechanism can be understood. Further studies could also investigate the effect the emulsifier concentration has on surface viscosity, viscoelastic effects and steric hindrance. 2. An EPM database has been started but needs to be built up to contain a comprehensive set of data. Without sufficient data in the database no new system would be fully utilised. Additional data needs to be added for many of the emulsifiers currently in commercial use. It may be found that relationships can be developed to predict the interfacial tension values rather than measuring every one. 3. Polarity of the oil may need to be also taken into account. The interfacial tension between an oil and water phase could equally apply to a high or a low HLB surfactant. 4. Intensive research done on microemulsions in connection with enhancing the recovery of petroleum from oil rock reservoir continues which has yielded equations to determine the conditions under which a microemulsion was formed. This work is detailed in Chapter 8 of Rosen (2004) and whilst this particular application and the use of microemulsions has little relevance to this work the HLD Method (hydrophilic- lipophilic deviation) has been adapted (Salager et al., 1983, 2000) to macroemulsion formation and this may now make this more

156 Chapter 8 relevant to the current work. The HLD method does take into consideration other components of the system (salinity (not relevant here), cosurfactant, alkane chain length, temperature and hydrophilic and hydrophobic groups of the surfactant (all relevant)) and so does have some similarities to the EPM technique. The current status and overview of the research of this technique should be evaluated at the time of further development because there may be some links here to help validate the EPM technique which should be considered. 8.5 FUTURE DIRECTION OF COSMETIC EMULSIONS The EPM technique was originally devised for cosmetic emulsion because this was the area of interest for the author. There is, of course, no reason why this could not be applied to other emulsion areas i.e., agrochemicals, food etc. However, because the aim of this work was cosmetic systems, the future direction of cosmetic emulsions must be considered when planning future work for this technique. The first model emulsion system covered in Chapter 7 was a cold processable emulsion that was stabilised by a polymer. These polymer systems are becoming increasingly popular because gel type emulsions as well as cold processed systems have increased in commerical popularity. As a further development of polymers, they are also being used to promote an emulsifierfree concept where the polymer is self-emulsifying and no other surfactant is required. Emulsions formed using the polymers are very stable and offer a light product that is rapidly absorbed into the skin. In actual fact, as shown in Figure 8.1 (Cognis GmbH, 2002) the oil becomes trapped in the voids of the polymer matrix rather than actually being emulsified into the water. This system can form creams/lotions for simple oilwater systems but can struggle with a high oil i.e., in sunscreens where a standard

157 Chapter 8 emulsifier is also required. These polymers are quite expensive which will slow their progress to replace standard emulsifiers but they will certainly play a significant part in cosmetic emulsions of the future. This area is being advanced also by the trend towards EO-free emulsions for apparent safety reasons. EO emulsifiers, like those studied in this thesis, remain by far the most common emulsifiers used in skincare due to the large range available and the consequent flexibility offered ot the formulator. However, to answer this trend and in addition to polymer alternatives, a number of new emulsifiers are appearing. Figure 8.1 Example of a Polymer Displaying Self-Emulsifying Properties Initially some of these alternate emulsifiers were quite inefficient and expensive i.w., cetearyl glucoside and could not significantly threaten the common and inexpensive nonionic emulsifiers. But since 2004 some quite efficient alternate emulsifiers have become available. Examples of these are sodium stearoyl glutamate and several sucrose esters which also meet the trend towards vegetable derived emulsifiers. These offer superior sensorial properties compared with EO emulsifiers, which can be a little tacky. In years to come these are likely to become more widespread in the cosmetic industry and so should be included in future work for the EPM technique

158 Chapter RECOMMENDATIONS FOR FURTHER WORK Requirements to validate the EPM technique were listed in Section 8.4. A mechanism for the EPM technique is the highest priority to understand and explain how this process can offer benefits. The importance of factors including oil polarity would also then be realised and a decision can be made if future work in this direction is also required. Even without a full, known mechanism work could be continued building up the emulsifier database. However, to limit the quantity of work (prior to a validated mechanism) the emulsifiers should be limited to those that can be used in combination with polymers in the newer, cosmetic emulsion types. If this is further limited to coldprocessable emulsions then this limits the emulsifier options further and makes the level of work required quite possible to achieve relatively quickly. Because this area of cold processable emulsions with polymers is still developing, this is a good opportunity to encourage the use of a new, improved emulsifier selection technique. The proposed EPM technique has given some initial good results and also raised some interesting questions regarding a higher surfactant concentration at the interface and a resulting, stronger interfacial film. There is much work still required but I hope that this current study has offered a different approach to emulsifier selection that will be worthy of future consideration

159 REFERENCES Alessi, P., Kikic, I. & Torriano, G. (1975), Correlation of Hydrocarbon Activity Coefficients with Solubility Parameters for Phthalate Esters, J. Chromatography 106 (1975), Ansmann, A., Baumöller, G., Koester, J., Salka, B., Tesmann, H & Wadle, A. (1995), Cosmetic O/W Emulsions for New Applications, Henkel Information (Cosmetic) VIII/95 Arrhenius, S. (1889), Z. Phys. Chem., 4, 226 Aveyard, R. & Clint, J.H. (2003), Adsorption and Aggregation of surfactants in Solution, Marcel Dekker, N.Y. Barton, A. (1990), Handbook of Solubility Parameters and Other Cohesion Parameters, CRC Press, Boca Raton, Florida Bashforth, F. & Adams, J. C. (1883), Theories of Capillary Action Cambridge University Press: London Becher, P. (1965), Emulsions: Theory and Practice, Reinhold, New York Becher, P. (1973), Pesticide Formulations W.Van Valkenburg, Marcel Dekker, N.Y., Becher, P. (1985), Applications of Emulsions, Encyclopedia of Emulsion Technology, Volume 2, Marcel Dekker, New York Becher, P. (2001), Emulsions: Theory and Practice, 3rd edition. American Chemical Society: New York

160 Becher, P. & Schick, M.J. (1987), Nonionic Surfactants, Surfactant Science Series Volume 23, Marcel Decker, Inc.: New York Beerbower, A. & Hill, M.W. (1972), Application of the Cohesive Energy Ratio (CER) concept to anionic emulsifiers, Am. Cosm & Perf 87, 86 Beerbower, A., Martin A. & Wu P.L. (1984), J. Pharm. Sci. 73, Boyd, J., Parkinson C. & Sherman P. (1972), J. Colloid Interface Sci., 41,359 British Standard (1993), Glossary of Terms Relating to Particle Technology, BS 2955: 1993 Broze, G. (Ed.) (1999), Handbook of Detergents Part A, Properties, Marcel Dekker, N.Y. Burke, J. (1984), Solubility Parameters: Theory and Application, AIC Book and Paper Group Annual, Volume 3, 13 58, Craig Jensen Ed. Clayden, J., Greeves, N., Warren S. & Wothers P. (2000), Organic Chemistry, Oxford University Press Cognis GmbH (1999), Care Chemicals Division CD-ROM Products and Guide Formulas for Cosmetic Applications, Duesseldorf Cognis GmbH (2002), Care Chemicals Division, Cosmedia SP, ICS Cowell, M.A., Kibbey, T.C.G., Zimmerman, J.B. & Hayes, K.F. (2000), Partitioning of ethoxylated nonionic surfactants in water/napl systems: Effects of surfactant and NAPL properties, Environmental Science and Technology 34 (8),

161 Daniels, R. (2002), Ultrasonic Velocity Measurements of the Shelf-life of Topical Formulations, Skin Care Forum, 28 Davies, J. T. & Rideal, E. K. (1961), Interfacial Phenomena, Acad. Press, N.Y Danov, K. D. (2001), On the Viscosity of Dilute Emulsions, J. Colloid Interface Sci., 235, Dominguez H. (2002), J. Phys. Chem. 106, 5915 Dominguez H. (2002), J. Colloid Interface Sci., 274, 665 Drelich J. & Miller J.D. (2000), Spreading Kinetics for Low Viscosity n-alkanes on a Water Surface as Recorded by the High Speed Video System, Annales UMCS Vol. LIV/LV, 7 Evans, G.M., Habgood, M.G., Galvin, K.P. & Biggs, S.R. (2002), A Description of Dynamic Interfacial Adsorption, Paper # 976, Ninth APCChE Congress & CHEMECA 2002, Christchurch NZ Everett, D.H. (1988), Basic Principles of Colloid Science, RSC Paperbacks Fairhurst D., Dukhin A. & Klein K. (2002), A New Way to Characterize Stability and Performance of Cosmetic Emulsions and Suspensions, ASCC Conference Proceedings Federal Bureau of Consumer Affairs (1991), Legislation Rule 1991, 327 Flory P.J. (1940), J. Am. Chem. Soc. 62,

162 Foerster, T.H., Schambil, F. & Tesmann, H. (1990), Emulsification by the Phase Inversion Temperature Method: the Role of Self-Bodying Agents and the Influence of Oil Polarity, Int. J. Cosmetic Sci. 12, Friedli, F. E. (Ed.) (2001), Detergency of Specialty Surfactants, Marcel Dekker, N.Y. a) Gasic, S., Jovanic, B. & Jovanic, S. (1998), Emulsion Inversion Point (EIP) as a Parameter in the Selection of Emulsifiers, J. Serbian Chem. Soc. 63 (7), b) Gasic, S., Jovanic, B. & Jovanic, S. (1998), Phase Inversion Temperature (PIT) as a Parameter in the Selection of an Appropriate Emulsifier, J. Serbian Chem. Soc. 63 (10), Gasic, S., Jovanic, B. & Jovanic, S. (2002), The Stability of Emulsions in the Presence of Additives, J. Serbian Chem. Soc. 67 (1), Gibbs, J.W. (1928), The Collected Works of J. W. Gibbs, Longmans, Green, London, I, 119 Greene, J.E. (1964), 100 Great Scientists, Washington Square Press, NY Griffin, W.C. (1949), Correlation between Emulsion Stability and Ethylene Oxide Content, J. Soc. Cosmetic Chemists, 1, 311 Griffin, W.C. (1954), Hydrophile Lipophile Balance, J. Soc. Cosmetic Chemists, 5, 249 Hansen, C.M. (1967), The Three Dimensional Solubility Parameter, J. Paint Technology 39, 505, ; 511, 500 Hawksbee, F. (the elder (1709)), Physico-mechanical experiments,

163 Hildebrand, J.H. (1915), The Entropy of Vaporization as a Means of Distinguishing Normal Liquids, J. Am. Chem. Soc. 37, Hildebrand, J.H. (1916), Solubility, J. Am. Chem. Soc. 38, Hildebrand, J.H. & Scott, R.L. (1950), The Solubility of Non-electrolytes, Reinhold Publishing Corporation, New York Hill K., Von Rybinski W. & Stoll G. (1997), Alkyl Polyglucosides: Technology, Properties and Applications, VCH Weinheim, Germany Hoar, T.P. & Schulman, J.H. (1943), The Formation of Translucent Emulsions, Nature, 152, 102 Holmberg, K., Jonsson, B. & Lindman, B. (2003), Chapter 1, Surfactants and Polymers in Aqueous Solution, 2 nd Edition, John Wiley & Sons Hunter, R.J. (2001), Foundations of Colloid Science, Oxford University Press, Second Edition, New York Jasper, J. J. (1972), Surface Tension of Liquids, J. Phys. Chem. Ref. Data, Volume 1, No. 4 Kageshima K., Takei T. & Sugitani, Y. (2003), Monitoring the Stability of an Emulsion by High-Frequency Spectroscopy, Analytical Sciences 19, Kegel, W.K. (1997), Macroscopic interfacial tension of polydispers droplet-type microemulsions, Langmuir 13 (4), Key Centre for Polymer Colloids (KCPC (2003)), Anionic Surfactants, Education Resources (2003), (

164 Key Centre for Polymer Colloids (KCPC (2003)), Nonionic Surfactants, Education Resources (2003), ( Kirk-Othmer (1993), Detegency, Encyclopedia of Chemical Technology 7, , Fourth Edition NY Kloet J. V. & Schramm L. L. (2002), J. Surfactants Detergents 5, 19 Koga, K. Ishitobi, Y., Iwata, M., Murakami, M. & Kawashima, S. (2002), A Simple Method for the Selection of a suitable Emulsifier Based on Color Difference, Biol. Pharm. Bull. 25 (12) Koopman, D.G., Kezic, S. & Verberk, M.M. (2004), Contact Dermatitis and Allergy, British J. Dermatology 150 (Issue 3), 493 Kunieda, H. & Ishikawa, N. (1985), Evaluation of the Hydrophile-Lipophile Balance (HLB) of Nonionic Surfactants: Commercial Surfactant Systems, J. Colloid Interface Sci. 107, Kunieda, H. & Miyajima, A. (1989), The Effect of the Mixing of Oils on the Hydrophile-Lipophile Balance (HLB) Temperature in a Water / Nonionic Surfactant / Oil System, J. Colloid Interface Sci. 128, Leszek, M., Valkenburg, V. & Wade, J. (1981), Cloud Point and Phenol Index of Nonionic Surfactants, Industrial & Engineering Chemistry, Product Research & Development. Vol. 20, 4, Li, Y., Zhang, P., Dong, F., Cao, X., Song, X. & Cui, X. (2005), The Array and Interfacial Activity of Sodium Dodecyl Benzene Sulphonate and Sodium Oleate at the Oil / Water Interface, J. Colloid Interface Sci. 290,

165 Lide, D. R. (1994), CRC Handbook of Chemistry and Physics, 75th Edition, CRC Press, Boca Raton, Florida Lochhead, R., Rulison, C. & Tisack-Kathman, M. (1999), Self-Assembly at the Oil- Water Interface, Formulations Forum 99, Orlando USA Luckham, P. (1986), Microemulsions and Solubilisation, Paper PL4, Technologically Important Aspects of Interface Science Mackay, R. (1997), Solubilisation Ch. 6, Nonionic Surfactants, Surfactant Science Series Volume 23 (Schick), Marcel Dekker, Inc.: New York Malvern Instruments (1997), Mastersizer Reference Manual, MAN0097 Markoe, G. E. (2000), Phoenicians, British Museum Press Martin, A., Wu, P.L., Liron, Z. & Cohen, S. (1985), Dependence of Solute Solubility Parameters on Solvent Polarity, J. Pharm. Sci. 74 (6), Meguro, K., Ueno, M. & Esumi, K. (1997), Micelle Formation in Aqueous Media Ch. 3, Nonionic Surfactants, Surfactant Science Series Volume 23 (Schick), Marcel Dekker, Inc.: New York Merck & Co (2001), The Merck Index An Encyclopedia of Chemicals, Drugs and Biologicals, Merck Research Laboratories, NJ Morrison I. D., & Ross S. (2002), Colloidal Dispersions: Suspensions, Emulsions and Foams, John Wiley and Sons, NY NICNAS (2003), NICNAS Existing Chemical Information Sheet 01 April

166 Padday, J. F. (1969), Surface and Colloid Science, Vol. 1, (E. Matijevic, ed), Wiley, New York Perez, M., Zambrano N., Ramirez, M., Tyrode E. & Salager, J. L. (2002), Surfactant-oil-water systems near the affinity inversion Part XII: Emulsion drop size versus formulation and composition, J. Dispersion Sci. Technology 23 (1/3) 55-63) Poly, W. (2002), Emulsions, Cognis GmbH Presentation, Cognis Deutchland Rekvig, L., Kranenburg, M., Hafskjold, B. & Smit, B. (2003), Effect of Surfactant Structure on Interfacial Properties, Europhys. Lett. 63 (6) Rekvig, L., Hafskjold, B. & Smit, B. (2004), Langmuir 20, Rosen, Milton J. (2004), Surfactants and Interfacial Phenomena, Wiley-Interscience Ruckenstein, E. (1999), Thermodynamic Insights on Macroemulsion stability, Advances in Colloid and Interface Science 79 (1), Salager, J. L., Minana-Perez, M., Perez-Sanchez, M., Ranfrey-Gouveia, M., Rojas, C. I. (1983), J. Disp. Sci. Technol. 4, 313 Salager, J. L., Marquez L., Lachaise, J., (2000), Langmuir 16, 5534 Salager, J. L., Marquez L., Mira I., Pena A., Tyrode E. & Zambrano N. (2002), Principles of Emulsion Formulation Engineering, Surfactants in Solution, Surfactant Science Series Chapter 24, , Marcel Dekker, New York Scatchard, G. (1915), Equilibria of Non-Electrolyte Solutions, J. Am. Chem. Soc. 38,

167 Schick, M.J. (1962), Surface Films of Ethylene Oxide Adducts, J. Colloid Sci. Vol. 17, 801 Schick, M.J. (1980), Nonionic Surfactants, Volume 1, Ed.; Marcel Decker, Inc.: New York, 1-7 Schoenfeldt, N. (1969), Grenzflachenactive Athylenoxid Addukte, Wissenschaftliche Verlagsgesellschaft MBH, Stuttgart Schoeller & Wittwer (1930), German Patents: 605,973 Ethoxylation of Hydroxyl- containing Compounds ; 667,744 Ethoxylation of Amides and Amines ; 694,178 Ethoxylation of Carboxyl-containing Compounds and of their Esters Schott, H. (1984), Solubility Parameter and Hydrophilic-Lipophilic Balance of Nonionic Surfactants, J. Pharm.Sci. 73, 6, 790 Schramm, L.L. (2001), Dictionary of Colloid and Interface Science, Wiley & Sons, New York Selllington, B. (1998), Chemistry in the Marketplace, 5 th Edition, Harcourt Brace & Company, Marrickville, Australia Shaw, D.J. (1993), Introduction to Colloid & Surface Chemistry, Fourth Edition,Butterworth-Heinemann Ltd, London Showell, M. S. (Ed.), (1998), Powdered Detergents, Marcel Dekker, N.Y. Shinoda, K. & Arai, H. (1964), The Correlation between Phase Inversion Temperature in Emulsions and Cloud Point in Solution of Nonionic Emulsifiers, J. Phys. Chem. 68,

168 Shinoda, K. & Arai, H. (1967), The Effect of Mixing Oils and of Nonionic Surfactants on the Phase Inversion Temperatures of Emulsions, J. Colloid Sci. 20, 93 Shinoda, K. (1968), Proc. 5th Int. Cong. Detergency, September 1968, Barcelona, II, 275 Shinoda, K. & Saito, H. (1969), J. Colloid Interface Sci. 30, Shinoda, K. & Takeda, H. (1970), J. Colloid Interface Sci. 32, 642 Sittig, M. (2002), Handbook of Toxins and Carcinogens, 4th Edition Sjoeblom, J. (1996), Emulsions and Emulsion Stability, Surfactant Science Series Vol. 61 Sjoeblom, J. (Ed. 2001), Chapter 26, Encyclopedic Handbook of Emulsion Technology, Marcel Dekker, New York, Sloan, K.B., Koch, S.A., Silver, K.G. & Flowers, F.P. (1986), Use of Solubility Parameters of Drug and Vehicle to Predict Flux Through the Skin, J. Investigative Dermatology 87, 2, Small, P. (1953) Some factors affecting the solubility of polymers, J. Applied Chemistry, 3, 71 Tesmann, H. (1988), Arlypon F, Information IV Turner, M. (2002), How to Simulate Shelf Life for Ageing Trials, Medical Device Technology Volume January/February Therapeutic Goods Administration (TGA (1994)), Sunscreen Stability Testing Guideline, Supplement to C29 Australian Code of GMP for Therapeutic Goods: Sunscreen Products

169 Therapeutic Goods Administration (TGA (2003)), Stablity Testing, Chapter 4 (E), ARGOM (OTC) Regulatory Guidelines Therapeutic Goods Administration (TGA (2004)), Stability of the Finished Product, ARGCM Complimentary Medicine Part 1 Appendix 3 Trapani, G., Altomare, C., Franco, M., Latrofa, A. & Liso, G. (1995), Determination of Hydrophile Lipophile Balance of some Polyethoxylated Nonionic Surfactants by Reversed Phase Thin Layer Chromatography, Int. J. of Pharm. Vol. 116, 1, 95-99, Unilever Australasia (2002), Fabric Cleaning, Consumer Education, 1-4 ( Vaughan, C.D. (1985), Using Solubility Parameters in Cosmetic Formulations, J. Soc. Cosmet. Chem. 36, Vaughan, C.D. (1988), Solubility Effects in Product, Package, Penetration and Preservation, Cosmetics & Toiletries Volume 103, 47 Vaughan, C.D. (1991), Solubility Parameter: What is it?, Cosmetics & Toiletries Volume 106, 69 Vaughan, C.D. (1993), Solubility Parameters for Characterising New Raw Materials, Cosmetics & Toiletries Volume 108, 57 Volmer, M. (1925), Z. Phys. Chem. 115, 253 Warr, G.G., Grieser, F. & Healy, T.W. (1983), Composition of mixed micelles of polydispersed surfactants, J. Phys. Chem. 87, Woodruff, D.P., Delchar, T.A. (1994), Modern Techniques of Surface Science, Second Edition, Cambridge University Press, Cambridge

170 Yamamoto, Y. (1994), Differential Scanning Calorimetry, J. Soc. Cosmet. Chem. Jpn., 27, 580 Young, T. (1805), Phil. Trans. Royal Society, London, 95, INTERNET INFORMATION & CORRESPONDING REFERENCES 1 st Holistic; Aubrey Organics; Begoun, P. (2002) from Hair Site; Key Centre for Polymer Colloids (KCPC) from Polco Pharma; Purist Company; Inilever;

171 APPENDIX

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