A mathematical model is developed for the simultaneous treatment of PLGA degradation and erosion and diffusive drug release with autocatalytic effects and nonconstant effective diffusivity of the drug. A mechanistic reaction-diffusion model with pore evolution coupled to hydrolysis and related to the effective diffusivity through hindered diffusion theory is proposed. Experimental background motivating the attention to the size-dependent effects of autocatalysis on drug release and a brief review of related mathematical models are presented. The model equations are derived, solved numerically with a computational code developed for this work and described in detail, and compared to the analytical solutions to the model in limiting cases. The model performance for the case of drug release from microspheres of different sizes is presented to highlight the capability of the model for predicting size-dependent, autocatalytic effects on the polymer and the release of drug.
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Modeling of controlled-release drug delivery from autocatalytically degrading polymer microspheres