Modeling small-molecule release from PLG microspheres: effects of polymer degradation and nonuniform drug distribution

Modeling release of small molecules from degradable microspheres is important to the design of controlled-release drug delivery systems. Release of small molecules from poly(D,L-lactide-co-glycolide) (PLG) particles is often controlled by diffusion of the drug through the polymer and by polymer degradation: In this study, a model is developed to independently determine the contributions of each of these factors by fitting the release of piroxicam from monodisperse 50-mu m microspheres made with PLG of different initial molecular weights. The dependence of the drug diffusivity on polymer molecular weight was determined from in vitro release of piroxicam from monodisperse 10-mu m PLG microspheres, and the polymer degradation rate was experimentally measured using gel permeation chromatography. The model also incorporates,the effect of nonuniform drug distribution within the microspheres, which is obtained from confocal fluorescence microscopy. The model results agree well with experiments despite using only one fit parameter. (c) 2004 Elsevier B.V. All rights reserved.