Selection of solid dosage form composition through drug-excipient compatibility testing

A drug-excipient compatibility screening model was developed by which poten tial stability problems due to interactions of drug substances with excipie nts in solid dosage forms can be predicted. The model involved storing drug -excipient blends with 20% added water in closed glass vials at 50 degrees C and analyzing them after 1 and 3 weeks for chemical and physical stabilit y. The total weight of drug-excipient blend in a vial was usually kept at a bout 200 mg. The amount of drug substance in a blend was determined on the basis of the expected drug-to-excipient ratio in the final formulation. Pot ential roles of several key factors, such as the chemical nature of the exc ipient, drug-to-excipient ratio, moisture, microenvironmental pH of the dru g-excipient mixture, temperature, and light, on dosage farm stability could he identified by using the model. Certain physical changes, such as polymo rphic conversion or change from crystalline to amorphous form, that could o ccur in drug-excipient mixtures were also studied. Selection of dosage form composition by using this model at the outset of a drug development progra m would lead to reduction of "surprise" problems during long-term stability testing of drug products.