An in vitro dissolution–digestion–permeation assay for the study of advanced drug delivery systems

Abstract Advanced drug delivery systems (ADDS) are widely explored to overcome poor aqueous solubility of orally administered drugs. However, the prediction of their in vivo performance is challenging, as in vitro models typically do not capture the interplay between processes occurring in the gut. In additions, different models are used to evaluate the different systems. We therefore present a method that allows monitoring of luminal processing (dissolution, digestion) and its interplay with permeation to better inform on the absorption of felodipine formulated as ADDS. Experiments were performed in a µFLUX-apparatus, consisting of two chambers, representing the intestinal and serosal compartment, separated by Caco-2 monolayers. During dissolution–digestion–permeation experiments, ADDS were added to the donor compartment containing simulated intestinal fluid and immobilized lipase. Dissolution and permeation in both compartments were monitored using in situ UV-probes or, when turbidity interfered the measurements, with HPLC analysis. The method showed that all ADDS increased donor and receiver concentrations compared to the condition using crystalline felodipine. A poor correlation between the compartments indicated the need for an serosal compartment to evaluate drug absorption from ADDS. The method enables medium-throughput assessment of: (i) dynamic processes occurring in the small intestine, and (ii) drug concentrations in real-time.