2种制备方法用于提高槲皮素纳米混悬剂生物利用度的研究  

Two preparation methods used to improve the bioavailability of quercetin nano-suspension

作　　者：郑光艳 罗永明 刘泽梅 车鑫 王立红 ZHENG Guang-yan;LUO Yong-ming;LIU Ze-mei;CHE Xin;WANG Li-hong(Guizhou University of Traditional Chinese Medicine,Guiyang 550000,China)

机构地区：[1]贵州中医药大学,贵阳550000

出　　处：《中国新药杂志》2024年第23期2529-2536,共8页Chinese Journal of New Drugs

基　　金：贵州省自然科学基金项目(贵州省科技基金-ZK[2021]-524);贵州省卫健委科技基金资助项目(GZWKJ2022-233)。

摘　　要：目的:比较微流体法与反溶剂沉淀法制备的槲皮素纳米晶(quercetin nanocrystals,QNCs)的各项性质。方法:采用微流体法和反溶剂沉淀法分别制备QNCs;通过贝克曼粒径仪、透射电子显微镜、溶出度仪、差示扫描量热计和X射线粉末衍射仪表征2种方法制备的QNCs;采用HPLC法研究2种方法制备的QNCs在大鼠体内的药动学差异。结果:2种方法制备的QNCs呈类球型,均为无定形状态;微流体法制备的QNCs平均粒径为(78.03±4.97)nm,反溶剂沉淀法制备的QNCs平均粒径为(554.25±84.75)nm;60 min时2种方法制备的QNCs的累积溶出率都超过了45%,而槲皮素却仅溶出了6.8%;微流体法制备QNCs的AUC_(0-∞)为185.711 mg·h·L^(-1),反溶剂沉淀法制备QNCs的AUC_(0-∞)为86.331 mg·h·L^(-1)。结论:2种方法制备的QNCs均可以显著提高其溶出度及口服生物利用度,微流体法制备的QNCs口服生物利用度更好。该研究结果表明,微流体技术在制备难溶性药物纳米晶并提高其生物利用度方面具有应用潜力。Objective:To compare the properties of quercetin nanocrystals(QNCs)prepared by microfluidic and antisolvent precipitation methods.Methods:QNCs were prepared by microfluidic and antisolvent precipitation methods,respectively.QNCs prepared by both methods were characterized by Beckman particle sizer,transmission electron microscopy,dissolution meter,differential scanning calorimetry(DSC)and X-ray powder diffractometer(XRPD).The pharmacokinetic differences of QNCs prepared by two methods in rats were studied by HPLC.Results:QNCs prepared by both methods were sphere-like and amorphous.The average particle size of QNCs prepared by the microfluidic method was(78.03±4.97)nm,and that prepared by antisolvent precipitation method was(554.25±84.75)nm.The cumulative dissolution rate of QNCs prepared by both methods exceeded 45%at 60 min,whereas QCT dissolved only 6.8%.AUC_(0-∞)of QNCs prepared by the microfluidic method was 185.711 mg·h·L^(-1),and that by antisolvent precipitation method was 86.331 mg·h·L^(-1).Conclusion:The preparation of QNCs by the two methods can significantly improve the dissolution and oral bioavailability of quercetin,while a better oral bioavailability was obtained by microfluidic method.The results showed that microfluidic technology had a potential in preparing insoluble drug nanocrystals and improving the bioavailability of insoluble drugs.

关 键 词：槲皮素 纳米晶 反溶剂沉淀法 微流体法 体内药动学 

分 类 号：R944.1[医药卫生—药剂学]