Preparation, characterization and improved solubility of ticagrelor salts
10.16438/j.0513-4870.2020-1470
- VernacularTitle:替格瑞洛新盐型的制备、表征及溶解性能研究
- Author:
Hong-mei YU
;
Zheng-yu FANG
;
Cheng XING
;
Kun HU
;
Ning-bo GONG
;
Yang LÜ
- Publication Type:Research Article
- Keywords:
salt;
ticagrelor;
characterization;
equilibrium solubility
- From:
Acta Pharmaceutica Sinica
2021;56(2):570-576
- CountryChina
- Language:Chinese
-
Abstract:
Four salts of ticagrelor, ticagrelor-3,5-dinitrobenzoic acid, ticagrelor-pyrazinamide, ticagrelor-D-proline and ticagrelor-L-proline were prepared by solvent suspension and liquid-assisted grinding to improve the solubility of ticagrelor. The compounds were characterized by powder X-ray diffraction, Fourier transform infrared spectroscopy, differential scanning calorimetry, nuclear magnetic resonance spectroscopy, elemental analysis, and the intermolecular salt-bonding forces were analyzed. The equilibrium solubility of salts and pure drug in hydrochloride buffer pH 1.2 and phosphate buffer pH 6.8 were measured by high-performance liquid chromatography. Ticagrelor was salted with 3,5-dinitrobenzoic acid, pyrazinamide, D-proline, L-proline all in a stoichiometric ratio of 1∶1; with the exception of ticagrelor-D-proline, the solubility of the other three salts provided significantly improved solubility in hydrochloride buffer pH 1.2, and the equilibrium solubility of ticagrelor-3,5-dinitrobenzoic acid was increased by approximately 1.7 folds as compared to pure drug. Salt-forming technology is convenient and can improve the solubility of ticagrelor.
