(571m) Release Kinetics From Polymer-Based Membranes Formed by Phase Inversion

The interplay between the dynamics of phase inversion, membrane formation, and drug release kinetics has been studied for solvent-cast films of a poly (n-butyl cyanoacrylate) (PBCA)-naproxen system. Films cast from solutions containing various amounts of polymer (PBCA), solvent (acetone) and nonsolvent (water) were analyzed via scanning electron microscopy to determine optimal compositions and casting conditions leading to the formation of desired porous morphologies. Drug release rates in phosphate buffer from dried films exhibit a non-monotonic pattern with drug loading (DL), depending on whether a collapsed, dense structure or a porous structure forms. A mathematical model has been developed to quantify the release kinetics from porous, hydrophobic polymer membranes of finite thickness with specified boundary conditions. The role of film morphologies with porous structures containing both amorphous drug and drug particles is accounted for in the model. The dissolution rate of drug particles is simulated with a delta type function combining a Noyes-Whitney equation, and the dissolution rate of the amorphous drug is assumed to follow a dynamic step function. Drug diffusion into the release medium is assumed to occur from liquid-filled pores. The coupled partial differential equations of the model can be converted to implicit integral solutions using the Green's function transform technique. Simulation results reveal that the diffusion rate depends on the porosity and tortuosity in the membrane, which are factors in the effective diffusion coefficient. Moreover, drug dissolution rate and distribution in the polymer matrix play important roles in the release rate demonstrating a controlled release rate at a higher drug loading. Asymptotic forms of the model, constructed using different forms for the dissolution source terms, enable comparisons of release predictions to classic models in the literature.