Puthli S, Vavia P
Department of Pharmaceutical Sciences, University Institute of Chemical Technology, University of Mumbai, Nathalal Parikh Marg, Mumbai, Maharashtra, India.
Eur J Pharm Sci. 2008 Nov 15;35(4):307-17. doi: 10.1016/j.ejps.2008.07.009. Epub 2008 Aug 8.
An injectable system of levonorgestrel (LNG) was developed using biodegradable polymer of natural origin. The parenteral system was optimized for particle size and higher drug loading. The microparticulate system was characterised by scanning electron microscopy, encapsulation efficiency, moisture content, IR, DSC, XRD, residual solvent content, sterility testing, test of abnormal toxicity and test for pyrogens. The microparticles were sterilised by gamma irradiation (2.5Mrad). The system was injected intramuscularly in rabbits and the blood levels of LNG were determined using radioimmunoassay technique. An optimized drug to polymer ratio of 0.3-1.0 (w/w ratio) gave improved drug loading of about 52%. In vivo studies in rabbits showed that the drug was released in a sustained manner for a period of 1 month. The AUC(0-t) was found to be 9363.6+/-2340pg/mLday(-1) with MRT calculated to be about 16 days and Kel of 0.01day(-1). LNG levels were maintained between 200 and 400pg/mL. In vivo release exhibited an initial burst effect which was not observed in the in vitro dissolution. This promising "Progestin-only" long-term contraceptive with improved user compliance is an alternative to the synthetic expensive polymeric carriers.
利用天然来源的可生物降解聚合物开发了一种左炔诺孕酮（LNG）注射系统。对该非肠道给药系统的粒径和更高载药量进行了优化。通过扫描电子显微镜、包封率、水分含量、红外光谱、差示扫描量热法、X射线衍射、残留溶剂含量、无菌检查、异常毒性检查和热原检查对微颗粒系统进行了表征。微颗粒通过γ射线辐照（2.5兆拉德）进行灭菌。将该系统肌肉注射到兔子体内，并使用放射免疫测定技术测定LNG的血药浓度。优化后的药物与聚合物比例为0.3 - 1.0（重量/重量比），载药量提高了约52%。在兔子身上进行的体内研究表明，药物以持续方式释放1个月。发现AUC(0 - t)为9363.6±2340pg/mL·day⁻¹，MRT计算约为16天，Kel为0.01day⁻¹。LNG水平维持在200至400pg/mL之间。体内释放表现出体外溶出中未观察到的初始突释效应。这种具有改善患者顺应性的有前景的“仅含孕激素”长效避孕药是合成昂贵聚合物载体的一种替代选择。
