自微乳化给药系统提高赤芍总苷的生物利用度(英文)

Enhanced bioavailability of total paeony glycoside by self-microemulsifying drug delivery system

赤芍总苷是从传统中药赤芍中提取纯化得到的有效部位,它具有许多的生物学活性。然而,由于其生物利用度很低,目前上市的赤芍总苷制剂很少。本研究将溶解性差的赤芍总苷制备成自微乳化给药系统以提高其生物利用度。通过构建三元相图,得到最优的处方组成:赤芍总苷18.70%、油酸乙酯16.27%、聚氧乙烯氢化蓖麻油43.34%和乙二醇单乙基醚21.73%。同时评价了赤芍总苷的理化性质,包括形态学特征、粒径、zeta电位、乳化时间及溶出度。结果显示,赤芍总苷自微乳化制剂稳定性良好,在4种不同的溶出介质中(0.1 mol.L-1 HCl、pH 6.8磷酸盐缓冲液、pH 7.4磷酸盐缓冲液和水)的溶出速率较快。通过赤芍总苷自微乳化制剂与赤芍总苷混悬液在大鼠体内药代动力学实验结果比较,显示其相对生物利用度为152%,表明自微乳化给药系统可以提高赤芍总苷的生物利用度。

Total paeony glycoside （TPG） is extracted and purified from a traditional Chinese herbal medicine It has many biological and pharmacological activities. However, there are few dosage forms of TPG in the market because of its low bioavailability. Self-microemulsifying drug delivery system （SMEDDS） is a vital tool in solving low bioavailability of poor absorption drugs. So the objective of this study is to develop a new TPG-SMEDDS for the oral delivery of poorly soluble TPG. Through the construction of pseudo-ternary phase diagrams, the optimum prescription was obtained, which consisted of 18.70% TPG, 16.27% ethyl oleate as oil, 43.34% Cremophor RH40 as surfactant and 21.73% Transcutol P as cosurfactant. The characterizations of TPG-SMEDDS including morphological characterization, droplet size, zeta-potential, emulsification time, and dissolution study of TPG-SMEDDS were evaluated. The results showed that TPG-SMEDDS is stable and its release rate is high in four different media （0.1 mol.L-1 HCI, pH 6.8 PBS, pH 7.4 PBS, and water）. The relative bioavailability of SMEDDS was dramatically enhanced in an average of 1.52-fold that of TPG-suspension. It is concluded that the bioavailability of TPG is enhanced greatly by SMEDDS.