Excipients for Rectal and Vaginal Drug Delivery - …

1 Pharmaceutical Performance Powered by Gattefoss Excipients for Rectal and Vaginal drug Deliveryour businessGattefoss is an independent global leader in the production of specialty lipidic Excipients and lipid-based drug Delivery systems. Working with healthcare industries for over a century, our expertise in oleochemistry has inspired the development of a diverse portfolio of products and formulation expertiseGattefoss has dedicated laboratories for R&D and Formulation. Our research aims to improve understanding of the physicochemical nature of lipids and their behaviour in drug Delivery systems, in vitro and in vivo. Our Formulation Laboratory provides consultancy in lipid formulations for Rectal , topical and oral dosage forms; bioavailability and sustained release and processing and QualityGattefoss principal manufacturing site is based at the global headquarters in Saint-Priest, France.

2 Production, quality and logistic operations are supported by SAP. Our manufacturing operations aim to be: Innovative in pilot and scale-up projects for custom product manufacturing Responsive to rapidly meet unexpected increases in demand Flexible in providing custom packaging and Delivery solutions Responsible implementing production methods that positively manage environmental impactsustainable developmentGattefoss is committed to conducting environmentally responsible business and takes sustainable development seriously. Our environmental impact is pro-actively measured and controlled. Manufacturing processes are developed to be clean, using degradable catalysts and solvent-free extraction processes in oleochemistry.

3 Our manufacturing is designed to utilize energy more efficiently and generate less gattefoss 2 Pharmaceutical performance powered by Gattefoss About Gattefoss Gattefoss products are manufactured in an ISO 9001 version 2000 certified facility. Quality and batch-to batch consistency are guaranteed by adhesion to the principles of and specialty productsGattefoss is a reputable global supplier of suppository bases. Suppocire products are hard fat semi-synthetic bases produced by inter-esterification or direct esterification of fatty acids. Their composition consists of a mixture of C12 C18 Suppocire catalogue offers standard Products and specialty semi-synthetic basesSuppocire semi-synthetic bases have superior performance features compared with certain natural or fully synthetic bases, these include:clinical properties Excellent safety and mucosal tolerance due to non-toxicity and non-irritant properties Softening and diffusion properties that deliver efficient and uniform drug properties Chemically inert and therefore compatible with a wide variety of APIs Excellent dispersion of active ingredient in the suppository mass Proven physical and chemical stability.

4 Colour, odour, drug release profile, low risk of properties Optimized solidification properties to minimise physical polymorphisms Different products provide solutions for a wide range of manufacturing equipmentGattefoss serviceGattefoss has produced Suppocire for more than 50 years. We can genuinely help speed up your time to market by providing: Rapid identification of the right Suppocire product for the API Access to a library of over 2,000 suppository formulations Product customization and laboratory scale formulation assistance Production and validation of pilot batches Scale-up and manufacturing Quality performance Product quality and performance is assured by conformity to international monographs.

5 EP, USP-NF, JPE Uniform physicochemical characteristics and batch-to-batch consistency ensure reproducible analytical and functional outcomes Repeat batch release quality assurance tests are undertaken for more sensitive Suppocire products The Suppocire and Ovucire manufacturing sites have consistently passed international safety and regulatory status Excipient safety is supported by in vitro and in vivo toxicity studies as well as history of use in internationally approved medicinal products. The Suppocire and Japocire range is referenced in a Type IV drug Master File registered with the FDA to assist clients with IND, NDA or ANDA and specialty productsstandard and specialty products3 Pharmaceutical performance powered by Gattefoss hydroxyl value (mg Koh/g)melting rangedrop point ( c)ai < 15 15-30 > 30 nai 25 a nai 50am a aPna 0 nana 15 nai 25 bm nb bP cm dm dSuppocire standard products4 Pharmaceutical performance powered by Gattefoss suppocire standard productssuppocire standard products contain a well-defined proportion of mono/di and triglycerides.

6 Their physicochemical features are adapted to meet the needs of different Active Pharmaceutical Ingredient (API) properties, formulation and manufacturing suppocire standard products are classified intofive major melting point (drop point) ranges: ai, a, b, c, d5 Pharmaceutical performance powered by Gattefoss m GradeSuppository bases derived from the AI, A, B, C and D product lines (obtained by inter-esterification of hydrogenated palm oil and hydrogenated palm kernel oil).The low hydroxyl value/low reactivity ensures: Minimal risk of interaction between free OH groups and acidic active ingredients. High crystallization rate in individual suppository units. Suitable for high-speed manufacturing.

7 Suitable for sensitive ai, a, b, c & d Product linesSuppository bases obtained by inter-esterification of hydrogenated palm oil and hydrogenated palm kernel oil. These are multipurpose vehicles covering a range of melting points (drop point). Result in a softer suppository unit which is self-lubricating due to the well-defined medium chain triglyceride content. Ideal for straightforward formulations and versatile for use with manual, semi and fully automated manufacturing n lineBases obtained by direct esterification of selected fatty acids with glycerol. The long chain triglyceride content confers rapid solidification resulting in harder suppository units with high mechanical low hydroxyl/low reactivity products provide: High crystallization rate in individual suppository unit.

8 Appropriate for high through-put/high speed manufacturing equipment. Suitable for sensitive active higher hydroxyl value products provide versatility for lower volume/lower speed production GradeBases consist of polyglycolized glycerides synthesised by esterification of selected fatty acids with polyethylene glycol (PEG) and glycerol. The amphiphilic base provides bioavailability enhancement through improved solubilization and absorption of API. Suitable for difficult to formulate active value (mg Koh/g)melting rangedrop point ( c) < 15 15-30 > 30 aiml nais 90aml as2 nas 40 as2X nas 50 nal nas 55 bml bs2 bs2X nbl nais 10 cs2X Letters indicate the type of modification and the resulting physicochemical and performance specialty products6 Pharmaceutical performance powered by Gattefoss Suppocire Specialty products provide solutions for more challenging formulation and manufacturing needs.

9 Functional and formulation properties are controlled by monoglyceride content and/or the inclusion of additives including phospholipids, beeswax, polyoxylethylene (POE) sorbitan specialty productss and s2 GradeContain a modified monoglyceride content: Products with a higher monoglyceride content yield bases with enhanced hydrophilic properties. Appropriate when fast release of API is an essential therapeutic feature of the finished GradeA phospholipid additive enables good dispersion of larger amounts of powdered API during formulation and homogenous distribution of drug in the suppository GradeContain an non-ionic emulsifying additive to enable the incorporation of API in aqueous solutions and/or hydroalcoholic extracts.

10 Appropriate for use to prevent the exudation of API in solution from the solidified suppository performance powered by Gattefoss The Ovucire products are specifically for Vaginal drug Delivery . These are bases with hydrophilic properties offering a melting point range optimised for Vaginal drug Delivery . melting range hydroxyl value specification drop Point ( c) (mg Koh/g) Japocire and OvucireSuppository bases specifically for Japanese healthcare industries. These products have physicochemical and performance features similar to those of the Suppocire Standard range, are registered with the appropriate Japanese authorities. melting range ( c) hydroxyl value specification Capillary Tube (mg Koh/g) Japocire na 0 < 3 Versatile base, suitable for all types of production equipment.