Mechanistic explanation of the (up to) 3 release phases of PLGA microparticles: Monolithic dispersions studied at lower temperatures

The aim of this study was to better understand the underlying drug release mechanisms in poly(lactic-co-glycolic acid) (PLGA) microparticles which is dispersed form tiny particles (“monolithic dispersions”). Differently sized diprophylline-loaded were prepared using a solid-in-oil-in-water solvent extraction/evaporation technique. characterized before and after exposure phosphate buffer pH 7.4 at 4, 20 37 °C. In vitro measured from ensembles single microparticles. GPC, DSC, SEM, gravimetric analysis, solubility measurements optical microscopy used elucidate importance polymer swelling & degradation, dissolution diffusion. diprophylline initially homogeneously distributed throughout crystals. burst (1st phase) strongly temperature-dependent likely attributable crystals with direct surface access (potentially via pores). about constant rate during 2nd phase also depended on temperature. It can probably be explained by near regions undergoing local swelling. During observation period, 3rd (again rapid) only observed °C, seems caused substantial PLGA entire This starts as soon critical molecular weight 25 kDa reached: Significant amounts water penetrate into systems, dissolving remaining substantially increasing mobility dissolved molecules. Thus, provides additional experimental evidence (obtained lower temperatures) confirming hypothesized root causes for containing particles.