A series of stable, metastable and unstable salts of Imatinib with improved solubility  

作　　者：Zheng-Yu Fang Bao-Xi Zhang Wen-Hui Xing Hong-Li Jia Xue Wang Ning-Bo Gong Yang Lu Guan-Hua Du 

机构地区：[1]Beijing Key Laboratory of Polymorphic Drugs,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China [2]State Key Laboratory of Natural and Biomimetic Drugs,School of Pharmaceutical Sciences,Peking University,Beijing 100191 China [3]Beijing City Key Laboratory of Drug Target Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China

出　　处：《Chinese Chemical Letters》2022年第4期2159-2164,共6页中国化学快报（英文版）

基　　金：CAMS Innovation Fund for Medical Sciences(Nos. 2017-I2M-1–010, 2020-I2M-1–003);Key National Research and Development Program (No. 2016YFC1000901);Construction and Application of Technology Integration System for Efficient Identification of Natural/Effective Active Small Molecules (No.2018ZX09711001–001);National Science and Technology Major Project:Resource Library of Traditional Chinese Medicine Component (No. 2019ZX09735002) for the financial support。

摘　　要：Pharmaceutical salt formation is the most preferred and effective method to enhance the physicochemical properties of APIs. The aim of the study was to design and synthesize a series of new salts to improve the solubility of Imatinib(IM). Two stable salts with malonic acid(S1) and citric acid(S5), one metastable salt with fumaric acid(S2), two unstable salts with citric acid(S3, S4) were obtained for the first time.Single crystal and powder X-ray diffraction, Fourier transform infrared, differential scanning calorimetry,and thermogravimetric analysis were used to characterize the novel salts. The solubility and stability of the solid were also evaluated, and three salts(S1, S2, S5) had a more than 20 folds of solubility and a faster dissolution rate improved as compared to the pure drug in water and p H 6.8 buffer, respectively.

关 键 词：IMATINIB SALT Characterization Stability SOLUBILITY 

分 类 号：TQ460.1[化学工程—制药化工]