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

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7~10 h,体内缓释时限达9~18 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_max=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 7~10 h in vitro,and 9~18 h in vivo,which shows good sustained-realease characteristics.