A unified mathematical model for the prediction of controlled release from surface and bulk eroding polymer matrices

Abstract

A unified model has been developed to predict release not only from bulk eroding and surface eroding systems but also from matrices that transition from surface eroding to bulk eroding behavior during the course of degradation. This broad applicability is afforded by fundamental diffusion/reaction equations that can describe a wide variety of scenarios including hydration of and mass loss from a hydrolysable polymer matrix. Together, these equations naturally account for spatial distributions of polymer degradation rate. In this model paradigm, the theoretical minimal size required for a matrix to exhibit degradation under surface eroding conditions was calculated for various polymer types and then verified by empirical data from the literature. An additional set of equations accounts for dissolution- and/or degradation-based release, which are dependent upon hydration of the matrix and erosion of the polymer. To test the model's accuracy, predictions for agent egress were compared to experimental data from polyanhydride and polyorthoester implants that were postulated to undergo either dissolution-limited or degradation-controlled release. Because these predictions are calculated solely from readily attainable design parameters, it seems likely that this model could be used to guide the design controlled release formulations that produce a broad array of custom release profiles.