Studies On SEDDS Of Extract From Angelica Sinensis And Ligusticum Chuanxiong

The recipe, comprised of Angelica sinensis and Ligusticum chuanxiong, is one of the important ’Duiyao’, which was proved to have a good function on treating ischemic cerebrovascular diseases on clinic for their active parts of ferulic acid and Z-ligustilide.It is hard for ferulic acid and Z-ligustilide to be absorbed because of their high hydrophilicity and high liposolubility respectively. Therefore, Self-Emulsifying Drug Delivery System（SEDDS）was selected as the carrier to promote the absorption and enhance the bioavailability of them in this paper.There are two focal points in this study. First, ferulic acid was complexed with phospholipid in order to enhance the liposolubility to meet the demand of preparing SEDDS. Then, SEDDS of ferulic acid and Z-ligustilide was optimized by screening the type and ratio of emulsifier and cosurfactant using pseudo-ternary phase diagrams.Firstly, an HPLC method was set up to determine the content of ferulic acid and Z-ligustilide in the preparation simultaneously, which shows good specificity, sensitivity and reproducibility.Secondly, ferulic acid-phospholipid complex was prepared with the nonaqueous solvent-vacuum drying method. The influence of preparation method and formulation factors on the complex ratio was investigated to pick out the best craft, such as solvent, reaction time, temperature and so on. Meanwhile, IR and X-ray diffraction analysis were used to confirm that the complex was formed. The apparent partition coefficient of the phytosome indicated that the liposolubility of ferulic acid was elevated from 10.92 to 30.72, which also suggested the formation of the complex.Thirdly, the solubility of ferulic acid-phospholipid complex in various excipients was also investigated. According to the results, the pseudo-ternary phase diagrams of two kinds of systems were studied. Taking the appearance of SEDDS, the emulsified time, and the appearance of emulsion aider self-emulsifying as indexes, the best formulation was screened as follows, ferulic acid-phospholipid complex: volatile oil: Cre EL-40: Propylene glycol= 12.1:30.0:48.2:9.7（mass value）. Effects of the temperature, dispersed intension, pH and volume of the media on the self-emulsifying efficiency were also studied, and the quality of SEDDS was evaluated. We also studied the drug release by bulk-equilibrium reverse dialysis bag technique.At last, the pharmacokinetics of SEDDS and commercial drop pills in rats was investigated. Compared with the drop pills, the T_max of SEDDS was shorter and the C_max was larger. The relative bioavailability was calculated to be 142.6％（ferulic acid）and 181.6％（ligustilide）respectively, which showed that the SEDDS prepared achieved the objective of the experimental design.