Simplified Biorelevant Media for Screening Dissolution Performance of Poorly Soluble Drugs

Abstract

8 INTRODUCTION Simulation of gastrointestinal conditions is essential to adequately predict the in vivo behavior of poorly soluble drugs. Simulating small intestinal conditions with biorelevant media such as fasted state simulated intestinal fluid (FaSSIF) and fed state simulated intestinal fluid (FeSSIF) has become standard practice in many dissolution laboratories (1–6). However, due to their complex composition, these media are expensive and, to date, need to be prepared on the day of the experiment. The aim of the present study was to develop media that are easier to prepare and are stable over a longer period, but can still serve the purpose of forecasting in vivo performance. Criteria for developing simplified test media also include cost-effectiveness and the ability to adequately reflect the physicochemical properties of the biorelevant media FaSSIF or FeSSIF (see Table 1). Another objective was to create mixed micelles like those formed by natural bile components. For this purpose, sodium taurocholate and lecithin were replaced with different types and concentrations of surfactants, and the physicochemical properties of the resulting mixtures were screened. Subsequently, simplified media with corresponding physicochemical properties were used for dissolution experiments. Since their oral bioavailability and dissolution rate performance have been reported to depend on the presence of dissolution enhancers (1, 3, 7–10), ketoconazole, glyburide and tamoxifen citrate were selected as model drugs for these experiments. Based on these observations, it was assumed that drug release from their formulations would be sensitive to the composition of the test media. Thus, they appeared to be optimal candidates to prove the applicability of the new set of media.