Dissolution testing as a prognostic tool for oral drug absorption: immediate release dosage forms

Abstract

Dissolution tests are used for many purposes in the pharmaceutical industry: in the development of new products, for quality control and, to assist with the determination of bioequivalence. Recent regulatory developments such as the Biopharmaceutics Classification Scheme have highlighted the importance of dissolution in the regulation of post-approval changes and introduced the possibility of substituting dissolution tests for clinical studies in some cases. Therefore, there is a need to develop dissolution tests that better predict the in vivo performance of drug products. This could be achieved if the conditions in the gastrointestinal tract were successfully reconstructed in vitro. The aims of this article are, first, to clarify under which circumstances dissolution testing can be prognostic for in vivo performance, and second, to present physiological data relevant to the design of dissolution tests, particularly with respect to the composition, volume, flow rates and mixing patterns of the fluids in the gastrointestinal tract. Finally, brief comments are made in regard to the composition of in vitro dissolution media as well as the hydrodynamics and duration of the test.