Encapsulation of water-soluble drugs by an o/o/o-solvent extraction microencapsulation method

Abstract

A new o/o/o-solvent extraction microencapsulation method based on less toxic solvents is presented in this study. The drug is dissolved/dispersed into a poly( d, l-lactide)/or poly ( d, l-lactide-co-glycolide) (PLGA) solution in a water-miscible organic solvent (e.g., dimethylsulfoxide or 2-pyrrolidone) (o 1), followed by emulsification into an oil phase (o 2) (e.g., peanut oil). This emulsion is added to the external phase (o 3) to solidify the drug-containing polymer droplets. The polymer solvent and the oil are extracted in an external phase (o 3) (e.g., ethanol), which is a nonsolvent for the polymer and miscible with both the polymer solvent and the oil. One major advantage of this method is the reduced amount of solvent/nonsolvent volumes. In addition, very high encapsulation efficiencies were achieved at polymer concentration of 20%, w/w for all investigated polymers and o 1/o 2 phase ratios with ethanol as the external (o 3) phase. The encapsulation efficiency was very low (<20%) with water as external phase. The particle size of the microparticles increased with increasing polymer concentration and o 1/o 2 phase ratio and larger microparticles were obtained with 2-pyrrolidone compared to dimethylsulfoxide as polymer solvent (o 1). After an initial burst, in vitro drug release from the microparticles increased for the investigated polymer as follows: Resomer ® RG 506 > RG 756 > R 206. A third more rapid release phase was observed after 6 weeks with Resomer ® RG 506 due to polymer degradation. Similar drug release patterns were obtained with the o/o/o and w/o/w multiple emulsion methods because of similar porous structures. This new method has the advantages of less toxic solvents, much lower preparation volume and solvent consumption and high encapsulation efficiencies when compared to the classical w/o/w method.