Puttipipatkhachorn S, Yonemochi E, Oguchi T, Yamamoto K, Nakai Y
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Chem Pharm Bull (Tokyo). 1990 Aug;38(8):2233-6. doi: 10.1248/cpb.38.2233.
The effect of grinding on the dehydration of crystal water of theophylline has been studied. It was observed that the water content of theophylline hydrate decreased with increased grinding time. As the grinding time proceeded, the results of differential scanning calorimetry (DSC) indicated that crystal water of ground theophylline hydrate dehydrated in three steps at ca. 58, 44, and 17 degrees C, respectively. Powder X-ray diffraction study revealed that the crystal lattice of theophylline monohydrate collapsed by grinding, and part of the theophylline molecules subsequently rearranged the collapsed lattice to form theophylline anhydrate. The result of Fourier transformed infrared spectroscopy demonstrated that the hydrogen bonds between crystal water molecules and theophylline molecules were weakened or destroyed to some extent by grinding. It was supposed that crystal water in the ground theophylline hydrate might exist at least in three molecular states of different hydrogen-bonding. From DSC study, it was suggested that the ruptured hydrogen bonds of water molecules in the ground theophylline hydrate were strengthened after storage under 96.5% relative humidity at 30 degrees C.
研究了研磨对茶碱结晶水脱水的影响。观察到水合茶碱的含水量随研磨时间的增加而降低。随着研磨时间的延长，差示扫描量热法（DSC）结果表明，研磨后的水合茶碱结晶水分别在约58、44和17℃分三步脱水。粉末X射线衍射研究表明，一水合茶碱的晶格因研磨而坍塌，部分茶碱分子随后重新排列坍塌的晶格形成无水茶碱。傅里叶变换红外光谱结果表明，研磨在一定程度上削弱或破坏了结晶水分子与茶碱分子之间的氢键。推测研磨后的水合茶碱中的结晶水可能至少以三种不同氢键的分子状态存在。从DSC研究中可知，研磨后的水合茶碱中水分子断裂的氢键在30℃、相对湿度96.5%的条件下储存后得到加强。
