双氢青蒿素羟丙基-β-环糊精包合物的制备与表征

采用正交设计法,以双氢青蒿素(dihydroartemisinin,DHA)和羟丙基-β-环糊精(hydroxypropyl-β-cyclodextrin,HP-β-CD)的摩尔比、包合温度和包合时间为考察因素,以包合物中DHA的包封产率和载药量为评价指标,优选包合工艺。用红外光谱法、差示扫描量热法和粉末X-射线衍射法表征制备的包合物,并采用分子模拟技术研究HP-β-CD包合DHA的可行性。结果显示,最佳包合条件:DHA与HP-β-CD的投料摩尔比为1∶5、包合温度为50℃、包合时间为1 h。红外光谱法、差示扫描量热法和粉末X-射线衍射分析均表明DHA与HP-β-CD形成了包合物,分子模拟结果揭示了DHA与HP-β-CD包合物具有较低的结合自由能和较高的溶剂可及表面积,HP-β-CD包合DHA可行,能显著提高DHA的水溶性。DHA-HP-β-CD包合工艺可行,为研究生产工艺提供了理论和实验依据。

Preparation and characterization of dihydroartemisinin/ hydroxypropyl-beta-cyclodextrin inclusion complex

To optimize the preparation method of the complex of dihydroartemisinin (DHA) included by hydroxypropyl-beta-cyclodextrin (HP-beta-CD), the molar ratio of DHA and HP-beta-CD, inclusion temperature and inclusion time were optimized by the orthogonal design method with the inclusion drug yield and drug loading as the evaluation indexes. The IR spectrum, DSC and PXRD analyses were employed to characterize the complex and the molecular simulation was processed to investigate the tendency of complex formation. The optimized molar ratio of DHA and HP-beta-CD was 1 : 5, and the optimized preparation was performed under 50 degrees C for 1 h. The IR spectrum, DSC and PXRD analyses indicated the formation of the complex. The low binding free energy and the high solvent accessible surface obtained by molecular simulation showed that DHA could be included by HP-beta-CD and its solubility could be improved significantly. In conclusion, the optimized conditions for the preparation of DHA-HP-beta-CD complex provide a theoretical and experimental basis for further scale-up research.