目的 通过制备木犀草素纳米混悬剂（luteolin nano-suspension，LNS），以提高木犀草素的水溶性、溶出速度和小肠吸收。方法 采用微沉淀-高压匀质法制备LNS，以粒径、稳定性、多分散指数（polydispersity index，PDI）、ζ电位为考察指标，通过单因素筛选法对处方进行了初步优化。采用动态光散射法、差示扫描量热法（differential scanning calorimetry，DSC）和X射线粉末衍射（X-ray powder diffraction，XRPD）对纳米混悬剂进行表征，再采用桨法考察纳米混悬剂的体外溶出度，通过大鼠外翻肠模型实验，考察十二指肠、空肠、回肠和结肠不同部位的肠段对药物的吸收情况。结果 以维生素E聚乙二醇琥珀酸酯（D-α-tocopherol polyethylene glycol 1000 succinate，TPGS）作为稳定剂，稳定剂与药物质量比为1∶1时，可以制备得到粒径为210 nm左右，分散性和储存稳定性良好的LNS；其ζ电位在（−16.30±0.78）mV，透射电子显微镜图显示，LNS呈均匀分散的球形或椭圆形纳米粒；DSC和XRPD研究结果表明，制备成LNS后，没有改变木犀草素的结晶状态；而体外溶出实验结果表明，LNS可以明显提高木犀草素的过饱和溶出度；外翻肠实验结果证实，LNS虽然不能改变木犀草素在小肠中的吸收部位，但可以大幅度提高木犀草素的吸收速率和吸收量。结论 所制备的LNS可以显著提高药物的水溶性、溶出速度和小肠吸收，用于木犀草素口服给药的潜在剂型。

Objective To improve the water solubility, dissolution rate and small intestine absorption of luteolin by preparing luteolin nano-suspension. Methods Luteolin nano-suspension was prepared by microprecipitation-high pressure homogenization method, and the prescription was optimized by single factor screening method with particle size, stability, polydispersity index (PDI) and ζ potential as indexes. The nano-suspensions were characterized by dynamic light scattering, differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD), and then the dissolution rate of nano-suspensions in vitro was investigated by the oar method. The drug absorption in different parts of duodenum, jejunum, ileum and colon was investigated by rat valvaration intestinal model experiment. Results When D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) with good biocompatibility were selected as stabilizer and the ratio of stabilizer to drug was 1:1, luteolin nano-suspensions with particle size of about 210 nm and good dispersion and storage stability could be prepared. The ζ potential was (−16.30 ±0.78) mV. Transmission electron microscopy showed that the nano-suspension were uniformly dispersed spherical or elliptical nanoparticles. The results of DSC and XRPD showed that the crystal state of luteolin was not changed after preparation of nano-suspension. The results of in vitro dissolution experiment showed that nano-suspension could greatly improve the supersaturated dissolution of luteolin. The results of eversion experiment confirmed that although the nano-suspension could not change the absorption site of luteolin in the small intestine, it could greatly improve the absorption rate and amount of luteolin. Conclusion The results of this study showed that the water solubility, dissolution rate and small intestinal absorption of luteolin nano-suspension prepared in this study could be significantly improved, which could be used as a potential dosage form for oral administration of luteolin.

R283.6

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