Preparation of uniform-sized PLA microcapsules by combining Shirasu Porous Glass membrane emulsification technique and multiple emulsion-solvent evaporation method

Relatively Uniform-sized biodegradable poly(lactide) (PLA) microcapsules were successfully prepared by combining a Shirasu Porous Glass (SPG) membrane emulsification technique and multiple emulsion-solvent evaporation method. An aqueous phase containing lysozyme was used as the internal water phase (w(1)), and PLA and Arlacel 83 were dissolved in a mixture solvent of dichloromethane (DCM) and toluene which 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 (5.25 mu m) of an SPG membrane into the external water phase by the pressure of nitrogen gas to form the uniform w(1)/o/w(2) droplets. Then, the solid polymer microcapsules were obtained by simply evaporating the solvent. It is necessary to avoid the phase separation of primary emulsion during the SPG membrane emulsification. It was found that when the density difference of the internal water phase and oil phase was reduced to nearly zero and Arlacel 83 was used as the oil emulsifier, the phase separation was not observed within 24 h. The w(1)/o/w(2) emulsion with uniform diameter was obtained only when Arlaecl 83 concentration was limited below 2.5 wt.% based on oil phase. The drug encapsulation efficiency was found to be related to several factors including PLA molecular weight, additive type and its concentration in the internal water phase, the emulsifier type and concentration in the oil phase, the NaCl concentration and the pH value in the external water phase. Comparing with the stirring method, it was found that the size was more uniform and the drug encapsulation efficiency was much higher when the microcapsules were prepared by SPG membrane emulsification technique and the highest drug encapsulation efficiency of 92.20% was obtained. This is the first study to prepare PLA microcapsules by combining an SPG membrane emulsification technique and multiple emulsion-solvent evaporation method. (c) 2004 Elsevier B.V. All rights reserved.