Long-acting delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate): their preparation, characterization and contraceptive tests on mice

The preparative technology for sustained release drug delivery microspheres of levo-norgestrol-poly(3-hydroxybutyrate) was optimized based on the in-l iquid-drying method. The formation of the drug microspheres was confirmed w ith differential thermal analysis. The appearance, particle size and distri bution, residual CHCl3, drug content, drug release characteristics in vitro , stability and anticonceptive effect on mice of the microspheres were all examined. The average particle size was 64 mum with over 90% of the microsp heres being in the range of 28.7-85.8 mum. The residual CHCl3 was lower tha n 0.001%. The drug release behaviour in vitro could be described by the Hig uchi equation and the drug release t(1/2) was prolonged by 1.8 times, compa red with the original drug LNG. The microspheres were stable for 3 months a nd showed significant sustained release and anticonceptive effect in mice, and lower toxicity compared with the original drug.