文献类型：期刊文献

英文题名：Study of Crystal Structures, Properties, and Form Transformations among a Polymorph, Hydrates, and Solvates of Apatinib

作者：Zhu, Bin[1];Fang, Xiaoxue[1];Zhang, Qi[3];Mei, Xuefeng[3];Ren, Guobin[1,2]

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 Chem Biol, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Shanghai Inst Mat Med, Pharmaceut Analyt & Solid State Chem Res Ctr, Shanghai 201203, Peoples R China

年份：2019

卷号：19

期号：5

起止页码：3060

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20191906879816);WOS:【SCI-EXPANDED(收录号:WOS:000466987600063)】；

基金：We thank the support from the National Natural Science Foundation of China (Grant Nos. 21776073 and 21576080); Natural Science Foundation of Shanghai (Grant No. 18ZR1447900).

语种：英文

外文关键词：Differential scanning calorimetry - X ray diffraction - Cell proliferation - Hydration - Endothelial cells - Thermogravimetric analysis - Amino acids - Single crystals

摘要：Apatinib (APA) is a targeted anti-neoplastic drug by inhibiting the vascular endothelial cell growth factor receptor of tyrosine kinase. Its therapeutic solid form, apatinib mesylate (ATM), is dissociated to APA neutral form instantaneously in aqueous solution. Hereby, we undertook a form screen of APA. A polymorph, two hydrates, and three solvates of APA were discovered and characterized by single-crystal X-ray diffraction, powder X-ray diffraction, Fourier transform infrared, and Raman spectroscopy. The relationships of phase transformation were assessed by differential scanning calorimetry, thermogravimetric analysis, and dynamic vapor sorption. Their thermal and hygroscopic stabilities were elaborated and found to be dependent on intermolecular interaction and crystal packing. Form A with superior solubility and stability appeared to be a promising alternative form to overcome the disproportionation of ATM.