摘要
目的制备布洛芬(ibuprofen,IBU)包合物原位凝胶,并考察体外释药行为和体内药代动力学特点。方法用冷冻干燥法制备布洛芬-羟丙基-β-环糊精包合物,以泊洛沙姆P407及P188为基质制备温度敏感型原位凝胶,无膜溶出法考察包合物原位凝胶体外释药情况,新西兰白兔肌注布洛芬溶液及包合物原位凝胶,高效液相色谱法(HPLC)测定血药浓度,3P97软件计算药代动力学参数。结果制得的包合物平均载药量10.24%,体外凝胶溶蚀及药物释放均符合零级动力学,与布洛芬溶液相比,布洛芬包合物原位凝胶能明显使tmax推迟,Cmax降低,t1/2延长,药时曲线下面积(AUC)显著增加。结论布洛芬包合物原位凝胶体内和体外均具有缓释效果,可作为一种优良的缓释注射剂,更好地发挥布洛芬解热镇痛抗炎作用,同时也为开发难溶性药物的温度敏感原位凝胶提供了借鉴。
Objective To prepare thermosensitive in situ gel of ibuprofen （IBU） inclusion complex with poloxamer and evaluate its release behavior in vitro and in vivo. Methods The IBU inclusion complexes were prepared by lyopyilization. The poloxamer 407 and 188 were added as a base for the preparation of gel. The release of inclusion complex gel was evaluated by membraneless models. The pharmacokinetics was evaluated after intramuscular injecting IBU solution or IBU inclusion complex gel to New Zealand white rabbits. The drug concentrations in the plasma were measured by HPLC. Results The loading amount of IBU was 10.24%. The corrosion of gel and the release of IBU correspond to zero-order kinetics. Compared with IBU solution, the tmax and t1/2 were prolonged and C was degraded while AUC was enhanced obviously. Conclusion The IBU inclusion complex gel is used as a good injection with sustained-release which can improve the analgesia and and-inflammatory effect of ibuprofen. And our study builds up the foundation for the use of water-insoluble drug in thermosensitive in situ gel.
出处
《第三军医大学学报》
CAS
CSCD
北大核心
2009年第18期1786-1789,共4页
Journal of Third Military Medical University
