chapter  7
36 Pages

Development of Dissolution Tests on the Basis of Gastrointestinal Physiology

WithSandra Klein, Erika Stippler, Martin Wunderlich, Jennifer Dressman

Almost half a century after the first attempts at dissolution testing, we are still grappling with the question of ‘‘which media to use to run which dissolution tests.’’ This is not a trivial question, since the outcome of a test can be greatly dependent on the dissolution medium, especially if the drug itself and/or key excipients are poorly soluble and/or ionizable. In addition, dissolution tests are run for different reasons at

different points in the product life cycle. In pre-clinical development, dissolution of the pure drug is often studied under biorelevant conditions to assess whether dissolution is likely to be a rate-limiting factor in the oral absorption of a drug. Later, various formulations will be compared, again under biorelevant conditions, to determine which are most suitable for taking into clinical studies. During the progression through phase II and III clinical trials, batch sizes are increased and the formulation is often optimized. At this stage, it may well be desirable to develop an in vitro-in vivo correlation (IVIVC) so that the biopharmaceutical properties after further scale-up and minor formulation changes in the product can be assessed with in vitro studies instead of having to perform a pharmacokinetic bioequivalence study. At this time, dissolution tests for routine quality control (QC) of the drug product are also being developed. These QC procedures should also reflect insofar as possible the gastrointestinal (GI) conditions under which the product has to perform. At times, this can be quite a challenge with today’s standard apparatus due to the parallel need to confirm that the product can release 100% (or near to) of the drug.