Screening chemical and physical stability of drug substances.

General multistep methods are described for the screening of the chemical and the physical stability and/or reactivity of new drug candidates. The chemical reactivity is studied in aqueous buffer solutions; the rate of degradation is measured as a function of pH. The products of the reaction mixture are evaluated at selected pH-values as a function of time and key reaction products are identified. Strategies for testing degradation products in stability studies are discussed. The purpose of the physical reactivity test is to obtain information on the existing solid-state form in relation to the thermodynamically stable form. A method for finding the stable form is described. When polymorphism is observed a search for additional polymorphs is performed and the different solid phases are characterized. Special tests are described for hydrates and anhydrous forms.