Microencapsulation techniques using ethyl acetate as a dispersed solvent: Effects of its extraction rate on the characteristics of PLGA microspheres

Ethyl acetate solvent evaporation and extraction processes were developed to prepare poly(d,l-lactide-co-glycolide) microspheres. The microencapsulation processes first emulsified a polymer-containing ethyl acetate solution with a 1% aqueous polyvinyl alcohol solution (W₁) to make an oil-in-water (O/W₁) emulsion. The O:W₁ phase ratio was carefully chosen so as to saturate the W, by a small proportion of the dispersed solvent and to form successfully embryonic microspheres without generating polymer precipitates. The effects of the O:W, phase ratio on the morphology and size of microspheres were interpreted in terms of the solvent miscibility with water, as well as the influence of the W, volume on breakup of the dispersed phase. The extraction rate of ethyl acetate from nascent microspheres was then adjusted by making use of both its miscibility with water and its volatility at atmospheric pressure. Variation of these parameters made it possible to fabricate hollow- or matrix-type microspheres with different size distributions. It was also found that the tendency of microspheres to aggregate on drying was related to the extent of microsphere hydration and the residual ethyl acetate in wet microspheres.