文献类型：期刊文献

英文题名：Influence Factor Investigation on the Solution-Mediated Polymorphic Transformation of Baricitinib Phosphate

作者：Hong, Minghuang[1];Guo, Sai[1];Wang, Kai[1];Ma, Lei[2];Ren, Guobin[1]

机构：[1]East China Univ Sci & Technol, Sch Pharm, Lab Pharmaceut Crystal Engn & Technol, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China

年份：2018

卷号：644

期号：15

起止页码：849

外文期刊名：ZEITSCHRIFT FUR ANORGANISCHE UND ALLGEMEINE CHEMIE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000441762600008)】；

基金：This work was supported by National Natural Science Foundation of China (No. 21576080) and the Fundamental Research Funds for the Central Universities (No. 222201714036).

语种：英文

外文关键词：Baricitinib phosphate; Polymorphism; Solution-mediated phase transformation; Crystal engineering

摘要：Baricitinib is the only once-daily oral selective Janus kinase (JAK1 and JAK2) inhibitor, currently in late-stage clinical development for inflammatory and autoimmune diseases. Two most developable forms of Baricitinib phosphate, form A and form X, were fully characterized using powder X-ray diffraction (PXRD), differential scanning calorimetry and thermogravimetric analysis. Furthermore, the solution-mediated polymorphic transformation from form A to form X was investigated by monitoring and identifying the transformation process through focused beam reflectance measurement probe combined with PXRD and UV/Vis spectrophotometer. The influence factors, such as system temperature, solvent composition, suspension density, stirring rate, and additives were studied. Results showed that higher temperature, larger mole fraction of acetonitrile, larger suspension density, faster stirring rate and some specific additives could accelerate the solution-mediated phase transformation process to some extent.