双氯芬酸钠缓释液体栓制备与体内外相关性研究

设计制备了以泊洛沙姆407/188为主要基质,卡波姆、氯化钠为添加剂,月桂酸二乙醇酰胺为增溶剂的双氯芬酸钠缓释液体栓,以凝胶温度、凝胶强度、生物黏附力和体外释放度为考察指标进行体外评价;测定双氯芬酸钠缓释液体栓在犬体内的血药浓度,进行体内筛选.采用3p97软件计算液体栓相关药动学参数,进行体内释药特性研究.加入0.9%月桂酸二乙醇酰胺使双氯芬酸钠增溶2.3倍.缓释液体栓体外释放符合零级模式,R20.9,释药时限大于6h;体内药物释放出现血药平台,具有良好的体内外相关性;体内过程为一室模型,t1/2(Ke)=5.553 3h,t1/2(Ka)=0.357 4h,cmax=7 712ng.mL-1,AUC0→∞=72 029ng.h.mL-1,MRT=7.61h.所制备的双氯芬酸钠缓释液体栓具有稳定的缓控释特性.

Preparation and Properties of Thermosensitive Diclofenac Sodium Sustained-Release Liquid Suppository in vitro and in vivo Correlation

According to the thermosensitive gel properties the thermosensitive diclofenac sodium sustained-release liquid suppository with poloxamer 407/188 was designed and prepared.The physicochemical properties such as gelation temperature,gel strength,bioadhesive force and the drug release of diclofenac sodium liquid suppositories in vitro were studied.Lauric diethanolamide 0.9% increased the solubility of diclofenac sodium in liquid suppository by 130%.The drug absorption in vivo was performed in Beagle dogs.The 3p97 program was used to calculate the pharmacokinetic parameters of liquid suppository.Drug release pattern in vitro was best described by zero-order kinetics and in vivo profile was demonstrated to fit one compartment model.The pharmacokinetic parameters were: t1/2(Ke)=5.553 3 h,t1/2(Ka)=0.357 40 h,cmax=7 712 ng·mL-1,AUC0→∞=72 029 ng·h·mL-1,MRT=7.61 h.which showed this preparation has the characteristic of sustained releasing.