In Vitro Sustained Release and Degradation Study of Biodegradable Poly(D, L-lactic acid) Microspheres Loading Theophylline

Microspheres from biodegradable poly(D, L-lactic acid) (PDLLA) incorporating theophylline were prepared with an oil-in-oil-type (O/O) emulsion method to study the effects of the preparation conditions on the in vitro release of theophylline. PDLLA was virtually immiscible with theophylline. The influencing factors studied in this work include operating temperature for solvent evaporation, soybean lecithin concentration, stirring speed, type of mixing, the molecular weight of PDLLA, and theophylline loading. The effect of these preparation conditions on theophylline release was evaluated based on the observation of the resulting microspheres by scanning electron microscopy (SEM) and the plot of the amount of theophylline released against time. It was found that the operating temperature for the solvent evaporation had a large influence on the structure of PDLLA microspheres loading theophylline. Increased concentration of surfactant yielded microspheres with smoother surface, less structural defects, and smaller size. When the effect of polymer molecular weight (Mw) on surface characteristics of microspheres was studied, microspheres prepared from higher Mw PDLLA had smoother surface than those prepared from low Mw PDLLA. The release rate of theophylline from the microspheres decreased by decreasing drug loading and increased PDLLA Mw. The kinetic of drug release and degradation study of PDLLA clearly indicated that theophylline molecules were released from PDLLA matrix through a diffusion controlled mechanism.