Basics impurity profiling and degradent characterization[134]
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The document discusses impurity profiling and degradant characterization in pharmaceuticals, highlighting types and sources of impurities, including organic, inorganic, and residual solvents. It emphasizes the significance of impurity control for ensuring the safety and efficacy of drug products and outlines the various degradation conditions such as hydrolytic, oxidative, photolytic, and thermal. The document further details the methods for identifying and quantifying impurities during the manufacturing process.
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Basics impurity profiling and degradent characterization[134]
- 1. BASICS IMPURITY PROFILING AND DEGRADENT CHARACTERIZATION PRSENTED BY:- MANGESH LAVANGE Guide- Dr. Poonam Piplani M PHARM SEM 1ST PHARMACEUTICAL ANALYSIS UIPS, Panjab University, Chandigarh- 160014
- 2. Impurity:- What is Impurity? • Impurities in pharmaceuticals are the unwanted chemicals that remain with the active pharmaceutical ingredients (APIs), or develop during formulation. • The presence of these unwanted chemicals even in small amounts may influence the efficacy and safety of the pharmaceutical products. Impurity Control– Why is it important. • Necessary to ensure the safety and efficacy of pharmaceutical products. • Required to determine the purity of the drug product.
- 3. TYPES OF IMPURITY Impurity type Impurity source 1.Process-related drug substance -Organic -Starting material -Intermediate 2.Process-related drug product -Organic or inorganic -Reagents, catalysts, etc. 3.Degradation drug substance -Organic product -Degradation product 4.Degradation drug product -Organic -Excipient interaction
- 4. Source of impurities in formulation Impurities associated with API Impurities created during formulation Organic impurities Inorganic impurities Residual solvents Process related Environmental related Dosage form related Functional group related
- 5. 1. Organic Impurities Arise from the manufacturing process and/or during storage. Organic Impurities includes:- • Starting materials • By-products • Intermediates • Degradation • Products • Reagents • Ligands • Catalysts.
- 6. IDENTIFICATION OF IMPURITIES Chemical reactions Reaction conditions Metabolic degradation pathways It is based on the reactions involved in the synthesis
- 7. 2. Inorganic Impurities • Arise from the manufacturing process known and identified. • Inorganic impurities are determined when the drug substance is tested, not in the final dosage form. • Include – Reagents, Ligands ,Catalysts ,heavy metals ,inorganic salts • Pharmacopeial method for testing for these types of impurities is called residue on ignition. • Used to determine amounts impurities of different metals.
- 8. 3. RESIDUAL SOLVENTS AND WATER • Residual solvents : solvents that are used during the manufacturing process. May be detected after the product is in its final form. E.g. benzene, Chloroform. • Comes from many different stages in the manufacturing process – Active substance granulation – Milling – Drug product coating. • The most common technique for measuring residual solvents is gas chromatography(GC).
- 9. DEGRADATION • Impurities resulting from chemical change in drug substance brought during manufacturing and/or storage of the new drug product by effect of light ,temperature, pH, water or reaction with excipient and immediate container closer system.
- 10. Forced degradation study Drug substance Drug product Solid Solution/ Suspensi on Solid Semisolid Solution/ Suspension Photolytic Thermal Thermal/ humidity Acid base hydrolysis oxidative Photolytic Thermal Thermal/ humidity oxidative Photolytic Thermal Thermal/ humidity Photolytic Thermal oxidative
- 12. HYDROLYTIC CONDITION • Hydrolysis is one of the most common degradation chemical reactions over a wide range of ph. • • Chemical process that includes decomposition of a chemical compound by reaction with water. • • Under acidic and basic condition involves. Acid or base stress testing involves forced degradation of a drug substance by exposure to acidic or basic conditions which generates primary degradants in desirable range.
- 13. Oxidation conditions • Hydrogen peroxide is widely used for oxidation of drug substances in forced degradation studies but other oxidizing agents such as metal ions, oxygen, and radical initiators can alsobeused. • It is reported that subjecting the solutions to 0.1–3% hydrogen peroxide at neutral pH and room temperature for seven days or upto a maximum 20% degradation could potentially generate relevant degradation products. • The oxidative degradation of drug substance involves an electron transfer mechanism to form reactive anions and cations. • Amines, sulphides and phenols are susceptible to electron transfer oxidation to give N-oxides, hydroxylamine, sulfones and sulfoxide.
- 14. Photolytic conditions • Photo stability studies are performed to generate primary degradants of drug substance by exposure to UVor fluorescent conditions. • Samples of drug substance and solid/liquid drug product should be exposed to a minimum of 1.2 million lx hand 200Wh/m2 light. The most commonly accepted wavelength of light is in the range of 300– 800 nm to cause the photolytic degradation. • The maximum illumination recommended is 6 million lx h . Light stress conditions can induce photo oxidation by free radical mechanism. • Functional groups like carbonyls, nitro aromatic, Noxide, alkenes, aryl chlorides, weak C–H and O–H bonds, sulphides and polyenes are likely to introduce drug photosensitivity.
- 15. Thermal conditions • Thermal degradation (e.g. , dry heat and wet heat) should be carried out at more strenuous conditions than recommended ICHQ 1 A accelerated testing conditions. • Samples of solid-state drug substances and drug products should be exposed to dry and wet heat, while liquid drug products should be exposed to dry heat. • Studies may be conducted at higher temperatures for a shorter period. Effect of temperature on thermal degradation of a substance is studied through the Arrhenius equation:
- 16. k=AeEa/RT Where k is specific reaction rate, A is frequency factor, Ea is energy of activation, R is gas constant(1.987cal/degmole) Thermal degradation study is carried out at 40–80℃.