Experiments and modeling of controlled release behavior of commercial and model polymer-drug formulations using dialysis membrane method.

Standard dissolution testing methods typically do not correlate strongly with the in vivo drug release behavior for the oral delivery products, since they only focus on the drug dissolution in the gastric/intestinal fluid and do not account for the intestinal absorption of drug. Artificial gastrointestinal systems attempt to bridge this gap by using dialysis membranes as a proxy for the intestinal membranes. We present a systematic proof-of-concept study of how the drug dissolution and drug absorption are mimicked in such systems for the case of polymer-drug formulations. We utilize a modified version of the conventional shaking-flask test, in which the drug formulation is placed inside a dialysis bag. Dissolution experiments are performed on a commercial aspirin formulation and model formulations of aspirin with varying amounts of poly-methyl-methacrylate-co-methacrylic acid (PMA-MAA), both for conventional and modified shaking-flask test. Results are successfully interpreted using a simple model that assumes first-order kinetics for both the drug release from the formulation and drug permeation through the membrane. The differences between the model and commercial formulations and the effects of shaking speed and drug loading are established by comparison of the first-order rate constants. Finally, comparison with a reported in vivo study demonstrates how the modified shaking-flask setup can be used to improve the in vitro in vivo correlation. Graphical abstract.