Influence of process parameters on the size distribution of PLA microcapsules prepared by combining membrane emulsification technique and double emulsion-solvent evaporation method

Abstract

Relatively uniform-sized biodegradable poly(lactide) (PLA) microcapsules with various sizes were successfully prepared by combining a glass membrane emulsification technique and water-in-oil-in-water (w 1/o/w 2) double emulsion-solvent evaporation method. A water phase was used as the internal water phase, a mixture solvent of dichloromethane (DCM) and toluene dissolving PLA and Arlacel 83 was used as the oil phase (o). These two solutions were emulsified by a homogenizer to form a w 1/o primary emulsion. The primary emulsion was permeated through the uniform pores of a glass membrane into the external water phase by the pressure of nitrogen gas to form the uniform w 1/o/w 2 double emulsion droplets. Then, the solid polymer microcapsules were obtained by simply evaporating solvent. The influence of process parameters on the size distribution of PLA microcapsules was investigated, with an emphasis on the effect of oil-soluble emulsifier. A unique phenomenon was found that a large part of emulsifier could adsorb on the interface of internal water phase and oil phase, which suppressed its adsorption on the surface of glass membrane, and led to the successful preparation of uniform-sized double emulsion. Finally, by optimizing the process parameters, PLA microcapsules with various sizes having coefficient of variation (CV) value under 14.0% were obtained. Recombinant human insulin (rhI), as a model protein, was encapsulated into the microcapsules with difference sizes, and its encapsulation efficiency and cumulative release were investigated. The result suggested that the release behavior could be simply adjusted just by changing precisely the diameters of microcapsule, benefited from the membrane emulsification technique.