Studying Drug Release through Polymeric Controlled Release Formulations in United States Pharmacopoeia 2 Apparatus Using Multiphysics Simulation and Experiments.

In vitro dissolution of oral drug formulations is often studied using the United States Pharmacopoeia (USP) apparatus. Although a well-stirred vessel or a perfect sink assumption is often employed in the modeling of in vitro dissolution in USP apparatus, such a limit is usually not realized in actual experimental conditions. The interplay of hydrodynamics in the vessel and the swelling and erosion of dosage forms often results in substantial deviations from the dissolution behavior obtained under perfect sink approximation. We develop a multiphysics model of drug release from controlled release tablets of polymeric excipients with active pharmaceutical ingredients (APIs). Simulations are performed in COMSOL for the USP 2 (paddle) apparatus and the effects of stirring speed, drug loading, erosion rate, and polymer swelling and erosion are analyzed in detail. We demonstrate that the drug release phenomena can be conveniently interpreted using the Weibull equation to fit the simulation results. This is further confirmed using drug release experiments performed on mechanically compressed tablets of naproxen sodium as the API with poly-methyl-methacrylate-co-methacrylic acid as the excipient. We show that the API-to-polymer ratio may be varied to obtain different regimes of controlled release.