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.