Impact of Membranes on In Vitro Release Assessment: a Case Study Using Dexamethasone.

ABSTRACT

In vitro release studies are commonly used to assess the product performance of topical dosage forms. In such studies, the mass transport of drugs through synthetic membranes into a receiving chamber filled with a release medium is measured. The release medium is also passed through filtration membranes prior to chromatographic analysis. There are no official guidelines directing membrane selection for in vitro release studies or for filtration. Considering the diversity in membrane materials and their physical properties, the aim of this study was to investigate membrane-drug binding and the effect of various membranes on the release performance of a model drug dexamethasone (DEX) using USP dissolution apparatus IV. Seven membranes of different pore sizes (0.45 and 1.2 µm) and materials (cellulose acetate, polyethersulfone, and nylon) were assessed. Two different methods, syringe filter and 24-h incubation, were used for the determination of membrane-drug binding effects at low drug concentrations and saturated concentration conditions. Cellulose acetate and nylon membranes showed significant drug binding after 24-h incubations at both drug concentrations. DEX diffusion through membranes was significantly slowed down in all the tested membranes when compared with DEX solution without membranes. The extent of the retardation varied due to the differences in membrane structures. In conclusion, materials and sources of membranes affected drug dissolution profiles and the results showed membrane-drug binding effects. Proper selection of membranes with low drug binding ability and low diffusion resistance is essential to ensure appropriate and reproducible in vitro release assessments and filtration studies. Graphical Abstract.