Effect of Solvent Composition During Preparation on the Characteristics of Enoxacin Microparticles

We have studied the effect of the solvent system during preparation on the morphology, encapsulation efficiency, and release characteristics of enoxacin microparticles intended for localized delivery to the bone for the treatment of bone infections. Microparticles of enoxacin were formulated using poly(glycolic acid-co-DL-lactic acid) (PGLA) of different viscosity grades by the solvent-evaporation technique. Microparticles prepared with pure dichloromethane had smoother surfaces and less tendency to aggregate than microparticles prepared with dichloromethane-acetone solvent mixtures, which had porous surfaces. Approximately 65% of the microparticles prepared with pure dichloromethane were < 125 microm in diameter compared with 16% (approx.) of microparticles prepared with dichloromethane-acetone mixtures. Increasing the proportion of acetone from dichloromethane-acetone, 10:0, to dichloromethane-acetone, 1:1, resulted in an increase in encapsulation efficiency from 25 to 37%, and an increase in the yield of microparticles harvested from 39 to 51%. Although a further increase in the amount of acetone to dichloromethane-acetone, 1:9, had no significant effect on the yield, aggregation, or fraction of microparticles below 125 microm in diameter, the encapsulation efficiency increased to 56%. Approximately 55% of enoxacin was released in 24 h for microparticles prepared with dichloromethane-acetone, 1:9, compared with 100% release in 10h and 2h for microparticles of the same size range prepared with dichloromethane-acetone, 1:1, and dichloromethane-acetone, 10:0, respectively. The results suggest that the composition of the dichloromethane-acetone solvent system significantly influences the encapsulation efficiency and the rate of release of enoxacin from microparticles. This is important for the formulation of sustained-release enoxacin microparticles for the localized treatment of osteomyelitis.