Suzuki Nobuyuki, Kasahara Ko, Hasegawa Hirokazu, Kawasaki Takao
Product Development Laboratories, Sankyo Co., Ltd, 2-58, Hiromachi 1-chome, Shinagawa-ku, Tokyo 140-8710, Japan.
Int J Pharm. 2002 Nov 6;248(1-2):71-80. doi: 10.1016/s0378-5173(02)00430-1.
Troglitazone, an oral antidiabetic agent, is an equal mixture of four stereoisomers involving two chiral centers. In the present study, the physical property of troglitazone were investigated. The solid state of troglitazone drug substance is characterized as a simple physical mixture of two diastereomers, as shown by the two endothermic peaks caused by the melting of the RR/SS and the RS/SR forms by differential scanning calorimetry (DSC). In addition, the powder X-ray diffraction pattern includes peaks resulting from both the RR/SS and the RS/SR forms. The water adsorption of troglitazone drug substance is due to the presence of the RR/SS diastereomer, which adsorbs water as a monohydrate. The solubility of troglitazone and the diastereomers were increased and the solubility ratios of the stereoisomers were changed by quenching. Troglitazone was proved to be stable against heat and humidity by the ratio of the stereoisomers and from the solid state form indicated by the DSC results.
曲格列酮是一种口服抗糖尿病药物，是一种包含两个手性中心的四种立体异构体的等量混合物。在本研究中，对曲格列酮的物理性质进行了研究。曲格列酮原料药的固态特征为两种非对映异构体的简单物理混合物，差示扫描量热法（DSC）显示，RR/SS和RS/SR形式的熔融导致两个吸热峰。此外，粉末X射线衍射图谱包括RR/SS和RS/SR形式产生的峰。曲格列酮原料药的水吸附归因于RR/SS非对映异构体的存在，该异构体以一水合物形式吸附水。通过骤冷提高了曲格列酮及其非对映异构体的溶解度，并改变了立体异构体的溶解度比。根据立体异构体的比例以及DSC结果表明的固态形式，证明曲格列酮对热和湿度稳定。
