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.
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。
