Dissolution behavior and thermodynamic properties of apixaban in pure and mixed solvents

被引:6
作者
Du, Cunbin [1 ]
Cong, Yang [1 ]
Zhang, Ying [1 ]
Xue, Yi [1 ,2 ]
Qiao, Bin [1 ]
Ye, Tingting [1 ]
Wang, Mingliang [1 ]
机构
[1] Southeast Univ, Sch Chem & Chem Engn, Nanjing 211189, Peoples R China
[2] Southeast Univ, Red Sun Res Ctr Intelligent Ind, Nanjing 211189, Peoples R China
关键词
Apixaban; Solubility; Co-solvency phenomenon; Thermodynamic properties; MAGNESIUM-DL-ASPARTATE; FACTOR XA INHIBITOR; P-TOLUIC ACID; ATRIAL-FIBRILLATION; SOLUBILITY; WATER; MIXTURES; ETHANOL; SAFETY; EVENTS;
D O I
10.1016/j.jct.2019.105949
中图分类号
O414.1 [热力学];
学科分类号
摘要
The solubility profile of apixaban in pure and mixed solvents within the temperature range from (288.15 to 328.15) K under atmosphere pressure (101.3 kPa) was studied and evaluated by some thermodynamics models. The solid state of apixaban in equilibrated form was characterized using powder X-ray diffraction (PXRD) technique. The maximum mole solubility in pure solvents was obtained in 1, 4-dioxane (3.648 x 10(-3)) at 328.15 K, and followed by methanol (1.967 x 10(-3)), acetone (7.885 x 10(-4)),ethanol (6.049 x 10(-4)), isopropanol (3.806 x 10(-4)), ethyl acetate (2.266 x 10(-4)), n-hexane (1.883 x 10(-4)), water (3.989 x 10(-5)). The solubility was quite small. Therefore, the solubility profile of apixaban in mixtures of (1, 4-dioxane + water) was further studied. Moreover, it increased at first and then decreased with the increasing mass fraction of 1, 4-dioxane. Moreover, the extended Hildebrand solubility approach (EHSA) was applied to evaluate the co-solvency phenomenon in mixed solvent at 298.15 K. In the following, the analysis of apparent thermodynamic properties indicates that the dissolution process in all selected solvents is an endothermic and entropy driven process. (C) 2019 Published by Elsevier Ltd.
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页数:7
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