Influence of processing on the stability and release properties of biodegradable microspheres containing thioridazine hydrochloride.

Biodegradable microspheres of poly(DL-lactic-co-glycolic acid) (PLGA) containing thioridazine HCl were produced by four emulsion-solvent evaporation methods including an O/W emulsion method, an O/O emulsion method, a W/O/W multiple emulsion method, and a W/O/O/O multiple emulsion method. Gel permeation chromatography was used to determine the molecular weight of the polymer before and after processing. Resultant microspheres were either incubated in an oven at 40 degrees C, or stored in a desiccated chamber at 20 degrees C. Change in the molecular weight of the polymer was monitored as a function of time. Premature degradation of the polymer was evident in microspheres produced by the O/W conventional solvent evaporation method. Thioridazine HCl catalyzed hydrolysis of PLGA was evident in normalized molecular weight distribution plots of the O/W microspheres. The in vitro release of thioridazine HCl from multiphase microspheres produced by potentiometric dispersion was compared with the release of drug from conventional microspheres prepared from the same polymer. Release of thioridazine HCl from multiphase microspheres of the W/O/O/O type occurred by diffusion during initial stages of drug release.