Forecasting the in vivo performance of four low solubility drugs from their in vitro dissolution data

Purpose. To assess the usefulness of biorelevant dissolution tests in predicting food and formulation effects on the absorption of four poorly soluble, lipophilic drugs. Methods. Dissolution was studied with USP Apparatus II in water, milk, SIFsp, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a rank order basis with existing in civet data for the tested products under fasted and fed state conditions. Results. All drugs/formulations showed more complete dissolution in bile salt/lecithin containing media and in milk than in water and SIFsp, (USP 23). Comparisons of the in vitro dissolution data in biorelevant media with in vivo data showed that in all cases it was possible to forecast food effects and differences in absorption between products of the same drug with the physiologically relevant media (FaSSIF, FeSSIF and milk). Differences between products (both in vitro or in vivo) were less pronounced than differences due to media composition (in vitro) or dosing conditions (in vivo). Conclusions. Although biorelevant dissolution tests still have issues which will require further refinement, they offer a promising in vitro tool for forecasting the in vivo performance of poorly soluble drugs.