温度敏感型布洛芬缓释液体栓的制备与体内外评价

Preparation and evaluation of thermosensitive ibuprofen sustained-release liquid suppository in vitro and in vivo

目的:以泊洛沙姆407(P407)和泊洛沙姆188(P188)为组合基质,添加生物黏附剂卡波姆(Cabopol)以及促渗透剂氮酮(Azone)制备温敏型布洛芬(IBU)缓释液体栓剂,考察液体栓释药的体内外相关性。方法:以凝胶温度、凝胶强度、生物黏附力和液体栓剂体外释放度为指标进行体外筛选;经比格犬直肠给药测定动物体内药物释放曲线进行体内筛选;用3P97程序计算药动学参数。结果:布洛芬体外释放结果符合零级模式,R2>0.9时,体内药物释放出现平台,显示了良好的体内外相关性;药动学研究结果表明,体内过程为一室模型,药动学参数为tmax=3.551 h,Cmax=21.483μg.mL-1,t1/2(Ke)=2.740 h,AUC0→∞=210.850μg.mL-1.h,MRT=7.670 h。结论:所制备的布洛芬液体栓剂具有良好的缓控释特征。

OBJECTIVE To prepare thermosensitive ibuprofen sustained-release liquid suppository with poloxamer 407, poloxamer 188, bioadhesive polymer-cabopol and permeability enhancer-azone and evaluate its characteristics of in vitro release and in vim absorption. METHODS The physicochemical properties such as gel temperature, gel strength ,bioadhesive force and the drug release of ibuprofen liquid suppositories in vitro were studied and the drug absorption in vivo was performed in Beagle dogs; The 3P97 program was used to calculate the pharmacokinetic parameters of ibuprofen. RESULTS Drug release pattern in vitro was the best described by zero-order kinetics and in vivo profile was demonstrated to fit one compartment model. The pharmacokinetic paramerers were：tmax = 3. 551 h, Cmax = 21. 483 μg·mL^-1, t1/2（Ke） = 2. 740 h, AUG0→∞=210.850g·mL^-1·h, MRT = 7. 670 h. CONCLUSION This preparation has the characteristic of sustained releasing.