Technical Information Kolliwax HCO September 2015 03_150617e_00/Page 1 of 8 WF-No. 129938 = Registered trademark in many countries Hydrogenated castor oil powder for pharmaceutical use
03_150617e_00 September 2015 Page 2 of 8 Kolliwax HCO PRD-No. 30554455 Article-No. 50253255 Regulatory Status Tradename Kolliwax HCO Compendial Name Ph. Eur.: Castor Oil Hydrogenated USP/NF: Hydrogenated Castor Oil JP: Hydrogenated Oil Chemical Structure Figure 1: Chemical structure of hydrogenated castor oil Kolliwax HCO is obtained by hydrogenation of castor oil. It mainly consits of the triglyceride of 12-hydroxystearic acid. Hydrogenated castor oil is compatible with most natural vegetable and animal waxes. Chemical characterization Typical Properties Value Method Melting Point [ C] 83 88 Ph. EUR. 2.2.14 Acid value max. 4.0 Ph. EUR. 2.5.1 Hydroxyl value 145 165 Ph. EUR. 2.5.3 method A Saponification value 176 182 USP/NF (401) Iodine value max. 5.0 Ph. EUR. 2.5.4 method A Furthermore Kolliwax HCO meets the test requirements of the following monographs (current version): Castor Oil, hydrogenated Ph. EUR. Hydrogenated castor oil NF Hydrogenated oil JP The chemical characterization shown in the table above is only for infomation purposes and should be interpreted as typical properties of Kolliwax HCO. The BASF standard specification can be found in a seperate document. Specification See separate document: Standard Specification (not for regulatory purpose) available via BASF s World account: http://worldaccount.basf.com (registered access).
03_150617e_00 September 2015 Page 3 of 8 Kolliwax HCO Differential scanning calorimetry (DSC) Test conditions: Heating range: 10 K/min Sample amount: 6 7 mg First heating cycle: -20 120 C Cooling cycle: 120-20 C Second heating cycle: -20 120 C Cycle T Onset T max 1 T max 2 T max 3 T Offset ΔH J/g 1. Heating 59 (±0,6)* 79 (±0,2)* 87 (±0,0)* / 91 (±0,2)* 142 (±1)* 2. Heating 51 (±0,3)* 60 (±0,4)* 80 (±0,2)* 86 (±0,1)* 89 (±0,1)* 135 (±1)* 3. Cooling 51 (±0,3)* 60 (±0,4)* 80 (±0,2)* 86 (±0,1)* 89 (±0,1)* 135 (±1)* Table 2: DSC Summary 4 Crystalization 2 Heat Flow (W/g) 0-2 1. Heating cycle>>> 57.85 C 142.1 J/g 50.54 C 134.9 J/g 69.26 C 78.68 C 86.74 C 90.85 C <<<Cooling cycle 89.07 C -4 2. Heating cycle>>> 59.53 C Melting 79.80 C 86.38 C -6-20 0 20 40 60 80 100 120 Temperature Figure 2: Typical DSC curve of Kolliwax HCO Dynamic vapor sorption Measurement conditions/setup parameters Time between cycles 20 min, Min. time per cycle 50 min, Max. time per cycle 36 Equilibrium condition 0.05% per 15 minutes The maximal water uptake at 90% rel humidity is at 0.1%. Therefore the material is not hygroscopic. Solubility information As per the Ph. Eur monograph. Castor oil, hydrogenated Kolliwax HCO is practically insoluble in water, slightly soluble in methylene chloride, very slightly soluble in anhydrous ethanol and practically insoluble in petroleum.
03_150617e_00 September 2015 Page 4 of 8 Kolliwax HCO Typical Physical Properties Particle size distribution Typical Particle size distribution D (10) D (50) D (90) Kolliwax HCO 11.3 µm 28 µm 58.65 µm D (v. 0.1) D (v. 0.5) D (V. 0.9) Kolliwax_HCO_0013176110 12,88507 µm 31.84153 µm 64,77189 µm Kolliwax_HCO_0013176110 12,63315 µm 31,79562 µm 65,87014 µm Kolliwax_HCO_0013176110 12,60156 µm 32,37804 µm 67,68516 µm 10 10 8 80 q (%) 6 4 60 40 Total: Q(r) (%) 2 20 0 0 0.010 0.010 1.000 10.00 100.0 1000 3000 Diameter (µm) Powder Properties Typical Powder Properties Value Unit Bulk Density g/ml 0.38 Tap Density g/ml 0.52 Hausner Factor 1,3743.2 Angle of repose 43.2 Specific surface area (BET) Method: Determination of the specific surface area of solids by gas adsorption BET method (ISO 9277:2010), English translation of DIN ISO 9277:2014-01 Typical values Value Unit BET-Surface area m 2 /g 1.13 C-Value 11 Langmuir-Surface area m 2 /g 2.06
03_150617e_00 September 2015 Page 5 of 8 Kolliwax HCO Scanning Electron Microscopy Pictures (SEM) 300 : 1 100 µm 1500 : 1 Application 20 µm Hydrogenated castor oil is a hard wax with a high melting point used in oral and topical pharmaceutical formulations is used as a lubricant for tablets and capsules. Furthermore HCO can be used to prepare a sustained released formulation for water soluble APIs (e.g. Alfuzosin-HCL, Aminophyllin, Lithiumcarbonat, Niacin, Sulfanilamid, Theophylline). It can either be used as lipophilic matrix former or as a coating ingredient. Kolliwax HCO can be used as a standalone solution as well as in combination with other sustained release polymers. In topical formulations HCO can be used as consistency factor to enhance the vis cosity of the formulation. The typical concentration it at about 0.1 2%. Hydro genated castor oil is compatible with most natural vegetable and animal waxes and can therefore be used in comibnation with fatty alcohols and other consitency factors.
03_150617e_00 September 2015 Page 6 of 8 Kolliwax HCO Lubricant Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine. Lubricants also ensure that tablet formation and ejection can occur with Iow friction. Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules. Lubricants are added in small quantities to tablet and capsule formulations to improve certain processing characteristics. In Tablet formulations Kolliwax HCO can be used as a lubricant as an effective alternative to magnesium stearate. Hydrogenated castor oil is compatible to a large number of actives and does not provide a metallic taste. The following study elaborates the optimal working concentration of Kolliwax HCO as a lubricant. This study was performed on direct compressible placebo formulations using Ludipress. The Sweet spot diagram shows the optimal working concentration balancing the lubrication effectiveness with the ejection force and the tablet characteristics (e.g. disintegration and hardness). Study design: Formulation 1 2 3 Ludipress 99.5% 99.0% 97.0% Kolliwax HCO 0.5% 1.0% 3.0% Blending time: Compression: Turbula blender with 2 / 5 / 10 minutes mixing time Korsch XL 100 rotary press, 10 mm flat, 300 mg tablet mass 3 kn / 5 kn / 10 kn / 15 kn / 20 Kn Evaluation parameter Compression behavior: Compression force upper punch, Compression force lower punch, Ejection force. Tablet characteristics: Weight, Height, Diameter, Hardness, Tensile strength, Disintegration time Sweet Spot Diagram Sweet Spot: Hardness 70 130 N Disintegration time 20 90 sec Ejection force < 300N Diagram 2: Sweet spot diagram for optimal working concentration of Kolliwax HCO as a lubricant The optimal working concentration of Kolliwax HCO as a lubricant is starting at 1.5%.
03_150617e_00 September 2015 Page 7 of 8 Kolliwax HCO Topical application Similar to emollients, waxes affect the sensory profile and the stability of a topical formulation. They are solid at ambient temperatures and stabilize emulsions as the viscosity is increased by formation of lamellar structures in oil-in-water formulations. Furthermore Kolliwax HCO can be used as consistency factor in all kind of O/W, W/O or anhydrous formulations. Kolliwax HCO has a special advantage because of its high melting point and is able to support the formulation stability particularly at elevated temperatures. However, please pay particularly attention that the oil phase of the formulation is thoroughly melted and well mixed. Please find below a placebo formulation example, which can be used as a starting point for further formulation work with different types of APIs. Phase Tradename Chemical Function % I Di Water Water Solvent 70.8 Glycerin Glycerin Humectant 5.0 Kolliphor CSS Sodium cetostearyl sulfate Emulsifier 1.0 II Kollicream IPM Isopropyl myristate Emollient 5.0 Kolliwax HCO Hydrogenated castor oil Consistency factor 8.0 III Preservative Preservative Preservative 0.2 IV API Active pharmaceutical ingredient API 10.0 Procedure: Heat the mixture phase I and II separately to 85 90 C: Make sure that Kolliwax HCO is molten. Mix phase I and II, homogenize 2 minutes at about 5000 rpm, transfer to impeller mixer, 4 flat blades at 250 rpm. At 40 C add III, cool down to 30 C and add to a sealed glass container. Allow to equilibrate for 24 hours prior to analytical testing and or evaluation. Safe use concentrations- FDA Inactive ingredient (IIG) Listing: Hydrogenated castor oil is used in various pharmaceutical formulations in topical as well a oral solid dosage forms. Please find enclose the information on the maximal concentrations included in the FDA IIG List. http://www.accessdata.fda.gov/scripts/cder/iig/getiigweb.cfm Last visited April 2015 INACTIVEINGREDIENT ROUTE; DOSAGE FORM CAS NUMBER UNII MAXIMUM POTENCY HYDROGENATED CASTOR OIL ORAL; CAPSULE 8001783 ZF94AP8MEY 8 MG HYDROGENATED CASTOR OIL ORAL; CAPSULE, EXTENDED 8001783 ZF94AP8MEY 2.4M G ORAL; CAPSULE, EXTENDED HYDROGENATED CASTOR OIL ORAL ; CAPSULE, SUSTAINED ACTION 8001783 ZF94AP8MEY 410.82 MG HYDROGENATED CASTOR OIL ORAL; TABLET 8001783 ZF94AP8MEY 37.6 MG HYDROGENATED CASTOR OIL ORAL; TABLET, DELAYED 8001783 ZF94AP8MEY 1.3 MG ACTION, ENTERIC COATED HYDROGENATED CASTOR OIL ORAL; TABLET, EXTENDED 8001783 ZF94AP8MEY 40 MG RELEASE HYDROGENATED CASTOR OIL ORAL; TABLET, FILM COATED 8001783 ZF94AP8MEY 10 MG HYDROGENATED CASTOR OIL ORAL; TABLET, SUSTAINED 8001783 ZF94AP8MEY 295 MG ACTION HYDROGENATED CASTOR OIL ORAL; TABLET, SUSTAINED 8001783 ZF94AP8MEY 5 MG ACTION, COATED HYDROGENATED CASTOR OIL ORAL-21;TABLET 8001783 ZF94AP8MEY 0.93 MG HYDROGENATED CASTOR OIL ORAL-28; TABLET 8001783 ZF94AP8MEY 0.93 MG HYDROGENATED CASTOR OIL SUBLINGUAL; TABLET 8001783 ZF94AP8MEY 1.6 MG HYDROGENATED CASTOR OIL TOPICAL; EMULSION, CREAM 8001783 ZF94AP8MEY HYDROGENATED CASTOR OIL TOPICAL; SUSPENSION 8001783 ZF94AP8MEY 2%
03_150617e_00 September 2015 Page 8 of 8 Kolliwax HCO Toxicology The toxicological abstracts are available on request. Individual reports can be shared under secrecy agreement. Stability and storage In originally sealed containers all the Kolliwax HCO can be stored for at least two years. It is important that they are protected from moisture and stored at less than 30 C. Handling and Disposal Please refer to the individual Material Safety Data Sheet (MSDS) for instructions on safe and proper handling and disposal. Disclaimer This document, or any answers or information provided herein by BASF, does not constitute a legally binding obligation of BASF. While the descriptions, designs, data and information contained herein are presented in good faith and believed to be accurate, it is provided for your guidance only. Because many factors may affect processing or application/use, we recommend that you make tests to determine the suitability of a product for your particular purpose prior to use. It does not relieve our customers from the obligation to perform a full inspection of the products upon delivery or any other obligation. NO WARRANTIES OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, ARE MADE REGARDING PRODUCTS DESCRIBED OR DESIGNS, DATA OR INFORMATION SET FORTH, OR THAT THE PRODUCTS, DESIGNS, DATA OR INFORMATION MAY BE USED WITHOUT INFRINGING THE INTELLECTUAL PROPERTY RIGHTS OF OTHERS. IN NO CASE SHALL THE DESCRIPTIONS, INFORMATION, DATA OR DESIGNS PROVIDED BE CONSIDERED A PART OF OUR TERMS AND CONDITIONS OF SALE. September 2015 BASF Nutrition & Health www.pharma-ingredients.basf.com