Mathematical Modeling of PLGA Microparticles: From Polymer Degradation to Drug Release

The present work is focused on the development and the validation of a mechanistic model describing the degradation of drug-loaded polylactic-co-glycolic acid microparticles and the drug release process from such devices. Microparticles' degradation is described through mass conservation equations; the application of population balances allows a detailed description of the hydrolysis kinetics, which also takes into account the autocatalytic behavior that characterizes bulk eroding polymers. Drug release considers both drug dissolution and the diffusion of dissolved active principle through the polymeric matrix. The diffusion of oligomers, water, and drug is assumed to follow Fickian behavior; the use of effective diffusion coefficients takes into account the diffusivity increase due to polymer hydrolysis. The model leads to a system of partial differential equations, solved by means of the method of lines. The model predictions satisfactorily match with different sets of literature data, indicating that the model presented here, despite its simplicity, is able to describe the key phenomena governing the device behavior.