Effect of solvent composition during preparation on the characteristics ofenoxacin microparticles

We have studied the effect of the solvent system during preparation on the morphology, encapsulation efficiency, and release characteristics of enoxac in microparticles intended for localized delivery to the bone for the treat ment of bone infections. Microparticles of enoxacin were formulated using poly(glycolic acid-co-DL-l actic 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 d ichloromethane-acetone solvent mixtures, which had porous surfaces. Approximately 65% of the microparticles prepared with pure dichloromethane were <125 mu m in diameter compared with 16% (approx.) of microparticles pr epared 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 a n increase in the yield of microparticles harvested from 39 to 51%. Althoug h a further increase in the amount of acetone to dichloromethane-acetone, 1 :9, had no significant effect on the yield, aggregation, or fraction of mic roparticles below 125 mu m in diameter, the encapsulation efficiency increa sed to 56%. Approximately 55% of enoxacin was released in 24 h for micropar ticles prepared with dichloromethane-acetone, 1:9, compared with 100% relea se in 10 h and 2 h for microparticles of the same size range prepared with dichloromethane-acetone, 1:1, and dichloromethane-acetone, 10:0, respective ly. The results suggest that the composition of the dichloromethane-acetone sol vent system significantly influences the encapsulation efficiency and the r ate of release of enoxacin from microparticles. This is important for the f ormulation of sustained-release enoxacin microparticles for the localized t reatment of osteomyelitis.