氯化钠强化硫酸吗啡缓释液体栓制备及其性能

氯化钠强化硫酸吗啡缓释液体栓制备及其性能 Preparation and Property of Morphine Sulfate Sustained-Release Liquid Suppository Reinforced by Sodium Chloride 丁明和 DING Minghe 1 first-author 娄杰 LOU Jie 1 洪春雪 HONG Chunxue 1 耿琴 GENG Qin 1 曹宇 CAO Yu 1 李星 LI Xing 1 束家有 SHU Jiayou 1 武汉大学药学院 武汉大学药学院 College of Pharmaceutical,Wuhan University College of Pharmaceutical,Wuhan University 根据温敏原位凝胶的特性制备了以泊洛沙姆407/188为主要基质,卡波姆、氯化钠、氮酮和2,6-二叔丁基-4-甲基苯酚为添加剂的硫酸吗啡缓释液体栓,测定了其凝胶温度、凝胶强度和生物黏附力,研究了其体外溶出和在Beagle犬体内的药物吸收.用3p97程序计算药物代谢动力学参数,进行体外释放和体内吸收的相关性研究.结果表明,一定量的氯化钠与卡波姆产生协同作用,使凝胶温度下降,凝胶强度增加.该缓释液体栓在体外释药符合零级模式,在Beagle犬体内释药过程符合一室模型.其中,经氯化钠强化的处方（卡波姆为0.8%,氯化钠为1.0%）相关药物代谢动力学参数为:峰浓度为409.7 ng.mL-1,血药浓度-时间曲线下面积（AUC）为5 708 ng.h.mL-1,体内平均滞留时间（MRT）为10.92 h,体外释药时间为7 1 0 h,体内缓释时限达9 1 8 h,显示出良好的缓控释特征. Morphine sulfate sustained-release liquid suppositories were prepared by morphine sulfate sustained-release liquid suppositories with poloxamer 407/188,cabopol,sodium chloride,azone,2,6-di-tert-butyl-4-methylphenol according to the properties of in situ gel.The physicochemical properties such as gelation temperature,gel strength,bioadhesive force were studied.The drug released from the morphine sulfate sustained-release liquid suppository was studied with new device,and the drug absorption was performed in beagle dogs.The 3p97 program was used to calculate the pharmacokinetic parameters of morphine sulfate sustained-release liquid suppositories,and their characteristics between in vitro release and in vivo absorption were evaluated.The drug release pattern in vitro is best described as zero-order kinetics and in vivo profile is demonstrated to fit one compartment model.The pharmacokinetics pharmerers of prescription reinforced by sodium chloride（cabopol 0.8%,NaCl 1.0%） are: ρ m ax=409.7 ng·mL-1,AUC=5 708 ng·h·mL-1,MRT=10.92 h.The release time of morphine sulfate sustained-release liquid suppositories reinforced by sodium chloride is 7 1 0 h in vitro,and 9 1 8 h in vivo,which shows good sustained-realease characteristics. 硫酸吗啡缓释液体栓 卡波姆 泊洛沙姆 水凝胶 药物代谢动力学 morphine sulfate sustained-release liquid suppository cabopol poloxamer hydroxylgel pharmacokinetics 10.14188/j.1671-8836.2011.04.012 R944 国家火炬计划项目（2010GH021397）资助 2011-04-01 2021-04-01 4 57