药学学报, 2021, 56(2): 585-592
引用本文:
吴秀娟, 庞遵霆, 杨思彤, 严梦梦, 高缘. 共无定形技术改善葛根素水溶性及增溶机制研究[J]. 药学学报, 2021, 56(2): 585-592.
WU Xiu-juan, PANG Zun-ting, YANG Si-tong, YAN Meng-meng, GAO Yuan. Mechanistic study on the solubility enhancement of puerarin by coamorphous technology[J]. Acta Pharmaceutica Sinica, 2021, 56(2): 585-592.

共无定形技术改善葛根素水溶性及增溶机制研究
吴秀娟, 庞遵霆, 杨思彤, 严梦梦, 高缘
中国药科大学中药学院, 江苏 南京 211198
摘要:
葛根素(PUE)为异黄酮类成分,具有广泛的药理活性,但其低水溶性限制了其口服固体制剂的开发。本研究以烟酰胺(NIC)为配体通过减压旋蒸法制备了PUE-NIC共无定形体系,同时联合粉末X-射线衍射(PXRD)、差示扫描量热法(DSC)和红外光谱(FT-IR)等多种手段对其进行表征,并对其溶出行为及增溶机制进行了系统的研究。结果表明,PUE-NIC共无定形仅存在单一的玻璃化转变温度(35.1℃),为单一均相二元体系。与PUE晶体相比,在溶出过程中,共无定形不仅发生“液-液相分离”(LLPS)现象,PUE与NIC还可形成摩尔比为1:1与1:2的Ap型络合物,这有利于显著增加PUE的溶解度,并能维持长时间的药物过饱和态优势,有利于药物吸收。
关键词:    葛根素      烟酰胺      溶出      液-液相分离      络合     
Mechanistic study on the solubility enhancement of puerarin by coamorphous technology
WU Xiu-juan, PANG Zun-ting, YANG Si-tong, YAN Meng-meng, GAO Yuan
School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
Puerarin (PUE), as an isoflavone component, has a wide range of pharmacological activities, while its poorly aqueous solubility limits the development of solid oral dosage forms. In this study, PUE along with nicotinamide (NIC) were prepared into the coamorphous system by solvent-evaporation method and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FT-IR). In addition, its dissolution behavior and solubilization mechanism were also investigated. PUE-NIC coamorphous was a single homogeneous binary system, with a single glass transition temperature at 35.1℃. In comparison to crystalline PUE, during the dissolution process, coamorphous PUE-NIC not only exhibited the "liquid-liquid phase separation" (LLPS) phenomenon, but the formation of Ap type complexation (1:1 and 1:2) between PUE and NIC molecules was also verified, which significantly improved the solubility of PUE and prolonged the supersaturation time, and would benefit its absorption.
Key words:    pueparin    nicotinamide    dissolution    liquid-liquid phase separation    complexation   
收稿日期: 2020-07-28
DOI: 10.16438/j.0513-4870.2020-1261
基金项目: 国家自然科学基金资助项目(81703712,81773675,81873012);中国药科大学“双一流”建设(CPU2018GY11,CPU2018GY27).
通讯作者: 高缘,Tel/Fax:86-25-83379418,E-mail:newgaoyuan@163.com
Email: newgaoyuan@163.com
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