Fabrication, characterization and in vivo studies of biodegradable gamma sterilized injectable microparticles for contraception.

摘要

A Levonorgestrel-loaded microparticulate system was developed with gelatin and bovine serum albumin using triple emulsion technique coupled with chemical cross-linking thermal rigidization method. The formulation was optimized for various formulation variables and process parameters. The microparticulate system was characterized by scanning electron microscopy, encapsulation efficiency, moisture content, IR, DSC, XRD, residual solvent content and evaluated for sterility, abnormal toxicity and absence of pyrogens. Microparticles were sterilized by gamma irradiation at 2.5 Mrad. The system was injected intramuscularly in rabbits and drug blood levels estimated using radioimmunoassay technique. An optimized drug to polymer ratio of 0.4:0.75 w/w gave drug encapsulation efficiency of about 40%. The in vitro drug release followed Higuchi square root kinetics. In in vivo studies the AUC0-t was found to be 12849.25 pg/mL.day(-1) with mean residence time calculated to be about 16 days and Kel of 0.02 day(-1). Levonorgestrel (LNG) levels were maintained between 200 and 400 pg/mL. The pharmacokinetic results indicate that LNG is released from the injectable microparticles for a period of one-month duration.