Supplemental information for: Predicting the Excess Solubility of
Acetanilide, Acetaminophen, Phenacetin, Benzocaine, and Caffeine in
Binary Water/Ethanol Mixtures via Molecular Simulation
Andrew S. Paluch,1 Sreeja Parameswaran,2 Shuai
Liu,3 Anasuya Kolavennu,2 and David L. Mobley3, 4
1
Department of Chemical, Paper, and Biomedical Engineering,
Miami University, Oxford, Ohio, 45056, USA∗
2
Department of Chemistry, University of New Orleans,
New Orleans, Louisiana, 70148, USA
3
Department of Pharmaceutical Sciences,
University of California Irvine, Irvine, California, 92697, USA†
4
Department of Chemistry, University of California Irvine, Irvine, California, 92697, USA‡
(Dated: December 18, 2014)
∗
Previous Address: Department of Chemical and Biomolecular Engineering, University of Notre Dame, Notre Dame,
Indiana 46556, USA; Electronic address: PaluchAS@MiamiOH.edu; To whom correspondence should be addressed.
†
Previous Address: Department of Chemistry, University of New Orleans, New Orleans, Louisiana, 70148, USA
‡
Previous Address: Department of Chemistry, University of New Orleans, New Orleans, Louisiana, 70148, USA;
Electronic address: DMobley@uci.edu
1
List of Tables
I
II
III
IV
V
A summary of the molar volume and molar configurational enthalpy computed via
molecular simulation for the binary water/ethanol solvent.
3
A summary of the dimensionless residual chemical potential and log excess solubility of acetanilide, acetaminophen, and phenacetin in the water/ethanol solvent.
4
A summary of the dimensionless residual chemical potential and log excess solubility of benzocaine and caffeine in the water/ethanol solvent.
5
Experimental solubility data for acetanilide, phenacetin, benzocaine, and caffeine
in the water/ethanol solvent from ref. 1.
6
Experimental solubility data for acetaminophen in the water/ethanol solvent from
refs. 2 and 3.
7
2
TABLE I: A summary of the molar volume (v b ) and molar configurational enthalpy (hb = ub + pV )
computed via molecular simulation for the binary water(2)/ethanol(3) solvent at 25 ◦ C and 1 bar. The
[
(
) ]
molar excess volume and enthalpy are computed as v b,E = v b − xb2 v2 + 1 − xb2 v3 and hb,E = hb −
(
]
[ b
)
x2 h2 + 1 − xb2 h3 , respectively. Note that since hb , h2 , and h3 are at the same temperature, the excess
enthalpy and excess configurational enthalpy are equivalent.
xb2 [mol frac]
0.0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1.0
v b [cm3 /mol]
60.336±0.015
55.582±0.013
51.049±0.042
46.675±0.024
42.250±0.025
38.017±0.034
33.732±0.020
29.566±0.017
25.478±0.023
21.633±0.014
18.041±0.006
v b,E [cm3 /mol]
0.000±0.021
-0.524±0.019
-0.828±0.044
-0.973±0.026
-1.168±0.026
-1.171±0.034
-1.227±0.021
-1.164±0.019
-1.022±0.024
-0.638±0.015
0.000±0.009
3
hb [kJ/mol] hb,E [J/mol]
-39.899±0.022
0±27
-40.755±0.017
-186±22
-41.474±0.029
-235±31
-42.124±0.016
-215±19
-42.809±0.010
-230±14
-43.467±0.021
-218±23
-44.199±0.006
-280±9
-44.928±0.008
-339±10
-45.642±0.016
-383±17
-46.279±0.006
-350±8
-46.599±0.008
0±10
TABLE II: A summary of the dimensionless residual chemical potential (βµL,res,∞
) and log excess sol1,m
E
ubility (ln x1,m ) of acetanilide, acetaminophen, and phenacetin (component 1) in the water(2)/ethanol(3)
solvent.
xb2
Acetanilide
[mol frac]
ln xE1,m
0.0
-23.71±0.08 0.00±0.11
0.1
-23.65±0.08 0.53±0.10
0.2
-23.70±0.08 1.14±0.10
0.3
-23.63±0.08 1.65±0.10
0.4
-23.57±0.07 2.14±0.09
0.5
-22.79±0.07 1.92±0.09
0.6
-22.52±0.07 2.19±0.08
0.7
-22.13±0.07 2.33±0.08
0.8
-21.38±0.07 2.09±0.08
0.9
-20.12±0.06 1.32±0.07
1.0
-18.32±0.05 0.00±0.07
βµL,res,∞
1,m
Acetaminophen
βµL,res,∞
ln xE1,m
1,m
-32.33±0.10 0.00±0.14
-32.27±0.10 0.57±0.13
-32.40±0.09 1.32±0.12
-32.60±0.09 2.13±0.12
-31.99±0.08 2.13±0.10
-31.57±0.09 2.30±0.11
-31.98±0.09 3.31±0.10
-30.91±0.08 2.80±0.09
-29.95±0.08 2.40±0.09
-28.79±0.06 1.78±0.08
-26.48±0.05 0.00±0.07
4
Phenacetin
ln xE1,m
-29.36±0.08 0.00±0.12
-28.75±0.08 0.25±0.11
-29.06±0.08 1.42±0.11
-28.85±0.08 2.07±0.10
-28.85±0.08 2.91±0.10
-28.41±0.07 3.31±0.09
-28.27±0.08 3.99±0.09
-27.69±0.08 4.23±0.09
-26.10±0.08 3.42±0.09
-24.13±0.07 2.24±0.09
-21.13±0.06 0.00±0.08
βµL,res,∞
1,m
TABLE III: A summary of the dimensionless residual chemical potential (βµL,res,∞
) and log excess solu1,m
E
bility (ln x1,m ) of benzocaine and caffeine (component 1) in the water(2)/ethanol(3) solvent.
xb2
Benzocaine
[mol frac]
ln xE1,m
0.0
-23.54±0.07 0.00±0.10
-23.70±0.07 0.95±0.09
0.1
0.2
-23.30±0.06 1.34±0.08
0.3
-23.21±0.07 2.03±0.09
0.4
-23.33±0.07 2.92±0.08
0.5
-22.80±0.07 3.15±0.08
0.6
-22.81±0.07 3.92±0.08
0.7
-21.95±0.07 3.80±0.08
0.8
-20.84±0.07 3.42±0.08
0.9
-18.86±0.07 2.14±0.08
1.0
-16.03±0.05 0.00±0.08
L,res,∞
βµ1,m
5
Caffeine
ln xE1,m
-28.72±0.06 0.00±0.08
-29.51±0.06 1.08±0.08
-30.05±0.06 1.92±0.08
-30.19±0.06 2.35±0.07
-30.69±0.06 3.12±0.07
-30.64±0.06 3.35±0.07
-30.80±0.06 3.77±0.07
-30.51±0.06 3.73±0.07
-30.18±0.06 3.63±0.07
-28.96±0.06 2.62±0.07
-26.13±0.05 0.00±0.07
βµL,res,∞
1,m
TABLE IV: The experimental solubility data for acetanilide, phenacetin, benzocaine, and caffeine (component 1) in the water(2)/ethanol(3) solvent at 25 ◦ C and ambient pressure from ref. 1 used for comparison in
the present study. All concentrations are in units of mole fractions. Note, the two data sets for acetanilide
correspond to two unique sets.
xb2
0.0000
0.2652
0.4481
0.5819
0.6841
0.7646
0.8297
0.8834
0.9285
0.9669
1.0000
Acetanilide
x1,m
xb2
0.0819 0.0000
0.0714 0.1186
0.0649 0.2213
0.0578 0.3110
0.0403 0.3900
0.0202 0.5229
0.0129 0.6303
0.0058 0.7189
0.0027 0.7932
0.0012 0.8565
0.0008 0.9109
0.9584
1.0000
x1,m
0.1009
0.1039
0.1013
0.0924
0.0804
0.0544
0.0335
0.0183
0.0089
0.0038
0.0020
0.0013
0.0007
Phenacetin
xb2
x1,m
0.0000 0.0145
0.2652 0.0172
0.4481 0.0150
0.5819 0.0126
0.6841 0.0082
0.7646 0.0058
0.8297 0.0016
0.8834 0.0007
0.9285 0.0005
0.9669 0.0002
1.0000 0.0001
Benzocaine
xb2
x1,m
0.0000 0.1530
0.2652 0.1230
0.4481 0.0847
0.5819 0.0655
0.6841 0.0209
0.7646 0.0095
0.8297 0.0047
0.8834 0.0043
0.9285 0.0029
0.9669 0.0009
1.0000 0.0006
Caffeine
x1,m
0.0000 0.00170
0.2652 0.00603
0.4481 0.01151
0.5819 0.01439
0.6841 0.01470
0.7646 0.01138
0.8297 0.00982
0.8834 0.00707
0.9285 0.00507
0.9669 0.00332
1.0000 0.00209
xb2
The values reported in ref. 1 were converted to mole fractions using the following properties: the
molecular weight of water, ethanol, acetanilide, phenacetin, benzocaine, and caffeine is 18.015,
46.0684, 135.16, 179.22, 165.19, and 194.19 Da, respectively, and the density of water and ethanol
is 0.997045 and 0.78503 g/cm3 , respectively. The density of water and ethanol at 25 ◦ C and
ambient pressure was taken from ref. 4.
6
TABLE V: The experimental solubility data for acetaminophen(1) in the water(2)/ethanol(3) solvent at 25
◦ C and ambient pressure from refs. 2 and 3 used for comparison in the present study. All concentrations
are in units of mole fractions. The first data set corresponds to ref. 2 and the second data set corresponds to
ref. 3.
Acetaminophen
ref. 2
ref. 3
b
b
x2
x1,m
x2
x1,m
0.0000 0.0542 0.0000 0.0556
0.1460 0.0699 0.2652 0.0643
0.2652 0.0761 0.4481 0.0591
0.3643 0.0799 0.5819 0.0485
0.4481 0.0732 0.6841 0.0389
0.5198 0.0681 0.7646 0.0265
0.5819 0.0554 0.8297 0.0160
0.6841 0.0496 0.8834 0.0094
0.7646 0.0336 0.9285 0.0045
0.8834 0.0109 0.9669 0.0026
0.9285 0.0064 1.0000 0.0018
0.9669 0.0027
1.0000 0.0019
The values reported in refs. 2 and 3 were converted to mole fractions using the following properties: the molecular weight of water, ethanol and acetaminophen is 18.015, 46.0684 and 151.16 Da,
respectively, and the density of water and ethanol is 0.997045 and 0.78503 g/cm3 , respectively.
The density of water and ethanol at 25 ◦ C and ambient pressure was taken from ref. 4.
7
[1] A. Jouyban, Handbook of Solubility Data for Pharmaceuticals (CRC Press, Boca Raton, FL, 2010).
[2] S. Romero, A. Reillo, B. Escalera, and P. Bustamante, Chem. Pharm. Bull. 44, 1061 (1996).
[3] A. Jouyban, H. K. Chan, N. Y. K. Chew, M. Khoubnasabjafari, and W. E. Acree, Jr., Chem. Pharm.
Bull. 54, 428 (2006).
[4] J. P. E. Grolier and E. Wilhelm, Fluid Phase Equilib. 6, 283 (1981).
8