In Vitro Dissolution Curve Comparisons: A Critique of Current Practice

Many pharmacologically active molecules are formulated as solid dosage form drug products. Following oral administration, the diffusion of an active molecule from the gastrointestinal tract into systemic distribution requires the disintegration of the dosage form followed by the dissolution of the molecule in the stomach lumen. Its dissolution properties may have a direct impact on its bioavailability and subsequent therapeutic effect. Consequently, dissolution (or in vitro release) testing has been the subject of intense scientific and regulatory interest over the past several decades. Much interest has focused on models describing in vitro release profiles over a time scale, and a number of methods have been proposed for testing similarity of profiles. In this article, we review previously published work on dissolution profile similarity testing and provide a detailed critique of current methods in order to set the stage for a Bayesian approach.