文献类型：期刊文献

英文题名：Stable Cocrystals and Salts of the Antineoplastic Drug Apatinib with Improved Solubility in Aqueous Solution

作者：Zhu, Bin[1];Wang, Jian-Rong[3];Zhang, Qi[3];Li, Meiqi[3,4];Guo, Chunyang[1];Ren, Guobin[1,2];Mei, Xuefeng[3]

机构：[1]East China Univ Sci & Technol, Lab Pharmaceut Crystal Engn & Technol, Sch Pharm, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Chinese Acad Sci, Pharmaceut Analyt & Solid State Chem Res Ctr, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;[4]Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China

年份：2018

卷号：18

期号：8

起止页码：4701

外文期刊名：CRYSTAL GROWTH & DESIGN

收录：;EI(收录号：20182805538388);WOS:【SCI-EXPANDED(收录号:WOS:000440956100060)】；

基金：We acknowledge the support from the National Natural Science Foundation of China (Grant Nos. 21576080 and 21776073), Youth Innovation Promotion Association of CAS (Grant No. 2016257), and CAS Key Technology Talent Program, and SANOFI-SIBS Scholarship for funding.

语种：英文

外文关键词：Infrared spectroscopy - Single crystals - Solubility - X ray diffraction - Cell proliferation - Drug delivery - Endothelial cells - Amino acids - Differential scanning calorimetry

摘要：Apatinib (APA) belongs to the targeted antineoplastic family of drugs by inhibiting the vascular endothelial cell growth factor receptor (VEGFR-2) of tyrosine kinase. APA encounters poor aqueous solubility problems, and its therapeutic dosage form, apatinib mesylate (ATM), is unstable and dissociates completely to APA in aqueous solution. Here, we synthesized and evaluated three new cocrystals of APA with adipic acid (APA + ADA), sebacic acid (APA + SEA), and D/L-mandelic acid (APA + D/L-MA), and four new salts with succinic acid (APA + SUA-H2O), salicylic acid (APA + SA), 1-hydroxy-2-naphthoic acid (APA + HNA), and saccharin (APA + SAC). All the solid forms were characterized by powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and dynamic vapor sorption. The molecular components and structures were confirmed by single crystal X-ray diffraction. APA + SEA is able to overcome the instability problem and has improved solubility compared with ATM. Hence, APA + SEA has the potential to be a superior candidate for this important drug.