Formulation and pharmacokinetics of the parenteral fat nano-emulsion of ubenimex  

静脉注射用乌苯美司脂肪乳制备及药代动力学研究(英文)

作　　者：孙晓利[1] 刘东华[1] 李鹏[1] 徐文方[1] 张娜[1] 

机构地区：[1]山东大学药学院,山东济南250012

出　　处：《Journal of Chinese Pharmaceutical Sciences》2011年第5期483-492,共10页中国药学（英文版）

基　　金：Shandong Province Natural Science Foundation (Grant No.ZR2009CM011)

摘　　要：The fat nano-emulsion, which has been used as a drug carrier, especially for the poorly water soluble drug, has drawn favorable attention recently. Ubenimex is a poorly soluble drug with no parenteral treatment available for patients. This study was aimed at the manufacture of a ubenimex loaded fat nano-emulsion for intravenous delivery by SolEmuls~ technology. The formulation and the process parameters were optimized by single-factor design and the obtained ubenimex loaded fat nano-emulsion was stable even after autoclaving. The average particle size was near 200 nm with narrow size distribution and a negative zeta potential of -44 mV. The in vitro release behavior of ubenimex from the fat nano-emulsion could be described by the double phase kinetics model and expressed by the following equation： 100 - Q = 75.27e^-0.369t ＋ 15.94e^-0.0324t, Rα = 0.9863, Rβ = 0.9878. The pharmacokinetic study showed that the pharmacokinetic curves of both the ubenimex fat nano-emulsion and the i.v. ubenimex suspension, were similar and the main parameters showed no significant difference except t1/2. In conclusion, the fat nano-emulsion with ubenimex has potential as a safe and effective parenteral delivery system for poorly water soluble anti-cancer drugs.脂肪乳作为难溶性药物的载体受到广泛的关注。乌苯美司作为一种水难溶性药物,市场上没有可供注射用剂型。本文利用SolEmuls技术制备注射用乌苯美司脂肪乳,采用单因素设计优化处方,得到的乌苯美司脂肪乳高压灭菌前后均比较稳定。制备的乌苯美司脂肪乳平均粒径在200nm左右,zeta电位为-44mV,体外释放行为符合双相动力学方程:100-Q=75.27e^(0.369t)+15.94e^(-0.0324t),R_α=0.9863,R_β=0.9878。药代动力学实验表明乌苯美司脂肪乳和静注乌苯美司混悬液药代动力学参数只有t_(1/2)有显著性差异。实验结果表明,对于水难溶性药物乌苯美司来说,静脉注射用脂肪乳可以作为一种安全有效的给药方式。

关 键 词：Fat nano-emulsion UBENIMEX High pressure homogenization PHARMACOKINETICS 

分 类 号：R969.1[医药卫生—药理学]