2
0
2017
zha
che
0
journal
Original
Zhai, J.[Jinghuan]
Chen, Z.[Zhenzhen]
Liu, X.[Xijian]
Zhang, L.[Lijuan]
Lu, J.[Jie]
J. Chem. Thermodyn.
2017
2020-09-29
Solubility measurement, model evaluation and thermodynamic analysis of rivaroxaban polymorphs in organic solvents
This work measured the solubility of forms I and II of anticoagulant drug rivaroxaban in a series of organic solvents in which the solubility of form II was firstly reported as supplementary to the work of Zhang et al. [22]. A dynamic dissolution method was used to determine the solubility of both forms in acetonitrile, methyl acetate, acetone, 2-butanone, 3-pentanone and 2-hexanone from (273.15 to 318.15) K and in 1,4-dioxane from (288.15 to 333.15) K. The results showed that, the solubility of both forms generally increased with the temperature and decreased with an increase in the carbon number of ketones at the same temperature. The two forms were monotropically related and form II was the metastable form giving a higher solubility than form I. Meanwhile, such semiempirical thermodynamic models based on local composition concept as Wilson, nonrandom two-liquid (NRTL) and universal quasi chemical (UNIQUAC) equations with the correlation between model parameters and temperature were employed to model the studied solid-liquid equilibrium. It was found that UNIQUAC was the most appropriate model among the selected thermodynamic equations for the correlation of the solubility of rivaroxaban polymorphs in organic solvents. Finally, the apparent standard enthalpy change of dissolution was acquired from the experimental solubility data and the positive values of the apparent standard enthalpy change revealed that the dissolution of both forms of rivaroxaban in the selected solvents was an endothermic process.
Solubility
Polymorph
Rivaroxaban
Measurement
Thermodynamic modelling
10.1016/j.jct.2016.09.036
104
218-229
1
InChI=1S/C19H18ClN3O5S/c20-16-6-5-15(29-16)18(25)21-9-14-10-23(19(26)28-14)13-3-1-12(2-4-13)22-7-8-27-11-17(22)24/h1-6,14H,7-11H2,(H,21,25)/t14-/m0/s1
KGFYHTZWPPHNLQ-AWEZNQCLSA-N
Rivaroxaban
(S)-5-chloro-N-((2-oxo-3-(4-(3-oxomorpholino)phenyl)oxazolidin-5-yl)methyl)thiophene-2-carboxamide
5-chloro-N-(((5S)-2-oxo-3-(4-(3-oxo-4-morpholinyl)-phenyl)-1,3-oxazolidin-5-yl)methyl)-2-thiophenecarboxamide
C19H18ClN3O5S
1
Commercial source
1
None used
2
99.5
3
HPLC
2
InChI=1S/C2H3N/c1-2-3/h1H3
WEVYAHXRMPXWCK-UHFFFAOYSA-N
acetonitrile
cyanomethane
ethanenitrile
ethanonitrile
methanecarbonitrile
methyl cyanide
C2H3N
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
3
InChI=1S/C3H6O2/c1-3(4)5-2/h1-2H3
KXKVLQRXCPHEJC-UHFFFAOYSA-N
methyl ethanoate
acetic acid, methyl ester
ethanoic acid, methyl ester
methyl acetate
C3H6O2
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
4
InChI=1S/C4H8O2/c1-2-6-4-3-5-1/h1-4H2
RYHBNJHYFVUHQT-UHFFFAOYSA-N
1,4-dioxane
1,4-dioxacyclohexane
dioxane
p-dioxane
tetrahydro-1,4-dioxin
C4H8O2
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
5
InChI=1S/C3H6O/c1-3(2)4/h1-2H3
CSCPPACGZOOCGX-UHFFFAOYSA-N
acetone
2-propanone
dimethyl ketone
propan-2-one
propanone
pyroacetic ether
C3H6O
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
6
InChI=1S/C4H8O/c1-3-4(2)5/h3H2,1-2H3
ZWEHNKRNPOVVGH-UHFFFAOYSA-N
butanone
2-butanone
butan-2-one
ethyl methyl ketone
methyl ethyl ketone
C4H8O
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
7
InChI=1S/C5H10O/c1-3-5(6)4-2/h3-4H2,1-2H3
FDPIMTJIUBPUKL-UHFFFAOYSA-N
pentan-3-one
3-pentanone
diethyl ketone
C5H10O
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
8
InChI=1S/C6H12O/c1-3-4-5-6(2)7/h3-5H2,1-2H3
QQZOPKMRPOGIEB-UHFFFAOYSA-N
2-hexanone
butyl methyl ketone
hexanone-2
methyl butyl ketone
methyl n-butyl ketone
C6H12O
1
Commercial source
1
None used
2
99.7
3
Gas chromatography
9
InChI=1S/H2O/h1H2
XLYOFNOQVPJJNP-UHFFFAOYSA-N
water
H2O
1
Commercial source
1
Fractional distillation
2
99.8
3
Estimated by the compiler
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Triple point temperature, K
DSC
Crystal 1
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal 1
Liquid
Air at 1 atmosphere
1
501.41
5
1
7.83
2
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Molar enthalpy of transition or fusion, kJ/mol
DSC
Crystal 1
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal 1
Liquid
Air at 1 atmosphere
1
46.68
4
1
2.06
3
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mass density, kg/m3
Pycnometric method
Crystal 1
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal 1
1
Temperature, K
Crystal 1
2
Pressure, kPa
Crystal 1
1
298.15
5
2
101.325
6
1
1517.1
5
1
2.1
4
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mass density, kg/m3
Pycnometric method
Metastable crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Metastable crystal
1
Temperature, K
Metastable crystal
2
Pressure, kPa
Metastable crystal
1
298.15
5
2
101.325
6
1
1355.3
5
1
2.1
5
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mass density, kg/m3
X-ray diffraction
Crystal 1
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal 1
1
Temperature, K
Crystal 1
2
Pressure, kPa
Crystal 1
1
298.15
5
2
101.325
6
1
1516.7
5
1
7.4
6
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mass density, kg/m3
X-ray diffraction
Metastable crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Metastable crystal
1
Temperature, K
Metastable crystal
2
Pressure, kPa
Metastable crystal
1
298.15
5
2
101.325
6
1
1362.9
5
1
24.9
7
2
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
4.82e-05
3
1
5.4e-06
1
278.15
5
1
6.11e-05
3
1
6.8e-06
1
283.15
5
1
7.68e-05
3
1
8.6e-06
1
288.15
5
1
9.58e-05
3
1
1.07e-05
1
293.15
5
1
0.0001186
4
1
1.33e-05
1
298.15
5
1
0.0001458
4
1
1.63e-05
1
303.15
5
1
0.000178
4
1
1.99e-05
1
308.15
5
1
0.0002159
4
1
2.42e-05
1
313.15
5
1
0.0002602
4
1
2.92e-05
1
318.15
5
1
0.0003118
4
1
3.49e-05
8
2
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
0.0001167
4
1
1.31e-05
1
278.15
5
1
0.0001481
4
1
1.66e-05
1
283.15
5
1
0.0001864
4
1
2.09e-05
1
288.15
5
1
0.0002327
4
1
2.61e-05
1
293.15
5
1
0.0002883
4
1
3.23e-05
1
298.15
5
1
0.0003546
4
1
3.97e-05
1
303.15
5
1
0.0004332
4
1
4.85e-05
1
308.15
5
1
0.0005258
4
1
5.89e-05
1
313.15
5
1
0.0006343
4
1
7.11e-05
1
318.15
5
1
0.0007607
4
1
8.52e-05
9
3
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
3.2e-05
3
1
3.6e-06
1
278.15
5
1
4.05e-05
3
1
4.5e-06
1
283.15
5
1
5.07e-05
3
1
5.7e-06
1
288.15
5
1
6.31e-05
3
1
7.1e-06
1
293.15
5
1
7.79e-05
3
1
8.7e-06
1
298.15
5
1
9.54e-05
3
1
1.07e-05
1
303.15
5
1
0.0001162
4
1
1.3e-05
1
308.15
5
1
0.0001406
4
1
1.58e-05
1
313.15
5
1
0.0001691
4
1
1.89e-05
1
318.15
5
1
0.0002021
4
1
2.26e-05
10
3
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
8.52e-05
3
1
9.5e-06
1
278.15
5
1
0.0001077
4
1
1.21e-05
1
283.15
5
1
0.000135
4
1
1.51e-05
1
288.15
5
1
0.0001679
4
1
1.88e-05
1
293.15
5
1
0.0002073
4
1
2.32e-05
1
298.15
5
1
0.0002541
4
1
2.85e-05
1
303.15
5
1
0.0003095
4
1
3.47e-05
1
308.15
5
1
0.0003744
4
1
4.19e-05
1
313.15
5
1
0.0004503
4
1
5.05e-05
1
318.15
5
1
0.0005384
4
1
6.03e-05
11
4
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
288.15
5
1
0.000132
4
1
1.48e-05
1
293.15
5
1
0.0001584
4
1
1.77e-05
1
298.15
5
1
0.0001891
4
1
2.12e-05
1
303.15
5
1
0.0002244
4
1
2.51e-05
1
308.15
5
1
0.0002647
4
1
2.97e-05
1
313.15
5
1
0.0003107
4
1
3.48e-05
1
318.15
5
1
0.0003628
4
1
4.06e-05
1
323.15
5
1
0.0004217
4
1
4.72e-05
1
328.15
5
1
0.0004879
4
1
5.47e-05
1
333.15
5
1
0.0005619
4
1
6.3e-05
12
4
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
288.15
5
1
0.0003413
4
1
3.82e-05
1
293.15
5
1
0.0004095
4
1
4.59e-05
1
298.15
5
1
0.0004884
4
1
5.47e-05
1
303.15
5
1
0.0005791
4
1
6.49e-05
1
308.15
5
1
0.0006829
4
1
7.65e-05
1
313.15
5
1
0.0008011
4
1
8.98e-05
1
318.15
5
1
0.000935
4
1
0.0001048
1
323.15
5
1
0.0010861
5
1
0.0001217
1
328.15
5
1
0.0012558
5
1
0.0001407
1
333.15
5
1
0.0014458
5
1
0.000162
13
5
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
4.06e-05
3
1
4.6e-06
1
278.15
5
1
5.29e-05
3
1
5.9e-06
1
283.15
5
1
6.83e-05
3
1
7.7e-06
1
288.15
5
1
8.74e-05
3
1
9.8e-06
1
293.15
5
1
0.0001109
4
1
1.24e-05
1
298.15
5
1
0.0001396
4
1
1.56e-05
1
303.15
5
1
0.0001745
4
1
1.96e-05
1
308.15
5
1
0.0002164
4
1
2.42e-05
1
313.15
5
1
0.0002666
4
1
2.99e-05
1
318.15
5
1
0.0003263
4
1
3.66e-05
14
5
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
0.0001039
4
1
1.16e-05
1
278.15
5
1
0.0001354
4
1
1.52e-05
1
283.15
5
1
0.0001748
4
1
1.96e-05
1
288.15
5
1
0.0002236
4
1
2.51e-05
1
293.15
5
1
0.0002837
4
1
3.18e-05
1
298.15
5
1
0.0003571
4
1
4e-05
1
303.15
5
1
0.0004461
4
1
5e-05
1
308.15
5
1
0.0005532
4
1
6.2e-05
1
313.15
5
1
0.0006813
4
1
7.63e-05
1
318.15
5
1
0.0008337
4
1
9.34e-05
15
6
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
3.47e-05
3
1
3.9e-06
1
278.15
5
1
4.55e-05
3
1
5.1e-06
1
283.15
5
1
5.9e-05
3
1
6.6e-06
1
288.15
5
1
7.59e-05
3
1
8.5e-06
1
293.15
5
1
9.67e-05
3
1
1.08e-05
1
298.15
5
1
0.0001223
4
1
1.37e-05
1
303.15
5
1
0.0001535
4
1
1.72e-05
1
308.15
5
1
0.0001912
4
1
2.14e-05
1
313.15
5
1
0.0002364
4
1
2.65e-05
1
318.15
5
1
0.0002904
4
1
3.25e-05
16
6
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
9.24e-05
3
1
1.04e-05
1
278.15
5
1
0.0001212
4
1
1.36e-05
1
283.15
5
1
0.0001573
4
1
1.76e-05
1
288.15
5
1
0.0002024
4
1
2.27e-05
1
293.15
5
1
0.0002582
4
1
2.89e-05
1
298.15
5
1
0.0003266
4
1
3.66e-05
1
303.15
5
1
0.00041
4
1
4.59e-05
1
308.15
5
1
0.000511
4
1
5.73e-05
1
313.15
5
1
0.0006323
4
1
7.08e-05
1
318.15
5
1
0.0007773
4
1
8.71e-05
17
7
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
2.43e-05
3
1
2.7e-06
1
278.15
5
1
3.11e-05
3
1
3.5e-06
1
283.15
5
1
3.94e-05
3
1
4.4e-06
1
288.15
5
1
4.95e-05
3
1
5.5e-06
1
293.15
5
1
6.17e-05
3
1
6.9e-06
1
298.15
5
1
7.64e-05
3
1
8.6e-06
1
303.15
5
1
9.39e-05
3
1
1.05e-05
1
308.15
5
1
0.0001147
4
1
1.29e-05
1
313.15
5
1
0.0001392
4
1
1.56e-05
1
318.15
5
1
0.0001678
4
1
1.88e-05
18
7
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
6.39e-05
3
1
7.2e-06
1
278.15
5
1
8.14e-05
3
1
9.1e-06
1
283.15
5
1
0.0001027
4
1
1.15e-05
1
288.15
5
1
0.0001286
4
1
1.44e-05
1
293.15
5
1
0.0001599
4
1
1.79e-05
1
298.15
5
1
0.0001972
4
1
2.21e-05
1
303.15
5
1
0.0002416
4
1
2.71e-05
1
308.15
5
1
0.000294
4
1
3.29e-05
1
313.15
5
1
0.0003556
4
1
3.98e-05
1
318.15
5
1
0.0004276
4
1
4.79e-05
19
8
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
1.78e-05
3
1
2e-06
1
278.15
5
1
2.24e-05
3
1
2.5e-06
1
283.15
5
1
2.79e-05
3
1
3.1e-06
1
288.15
5
1
3.45e-05
3
1
3.9e-06
1
293.15
5
1
4.24e-05
3
1
4.8e-06
1
298.15
5
1
5.17e-05
3
1
5.8e-06
1
303.15
5
1
6.27e-05
3
1
7e-06
1
308.15
5
1
7.54e-05
3
1
8.4e-06
1
313.15
5
1
9.03e-05
3
1
1.01e-05
1
318.15
5
1
0.0001074
4
1
1.2e-05
20
8
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
4.75e-05
3
1
5.3e-06
1
278.15
5
1
5.97e-05
3
1
6.7e-06
1
283.15
5
1
7.43e-05
3
1
8.3e-06
1
288.15
5
1
9.19e-05
3
1
1.03e-05
1
293.15
5
1
0.0001129
4
1
1.27e-05
1
298.15
5
1
0.0001376
4
1
1.54e-05
1
303.15
5
1
0.0001667
4
1
1.87e-05
1
308.15
5
1
0.0002007
4
1
2.25e-05
1
313.15
5
1
0.0002402
4
1
2.69e-05
1
318.15
5
1
0.0002858
4
1
3.2e-05
21
9
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
1
1
Temperature, K
Liquid
2
Pressure, kPa
Liquid
1
298.15
5
2
101.3
4
1
8.25e-05
3
1
9.2e-06
22
9
1
1
1
Principal objective of the work
AB
TRC
4/5/2017
1
Mole fraction
gravimetric
1
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
1
1
Temperature, K
Liquid
2
Pressure, kPa
Liquid
1
298.15
5
2
101.3
4
1
0.0001403
4
1
1.57e-05