[关键词]
[摘要]
目的 制备柚皮素纳米晶体,并进行药剂学性质研究。方法 采用介质研磨-喷雾干燥法制备柚皮素纳米晶体;用马尔文激光粒度测定仪测定柚皮素纳米晶体的平均粒径和多分散指数(PDI);用扫描电镜观察晶体形态;用X-射线粉末衍射法、差示扫描量热法及傅里叶红外光谱法考察晶型和化学结构是否变化;用转篮法测定纳米晶体的溶出度。结果 柚皮素纳米晶体平均粒径为(400.7±6.9)nm,PDI为0.23;制备成纳米晶体后,柚皮素晶型及化学结构未发生明显变化;溶解度明显提高(在pH 1.2盐酸溶液和pH 4.5磷酸盐溶液中,P<0.01;在pH 6.8磷酸盐溶液和水中,P<0.05);溶出度明显改善,药物溶出参数T50、Td(药物溶出50%和63.2%所需时间)显著减小(P<0.01)。结论 优选的柚皮素纳米晶体制备工艺稳定可行,制备的纳米晶体粒径小且较为均匀,纳米化后柚皮素仍为结晶态,溶解和溶出得到明显改善,这为柚皮素进一步开发提供了依据。
[Key word]
[Abstract]
Objective To prepare and investigate the pharmaceutical characteristics of naringenin (NAR) nanocrystals. Methods NAR nanocrystals were prepared by media milling combined with spray drying method. The mean particle size and polydispersity index (PDI) of NAR nanocrystals were analyzed by Malvern Zetasizer. The morphology of the nanoparticles was observed by scanning electron microscope (SEM). The crystalline state and the chemical structure of NAR before and after nanonization were characterized using X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and fourier transform infrared spectrometry (FT-IR). Dissolution rate of NAR before and after nanonization were studied using rotary basket method. Results The mean particle size of NAR nanocrystals was (400.7 ±6.9) nm, and PDI value was 0.23. After nanonization, the crystalline state and chemical structure of NAR were not obviously altered, and the solubility was significantly increased (in pH 1.2 hydrochloric acid solution and pH 4.5 phosphate solution, P < 0.05; in pH 6.8 phosphate solution and water, P < 0.01). The dissolution was obviously improved, T50 and Td were visibly decreased (P < 0.01). Conclusion The optimized process is stable and feasible for the preparation of NAR nanocrystals. NAR nanocrystals have a tiny and uniform particle size. After nanonization, NAR was still crystalline, the solubility and the dissolution were significantly increased, which can provide the basis for the further development of NAR.
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[基金项目]
河北省自然科学基金资助项目(H2014208151);河北省高等学校科学技术研究项目(ZD2014079)