Formation Mechanism and In Vitro Evaluation of Risperidone-Containing PLGA Microspheres Fabricated by Ultrafine Particle Processing System

Abstract

Ultrafine particle processing system (UPPS) was developed previously by our group to provide a new solution to microsphere fabrication. The UPPS was supposed to possess many featured advantages, but the microsphere formation mechanism during UPPS processing was still unknown. The objective of this study was to perform the formation mechanism investigation and in vitro evaluation on risperidone-containing poly(d, l-lactic-co-glycolic acid) microspheres (RIS-PLGA MS) fabricated by UPPS. Evaporation profile and viscosity of the PLGA-containing solutions were considered as the critical factors for the microsphere formation mechanism and were determined in present study. The formation mechanism of RIS-PLGA MS was put forward by semiquantitative analysis on the basis of the evaporation profile, viscosity, and scanning electron microscopy results. It was established that the evaporation profile and viscosity would have an impact on the evaporation velocity and PLGA molecular diffusion velocity during solidification process, resulting in different appearance of the microspheres. Furthermore, comprehensive in vitro evaluations of RIS-PLGA MS were conducted, including particle size distribution, micromeritics, morphology, drug loading, encapsulation efficiency, residual organic solvent, syringeability, and in vitro release behavior. The results revealed that RIS-PLGA MS was a promising candidate for intramuscular administration, and meanwhile UPPS was a qualified technology for microsphere production.