Citation: Zheng-Yu Fang, Bao-Xi Zhang, Wen-Hui Xing, Hong-Li Jia, Xue Wang, Ning-Bo Gong, Yang Lu, Guan-Hua Du. A series of stable, metastable and unstable salts of Imatinib with improved solubility[J]. Chinese Chemical Letters, ;2022, 33(4): 2159-2164. doi: 10.1016/j.cclet.2021.10.056 shu

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

Zheng-Yu Fang ^a ,
Bao-Xi Zhang ^a ,
Wen-Hui Xing ^a ,
Hong-Li Jia ^b ,
Xue Wang ^a ,
Ning-Bo Gong ^{a, *,} ,
Yang Lu ^{a, *,} ,
Guan-Hua Du ^c

a.
Beijing Key Laboratory of Polymorphic Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
b.
State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
c.
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

gnb@imm.ac.cn

luy@imm.ac.cn

Received Date: 19 July 2021
Revised Date: 29 September 2021
Accepted Date: 19 October 2021
Available Online: 26 October 2021

Figures(7)

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 pH 6.8 buffer, respectively.
- Imatinib,
- Salt,
- Characterization,
- Stability,
- Solubility
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