Suzuki Nobuyuki, Kasahara Ko, Watanabe Yoshiaki, Kinoshita Suzue, Hasegawa Hirokazu, Kawasaki Takao
Product Development Laboratories, Sankyo Co., Ltd., Shinagawa-ku, Tokyo, Japan.
Drug Dev Ind Pharm. 2003 Aug;29(7):805-12. doi: 10.1081/ddc-120021780.
Rapid and slow crystallization methods (A and B) were applied for troglitazone, an equal mixture of four stereoisomers. Differences in the powder x-ray diffractometry patterns and hygroscopic patterns were observed among the samples crystallized by these methods, suggesting that troglitazone has solid-state variation. In this article, troglitazone recrystallized by method A was evaluated to clarify its structural characteristics and physical property. The crystal structure of predried troglitazone recrystallized by method A was proved to be a dihydrate. By drying, it changed reversibly to an anhydrate, which is the same structure as the RS/SR form, keeping the same enantiomer ratio. The solubility of the troglitazone by method A higher than that by method B at all enantiomer levels. But making the troglitazone amorphous equalized the enantiomeric solubilities of the substances by both methods as well as increased the intrinsic solubilities. Troglitazone by both methods was proved to be stable and retained the ratio of the stereoisomers.
快速和慢速结晶方法（A和B）应用于曲格列酮，它是四种立体异构体的等量混合物。通过这些方法结晶的样品之间观察到粉末X射线衍射图谱和吸湿图谱存在差异，这表明曲格列酮存在固态变化。在本文中，对通过方法A重结晶的曲格列酮进行了评估，以阐明其结构特征和物理性质。通过方法A重结晶的预干燥曲格列酮的晶体结构被证明是二水合物。通过干燥，它可逆地转变为无水合物，其结构与RS/SR形式相同，保持相同的对映体比例。在所有对映体水平上，通过方法A得到的曲格列酮的溶解度高于通过方法B得到的。但是将曲格列酮制成无定形会使两种方法得到的物质的对映体溶解度相等，同时也增加了固有溶解度。两种方法得到的曲格列酮都被证明是稳定的，并且保留了立体异构体的比例。
