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

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%。

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.