Drug Stability for Pharmaceutical Scientists

<p>I. Principles of drug degradation (the solution kinetics and mathematical treatment):1. Zero, first, second and third order reactions2. Complex reactions (e.g. reversible reactions, parallel reactions, consecutive reactions, steady state, enzyme kinetics etc.)3. Effect of temperature (e.g. Arrhenius, Q10-values, Collision theory, Transition state theory, Eyring equation etc.)4. Effect of pH (Specific acid/base catalysis, pH-rate profiles)5. Effect of buffer salts (General acid/base catalysis or buffer catalysis)6. Ionic strength7. Solvent effects (e.g. dielectric constant)8. Surface active compounds (micelle effect)9. Effect of complexation (e.g. cyclodextrins, metal ions and carbohydrates)10. Effect of light, oxygen and other catalytic compounds.II. Degradation pathwaysSelected examples of drug degradation with examples and mathematical calculations.1. Hydrolysis (aspirin, procaine, procainamide, acetaminophen, β-lactam antibiotics, nitrogen mustards etc.)2. Oxidation (morphine, epinephrine, vitamin C, vitamin A, hydrocortisone, polyunsaturated fatty acids (autoxidation) etc.; antioxidants)3. Isomerization and racemization (ephedrine, tetracyclines, pilocarpine, vitamin A, thalidomide, etc.)4. Photodegradation5. Polymerization (β-lactam antibiotics etc.)6. Decarboxylation and elimination (p-aminosalicylic acid)7. Dehydration (prostaglandins etc.)III. Drug degradation in semi-solid state1. Ointments2. Creams (o/w and w/o emulsions)3. GelsIV. Drug degradation in solid state1. Physical stability of drugs (crystallization of amorphous drugs, polymorph transitions, crystal growth, moisture absorption and vapor absorption, nitroglycerine)2. Chemical stability (hydrolysis (aspirin), etc.)V. Stability of peptide and proteinsVI. Stability testing1. Stability testing during preformulation studies.2. Stability testing of the final product 3. Regulations of stability testing (including ICH guidelines)Appendix</p>