Development of a μDissolution-Permeation model with in situ drug concentration monitoring

Abstract

The objective of the present study was to develop a combined dissolution-permeation model, compatible with the μDiss Profiler™ (μD/P model), to ensure continuous in situ monitoring of dissolved and permeated drug, respectively.A μD/P model consisting of two connected compartments made of acrylic plastic was designed and constructed to fit in the μDiss Profiler™. A Caco-2 cell monolayer grown on a Snapwell™ membrane insert was mounted between the apical and basolateral compartment serving as a permeability barrier. Fasted state biorelevant medium consisting of HBSS pH 6.5 supplemented with bile salts and lecithin was used as the apical dissolution media, while HBSS pH 7.4 was used as the basolateral medium. The apparent permeability (Papp) and dissolution-time profiles for albendazole, felodipine and fenofibrate were determined concomitantly using the μD/P model, and separately using a previously validated, common cell transwell permeability setup with Caco-2 cells as the permeability barrier, and the μDiss Profiler™, respectively. The results were found to be in same range, when comparing data obtained using the different experimental setups.In conclusion, a μDiss compatible D/P model was developed enabling in situ measurement of apical drug concentrations and simultaneous determination of the amount of drug permeated across a Caco-2 cell monolayer.