How porosity and size affect the drug release mechanisms from PLGA-based microparticles

International Journal of Pharmaceutics
D KloseJuergen Siepmann

Abstract

Porous, poly(lactic-co-glycolic acid) (PLGA)-based microparticles were prepared using a water-in-oil-in-water (W/O/W) solvent extraction/evaporation technique. Lidocaine was used as a model drug and different-sized particle fractions were obtained by sieving. The physicochemical properties of the devices and changes thereof upon exposure to phosphate buffer pH 7.4 were studied using optical and scanning electron microscopy, size exclusion chromatography (SEC), differential scanning calorimetry (DSC), gravimetric analysis and in vitro drug release measurements. In contrast to non-porous microparticles of identical composition, the relative drug release rate was found to decrease with increasing system size. SEC, DSC and gravimetric analysis showed that the degradation rate of the polymer increased with increasing microparticle dimension, indicating that autocatalytic effects play an important role even in small and highly porous PLGA-based microparticles. However, these effects were much less pronounced than in non-porous devices. Importantly, they were overcompensated by the effects of the increasing diffusion pathway lengths with increasing system dimension. Thus, high initial microparticle porosities do not only lead to incre...Continue Reading

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