醋柳黄酮自微乳化给药系统的体内外评价
In vitro and in vivo evaluation of total flavones of hippophae rhamnoides self-microemulsifying drug delivery system
-
摘要:
本文的目的在于对醋柳黄酮自微乳化给药系统进行评价, 该给药系统用于提高难溶性药物醋柳黄酮的口服生物利用度。评价指标包括自微乳化时间、粒径及多分散指数、形态学特征、体外分散性、稳定性、在体小肠吸收及生物利用度。结果表明, 该自微乳化给药系统在3 min内即形成微乳, 平均粒径低于40 nm, 多分散指数低于0.2, 电镜下观察粒子形态为球形; 20 min时体外累积释放百分率 (以槲皮素计) 接近90%, 显著高于普通胶囊剂; 加速试验条件下放置6个月, 自微乳化给药系统的所有指标均未发生明显改变; 该自微乳化给药系统的在体小肠吸收速率常数 (以槲皮素计) 显著高于醋柳黄酮乙醇溶液 (P < 0.05); 以醋柳黄酮的混悬液为参比制剂, 自微乳化给药系统的大鼠灌胃给药相对生物利用度 (以槲皮素计) 为518%。
Abstract:The goal of the study is to evaluate the self-microemulsifying drug delivery system (SMEDDS) which enhances the oral bioavailability of the poorly water-soluble drug, total flavones of hippophae rhamnoides (TFH). It is orally administered for the protection of human cardiovascular system. Self-microemulsifying time, particle size, polydispersity index (PDI), morphological characterization, in vitro dispersity, stability, in situ intestinal absorption and relative bioavailability were investigated in detail. The TFH-SMEDDS rapidly formed fine oil-in-water microemulsions with 0.1 mol·L−1 hydrochloride solution, with average size of which was less than 40 nm, PDI was below 0.2, and the particles of which were observed round-shaped under transmission electron microscope. Almost 90% of TFH (expressed with quercetin) was released from SMEDDS within 20 min, which was remarkably higher than that from common capsules. The stability test showed the TFH-SMEDDS maintained stable in 6 months under accelerated condition. In situ absorption study demonstrated the absorption rate constant of TFH-SMEDDS (expressed with quercetin) was significantly higher than that of TFH in ethanolic solution (P < 0.05). The absorption of TFH from SMEDDS showed a 4.18-fold increase in relative bioavailability (expressed with quercetin) compared with that of the suspension. The results suggest that SMEDDS is a promising drug delivery system to increase the oral bioavailability of TFH.
下载: