2
0
2017
zha
zha
0
journal
Original
Zhai, J.[Jinghuan]
Zhao, J.[Junrui]
Chen, Z.[Zhenzhen]
Xiao, C.[Changwei]
Liu, X.[Xijian]
Zhang, L.[Lijuan]
Lu, J.[Jie]
J. Chem. Eng. Data
2017
2020-09-29
Solubility Measurement and Correlation of Two Erlotinib Hydrochloride Polymorphs in Alcohols and Ketones from 273.15 to 323.15 K
The solubility of two erlotinib hydrochloride polymorphs (form A and form B) in methanol, ethanol, isopropanol, acetone, methyl ethyl ketone and methyl isobutyl ketone from (273.15 to 323.15) K were determined by means of high-performance liquid chromatography (HPLC). The modified Apelblat equation and the Buchowski-Ksiazczak eh equation were used to correlate the experimental solubility data. The results showed that the solubility of both forms generally increased with the temperature and at a given temperature decreased with the increase of the carbon number of alcohols, furthermore, methyl isobutyl ketone showed the largest solubility in the studied ketones. Meanwhile form A had a higher solubility than form B which demonstrated that form A was the metastable form. Furthermore, both models mentioned above gave satisfactory correlation results, in which the modified Apelblat equation worked better than the Buchowski-Ksiazczak eh equation.
Solubility
Solid-Liquid Equilibrium
Organic Solvents
Polymorphs
Erlotinib Hydrochloride
Correlation
10.1021/acs.jced.6b00796
1
62
516-524
1
InChI=1S/CH4O/c1-2/h2H,1H3
OKKJLVBELUTLKV-UHFFFAOYSA-N
methanol
methyl alcohol
CH4O
1
Commercial source
1
99.5
3
Gas chromatography
2
InChI=1S/C2H6O/c1-2-3/h3H,2H2,1H3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N
ethanol
ethyl alcohol
C2H6O
1
Commercial source
1
99.5
3
Gas chromatography
3
InChI=1S/C3H8O/c1-3(2)4/h3-4H,1-2H3
KFZMGEQAYNKOFK-UHFFFAOYSA-N
propan-2-ol
2-propanol
isopropanol
isopropyl alcohol
sec-propyl alcohol
C3H8O
1
Commercial source
1
99.5
3
Gas chromatography
4
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
99.5
3
Gas chromatography
5
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
99.5
3
Gas chromatography
6
InChI=1S/C6H12O/c1-5(2)4-6(3)7/h5H,4H2,1-3H3
NTIZESTWPVYFNL-UHFFFAOYSA-N
4-methylpentan-2-one
4-methyl-2-pentanone
isobutyl methyl ketone
isopropyl acetone
methyl isobutyl ketone
C6H12O
1
Commercial source
1
99.5
3
Gas chromatography
7
InChI=1S/C4H10O/c1-2-3-4-5/h5H,2-4H2,1H3
LRHPLDYGYMQRHN-UHFFFAOYSA-N
butan-1-ol
1-butanol
n-butanol
n-butyl alcohol
C4H10O
1
Commercial source
1
99.5
3
Gas chromatography
8
InChI=1S/C16H16ClNO2S.H2O4S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14;1-5(2,3)4/h2-5,7,9,15H,6,8,10H2,1H3;(H2,1,2,3,4)/t15-;/m0./s1
FDEODCTUSIWGLK-RSAXXLAASA-N
(S)-(+)-Clopidogrel hydrogen sulfate
(+)-(S)-5-[(2-Chlorophenyl)(methoxycarbonyl)methyl]-4,5,6,7-tetrahydrothieno[3,2-c]-pyridin-5-ium hydrogen sulfate]
C16H18ClNO6S2
1
Commercial source
1
99.5
3
HPLC
9
InChI=1S/C22H23N3O4.ClH/c1-4-16-6-5-7-17(12-16)25-22-18-13-20(28-10-8-26-2)21(29-11-9-27-3)14-19(18)23-15-24-22;/h1,5-7,12-15H,8-11H2,2-3H3,(H,23,24,25);1H
GTTBEUCJPZQMDZ-UHFFFAOYSA-N
N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)quinazolin-4-amine hydrochloride
erlotinib hydrochloride
C22H24ClN3O4
1
Commercial source
1
99.5
3
HPLC
1
9
1
Principal objective of the work
EP
EP
11/2/2016
1
Triple point temperature, K
DSC
Crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal
Liquid
Air at 1 atmosphere
1
502.1
4
1
1.2
2
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Triple point temperature, K
DSC
Metastable crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Metastable crystal
Liquid
Air at 1 atmosphere
1
479.6
4
1
1.2
3
9
1
Principal objective of the work
EP
EP
11/2/2016
1
Molar enthalpy of transition or fusion, kJ/mol
DSC
Crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Crystal
Liquid
Air at 1 atmosphere
1
61.8
3
1
1.7
4
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Molar enthalpy of transition or fusion, kJ/mol
DSC
Metastable crystal
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Metastable crystal
Liquid
Air at 1 atmosphere
1
52.8
3
1
1.6
5
1
1
9
1
Principal objective of the work
EP
EP
11/16/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
1.678e-05
4
1
6.71e-06
1
278.15
5
1
2.151e-05
4
1
8.6e-06
1
283.15
5
1
2.733e-05
4
1
1.093e-05
1
288.15
5
1
3.443e-05
4
1
1.377e-05
1
293.15
5
1
4.304e-05
4
1
1.722e-05
1
298.15
5
1
5.339e-05
4
1
2.136e-05
1
303.15
5
1
6.578e-05
4
1
2.631e-05
1
308.15
5
1
8.048e-05
4
1
3.219e-05
1
313.15
5
1
9.784e-05
4
1
3.914e-05
1
318.15
5
1
0.0001182
4
1
4.73e-05
1
323.15
5
1
0.000142
4
1
5.68e-05
6
1
1
9
1
Principal objective of the work
EP
EP
11/16/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
7.348e-06
4
1
2.939e-06
1
278.15
5
1
9.44e-06
4
1
3.776e-06
1
283.15
5
1
1.202e-05
4
1
4.81e-06
1
288.15
5
1
1.518e-05
4
1
6.07e-06
1
293.15
5
1
1.901e-05
4
1
7.6e-06
1
298.15
5
1
2.364e-05
4
1
9.46e-06
1
303.15
5
1
2.918e-05
4
1
1.167e-05
1
308.15
5
1
3.578e-05
4
1
1.431e-05
1
313.15
5
1
4.391e-05
4
1
1.756e-05
1
318.15
5
1
5.265e-05
4
1
2.106e-05
1
323.15
5
1
6.347e-05
4
1
2.539e-05
7
2
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
8.363e-06
4
1
8.37e-07
1
278.15
5
1
1.016e-05
4
1
1.02e-06
1
283.15
5
1
1.226e-05
4
1
1.23e-06
1
288.15
5
1
1.47e-05
4
1
1.47e-06
1
293.15
5
1
1.751e-05
4
1
1.75e-06
1
298.15
5
1
2.074e-05
4
1
2.07e-06
1
303.15
5
1
2.442e-05
4
1
2.44e-06
1
308.15
5
1
2.861e-05
4
1
2.86e-06
1
313.15
5
1
3.335e-05
4
1
3.34e-06
1
318.15
5
1
3.869e-05
4
1
3.87e-06
1
323.15
5
1
4.468e-05
4
1
4.47e-06
8
2
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
5.174e-06
4
1
5.18e-07
1
278.15
5
1
6.246e-06
4
1
6.25e-07
1
283.15
5
1
7.491e-06
4
1
7.49e-07
1
288.15
5
1
8.927e-06
4
1
8.93e-07
1
293.15
5
1
1.058e-05
4
1
1.06e-06
1
298.15
5
1
1.246e-05
4
1
1.25e-06
1
303.15
5
1
1.459e-05
4
1
1.46e-06
1
308.15
5
1
1.701e-05
4
1
1.7e-06
1
313.15
5
1
1.973e-05
4
1
1.97e-06
1
318.15
5
1
2.278e-05
4
1
2.28e-06
1
323.15
5
1
2.618e-05
4
1
2.62e-06
9
3
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
7.562e-06
4
1
7.56e-07
1
278.15
5
1
9.179e-06
4
1
9.18e-07
1
283.15
5
1
1.111e-05
4
1
1.11e-06
1
288.15
5
1
1.331e-05
4
1
1.33e-06
1
293.15
5
1
1.573e-05
4
1
1.57e-06
1
298.15
5
1
1.864e-05
4
1
1.86e-06
1
303.15
5
1
2.187e-05
4
1
2.19e-06
1
308.15
5
1
2.574e-05
4
1
2.57e-06
1
313.15
5
1
2.995e-05
4
1
3e-06
1
318.15
5
1
3.499e-05
4
1
3.5e-06
1
323.15
5
1
4.045e-05
4
1
4.05e-06
10
3
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
5.104e-06
4
1
5.11e-07
1
278.15
5
1
6.017e-06
4
1
6.02e-07
1
283.15
5
1
7.112e-06
4
1
7.11e-07
1
288.15
5
1
8.294e-06
4
1
8.3e-07
1
293.15
5
1
9.647e-06
4
1
9.65e-07
1
298.15
5
1
1.115e-05
4
1
1.12e-06
1
303.15
5
1
1.28e-05
4
1
1.28e-06
1
308.15
5
1
1.474e-05
4
1
1.47e-06
1
313.15
5
1
1.689e-05
4
1
1.69e-06
1
318.15
5
1
1.919e-05
4
1
1.92e-06
1
323.15
5
1
2.159e-05
4
1
2.16e-06
11
4
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
2.439e-06
4
1
2.44e-07
1
278.15
5
1
2.739e-06
4
1
2.74e-07
1
283.15
5
1
3.022e-06
4
1
3.02e-07
1
288.15
5
1
3.314e-06
4
1
3.31e-07
1
293.15
5
1
3.635e-06
4
1
3.64e-07
1
298.15
5
1
3.973e-06
4
1
3.97e-07
1
303.15
5
1
4.331e-06
4
1
4.33e-07
1
308.15
5
1
4.707e-06
4
1
4.71e-07
1
313.15
5
1
5.103e-06
4
1
5.1e-07
1
318.15
5
1
5.518e-06
4
1
5.52e-07
1
323.15
5
1
5.952e-06
4
1
5.95e-07
12
4
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
1.45e-06
4
1
1.45e-07
1
278.15
5
1
1.613e-06
4
1
1.61e-07
1
283.15
5
1
1.775e-06
4
1
1.78e-07
1
288.15
5
1
1.95e-06
4
1
1.95e-07
1
293.15
5
1
2.126e-06
4
1
2.13e-07
1
298.15
5
1
2.322e-06
4
1
2.32e-07
1
303.15
5
1
2.535e-06
4
1
2.54e-07
1
308.15
5
1
2.76e-06
4
1
2.76e-07
1
313.15
5
1
3.005e-06
4
1
3.01e-07
1
318.15
5
1
3.255e-06
4
1
3.26e-07
1
323.15
5
1
3.507e-06
4
1
3.51e-07
13
5
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
1.386e-06
4
1
1.39e-07
1
278.15
5
1
1.625e-06
4
1
1.63e-07
1
283.15
5
1
1.895e-06
4
1
1.9e-07
1
288.15
5
1
2.199e-06
4
1
2.2e-07
1
293.15
5
1
2.538e-06
4
1
2.54e-07
1
298.15
5
1
2.915e-06
4
1
2.92e-07
1
303.15
5
1
3.333e-06
4
1
3.33e-07
1
308.15
5
1
3.795e-06
4
1
3.8e-07
1
313.15
5
1
4.302e-06
4
1
4.3e-07
1
318.15
5
1
4.859e-06
4
1
4.86e-07
1
323.15
5
1
5.466e-06
4
1
5.47e-07
14
5
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
9.22e-07
4
1
9.22e-08
1
278.15
5
1
1.069e-06
4
1
1.07e-07
1
283.15
5
1
1.232e-06
4
1
1.23e-07
1
288.15
5
1
1.414e-06
4
1
1.41e-07
1
293.15
5
1
1.614e-06
4
1
1.61e-07
1
298.15
5
1
1.835e-06
4
1
1.84e-07
1
303.15
5
1
2.078e-06
4
1
2.08e-07
1
308.15
5
1
2.343e-06
4
1
2.34e-07
1
313.15
5
1
2.632e-06
4
1
2.63e-07
1
318.15
5
1
2.945e-06
4
1
2.95e-07
1
323.15
5
1
3.285e-06
4
1
3.29e-07
15
6
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Metastable crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
2.66e-06
4
1
2.66e-07
1
278.15
5
1
3.071e-06
4
1
3.07e-07
1
283.15
5
1
3.528e-06
4
1
3.53e-07
1
288.15
5
1
4.032e-06
4
1
4.03e-07
1
293.15
5
1
4.588e-06
4
1
4.59e-07
1
298.15
5
1
5.198e-06
4
1
5.2e-07
1
303.15
5
1
5.865e-06
4
1
5.87e-07
1
308.15
5
1
6.592e-06
4
1
6.59e-07
1
313.15
5
1
7.381e-06
4
1
7.38e-07
1
318.15
5
1
8.235e-06
4
1
8.24e-07
1
323.15
5
1
9.157e-06
4
1
9.16e-07
16
6
1
9
1
Principal objective of the work
EP
EP
11/4/2016
1
Mole fraction
Chromatography
9
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal
9
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
1.915e-06
4
1
1.92e-07
1
278.15
5
1
2.168e-06
4
1
2.17e-07
1
283.15
5
1
2.445e-06
4
1
2.45e-07
1
288.15
5
1
2.745e-06
4
1
2.75e-07
1
293.15
5
1
3.069e-06
4
1
3.07e-07
1
298.15
5
1
3.42e-06
4
1
3.42e-07
1
303.15
5
1
3.796e-06
4
1
3.8e-07
1
308.15
5
1
4.2e-06
4
1
4.2e-07
1
313.15
5
1
4.632e-06
4
1
4.63e-07
1
318.15
5
1
5.093e-06
4
1
5.09e-07
1
323.15
5
1
5.583e-06
4
1
5.58e-07
17
7
1
8
1
Principal objective of the work
AB
TRC
4/17/2019
1
Mole fraction
Chromatography
8
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 2
8
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
293.15
5
1
0.00125
4
1
0.000125
1
295.65
5
1
0.001424
4
1
0.000142
1
298.15
5
1
0.001632
4
1
0.000163
1
300.65
5
1
0.001842
4
1
0.000184
1
303.15
5
1
0.002087
4
1
0.000209
1
305.65
5
1
0.00236
4
1
0.000236
1
308.15
5
1
0.002664
4
1
0.000266
1
310.65
5
1
0.003
4
1
0.0003
1
313.15
5
1
0.003323
4
1
0.000332
1
315.65
5
1
0.003785
4
1
0.000379
1
318.15
5
1
0.00424
4
1
0.000424
18
7
1
8
1
Principal objective of the work
AB
TRC
4/17/2019
1
Mole fraction
Chromatography
8
Liquid
Direct value, X
1
Data file compiler
Propagation of evaluated standard uncertainties
95
Liquid
Crystal 1
8
1
Pressure, kPa
Liquid
101.3
4
1
Temperature, K
Liquid
1
273.15
5
1
0.001759
4
1
0.000176
1
278.15
5
1
0.001921
4
1
0.000192
1
283.15
5
1
0.002239
4
1
0.000224
1
288.15
5
1
0.002576
4
1
0.000258
1
292.85
5
1
0.00297
4
1
0.000297
1
298.35
5
1
0.003458
4
1
0.000346
1
303.35
5
1
0.003952
4
1
0.000395
1
308.5
5
1
0.004513
4
1
0.000451
1
313.25
5
1
0.005182
4
1
0.000518
1
318.15
5
1
0.005993
4
1
0.000599