The aim of this study was to understand the pore formation mechanisms of degrading poly(d,l-lactic-co-glycolic acid) (PLGA) microparticulate systems. This was investigated through an original microparticles cross-section imaging method. Atorvastatin (ATV)-loaded 16- to 18-μm spherical microparticles with polymers of varying molecular weights (8 to 45 kDa) were prepared. The evolution of the particles during in vitro drug release experiments was monitored in terms of molecular weight, pore formation and glass transition temperature. During the 2nd phase of release, two types of pores were observed: small pores near the particle's periphery and larger pores in the core. The pattern of pore formation was shown to be related to the shape of the drug release curve. At the onset of the 3rd phase, the polymer transitions to a less glassy state, allowing for the swelling of the microparticles. Overall, we present evidence that pore formation is not uniformly distributed throughout PLGA microparticles, and that it could determine the drug release kinetics.
Keywords: Atorvastatin; Drug release mechanism; Erosion; Molecular weight; PLGA microparticles; Pores; Swelling.
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