布洛芬包合物凝胶体外释药行为及体内药代动力学 ... - 第三军医大学学报.DOC

布洛芬包合物凝胶体外释药行为及体内药代动力学研究 李欣宇1，朱照静2(，车坷科3，王丽娟4，吴青4 （1重庆医科大学附属第一医院药剂科，重庆400016；2重庆医药高等专科学校，重庆400030；3重庆市第三人民医院，重庆400014；4重庆医科大学药学院，重庆400016） ：目的 制备布洛芬（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，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，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：布洛芬；包合物原位凝胶；泊洛沙姆；无膜溶出法；药代动力学, ZHU Zhao-jing2(, CHE Ke-ke3, WANG Li-juan4, WU Qing4 (1 Dpt.of Pharmacy ,the First Affiliated Hospital of Chongqing Medical University,chongqing 400016; 2 Dpt.of Pharmacy,Chongqing Medical and Pharmaceutical College, Chongqing 400030; 3 Dpt.of Pharmacy,the Third Hospital of Chongqing, Chongqing 400014; 4 Teaching Section of Pharmaceutics,Chongqing University of Medical Sciences, Chongqing 400016) Abstract: Objective To prepare ibuprofen (IBU) inclusion complex poloxamer gel and evaluate the release behavior in vitro/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 drug concentrations in plasma were measured by HPLC after intramuscularly giving IBU solution and IBU inclusion complex gel. 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, t1/2 were prolonged and Cmax was degraded while AUC was enhanced obviously. Conclusion The IBU inclusion complex gel is a good injectable sustained-release preparation which can optimize the analgesia and anti-inflammatory effect of Ibuprofen, and build up the fundation for the use of water-insoluble drug in thermosensitive in situ gel. Key words: ibuprofen; inclusion complex in situ gel; poloxamer; membraneless models; pharmacokinetic 布洛芬（Ibuprofen, IBU）是临床应用比较广泛的首个烷基苯丙酸非甾体抗炎药，常用于治疗类风湿