双嘧达莫低共熔药物体系的筛选、表征及性质评价

Screening,characterization and property evaluation of dipyridamole eutectic drug system

采用双组分二元相图分析方法筛选难溶性药物双嘧达莫的低共熔体系,采用差示扫描量热法(DSC)、粉末X线衍射(PXRD)及傅里叶变换红外光谱(FTIR)技术对低共熔体系进行表征,测定低共熔体系中双嘧达莫的溶解度和溶出度等特性参数,并采用荧光淬灭和相溶解度法研究低共熔体系的增溶机制.结果表明:双嘧达莫与烟酰胺形成“V”型二元相图且具有单一熔点,证明二者形成了低共熔体系.该体系提高了双嘧达莫的溶解度和溶出速率,荧光光谱表明此体系中双嘧达莫与烟酰胺之间存在络合效应,相溶解度结果进一步说明二者之间形成了可溶性络合物,且物质的量比为1∶1,25、37℃时的络合常数分别为150.22、85.14 L/mol,该络合反应为吸热反应,升温不利于二者的络合.

Two component binary phase diagram analysis method was used to screen the eutectic system of the insoluble drug dipyridamole,and DSC,PXRD and FTIR techniques were used to characterize it.Subsequently,the solubility and dissolution of dipyridamole in the eutectic system were studied,and the solubilization mechanism of the eutectic system was studied by fluorescence quenching and phase solubility methods.The results showed that dipyridamole and nicotinamide formed a“V”type binary phase diagram with a single melting point,which proved that they formed a eutectic system.The solubility and dissolution rate of dipyridamole were improved by this system.Fluorescence spectra showed that there was a complexation effect between dipyridamole and nicotinamide.The phase solubility results further showed that a soluble complex was formed between the two,and the molar ratio of 1∶1.The complexation constants at 25℃and 37℃were 150.22 L/mol and 85.14 L/mol,respectively.The complexation reaction was endothermic,and the temperature rise was not conducive to the complexation of dipyridamole and nicotinamide.