Preparation and characterization of high-content aripiprazole-loaded core-shell structure microsphere for long-release injectable formulation.

Abstract

The aim of this study was to obtain injectable high-drug-loading core-shell structure microspheres that release aripiprazole over 2 months. The microparticles were prepared by the oil-in-water emulsion solvent evaporation method and characterized. The microparticles were prepared with aripiprazole and 3 types of poly(lactic acid) (PLA) (DL-PLA: molecular weight (MW), ca. 20000; DL-PLA: MW, ca. 95000; or L-PLA: MW, ca. 110000), which were dissolved within the organic phase, and prepared in 3 temperature conditions for the external aqueous phase (two fixed temperature conditions and a gradually increased temperature condition). The theoretical drug loading in the particles was set to 80%. When prepared at fixed temperature conditions, all of the microparticles that were prepared with the 3 types of PLA were not spherical or smooth-surfaced. These microparticles released 100% of the drug within 1 week in the in vitro study. However, the microparticles that were prepared with DL-PLA (MW, 95000) in the gradually increased temperature condition were spherical with a smooth surface. The dissolution profile of the microparticles showed a long release over 7 weeks in vitro. The actual drug loading in the microspheres was 73-80%. A core-shell structure was observed in the inner structure of the microspheres. The core-shell microspheres were injected subcutaneously into rabbits. Aripiprazole was detected in the serum over 12 weeks. Production of high-drug-loading core-shell structure microspheres was successfully achieved by using high molecular weight of PLA and specific temperature condition at preparation. It showed long release profile in vitro and in vivo.