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-liquid-drying method. The formation of the drug microspheres was confirmed with differential thermal analysis. The appearance, particle size and distribution, 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 microm with over 90% of the microspheres being in the range of 28.7-85.8 microm. The residual CHCl3 was lower than 0.001%. The drug release behaviour in vitro could be described by the Higuchi equation and the drug release t1/2 was prolonged by 1.8 times, compared with the original drug LNG. The microspheres were stable for 3 months and showed significant sustained release and anticonceptive effect in mice, and lower toxicity compared with the original drug.