Excipients selection for high risk formulations Smita Rajput
Fixed Dose Combinations- WHO Meet
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3. What are Fixed Dose Combinations??? Practical problems in developing FDCs & Bilayer tablets…..
4. Fixed Dose combination (FDC) “ A combination of two or more actives in a fixed ratio of doses.” Source: WHO Technical report series, No. 929, p.no-107, 2005 Examples of FDCs in WHO’s list of essential drugs Anti- Infective: Sulfamethoxazole + Trimethoprim Anti-Tuberculosis: Rifampicin + Isoniazid Antiviral: Stavidine + Lamivudine + Neviparine Antimalarial : Artesunate + Amodiaquine Practical problems in developing FDCs & Bilayer tablets…..
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7. POLY -PHARMACY Rationale…. Combination drugs that target the same indication Pain Ulcers AIDS Allergy/Asthma Malaria Hypertension Tuberculosis Diabetes
25. Evaluation studies …… Characterization of impurities Stability Indicating Assay Related Compounds Dissolution Profile Content Uniformity OVI / Residual Solvents Impurity profile study Drug : Excipients compatibility study
26. The starting formulation may be based on INTUITION but the ending formulation must be based on SCIENCE Science means: There will be no weak eye in the pharmaceutical development chain
27. Research & Development (Formulations)….. New Product Introduction Validation Tech. Transfer Regulatory Evaluation Development Identification Divisions Product Development Medical Marketing R&D Analytical Research Pharmacology Evaluation Regulatory Affairs R&D Production Validation team R&D Production Q.A.
28. Pre-formulation Establish Drug : Excipients compatibility Development lots Mini experimental trials to decide the formula / process Process optimization Fine tuning to avoid scale-up problem Process qualification To define critical processing steps (Scale-up batch) and test parameters usually mimics production conditions Pivotal batch Samples are used to perform the bio- equivalence study / clinical trials. Product development For PAI visit report & Submission Development Program Timelines….. 3 4 2 4 2 Stability Studies ~ 15 Months for Product Development, by Following ICH Guidelines Months Stages Activities
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30. Product Quality Design….. Existing knowledge & new scientific data generated in the process Interaction of input variables & process parameters that provides Quality Product Includes Input material controls, Process controls & FPP control tests Design space Knowledge space Control strategy Development of ‘ ASSURED QUALITY PRODUCT’ DESIGN SPACE CONTROL STRATEGIES
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