Chen Ying, Li Gao, Wu Xianggen, Chen Zhiyu, Hang Jiangeng, Qin Bei, Chen Song, Wang Ruihua
Department of Pharmacy, Wuhan General Hospital, Wuhan 430070, P. R. China.
Biol Pharm Bull. 2008 Jan;31(1):118-25. doi: 10.1248/bpb.31.118.
A new self-microemulsifying drug delivery system (SMEDDS) has been developed to increase the solubility, dissolution rate and oral bioavailability of vinpocetine (VIP), a poor water-soluble drug. The formulations of VIP-SMEDDS were optimized by solubility assay, compatibility tests, and pseudo-ternary phase diagrams analysis. The optimal ratio in the formulation of SMEDDS was found to be Labrafac : oleic acid : Cremophor EL : Transcutol P=40 : 10 : 40 : 10 (w/w). The average particle diameter of VIP was less than 50 nm. In vitro dissolution study indicated that the dialysis method in reverse was better than the ultrafiltration method and the dialysis method in simulating the drug in vivo environment. Comparing with VIP crude drug power and commercial tablets, (-)VIP-SMEDDS caused a 3.4- and 2.9-fold increase in the percent of accumulated dissolution at 3 h. Further study on the absorption property of VIP-SMEDDS employing in situ intestine of rats demonstrated that VIP in SMEDDS could be well-absorbed in general intestinal tract without specific absorption sites. In addition, the developed SMEDDS formulations significantly improved the oral bioavailability of VIP in rats. Relative bioavailability of (-)VIP-SMEDDS and (+)VIP-SMEDDS increased by 1.85- and 1.91-fold, respectively, in relative of VIP crude powder suspension. The mechanisms of enhanced bioavailability of VIP might contribute to the improved release, enhanced lymphatic transport, and increased intestinal permeability of the drug.
一种新型的自微乳化药物递送系统（SMEDDS）已被开发出来，用于提高长春西汀（VIP）的溶解度、溶解速率和口服生物利用度，长春西汀是一种水溶性差的药物。通过溶解度测定、相容性试验和伪三元相图分析对VIP-SMEDDS的配方进行了优化。发现SMEDDS配方中的最佳比例为Labrafac：油酸：聚氧乙烯蓖麻油EL：肉豆蔻酸异丙酯=40：10：40：10（w/w）。VIP的平均粒径小于50nm。体外溶出度研究表明，反向透析法优于超滤法，且模拟药物体内环境的透析法更佳。与VIP原料药粉和市售片剂相比，（-）VIP-SMEDDS在3小时时的累积溶出百分比提高了3.4倍和2.9倍。采用大鼠原位肠对VIP-SMEDDS的吸收特性进行的进一步研究表明，SMEDDS中的VIP在整个肠道中均可被良好吸收，无特定吸收部位。此外，所开发的SMEDDS制剂显著提高了VIP在大鼠体内的口服生物利用度。与VIP粗粉混悬液相比，（-）VIP-SMEDDS和（+）VIP-SMEDDS的相对生物利用度分别提高了1.85倍和1.91倍。VIP生物利用度提高的机制可能有助于药物释放的改善、淋巴转运的增强和肠道通透性的增加。
