Incorporation of water-soluble drugs in PLGA microspheres.

Poly(lactide-co-glycolide) (PLGA) microspheres containing blue dextran, as a model of water-soluble drugs, were prepared from w(1)/o/w(2) emulsions by using a microhomogenizer and a solvent evaporation method. Effects of preparation conditions, such as, concentration of poly(vinyl alcohol) (PVA) in w(2) phase, viscosity of inner soluble water phase, volume ratio of oil phase to w(1) phase in primary emulsion, PLGA concentration in oil phase, and molecular weight or composition of PLGA, upon the properties of PLGA microspheres containing water-soluble drugs were examined. Concentration of poly(vinyl alcohol) (PVA), the dispersant dissolved in w(2) phase of secondary emulsion did not show any effects on the final particle size. On the other hand, volume ratio of oil phase to water one in primary emulsion affected the final particle size, which seemed to be related to the local PLGA concentration in w(1)/o emulsions. That is, the particle size increased as the volume ratio of w(1) phase against oil phase, w(1)/o (v/v), increased. The loading efficiency, however, was not affected by the volume ratio of w(1)/o (v/v), but affected by blue dextran concentration in w(1) phase. Higher loading efficiency was observed in PLGA microspheres prepared from w(1) phase containing lower concentration of blue dextran. Blue dextran solution (inner water phase) with the lower viscosity may result in the lower leakage ratio of blue dextran during the preparation procedure. Increases in concentration and molecular weight of PLGA made particle size larger.