Chemical Mapping of Pharmaceutical Cocrystals Using Terahertz Spectroscopic Imaging
Chemical Mapping of Pharmaceutical Cocrystals Using Terahertz Spectroscopic Imaging
复制标题
DOI：
10.1021/ac302852n
复制
发表时间：
2013-02-19
影响因子：
7.4
通讯作者：
Ueno, Yuko
中科院分区：
文献类型：
--
作者：
Charron, Danielle M.;Ajito, Katsuhiro;Ueno, Yuko
太赫兹 (THz) 光谱成像是一种很有前途的技术，可用于区分分子组成相似但晶体结构不同的药物。通过共结晶等方法改变药物的晶体结构来控制物理化学性质，例如生物利用度。共晶体是具有与其纯组分不同的晶体结构的分子复合物。需要一种识别这些替代形式的二维分布的技术。在这里，我们首次展示了共晶体的太赫兹光谱成像。在低温下测量的咖啡因-草酸共晶的太赫兹光谱表现出尖锐的峰，使我们能够可视化不均匀片剂中的共晶分布。使用太赫兹光谱数据清楚地识别了共晶分布，并且计算出的共晶浓度与已知总浓度的误差为 0.3-1.3% w/w。根据这一结果，太赫兹光谱定量共晶的化学图谱，并为研究人员和药物开发商提供了一种新的分析工具。
Terahertz (THz) spectroscopic imaging is a promising technique for distinguishing pharmaceuticals of similar molecular composition but differing crystal structures. Physicochemical properties, for instance bioavailability, are manipulated by altering a drug's crystal structure through methods such as cocrystallization. Cocrystals are molecular complexes having crystal structures different from those of their pure components. A technique for identifying the two-dimensional distribution of these alternate forms is required. Here we present the first demonstration of THz spectroscopic imaging of cocrystals. THz spectra of caffeine-oxalic acid cocrystal measured at low temperature exhibit sharp peaks, enabling us to visualize the cocrystal distribution in nonuniform tablets. The cocrystal distribution was clearly identified using THz spectroscopic data, and the cocrystal concentration was calculated with 0.3-1.3% w/w error from the known total concentration. From this result, THz spectroscopy quantitative chemical mapping of cocrystals and offers researchers and drug developers a new analytical tool.