药物共晶可以改善药物活性成分的物理化学性质,这一特性使其在改善药物性质特征方面具有很大的应用潜力.本文采用固体研磨的方法制备由吡拉西坦(Piracetam)和3-羟基苯甲酸(3-Hydroxybenzoic acid,3HBA)作为原料药的药物共晶体,应用傅里叶变换红外(FTIR)、拉曼(Raman)和太赫兹(THz)光谱方法对研磨获得的共晶样品进行表征,并对两原料药和共晶体的分子振动模式进行归属.FTIR,Raman和THz光谱均表明共晶体的振动模式与原料药有着显著的区别.另外,使用Raman和THz光谱技术深入分析共晶体形成的动态过程,实验结果表明在研磨的最初几分钟反应迅速,之后共晶体形成的反应速率变得缓慢,在研磨35 min之后,共晶体的形成过程结束.这一结果为药学领域中有关药物共晶形成的实时监控及其定量分析提供了理论依据和一种有效的技术方法。

Pharmaceutical cocrystal can improve physical and chemical properties of active pharmaceutical ingredient(API),meanwhile this feature has shown great potential in improving the pharmaceutical’s properties and characteristics.In this study,cocrystal formation between piracetam and 3-hydroxybenzoic acid(3HBA) using grinding method has been characterized by Fourier transform infrared(FTIR),Raman and terahertz(THz) spectroscopical techniques.The vibrational modes of different motions are obtained by the assignment of the peaks in the spectra of the starting materials and the cocrystal components.FTIR,Raman and THz spectroscopical results show that the vibrational modes of the cocrystal are different from those of the starting materials.In addition,the dynamic process of the above cocrystal formation is investigated in-depth with Raman and THz spectra.Piracetam-3HBA cocrystal is formed pretty fast in first several minutes,and then the formation rate becomes slow.After 35 minutes,such formation process has been completed.The results offer the theoretical benchmark and unique means for real-time monitoring pharmaceutical cocrystal formation and also the corresponding quantitative analysis in the pharmaceutical field.