传递体促进难溶性药物口服吸收的研究.pdfVIP

传递体促进难溶性药物口服吸收的研究 1 1 2 1 3 1* 陈雅娉 , 卢懿 ， 陈建明 ，何伟 ，胡富强 ，吴伟 (1. 复旦大学药学院，上海 201203 ； 2. 第二军医大学药学院，上海 200433 ；浙江大学药学院，杭州 310058) 摘要： 目的 制备载难溶性药物非诺贝特传递体，考察其提高非诺贝特的口服生物利用度。 方法 以大豆磷脂和脱氧胆酸钠为材料，采用改良的薄膜分散法制备非诺贝特传递体口服给 药系统。考察了传递体的粒径、包封率及其影响因素，作为优化处方和工艺的依据。考察了 传递体的脂质膜流动性及其微观结构。以微粉化胶囊和脂质体作为对照，考察了传递体中非 诺贝特的体外释放和体内生物利用度。结果 传递体粒径的影响因素主要有脱氧胆酸钠/大 豆磷脂、非诺贝特/大豆磷脂、均质参数和pH。包封率影响因素主要有脱氧胆酸钠/大豆磷脂 和pH。传递体微观结构为近球形形态，且非诺贝特对传递体的膜结构没有明显影响。非诺贝 特传递体的膜流动性主要受脱氧胆酸钠/大豆磷脂比的影响，脱氧胆酸钠/大豆磷脂比越大， 传递体的膜流动性越大，变形性越好。非诺贝特传递体的体外释放性质考察结果表明，非诺 贝特从传递体中释放速率与从脂质体中释放速率相近，2h的释放百分率仅为20%，而相同时 间内非诺贝特从微粉化胶囊中溶出大于90%。非诺贝特口服后体内生物利用度结果表明，非 诺贝特传递体和脂质体的生物利用度分别是微粉化胶囊的5.17和3.28倍，结论 传递体使非 诺贝特在犬体内生物利用度明显提高，且脱氧胆酸钠起到了一定的作用。 关键词：传递体；脱氧胆酸钠；非诺贝特；口服；生物利用度 Study on enhanced oral absorption of the poorly water-soluble drug by using transfersomes 1 1 2 1 3 1* Yaping Chen , Yi Lu , Jianming Chen , Wei He , Fuqiang Hu , WeiWu (1. School of Pharmacy, Fudan University, Shanghai 201203; 2. School of Pharmacy, Second Military Medical University, Shanghai 200433; 3.School of Pharmacy, Zhejiang University, Hangzhou 310058) ABSTRACTS ：OBJECTIVE The main purpose of this study was to evaluate oral bioavailability of the poorly water-soluble drug fenofibrate when transfersomes were used as oral drug delivery systems. METHODS Transfersomes were prepared by a dry-film dispersing method coupled with sonication and homogenization with soybean phosphotidylcholine (SPC) and sodium deoxycholate (SDC) as carrier materials . Several properties of the transfersomes, including particle size, entrapment efficiency and membrane fluidity, w ere extensively characterized. RESULTS In vitro release experiments indicated that no more than 20% of total fenofibrate was released from SPC/cholesterol (CL) and SPC/SDC liposomes at 2 h, in contrast with near complete release for micr