Simulation of drug release from biodegradable polymeric microspheres with bulk and surface erosions

Abstract

New models are developed to account for the kinetics of drug release from porous, biodegradable polymeric microspheres under the schemes of bulk erosion and surface erosion of the polymer matrix, respectively. Three mechanisms of drug release, namely, drug diffusion, drug dissolution, and polymer erosion jointly govern the overall release process. For bulk erosion, the model incorporates an erosion term into the dissolution and diffusion equation and is solved numerically for various boundary conditions. Dissolution and erosion are defined in the model by introducing three equations which take into account the drug concentration in the liquid phase, virtual solid phase, and effective solid phase. For surface erosion, drug concentrations in liquid and solid phases are defined and a substitution is introduced to convert the moving-boundary problem to a fixed-boundary problem. The resulting differential equations are solved simultaneously to obtain the concentration profile in the liquid and solid phases, respectively. Numerical solutions are provided to illustrate the effects of drug dissolution constant, drug diffusion coefficient, and erosion rate constant. In general, increasing erosion rate, diffusivity, dissolution, and decreasing particle radius enhance the drug release rate. Predictions from the models are also compared with experimental data to verify their validity and possible improvements are proposed. © 2003 Wiley-Liss, Inc. and the American Pharmacists Association.