共无定形技术改善葛根素水溶性及增溶机制研究

Mechanistic study on the solubility enhancement of puerarin by coamorphous technology

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。

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 at35.1℃.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.