Excipients for Pharmaceuticals

Transcription

1 Excipients for Pharmaceuticals

2 Contents Foreword... 5 Liquid lipids... 6 Solid triglycerides... 8 Partial glycerides Emulsifiers Specialities Register of chemical/monograph names or synonyms Register of trademarks and product names Abbreviations: CFR = Code of Federal Regulations DAB = Deutsches Arzneibuch DMF = Drug Master File GRAS = Generally Recognized As Safe JCIC = Japanese Cosmetic Ingredients Codex JPE = Japanese Pharmaceutical Excipients Ph. Eur. = European Pharmacopoeia USP-NF = United States Pharmacopoeia-National Formulary.

3 Foreword CREMER OLEO produces raw materials based on vegetable origin like fatty acids, glycerol, esters up to structured lipids. With headquarters in Hamburg we operate three production sites in Germany Witten, Wittenberge, Rodleben and serve customers worldwide through own subsidiaries in 30 countries, exclusive distributors and agents. With our strong commitment to R&D we provide our valued customers state-of-the-art tailormade oleochemical solutions. 1 Under the roof of CremerHealth we have gathered our activities for the pharmaceutical industry: Our expert team with decades of experience will be happy to provide you individual solutions for pharmaceutical excipients (for i.e. topical, oral, rectal, enteral applications) as well as oleochemical based active pharmaceutical ingredients for enteral and parenteral formulations. As backward integrated producer we are market leader for MCT oils and related C 8 /C 10 fatty acid esters under the MIGLYOL brand. The WITEPSOL product range is the worldwide leading market standard for hard fats (suppositories bases). The IMWITOR product family provides functionalized lipids for drug delivery systems. With DYNASAN we offer you monoacid triglycerides for various applications which requires very precise physico-chemical characteristics (e.g. lubricants, hot melt coatings). Highest quality standards (GMP) are continously improved and controlled by German authorities and the US FDA. Please take a look into our catalogue of specialties for the pharmaceutical industry and convince yourself of the excellent product quality, the exact reproducibility of important specification parameters, the high reliability of supply from our independent production sites. Please ask us for further information, quotations, samples, technical advice and our experienced staff will be happy to assist you in any way possible. Stefan Cremer Director and Shareholder Peter Cremer Holding GmbH & Co. KG Patrick Knüppel Global Business Unit Manager Oleochemicals Foreword 5

4 2 Liquid lipids Liquid lipids are fatty acid esters. They are neutral carriers for various pharmaceutical applications. Because of their high polarity, they have superior solvent characteristics for active drugs (compared to hydrocarbons). 2 Product Chemical description/monograph name Listed in Appearance Viscosity mpa s 20 C Properties and applications C 8 /C 10 Tryglycerides CremerCOOR MCT 60/40 EP Caprylic/Capric/Triglyceride Ph. Eur., USP-NF, JPE CremerCOOR MCT 70/30 EP Caprylic/Capric/Triglyceride Ph. Eur., USP-NF, JPE CremerCOOR MCT C7 Triheptanoin Ph. Eur., USP-NF, JPE MIGLYOL 808 Tricaprylin Ph. Eur., USP-NF, JPE MIGLYOL 810 N Caprylic/Capric/Triglyceride Ph. Eur., USP-NF, JPE, DMF MIGLYOL 812 N Caprylic/Capric/Triglyceride Ph. Eur., USP-NF, JPE, DMF MIGLYOL 818 Caprylic/Capric/Linoleic Triglyceride MIGLYOL 829 Caprylic/Capric/Succinic Triglyceride JCIC, DMF MIGLYOL 8108 Caprylic/Capric Triglyceride Ph. Eur., USP-NF, JPE clear liquid 25 to 32 Neutral, stable, penetration enhancer, drug carrier, solvent, oral use, dermal use, i.v. applications. clear liquid 26 to 32 Neutral, stable, penetration enhancer, drug carrier, solvent, oral use, dermal use, i.v. applications. oily liquid * 20 to 28 Emollient with good spreadability and solvency for actives like UV-filters. oily liquid * ~ 23 Neutral, stable, penetration enhancer, drug carrier, dermal and oral use, solvent. oily liquid * ~ 26 Neutral, stable, penetration enhancer, drug carrier, solvent, oral use, dermal use, i.v. applications. oily liquid * ~ 28 Neutral, stable, penetration enhancer, drug carrier, solvent, oral use, dermal use, i.v. applications. oily liquid * ~ 33 Neutral, stable, penetration enhancer, drug carrier, solvent, oral use, dermal use, i.v. applications. oily liquid * ~ 300 Neutral, stable, oil of high viscosity, based on MCT and succinic acid. oily liquid * ~ 25 Neutral, stable, penetration enhancer, drug carrier, dermal and oral use, solvent. C 8 /C 10 Esters CremerCOOR Coco 810 Coco-Caprylate/Caprate CremerCOOR PPG 810 Propylene Glycol Dicaprylate/Dicaprate CremerCOOR PPD 810 Veg. Propanediol Dicaprylate/Caprate MIGLYOL 840 Propylene Glycol Dicaprylocaprate/Dicaprate Ph. Eur., JCIC, USP-NF MIGLYOL 8810 Butylene Glycol Dicaprylate/Dicaprate oily liquid n. d. Fast spreading emollient, refatting agent. oily liquid * ~ 11 Oil component, medium to high spreading emollient. oily liquid * ~ 10 Oil component, medium to high spreading emollient, natural origin. oily liquid * ~ 10 Neutral, stable, oil of low viscosity, dermal use, i.m. in veterinary preparations. oily liquid * ~ 11 Neutral, stable, penetration enhancer, drug carrier, dermal use, solvent. Other Esters CremerCOOR OE Oleyl Erucate JCIC oily liquid, light yellowish ~ 30 Unsaturated wax ester, dermal use, similar to Jojoba oil. CremerCOOR DO Decyloleate Ph. Eur. DYNACET 285 Diacetylated Monoglycerides 21 CFR MIGLYOL 612 Glyceryl Trihexanoate oily liquid * ~ 18 Liquid wax, unsaturated. Petrolatum substitute in pomades. oily liquid * ~ 30 Food grade softener, plasticiser and solvent. Stable polaric oil. oily liquid * ~ 15 Neutral, stable, penetration enhancer, solvent, oral use. SOFTISAN 645 Bis-Diglyceryl Polyacyladipate-1 JCIC yellowish thin liquid syrup ~ Liquid lanolin substitute, emollient, high water binding capacity, good adhesion to skin and mucous membranes, non-occlusive. SOFTISAN 649 Bis-Diglyceryl Polyacyladipate-2 JCIC, DMF sticky paste ~ 540 at 50 C Semisolid lanolin substitute, emollient, high water binding capacity, good adhesion to skin and mucous membranes, non-occlusive. * Almost colourless and odourless. 6 Liquid lipids Liquid lipids 7

5 Solid triglycerides 3 Apart from suppository manufacturing, solid triglycerides (hard fats) are used as carriers in capsule fillings, inlets, ointments and creams and in dental products. They also act as surface treatment and binder in tablets. Solid triglycerides are manufactured through direct esterification of glycerol with defined fatty acid blends and have therefore precise properties regarding melting point, polarity (Hydroxyl Value) and consistency. Being glycerol esters of edible fatty acids, they are classified as food additives. All suppository hard fats have a low content of short chain fatty acids (C 8 /C 10 ), convenient for improved application. The solid fat index curve is very stable. Hence WITEPSOLs are still solid and applicable, even a few degrees below melting point. EXCEPTION: the more soft adjusted WITEPSOL H 35. Important selection criteria are melting point and hydroxyl value. During formulation developments the tendency of the post hardening effect should be observed. Our technical application department in Witten will be glad to advise you. 3 Product Chemical description/monograph name Listed in Melting Point C Hydroxyl value mg KOH/g Properties and applications Hard fat suppository bases WITEPSOL H 5 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL H 12 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL H 15 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF 34.0 to to 33.5 max. 5 5 to 15 WITEPSOL H grades are hard fats with a low hydroxyl value of max. 15. They comprise mainly triglycerides with proportions of max. 15% of diglycerides and max. 1% of monoglycerides to to 15 WITEPSOL H 19 Hard Fat, Adeps solidus WITEPSOL H 185 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL H 32 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL H 35 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL H 37 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF 33.5 to to to to to 33.0 max to 35.5 max to 38.0 max. 3 They are characterized by a short gap between melting and solidification temperatures, showing a low tendency of post-hardening. Shock cooling should be avoided because of their brittleness. WITEPSOL W WITEPSOL W 25 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL W 31 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL W 32 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL W 35 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF WITEPSOL W 45 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE, DMF 33.5 to to to to 35 WITEPSOL W grades are hard fats with hydroxyl values between They comprise a mixture of 65 80% of triglycerides, 10 35% of diglycerides and 1 5 % of monoglycerides. (Correspondingly they have a wider gap between melting and solidification 32.0 to to 50 temperatures and are therefore more insensitive (elastic) to shock cooling.) They solidify more slowly. The amount of partial glycerides delays the sedimentation of solid 33.5 to to 50 active ingredients and promotes wetting of mucous membranes to to 50 WITEPSOL S WITEPSOL S 51 WITEPSOL S 55 * + Ceteareth-25 + Glyceryl Ricinoleate ** + Ceteareth-25 + Beeswax 30.0 to 32.0 ca. 35 *** 55 to to 65 WITEPSOL S grades contain special additives. They are suitable for manufacturing vaginal and rectal preparations, requiring a more intensive wetting of mucosae, a greater dispersability or an enhanced absorption. They all contain an ethoxylated emulsifier (Ph. Eur.) which makes them suitable for use in aquaeous or ethanolic/aquaeous active ingredients (emulsion suppositories). WITEPSOL S 58 + Ceteareth-25 + Glyceryl Ricinoleate ** 31.5 to to 70 * Compound, single components Ph. Eur. + USP-NF. ** Compounds contain unsaturated components, interactions with oxygen must be considered. *** Due to additive beeswax Ph. Eur. grade, determination of solidification point is recommended. 8 Solid triglycerides Solid triglycerides 9

6 Solid triglycerides (continued) 3 3 Product Chemical description/monograph name Listed in Melting Point C Hydroxyl value mg KOH/g Properties and applications Hard fat suppository bases WITEPSOL E 75* + Beeswax USP-NF, Ph. Eur.* WITEPSOL E 76 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE WITEPSOL E 85 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JPE ca. 38 ** 37.0 to 39.0 max to 40 WITEPSOL E grades are hard fats with a melting range above body temperature. They can be used to raise the melting point in case of active ingredients that decrease the melting point to to 15 SOFTISAN 378 Hard Fat, Adeps solidus USP-NF, Ph. Eur., JCIC ~ 30 7 to 17 Hard fat with softer consistency, similar to natural lard, but stable, odourless, emollient in creams, capsule filling mass. Solid Wax Esters 1) CremerCOOR CP Cetyl Palmitate USP-NF, Ph. Eur., JCIC ~ 50 max. 6 Stable waxy ester, replacement for natural spermaceti, consistency agent in creams, for coating, sustained release. Triglycerides with Melting Point above Body Temperature DYNASAN 110 Tricaprin DYNASAN 112 Trilaurin DYNASAN 114 Trimyristin DYNASAN 116 Tripalmitin DYNASAN 118 Tristearin CFR DYNASAN 122 Tribehenate FCC DYNASAN P 60 Hydrogenated Palm Oil max. 10 In powders as fast melting component without the powder being sticked together max. 10 In ointments and creams as body-imparting and structure forming component max. 10 A high melting point lipid for use in modified/sustained release in oral solid dosage matrices. Effective lubricant for tablets/capsules max max max to 62 max. 10 Palmitic/stearic triglycerides, similar to hydrogenated vegetable oil, USP type I. SOFTISAN 154 Hydrogenated Palm Oil WITOCAN 42/44 Hard Fat, Adeps solidus USP-NF, Ph. Eur. 53 to 58 max to 44 max. 15 (Consistency agent, coating, sustained release) Micro fine powder * Compound, single components Ph. Eur. + USP-NF. 1) Other wax esters on request. ** Due to additive beeswax, determination of solidification point is recommended. 10 Solid triglycerides Solid triglycerides 11

7 4 Partial glycerides Partial glycerides are esters of glycerol with fatty acids, whereby only a part of the existing hydroxyl groups are esterified. Some hydroxyl groups within the glycerol ester are free contributing to the polaric properties of the material. Short chain partial glycerides are more polaric and have excellent solvent properties for many hard-to-solubilize drugs. 4 Product Chemical description/monograph name Listed in Glyceryl Monostearates (GMS) Appearance Melting Point C Content of monoglycerides Properties and applications IMWITOR 491 Glyceryl Monostearate USP*-NF IMWITOR 900K Glyceryl Monostearate 40 55%, Type ll Ph. Eur., JCIC, USP-NF IMWITOR 900 P Glyceryl Monostearate 40 55%, Type l Ph. Eur., JCIC, USP-NF IMWITOR 960 K Glyceryl Monostearate, Self-emulsifying BP, JCIC off-white powder 66 to 77 > 90% Lipophilic matrix for oral solid dosage forms (granulation, hot melt technique). Tablet lubricant, emulsion stabilizer, off-white powder 54 to to 55% dispersing agent for pigments. off-white powder 54 to to 55% off-white powder 56 to 61 > 30% Self-emulsifying GMS containing sodium stearate. Short Chain Partial Glycerides CremerCOOR GC8 Glyceryl Monocaprylate, Type ll Ph. Eur., USP-NF IMWITOR 308 Glyceryl Monocaprylate, Type ll Ph. Eur., USP-NF IMWITOR 642 Mono-, Di-, Tri - Hexanoate USP*-NF IMWITOR 742 Glyceryl Monocaprylocaprate, Type l Ph. Eur., DAB 1999, USP* -NF, JCIC, DMF IMWITOR 928 Glyceryl Cocoate USP*-NF, JCIC MIGLYOL 988 Glyceryl Monocaprylate, Type l USP*-NF, JCIC solid 27 to 33 > 80% Emulsifier, co-surfactant, excellent antibacterial properties. white, soft, crystals 30 to 34 White, solid, crystalline mass, penetration enhancer, solvent, absorption promoter. clear, oily liquid ~ to 55% Excellent solvent for active ingredients. clear, oily liquid ~ to 55% Penetration enhancer, solvent, defoaming agent in effervescent tablets. white, similar to hard fat ~ to 55% Dispersing agent of solids and oils, solubilizer in suppositories. clear, oily liquid ~ to 55% Penetration enhancer, solvent. Unsaturated Partial Glycerides CremerCOOR GMO 90 Glyceryl Mono-Oleate Ph. Eur., USP-NF IMWITOR 948 Glyceryl Mono-Oleate Ph. Eur., USP-NF SOFTIGEN 701 Glyceryl Ricinoleate ** JCIC yellowish liquid liquid > 90% W/O emulsifier, O/W stabilizer, forms gels in excess water. yellowish liquid liquid > 40% W/O emulsifier, O/W stabilizer, forms gels in excess water. yellowish liquid liquid > 40% Emulsifier and stabilizer, high water binding capacity, protects irritated skin, used in vaginal products. * USP-NF: Mono- and Diglycerides Fatty acids from edible oils Direct food additives affirmed GRAS = Generally Recognized As Safe CFR ** Compounds contain unsaturated components, interactions with oxygen must be considered. 12 Partial glycerides Partial glycerides 13

8 Emulsifiers 5 5 Product Chemical description/monograph name Listed in Appearance HLB Properties and applications W/O Emulsifiers (see also partial glycerides) CremerCOOR PG3 DIS Polyglyceryl-3 Diisostearate IMWITOR 600 Polyglyceryl-3 Polyricinoleate E 476 IMWITOR 491 Glyceryl Monostearate USP-NF IMWITOR 900 K Glyceryl Monostearate 40 55%, Type ll Ph. Eur., JCIC, USP-NF IMWITOR 900 P Glyceryl Monostearate 40 55%, Type l Ph. Eur., JCIC, USP-NF yellow liquid ~ 6 Emulsifier W/O, cold processing. yellow liquid ~ 4 Food approved W/O emulsifier for systems of low viscosity. powder ~ 4 to 5 More than 90% of monoglycerides, stabilizer, stiffening and dispersing agent. white powder ~ 3 40 to 55% of monoglycerides, used as tablet lubricant, emulsifier and for sustained release. white powder ~ 3 40 to 55% of monoglycerides, used as tablet lubricant, emulsifier and for sustained release. O/W Emulsifier Basis: Ester IMWITOR 960 K Glyceryl Monostearate, Self-emulsifying BP, JCIC flakes ~ 7 Self emulsifying GMS, for dermal use. Basis: Alpha-Hydroxy Acids IMWITOR 372 P Glyceryl Stearate Citrate E 472 b/c, JCIC IMWITOR 375 Glyceryl Citrate/Lactate/Linoleate/Oleate E 472 b/c flakes ~ 10 to 12 Food approved in Europe, partly ionic, still oil soluble emulsifiers, similar to lecithin for stable emulsions at ph range 4 to 7. sticky syrup ~ Emulsifiers Emulsifiers 15

9 6 Specialities Fatty acid esters, further modified or compounded, create specific tools in pharmaceutical formulations. 6 Product Chemical description/monograph name Listed in Appearance Melting point C Properties and applications Special Esters CremerCOOR PG2 C10 Polyglyceryl-2 Caprate CremerlinPURA Olus Oil clear liquid Refatting agent, active as deodorant ingredient. white, semi-solid ~ 45 to 55 Emollient, petrolatum substitute, high occlusivity, non sticky. Base for lotions, creams and ointments. MIGLYOL Gel B Caprylic/Capric Triglyceride (and) Stearalkonium Hectorite oleogel, brownish softpaste N/A Heat stable oleogels, maintain viscosity between 0 C and 100 C. F. i. for water- and temperature resistant formulations. Soft lamellar structure for easy distribution on skin. MIGLYOL 840 Gel B MIGLYOL Gel T Propylene Glycol Dicaprylate Dicaprate (and) Stearalkonium Hectorite Caprylic/Capric Triglyceride (and) Stearalkonium Bentonite oleogel, brownish softpaste oleogel, greenish softpaste N/A N/A Emollient creating silky touch, non tacky. Consistency and viscosity stabilizer in emulsions. DYNACET 211 P Acetylated Glycerides E 472 a DYNACET 212 P Acetylated Glycerides E 472 a DYNACET 285 Diacetylated Monoglycerides 21 CFR waxy solid ~ 41 to 47 Consistency regulator and emulsion stabilizer in ointments and creams. waxy solid ~ 36 to 44 Consistency regulator and emulsion stabilizer in ointments and creams. clear liquid liquid Consistency regulator and emulsion stabilizer in ointments and creams. SOFTISAN 601 Glyceryl Cocoate (and) Hydrogenated Coconut Oil (and) Ceteareth-25 single ingredients Ph. Eur., USP-NF off-white soft pastilles ~ 40 to 45 Waterfree self emulsifying system, ready-to-use O/W cream base, suitable for a variety of pharmaceutical active ingredients. SOFTISAN 645 Bis-Diglyceryl Polyacyladipate-1 JCIC SOFTISAN 649 Bis-Diglyceryl Polyacyladipate-2 JCIC, DMF SOFTIGEN 701 Glyceryl Ricinoleate* JCIC SOFTIGEN 767 Macrogol 6 Glyceryl Caprylocaprate Ph. Eur., USP-NF, DMF yellow syrup Liquid lanolin substitute, adhesive to skin and wet mucous membranes, for wound dressing systems and irritated skin, non occlusive. off-white opaque mass 35 Semi solid lanolin substitute, adhesive to skin and wet mucous membranes, for wound dressing systems and irritated skin, non occlusive. yellowish substance 25 Skin protective agent, waterdispersible W/O co-emulsifier. clear liquid Solubilizer for drugs, refatting agent. Soluble in water and polar oils (MCT). Glycerine CremerPHARM 995 1,2,3-Propantriol/Glycerine E442, Ph. Eur., USP, JP, BP CremerGLYC 86,5 1,2,3-Propantriol/Glycerine Ph. Eur., USP, JP, BP clear, colourless liquid Solubilizer, humectant, laxative. clear, colourless liquid Solubilizer, humectant, laxative. * Compounds contain unsaturated components, interactions with oxygen must be considered. 16 Specialities Specialities 17

10 7 Register of chemical/monograph names or synonyms 7 Chemical/monograph name/synonym Product Page Chemical/monograph name/synonym Product Page A Acetylated Glycerides DYNACET 211 P, 212 P, 285 6, 16 G Glycerine CremerPHARM 995 CremerGLYC 86,5 16 B C D Bis-Diglyceryl Polyacyladipate-1 SOFTISAN 645 6, 16 Bis-Diglyceryl Polyacyladipate-2 SOFTISAN 649 6, 16 Butylene Glycol Dicaprylate/Dicaprate MIGLYOL Caprylic/Capric/Linoleic Triglyceride MIGLYOL Caprylic/Capric/Succinic Triglyceride MIGLYOL Caprylic/Capric Triglyceride MIGLYOL 810, 812, 8108 CremerCoor MCT 60/40 CremerCoor MCT 70/30 Caprylic/Capric Triglyceride (and) Stearalkonium Bentonite Caprylic/Capric Triglyceride (and) Stearalkonium Hectorite MIGLYOL GEL T 16 MIGLYOL GEL B 16 Cetyl Palmitate CremerCOOR CP 10 Decyloleate CremerCOOR DO 6 Diacetylated Monoglycerides DYNACET Glyceryl Citrate/Lactate/Linoleate/Oleate IMWITOR Glyceryl Cocoate IMWITOR Glyceryl Cocoate (and) Hydrogenated Coconut Oil (and) Ceteareth-25 SOFTISAN Glyceryl Monocaprylate, Type l IMWITOR 988/CremerCOOR GC8 12 Glyceryl Monocaprylate, Type ll IMWITOR Glyceryl Monocaprylocaprate, Type l IMWITOR Glyceryl Mono-, Di-, Tri - Hexanoate IMWITOR Glyceryl Mono-Oleate IMWITOR 948/CremerCOOR GMO Glyceryl Monostearate IMWITOR , 14 Glyceryl Monostearate, Self-emulsifying IMWITOR 960 K 12, 14 Glyceryl Monostearate 40 55% IMWITOR 900 P, 900 K 12, 14 Glyceryl Ricinoleate SOFTIGEN , 16 Glyceryl Stearate Citrate IMWITOR 372 P 14 Glyceryl Trihexanoate MIGLYOL Register of chemical/monograph names or synonyms Register of chemical/monograph names or synonyms 19

11 7 Register of chemical/monograph names or synonyms 7 Chemical/monograph name/synonym Product Page Chemical/monograph name/synonym Product Page H Hard Fat, Adeps solidus SOFTISAN 378 WITEPSOL H 5-H 185 WITEPSOL W 25-W45, E 76, E 85 WITOCAN 42/44 8, 10 O Oleyl Erucate CremerCOOR OE 6 Olus Oil CremerlinPURA 16 + Beeswax WITEPSOL E P 1,2,3-Propantriol CremerPHARM 995 CremerGLYC 86, Ceteareth-25 + Beeswax + Ceteareth-25 + Glyceryl Ricinoleate + Glyceryl Ricinoleate WITEPSOL S 55 8 WITEPSOL S 58, S 51 8 WITEPSOL H 19 8 Hydrogenated Palm Oil DYNASAN P 60, SOFTISAN Polyglyceryl-3 Diisostearate CremerCOOR PG3 DIS 14 Polyglyceryl-3 Polyricinoleate IMWITOR Propanediol Dicaprylate/-caprate CremerCOOR PPD 810 Veg. 6 Propylene Glycol Dicaprylate/Dicaprate (and) Stearalkonium Hectorite MIGLYOL 840 Gel B 16 Propylene Glycol Dicaprylocaprate/Dicaprate MIGLYOL 840/CremerCOOR PPG 810 6, 16 M Macrogol 6 Glyceryl Caprylocaprate SOFTIGEN T Tribehenate DYNASAN Tricaprin DYNASAN Tricaprylin MIGLYOL Trilaurin DYNASAN Triheptanoin CremerCOOR MCT C7 6 Trimyristin DYNASAN Tripalmitin DYNASAN Tristearin DYNASAN Register of chemical/monograph names or synonyms Register of chemical/monograph names or synonyms 21

12 8 Register of trademarks and product names 8 Product Chemical/monograph name/synonym Page Product Chemical/monograph name/synonym Page C CremerCOOR Coco 810 Coco-Caprylate/Caprate 6 CremerCOOR CP Cetyl Palmitate 10 D DYNACET 211 P Acetylated Glycerides 16 DYNACET 212 P Acetylated Glycerides 16 CremerCOOR DO Decyloleate 6 DYNACET 285 Diacetylated Monoglycerides 6, 16 CremerCOOR GC 8 Glyceryl Caprylate 12 DYNASAN 110 Tricaprin 10 CremerCOOR GMO Glyceryl Mono-Oleate 12 DYNASAN 112 Trilaurin 10 CremerCOOR MCT 60/40 EP Caprylic/Capric Triglyceride 6 DYNASAN 114 Trimyristin 10 CremerCOOR MCT 70/30 EP Caprylic/Capric Triglyceride 6 DYNASAN 116 Tripalmitin 10 CremerCOOR MCT C7 Triheptanoin 6 DYNASAN 118 Tristearin 10 CremerCOOR OE Oleyl Erucate 6 DYNASAN 122 Tribehenate 10 CremerCOOR PG 2 C 10 Polyglyceryl-2 Caprate 16 DYNASAN P 60 Hydrogenated Palm Oil 10 CremerCOOR PG 3 DIS Polyglyceryl-3 Diisostearate 14 CremerCOOR PPD 810 Veg. Propanediol Dicaprylate/-caprate 6 CremerCOOR PPG 810 Propylene Glycol Dicaprylocaprate/Dicaprate 16 I IMWITOR 308 Glyceryl Monocaprylate, Type ll 12 IMWITOR 372 P Glyceryl Stearate Citrate 14 CremerGLYC 86,5 1,2,3-Propantriol/Glycerine 16 IMWITOR 375 Glyceryl Citrate/Lactate/Linoleate/Oleate 14 CremerPHARM 995 1,2,3-Propantriol/Glycerine 16 IMWITOR 491 Glyceryl Monostearate 12, 14 CremerlinPURA Olus Oil 16 IMWITOR 600 Polyglyceryl-3-Polyricinoleate 14 IMWITOR 642 Glyceryl Mono-, Di-, Tri - Hexanoate 12 IMWITOR 742 Glyceryl Monocaprylocaprate, Type l 12 IMWITOR 900 K Glyceryl Monostearate 40-55, Type ll 12 IMWITOR 900 P Glyceryl Monostearate 40-55, Type l 12 IMWITOR 928 Glyceryl Cocoate 12 IMWITOR 948 Glyceryl Mono-Oleate 12 IMWITOR 960 K Glyceryl Monostearate, Self-emulsifying 12, 14 IMWITOR 988 Glyceryl Caprylate Monocaprylate, Type l Register of trademarks and product names Register of trademarks and product names 23

13 8 Register of trademarks and product names 8 Product Chemical/monograph name/synonym Page Product Chemical/monograph name/synonym Page M MIGLYOL 612 Glyceryl Trihexanoate 6 MIGLYOL 808 Tricaprylin 6 S SOFTIGEN 701 Glyceryl Ricinoleate 12, 16 SOFTIGEN 767 Macrogol 6 Glyceryl Caprylocaprate 16 MIGLYOL 810 Triglycerides, Medium-Chain 6 SOFTISAN 154 Hydrogenated Palm Oil 8 MIGLYOL 812 Triglycerides, Medium-Chain 6 SOFTISAN 378 Hard Fat, Adeps solidus 10 MIGLYOL 818 Caprylic/Capric/Linoleic Triglyceride 6 MIGLYOL 829 Caprylic/Capric/Linoleic Triglyceride 6 SOFTISAN 601 Glyceryl Cocoate (and) Hydrogenated Coconut Oil (and) Ceteareth MIGLYOL 840 Propylene Glycol Dicaprylocaprate/Dicaprate 6 MIGLYOL 840 Gel B Propylene Glycol Dicaprylate/Dicaprate (and) Stearalkonium Hectorite 16 SOFTISAN 645 Bis-Diglyceryl Polyacyladipate-1 6, 16 SOFTISAN 649 Bis-Diglyceryl Polyacyladipate-2 6, 16 MIGLYOL 8108 Caprylic/Capric Triglyceride 6 MIGLYOL 8810 Butylene Glycol Dicaprylate/Dicaprate 6 W WITEPSOL E 75 + Beeswax 10 WITEPSOL E 76 Hard Fat, Adeps solidus 8 MIGLYOL Gel B Caprylic/Capric Triglyceride (and) Stearalkonium Hectorite 16 WITEPSOL E 85 Hard Fat, Adeps solidus 8 WITEPSOL H 5 Hard Fat, Adeps solidus 8 MIGLYOL Gel T Caprylic/Capric Triglyceride (and) Stearalkonium Bentonite 16 WITEPSOL H 12 Hard Fat, Adeps solidus 8 WITEPSOL H 15 Hard Fat, Adeps solidus 8 WITEPSOL H 19 + Glyceryl Ricinoleate 8 WITEPSOL H 32 Hard Fat, Adeps solidus 8 WITEPSOL H 35 Hard Fat, Adeps solidus 8 WITEPSOL H 37 Hard Fat, Adeps solidus 8 WITEPSOL H 185 Hard Fat, Adeps solidus 8 24 Register of trademarks and product names Register of trademarks and product names 25

14 8 Register of trademarks and product names Product Chemical/monograph name/synonym Page W WITEPSOL S 51 + Ceteareth-25 8 WITEPSOL S 55 + Ceteareth-25 + Beeswax 8 WITEPSOL S 58 + Ceteareth-25 + Glyceryl Ricinoleate 8 WITEPSOL W 25 Hard Fat, Adeps solidus 8 WITEPSOL W 31 Hard Fat, Adeps solidus 8 WITEPSOL W 32 Hard Fat, Adeps solidus 8 WITEPSOL W 35 Hard Fat, Adeps solidus 8 WITEPSOL W 45 Hard Fat, Adeps solidus 8 WITOCAN 42/44 Hard Fat, Adeps solidus 10 All registered trademarks displayed in this brochure are the property of the CREMER Group of Companies. Users of this brochure are not permitted to use these trademarks without the prior written consent of their proprietor. All rights are reserved. All rights not expressly granted are reserved. We reserve the right to make any changes as a result of technological progress or developments. No guarantee or warranty is implied or intended as to any particular properties of our products. The customer is not exempted from the obligation to conduct careful inspection and testing of incoming goods. Reference to trademarks used by other companies is neither a recommendation, nor should it give the impression that products of other companies cannot be used. All CREMER business transactions are exclusively governed by our General Business Conditions please see (terms and conditions) 26 Register of trademarks and product names

15 Headquarter GERMANY Cremer Oleo GmbH & Co. KG Glockengiesserwall Hamburg, Germany Telefon: +49 (0) Telefax: +49 (0) global@cremer.de Our branch offices EUROPE FRANCE Cremer Oleo (France) SARL Phone: peter.cremer.france@petercremerfrance.com IT ES GR Cremer Oleo Southern Europe Phone: f. chirvase@cremer.de CZ SK HU PL Peter Cremer Central Europe s.r.o. Phone info@cremer-gruppe.cz SWITZERLAND Cremer Oleo GmbH & Co. KG Phone: +49 (0) t.weigt@cremer.de Phone: f.chirvase@cremer.de AUSTRIA Cremer Oleo GmbH & Co. KG Phone: +49 (0) t.weigt@cremer.de GREAT BRITAIN Cremer Oleo UK Phone: enquiries@cremeroleo.co.uk NORTH AMERICA USA Peter Cremer North America L.P. Phone: bpagliocca@petercremerna.com ASIA SINGAPORE Peter Cremer (Singapore) GmbH Phone: info@cremeroleo.com CHINA Peter Cremer (Shanghai) Co., Ltd. Phone: dkrueger@cremer.com.cn