Merits of sponge-like PLGA microspheres as long-acting injectables of hydrophobic drug

Abstract

Our study was initiated to challenge the preconception that nonporous PLGA microspheres with compact matrices should be used to develop long-acting depot injectables of hydrophobic drugs. A simple, new oil-in-water emulsion technique was utilized to produce porous PLGA microspheres with a sponge-like skeleton. Then, their applicability to developing sustained-release depots of hydrophobic drugs was explored in this study. As control, nonporous microspheres with a compact matrix were produced following a typical solvent evaporation process. Both microsphere manufacturing processes used non-halogenated isopropyl formate and progesterone as a dispersed solvent and a model hydrophobic drug, respectively. Various attempts were made to evaluate critical quality attributes of the porous microspheres and the nonporous ones. Surprisingly, the former displayed interesting features from the viewpoints of manufacturability and microsphere quality. For example, the spongy microspheres improved drug encapsulation efficiency and particle size uniformity, inhibited drug crystallization during microencapsulation, and minimized the residual solvent content in microspheres. Furthermore, the porous microspheres provided continual drug release kinetics without a lag time and much faster drug release than the non-porous microspheres did. In summary, the porous and sponge-like PLGA microspheres might find lucrative applications in developing sustained release dosage forms of hydrophobic drugs.

Keywords: microspheres; microencapsulation; poly--lactide--glycolide; spongy morphology.