Physicochemical Characterization and Pharmacokinetics of Agomelatine-Loaded PLGA Microspheres for Intramuscular Injection

Abstract

The aim of this study was to design agomelatine loaded long acting injectable microspheres, with an eventual goal of reducing the frequency of administration and improving patient compliance in treatment of depression. AGM-loaded microspheres were prepared by an O/W emulsion solvent evaporation method. The physicochemical properties and in vitro performance of the microspheres were characterized. The pharmacokinetics of different formulations with various particle sizes and drug loadings were evaluated. AGM-loaded microspheres with drug loading of 23.7% and particle size of 60.2μm were obtained. The in vitro release profiles showed a small initial burst release (7.36%) followed by a fast release, a period of lag time and a second accelerated release. Pore formation and pore closure were observed in vitro, indicating that the release of drug from microspheres is dominated by water-filled pores. Pharmacokinetic studies showed that AGM microspheres could release up to 30days in vivo at a steady plasma concentration. As well, particle size and drug loading could significantly influence the in vivo release of AGM microspheres. AGM-loaded microspheres are a promising carrier for the treatment of major depressant disorder.