双氯芬酸钠缓释液体栓制备与体内外相关性研究  

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

作　　者：洪春雪[1] 束怡[1] 曹宇[1] 李晨[1] 王磊[1] 束家有[1] 

机构地区：[1]武汉大学药学院,湖北武汉430072

出　　处：《武汉大学学报（理学版）》2012年第4期281-285,共5页Journal of Wuhan University:Natural Science Edition

基　　金：科技部科技人员服务企业项目(2009GJD10040)

摘　　要：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,R2>0.9,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.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 gela- tion temperature, gel strength, bioadhesive force and the drug release of diclofenac sodium liquid suppositories in vitro were studied. Laurie 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 pharmacoki- netic 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： t~/z（K~ = 5. 553 3 h,t~/2（K~=0.357 40 h,cm^x=7 712 ng＇mL 1,AUC0＋~=72 029 ng＇h＇mL ~,MRT=7.61 h. which showed this preparation has the characteristic of sustained releasing.

关 键 词：双氯芬酸钠缓释液体栓 体内外相关性 药代动力学 

分 类 号：R944[医药卫生—药剂学]