Pan Yinhu, Xiao Tong, Wang Yan, Pan Zhiying, Du Shichao, Xue Fumin
School of Pharmaceutical Sciences (Shandong Analysis and Test Center), Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, China.
Molecules. 2024 Oct 4;29(19):4696. doi: 10.3390/molecules29194696.
Axitinib (AXTN) is an oral tyrosine kinase inhibitor for the treatment of early to advanced renal cell carcinoma. In this work, solvates of AXTN were prepared in five solvents and subjected to desolvation treatment. The crystal form A of AXTN can form solvates in acetonitrile, DMF, acetic acid, acetic acid + water, and methanol. Different ratios of AXTN and acetic acid will form different products (solvate or directly crystallized into another crystal form (form IV)). The characterization results of thermal analyses confirmed the types of the five solvates. The obtained solvates were desolvated using methods of solid-phase desolvation (heating, exposure to solvent steam, microwave) and solvent-mediated phase transformation (SMPT). The desolvated solids were characterized by PXRD, TGA, DSC, FT-IR, and SEM, and it was ultimately inferred that a new crystal form (form Z) of AXTN could be formed after desolvation. In addition, the solvates obtained in this work experienced mutual transformation via SMPT, which depends on the type of solvents or mixed solvents. The phase transformations of different solid forms were summarized. This study is instructive for exploring solvates and polymorphs of AXTN and understanding phase transitions under different environments.
阿昔替尼（AXTN）是一种用于治疗早期至晚期肾细胞癌的口服酪氨酸激酶抑制剂。在本研究中，在五种溶剂中制备了AXTN的溶剂化物，并进行了去溶剂化处理。AXTN的晶型A可在乙腈、N,N-二甲基甲酰胺、乙酸、乙酸+水和甲醇中形成溶剂化物。AXTN与乙酸的不同比例会形成不同的产物（溶剂化物或直接结晶为另一种晶型（晶型IV））。热分析的表征结果证实了这五种溶剂化物的类型。使用固相去溶剂化方法（加热、暴露于溶剂蒸汽、微波）和溶剂介导的相变（SMPT）对所得溶剂化物进行去溶剂化处理。通过粉末X射线衍射（PXRD）、热重分析（TGA）、差示扫描量热法（DSC）、傅里叶变换红外光谱（FT-IR）和扫描电子显微镜（SEM）对去溶剂化后的固体进行表征，最终推断AXTN去溶剂化后可形成一种新的晶型（晶型Z）。此外，本研究中获得的溶剂化物通过SMPT发生相互转化，这取决于溶剂或混合溶剂的类型。总结了不同固体形式的相变情况。本研究对于探索AXTN的溶剂化物和多晶型物以及理解不同环境下的相变具有指导意义。
