不同稳定剂对槲皮素纳米晶体外溶出及大鼠体内口服药动学的影响  

Effect of different stabilizers on in vitro dissolution and oral pharmacokinetics of quercetin nanocrystals in rats

作　　者：胡菲 沈成英 申宝德 朱卫丰[1] 袁海龙 HU Fei;SHEN Cheng-ying;SHEN Bao-de;ZHU Wei-feng;YUAN Hai-long(College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Department of Pharmacy,Air Force Medical Center,PLA,Beijing 100142,China)

机构地区：[1]江西中医药大学药学院,江西南昌330004 [2]空军特色医学中心药学部,北京100142

出　　处：《中草药》2021年第21期6485-6492,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81803741);国家自然科学基金资助项目(81873092)。

摘　　要：目的制备不同稳定剂修饰的槲皮素纳米晶(quercetin nanocrystals,QT-NCs),探讨稳定剂种类对QT-NCs体外溶出和口服药动学的影响。方法分别以羟丙甲纤维素E15(HPMC-E15)、普朗尼克F127(F127)和甘草酸(glycyrrhizinic acid,GL)为稳定剂,采用介质研磨法分别制备3种QT-NCs,即QT-NCs/F127、QT-NCs/HPMC E15、QT-NCs/GL,并进行形态、晶型表征,考察其体外溶出及口服药动学。结果3种稳定剂修饰的QT-NCs的粒径均约为200 nm,PDI约为0.20,扫描电子显微镜显示QT-NCs均呈短棒状及不规则的颗粒状;X射线衍射结果显示QT-NCs均以结晶态存在;体外溶出结果显示,与槲皮素原料药相比,3种稳定剂修饰的QT-NCs的累积溶出度均明显提高,且30 min内累积溶出率QT-NCs/F127(74.90%)>QT-NCs/GL(59.30%)>QT-NCs/HPMC E15(53.65%);药动学结果显示,与槲皮素原料药相比,3种稳定剂修饰的QT-NCs口服生物利用度均显著提高,且AUC_(0~t)呈如下顺序:QT-NCs/E15(78.09±6.05)mg·h/L>QT-NCs/GL(61.72±7.59)mg·h/L>QT-NCs/F127(49.94±9.30)mg·h/L。结论纳米晶能够显著改善槲皮素的体外溶出及口服生物利用度,稳定剂种类对QT-NCs的体外溶出和口服药动学有显著影响。Objective To prepare quercetin nanocrystals(QT-NCs)modified by different stabilizers and explore the effects of different stabilizers on in vitro dissolution and oral pharmacokinetics of QT-NCs.Methods QT-NCs stabilized by three types of stabilizers including hydroxypropyl methyl cellulose E15(HPMC E15),pluronic F127(F127),and glycyrrhizin acid(GL)were respectively prepared by wet media milling method,namely QT-NCs/HPMC E15,QT-NCs/F127,and QT-NCs/GL,and then characterized by morphology and crystal state.Their dissolution in vitro and oral pharmacokinetics were also investigated.Results The particle size of QT-NCs modified by three types of stabilizers were about 200 nm with PDI was about 0.20.Scanning electron microscopy showed that QT-NCs were all short rods and irregular particles,while X-ray diffraction results showed that QT-NCs existed in crystalline state.The in vitro dissolution results showed that the cumulative dissolution of QT-NCs modified by three types of stabilizers were significantly improved as compared to QT,and the cumulative dissolution rate within 30 min was in an order of QT-NCs/F127(74.90%)>QT-NCs/GL(59.30%)>QT-NCs/HPMC E15(53.65%).The pharmacokinetic results showed that,compared with quercetin,the oral bioavailability of QT-NCs modified with three types of stabilizers were significantly enhanced,and their AUC_(0-t)was in the following order:QT-NCs/E15(78.09±6.05)mg∙h/L>QT-NCs/GL(61.72±7.59)mg∙h/L>QT-NCs/F127(49.94±9.30)mg∙h/L.Conclusion NCs can significantly improve the in vitro dissolution and oral bioavailability of poorly soluble drugs,and the stabilizer’s types significantly affect the in vitro dissolution and oral pharmacokinetics of NCs.

关 键 词：纳米晶 稳定剂 槲皮素 体外溶出 药动学 羟丙甲纤维素 普朗尼克 甘草酸 

分 类 号：R283.6[医药卫生—中药学]