WITEPSOL - IOI Oleo GmbH

1 WITEPSOL . IOI OLEOCHEMICAL PHARMA. WITEPSOL . Hard fats for suppositories and ovules IOI Oleo GmbH. Hamburg, Germany | +49 40 28 00 31-0. IOI Oleo GmbH. | 18 1. WITEPSOL WITEPSOL . CONTENTS. 1. HARD FACTS ABOUT OUR HARD FATS 5. 2. PRODUCT RANGE 6. WITEPSOL H 6. WITEPSOL W 7. WITEPSOL S 7. WITEPSOL E 7. 3. PRODUCTION AND QUALITY CONTROL 8. 4. PROCESSING 10. General guidelines 10. Processing methods 10. Dosage in suppositories 11. Testing of suppositories 13. Challenges in suppository production 15. References 15. 5. OVERVIEWS 16. Hard fat recommendations for active pharma- 16. ceutical ingredients Abbreviations: JPE = Japanese Pharmaceutical Excipients Ph.

2 Eur. = European Pharmacopoeia USP-NF = United States Pharmacopeia-National Formulary 2 3. WITEPSOL WITEPSOL . 1|HARD FACTS ABOUT. OUR HARD FATS. The brand name WITEPSOL is synonym for hard fats mainly used in suppositories and ovules. Development and production of WITEPSOL started back in the 1950s at the former Chemische Werke Witten, now known as IOI Oleo GmbH. Manufacturing takes place in a fully automated process, including pastillation and packaging line operating under clean room-condition. This state-of-the-art production guarantees the highest possible standard, and in turn the quality of medicine in our ethical environment.

3 The site in Witten repeatedly has been granted EU GMP-certification and is US FDA-approved. Based on our cGMP production, our regulatory set-up and our experience - quality you can rely on Made in Germany . Pastillation belt 4 Packaging line 5. WITEPSOL WITEPSOL . 2|PRODUCT RANGE WITEPSOL W WITEPSOL E. WITEPSOL products of series W are hard fats with WITEPSOL products of series E are hard fat com- For the preparation of an optimal form of rectal medicine or ovule, a single grade is not suf cient. To allow for a better hydroxyl values of 20 50. They consist of a mixture pounds having a melting point above body temperature. overview of this range, the WITEPSOL grades are divided into four classes and, within these classes, are arranged in of triglycerides (65 80%), diglycerides (10 35%), and They are used if active compounds lower the melting order of increasing melting point.

4 Monoglycerides (1 5%). As a result of their composition, point of the main hard fat because of their fat solubility. these WITEPSOL grades have a larger gap between melting and solidi cation points, they are less sensitive They are characterized by their melting point and WITEPSOL H WITEPSOL S to shock cooling (more elastic), solidify more slowly and hydroxyl value. WITEPSOL E 75 additionally contains WITEPSOL products of series H are hard fats which are WITEPSOL products of series S are special hard fats with can be readily processed both with automatic machines beeswax (cera alba). characterized by a low hydroxyl value. a non-ionic ethoxylated emulsifier as main additive.

5 And with small-scale equipment. The partial glyceride content also slows down the sedimentation of solids WITEPSOL W WITEPSOL E and promotes the absorption of less readily absorbable WITEPSOL E 75 melting point approx. 38 C HV = max. 15. WITEPSOL products of series W are hard fats which are WITEPSOL products of series E are hard fats having mel- active compounds. WITEPSOL E 76 melting point 37 39 C HV = 30 40. characterized by a higher hydroxyl value. ting points above body temperature. WITEPSOL E 85 melting point 42 44 C HV = 5 15. WITEPSOL W 32 melting point 32 C HV = 40-50. WITEPSOL W 25 melting point C HV = 20-30. WITEPSOL H WITEPSOL W 35 melting point C HV = 40-50.

6 WITEPSOL W 45 melting point C HV = 40-50. WITEPSOL products of series H (except H 19) are hard COMPOUNDS FOR SUSPENSION SUPPOSITORIES. fats with hydroxyl values up to 15. They mostly consist HAVING A PROPORTION OF SOLID ACTIVE WITEPSOL W 45 is a special grade which is cha- of triglycerides with a portion of, at most, 15% of COMPOUNDS OF LESS THAN 25% racterized by a higher monoglyceride content of up to diglycerides and not more than 1% of monoglycerides. 15%, which supports increased absorption promotion of WITEPSOL H 35 melting point C HV = max. 3. They are characterized by a very small gap between active compounds and faster solidi cation.

7 The melting and solidi cation temperatures , have only WITEPSOL H 5 melting point 34 36 C HV = max. 5. a minor tendency to the posthardening phenomenon WITEPSOL H 15 melting point C HV = 5 15. (maximum C) and can be processed both with automatic casting machines and, on a small scale, using the cream melting process (precrystallization) at WITEPSOL S. casting temperatures around the stated melting point. WITEPSOL products of series S are special grades COMPOUNDS FOR SUSPENSION SUPPOSITORIES. Shock cooling should be avoided. This series of grades AND LIPOPHILIC ACTIVE COMPOUNDS; which contain particular auxiliaries in addition to the also includes compounds having hydroxyl values (HV) FOR MELTING POINT CORRECTION hard fat of pharmacopoeias.

8 Between 0 and 5 which avoid interactions between the WITEPSOL H 37 melting point 36 38 C HV = max. 3. free OH groups and acidic active compounds They are used for the preparation of vaginal and rectal (ASA, Diclofenac, etc.). forms of medicines which require better wetting of mucous membranes and enhanced dispersibility and are intended to promote absorption. Besides other ingredients like beeswax or glyceryl ricinoleate the most COMPOUNDS FOR SUSPENSION important auxiliary is an ethoxylated cetylstearyl alcohol. SUPPOSITORIES HAVING A PROPORTION OF. SOLID ACTIVE COMPOUNDS OF OVER 25%. WITEPSOL S 51 melting point 30 32 C HV = 55 70.

9 WITEPSOL H 32 melting point 31 33 C HV = max. 3. WITEPSOL S 55 melting point C HV = 50 65. WITEPSOL H 12 melting point 32 C HV = 5-15. WITEPSOL S 58 melting point C HV = 60 70. WITEPSOL H 19 melting point C HV = 20-30. 6 7. WITEPSOL WITEPSOL . 3|PRODUCTION AND. QUALITY CONTROL. Production WITEPSOL suppository compounds consist of glycerol The crude reaction mixture is subsequently processed esters of vegetable saturated fatty acids, mainly lauric as follows: acid. Starting materials are puri ed, specially selected Alkali washing to remove free fatty acids (as soaps). coconut and palm kernel oils from tropical plantations. and the catalyst (as fat-insoluble basic compounds).

10 Neutral washing to remove excess alkali After preliminary puri cation, the oils are cleaved into Drying in vacuum their fatty acids and glycerol by means of water at high Adsorptive treatment to remove chromogenic products pressure and acidic or alkaline catalysts. The fatty acid and traces of catalyst mixture is subjected to catalytic hydrogenation and Steam distillation in vacuum and repeated drying subsequently to fractional vacuum distillation, and the Deep-bed ltration under pressure low molecular weight caproic, caprylic, and capric acids (C6 C10) are removed. The C12 C18 fatty acids are Some of the WITEPSOL grades are then mixed with adjusted to the correct mixture for the grade in charge emulsi ers or consistency modifying waxes.