Solubility of Salicylamide
in (n-propanol, water) and their binary solvent mixtures at T= (288.15 to
313.15) K
Ramesh R. Pawar1*, Atul S. Kale1,
Sachin S. Kale2
1Department of Chemistry, M.S.G. College, Malegaon Camp,
Dist - Nashik (Maharashtra) India
2Department of Chemistry, A.S.C. College, Navapur, Dist
- Nandurbar (Maharashtra) India
*Corresponding
Author E-mail: atulkalemalegaon@gmail.com
ABSTRACT:
The solubility of salicylamide in pure water,
n-propanol, and also in water-n-propanol binary mixtures were experimentally
measured using a gravimetric method at temperatures (288.15, 291.15, 293.15,
296.15, 298.15, 301.15, 303.15, 306.15, 308.15, 311.15 and 313.15) K.
Solubility values was correlated by the modified Apelblat equation.
Thermodynamic properties including ΔHsoln°, ΔGsoln°,
and ΔSsoln° of salicylamide in pure and mixed solvents were
calculated according to the van’t Hoff equation.
KEYWORDS:
n-Propanol, Solubility, Binary solvents, Thermodynamics, Apelblat equation.
INTRODUCTION:
Solubility data in aqueous and non-aqueous
solvents are providing crucial information for the solid phase properties,
preparation of drug formulation and development of pharmaceutical analysis in
the drug discovery and development1-3. Salicylamide is a slight
analgesic with antipyretic and anti-inflammatory properties4.
Fredrik L. Nordstrom and Ake C. Rosmuson
determined solubility of salicylamide in methanol, acetic acid, acetonitrile,
acetone, ethyl acetate and water from 10 to 50°C5. However there is
very little data available for solubility of salicylamide in pure n-propanol
and water-n-propanol solvent mixtures.
In the present study, solubility of
salicylamide in pure n-propanol, water and water-n-propanol solvent mixtures at
288.15 to 313.15 K are reported.
MATERIAL AND METHODS:
Material:
Salicylamide was provided by Loba chemie with purity
99%. n-propanol Provided by Spectrochem with purity 99.8%.
Apparatus and Procedure:
The solubility of acetanilide
was measured using an apparatus similar to that described as in the literature6-8.
An excess amount of salicylamide was added to the binary solvent mixture
prepared by weight (Scale-Tec) with an accuracy of ± 0.0001g, in a specially
designed 100 ml double jacketed flask. Water was circulated at constant
temperature between the outer and inner walls of the flask. The temperature of
the circulating water was controlled by thermostat within (±0.1) K. The
solution was continuously stirred using a magnetic stirrer for long time so
that equilibrium is assured, and the temperature of solution is same as that of
circulating water; the stirrer was switched off; and the solution was allowed
to stand for 2 hour to ensure complete settlement of un-dissolved suspended
substance. Then a fixed quantity of the supernatant liquid was withdrawn from
the flask in a weighing bottle with the help of pipette which is hotter than
the solution. The mass of solution were weighed by electronic analytical
balance, and kept in an oven at 343 K until constant sample weight. The
solubility has been calculated using weight of solute and weight of solution.
The experiment was repeated three times and the average value were used to
calculate the mole fraction solubility
of
salicylamide.
RESULTS AND DISCUSSION:
Solubility data:
Table 1 reports the experimental and
calculated (using Apelblat equation) values of solubility of salicylamide at 288.15 to 313.15 K in water +
n-propanol. Variation of solubility with 
is visually shown in Figures 1.
Table 1: Experimental 
(exp.) and calculated 
mole fraction solubility of salicylamide for various
initial mole fractions, 
, of n-propanol at temperatures (288.15 to 313.15) K.
|
T/K
|
|
|
|
RD
|
T/K
|
|
|
RD
|
|
288.15
|
0.0000
|
0.0029
|
0.0037
|
-0.2827
|
303.15
|
0.0361
|
0.0394
|
-0.0910
|
|
0.0322
|
0.0194
|
0.0183
|
0.0594
|
0.0858
|
0.0862
|
-0.0047
|
|
0.0697
|
0.1147
|
0.1131
|
0.0133
|
0.3156
|
0.3116
|
0.0126
|
|
0.1139
|
0.3569
|
0.3586
|
-0.0048
|
0.7602
|
0.7659
|
-0.0076
|
|
0.1666
|
0.7201
|
0.7197
|
0.0006
|
1.3673
|
1.3645
|
0.0020
|
|
0.2306
|
1.1593
|
1.1539
|
0.0047
|
2.0807
|
2.0877
|
-0.0034
|
|
0.3102
|
1.6634
|
1.6792
|
-0.0095
|
2.9147
|
2.9294
|
-0.0051
|
|
0.4116
|
2.2963
|
2.2933
|
0.0013
|
3.8246
|
3.8320
|
-0.0019
|
|
0.5453
|
2.8803
|
2.8793
|
0.0003
|
4.6647
|
4.6694
|
-0.0010
|
|
0.7296
|
3.1069
|
3.1476
|
-0.0131
|
4.9407
|
4.9803
|
-0.0080
|
|
1.0000
|
2.3997
|
2.3639
|
0.0149
|
4.2163
|
4.0894
|
0.0301
|
|
291.15
|
0.0000
|
0.0069
|
0.0073
|
-0.0563
|
306.15
|
0.0394
|
0.0468
|
-0.1882
|
|
0.0322
|
0.0231
|
0.0266
|
-0.1511
|
0.1037
|
0.1072
|
-0.0338
|
|
0.0697
|
0.1386
|
0.1407
|
-0.0150
|
0.3730
|
0.3732
|
-0.0005
|
|
0.1139
|
0.4192
|
0.4210
|
-0.0044
|
0.8673
|
0.8806
|
-0.0153
|
|
0.1666
|
0.8160
|
0.8172
|
-0.0016
|
1.5493
|
1.5524
|
-0.0020
|
|
0.2306
|
1.2895
|
1.2990
|
-0.0073
|
2.3406
|
2.3507
|
-0.0043
|
|
0.3102
|
1.8706
|
1.8698
|
0.0004
|
3.2887
|
3.2912
|
-0.0008
|
|
0.4116
|
2.5318
|
2.5365
|
-0.0019
|
4.2651
|
4.2571
|
0.0019
|
|
0.5453
|
3.1706
|
3.1719
|
-0.0004
|
5.1409
|
5.1424
|
-0.0003
|
|
0.7296
|
3.4013
|
3.4035
|
-0.0006
|
5.4321
|
5.5636
|
-0.0242
|
|
1.0000
|
2.6460
|
2.6641
|
-0.0069
|
4.4042
|
4.4995
|
-0.0216
|
|
293.15
|
0.0000
|
0.0176
|
0.0109
|
0.3811
|
308.15
|
0.0458
|
0.0500
|
-0.0902
|
|
0.0322
|
0.0340
|
0.0335
|
0.0158
|
0.1239
|
0.1221
|
0.0147
|
|
0.0697
|
0.1591
|
0.1620
|
-0.0180
|
0.4134
|
0.4194
|
-0.0144
|
|
0.1139
|
0.4685
|
0.4674
|
0.0024
|
0.9611
|
0.9644
|
-0.0034
|
|
0.1666
|
0.8920
|
0.8897
|
0.0026
|
1.6942
|
1.6922
|
0.0012
|
|
0.2306
|
1.4064
|
1.4058
|
0.0004
|
2.5401
|
2.5442
|
-0.0016
|
|
0.3102
|
2.0318
|
2.0111
|
0.0102
|
3.5561
|
3.5599
|
-0.0010
|
|
0.4116
|
2.7045
|
2.7144
|
-0.0036
|
4.5773
|
4.5683
|
0.0020
|
|
0.5453
|
3.3737
|
3.3833
|
-0.0028
|
5.4722
|
5.4837
|
-0.0021
|
|
0.7296
|
3.6366
|
3.5998
|
0.0101
|
6.0108
|
6.0092
|
0.0003
|
|
1.0000
|
2.8597
|
2.8769
|
-0.0060
|
4.7134
|
4.7839
|
-0.0150
|
|
296.15
|
0.0000
|
0.0198
|
0.0180
|
0.0893
|
311.15
|
0.0519
|
0.0511
|
0.0148
|
|
0.0322
|
0.0504
|
0.0461
|
0.0846
|
0.1414
|
0.1451
|
-0.0261
|
|
0.0697
|
0.2019
|
0.1989
|
0.0153
|
0.4956
|
0.4968
|
-0.0022
|
|
0.1139
|
0.5511
|
0.5447
|
0.0116
|
1.1011
|
1.1018
|
-0.0006
|
|
0.1666
|
1.0112
|
1.0110
|
0.0002
|
1.9268
|
1.9261
|
0.0004
|
|
0.2306
|
1.5810
|
1.5828
|
-0.0012
|
2.8724
|
2.8645
|
0.0028
|
|
0.3102
|
2.2714
|
2.2467
|
0.0109
|
3.9368
|
4.0094
|
-0.0184
|
|
0.4116
|
3.0233
|
3.0071
|
0.0054
|
5.0701
|
5.0811
|
-0.0022
|
|
0.5453
|
3.7332
|
3.7269
|
0.0017
|
6.0232
|
6.0380
|
-0.0025
|
|
0.7296
|
3.9978
|
3.9381
|
0.0149
|
6.7201
|
6.7764
|
-0.0084
|
|
1.0000
|
3.1333
|
3.2149
|
-0.0260
|
5.1961
|
5.2263
|
-0.0058
|
|
298.15
|
0.0000
|
0.0230
|
0.0238
|
-0.0364
|
313.15
|
0.0602
|
0.0495
|
0.1771
|
|
0.0322
|
0.0558
|
0.0561
|
-0.0060
|
0.1641
|
0.1604
|
0.0224
|
|
0.0697
|
0.2277
|
0.2270
|
0.0029
|
0.5573
|
0.5542
|
0.0056
|
|
0.1139
|
0.6077
|
0.6018
|
0.0098
|
1.2141
|
1.2018
|
0.0101
|
|
0.1666
|
1.0951
|
1.1012
|
-0.0056
|
2.0982
|
2.1000
|
-0.0008
|
|
0.2306
|
1.7086
|
1.7131
|
-0.0026
|
3.0974
|
3.1000
|
-0.0009
|
|
0.3102
|
2.4216
|
2.4213
|
0.0001
|
4.4248
|
4.3436
|
0.0184
|
|
0.4116
|
3.2332
|
3.2212
|
0.0037
|
5.4608
|
5.4565
|
0.0008
|
|
0.5453
|
3.9887
|
3.9750
|
0.0034
|
6.4588
|
6.4378
|
0.0032
|
|
0.7296
|
4.2442
|
4.1966
|
0.0112
|
7.5073
|
7.3635
|
0.0192
|
|
1.0000
|
3.3686
|
3.4527
|
-0.0250
|
5.5702
|
5.5312
|
0.0070
|
|
301.15
|
0.0000
|
0.0321
|
0.0333
|
-0.0366
|
|
|
0.0322
|
0.0739
|
0.0733
|
0.0076
|
|
0.0697
|
0.2750
|
0.2752
|
-0.0004
|
|
0.1139
|
0.6977
|
0.6964
|
0.0019
|
|
0.1666
|
1.2562
|
1.2522
|
0.0032
|
|
0.2306
|
1.9550
|
1.9289
|
0.0133
|
|
0.3102
|
2.6977
|
2.7130
|
-0.0057
|
|
0.4116
|
3.5546
|
3.5739
|
-0.0054
|
|
0.5453
|
4.3801
|
4.3783
|
0.0004
|
|
0.7296
|
4.6310
|
4.6410
|
-0.0022
|
|
1.0000
|
4.0342
|
3.8276
|
0.0512
|
Fig. 1: Plot of mole fraction solubility () of salicylamide versus initial mole fraction () of n-propanol at temperatures (288.15 to 313.15) K.
The solubility of salicylamide increases with
increasing temperature. Salicylamide is an organic compound; naturally the
solubility is more in n-propanol as compared with water. In mixed solvents with
water as the proportion of organic solvent increases, as expected the
solubility also increases.
Modified Apelblat Equation:
The modified Apelblat equation can be
expressed as equation 19, 10 which is semi-empirical equation; it
describes the relation between solubility and temperature.
(1)
A, B, and C are the parameters of the equation and
T is temperature in Kelvin. The value A and B represents the variation in the
solution coefficient and the C value represents the effect of temperature on
the fusion enthalpy. Relative deviation (RD) 11 was calculated
using equation 2.
(2)
From table 1 it can be seen that there is
an excellent agreement between experimental and calculated values of mole
fraction solubility. The values of parameters A, B and C along
with co-relation coefficient (R2) are listed in table 2.
Table 2: Parameters and correlation coefficient (R2)
of modified Apelblat equation
|
Solvents
|
|
A
|
B
|
C
|
R2
|
|
n-Propanol
+
Water
|
0.0000
|
6223.62
|
-287097
|
-924.782
|
0.9521
|
|
0.0322
|
1690.09
|
-82698.7
|
-249.264
|
0.9934
|
|
0.0697
|
243.925
|
-16071.3
|
-34.4196
|
0.9995
|
|
0.1139
|
85.4697
|
-7766.18
|
-11.3266
|
0.9995
|
|
0.1666
|
-187.589
|
4915.71
|
29.2393
|
0.9999
|
|
0.2306
|
-152.204
|
3603.72
|
23.8786
|
0.9997
|
|
0.3102
|
-258.085
|
8477.81
|
39.6536
|
0.9989
|
|
0.4116
|
-187.867
|
5601.94
|
29.0724
|
0.9998
|
|
0.5453
|
-117.941
|
2670.10
|
18.5623
|
0.9999
|
|
0.7296
|
-547.644
|
21779.7
|
82.7407
|
0.9978
|
|
1.0000
|
180.237
|
-10830.7
|
-25.8488
|
0.9924
|
Thermodynamic functions of dissolution:
According to the van’t Hoff equation, the
standard molar enthalpy change of solution 
is generally obtained from the slope of the ln
versus (1/T − 1/Thm) plot.
Average temperature Thm is introduced to obtain a single
value of 
and 
in the temperature range studied
(3)
Where n is the number of experimental
points. In the present work, Thm = 300.8773 K and the
temperature range is (288.15 to 313.15) K in both pure solvents and binary
solvent mixtures.
Table 3: Slope (m) and intercept (c)
of the ln versus (1/T − 1/Thm) plot
along with R2.
|
Salicylamide + n-Propanol + Water
|
|
|
m
|
c
|
R2
|
|
0.0000
|
-9276
|
-8.348
|
0.850
|
|
0.0322
|
-7799
|
-7.327
|
0.981
|
|
0.0697
|
-5728
|
-5.924
|
0.999
|
|
0.1139
|
-4362
|
-4.984
|
0.999
|
|
0.1666
|
-3870
|
-4.381
|
0.999
|
|
0.2306
|
-3571
|
-3.950
|
0.999
|
|
0.3102
|
-3437
|
-3.603
|
0.997
|
|
0.4116
|
-3133
|
-3.330
|
0.998
|
|
0.5453
|
-2907
|
-3.130
|
0.999
|
|
0.7296
|
-3082
|
-3.051
|
0.989
|
|
1.0000
|
-3063
|
-3.281
|
0.991
|
The values of slope and intercept of lnxB
versus (1/T − 1/Thm) plot for different solutions
including pure solvents and binary solvent mixtures are listed in table 3, form
which enthalpy, entropy and standard Gibbs energies of dissolution can be
obtained 12.
Table 4: Thermodynamic parameters for salicylamide at
mean harmonic temperature Thm = 300.8773 K
|
|
 /kJ
·K−1·mol−1
|
 /kJ
·K−1·mol−1
|
 /kJ
·K−1·mol−1
|
 /kJ
·K−1·mol−1
|
% ζH
|
% ζTS
|
|
Salicylamide + n-Propanol + Water
|
|
0.0000
|
77.1265
|
20.8830
|
0.1869
|
56.2435
|
57.8290
|
42.1710
|
|
0.0322
|
64.8475
|
18.3300
|
0.1546
|
46.5176
|
58.2297
|
41.7703
|
|
0.0697
|
47.6301
|
14.8206
|
0.1090
|
32.8095
|
59.2123
|
40.7877
|
|
0.1139
|
36.2715
|
12.4674
|
0.0791
|
23.8040
|
60.3765
|
39.6235
|
|
0.1666
|
32.1760
|
10.9610
|
0.0705
|
21.2150
|
60.2649
|
39.7351
|
|
0.2306
|
29.6918
|
9.8829
|
0.0658
|
19.8089
|
59.9826
|
40.0174
|
|
0.3102
|
28.5778
|
9.0149
|
0.0650
|
19.5628
|
59.3631
|
40.6369
|
|
0.4116
|
26.0544
|
8.3322
|
0.0589
|
17.7222
|
59.5168
|
40.4832
|
|
0.5453
|
24.1730
|
7.8319
|
0.0543
|
16.3410
|
59.6657
|
40.3343
|
|
0.7296
|
25.6254
|
7.6323
|
0.0598
|
17.9931
|
58.7489
|
41.2511
|
|
1.0000
|
25.4716
|
8.2074
|
0.0574
|
17.2642
|
59.6025
|
40.3975
|
The relative contribution of enthalpy (ζH) and
entropy (ζTS) to Gibbs
energy of solution process is calculated by equation 4 and 5 respectively. The
results are shown in table 4,
(4)
(5)
The values
of and for all the solutions are positive indicating the
solution process as endothermic. The contribution of enthalpy to positive molar
Gibbs energy is more as compared to entropy for all solutions.
Fig. 2: Plot of ln versus (1/T − 1/Thm) for
Salicylamide + water + n-propanol system
CONCLUSION:
This study presents experimental data for
the solubility of salicylamide in pure water, n-propanol and binary mixtures of
water-n-propanol from (288.15-313.15) K. the solubility of salicylamide in pure
and binary solvents increases with upward temperature. The modified Apelblat
equation is use to correlate the measured solubility data. The calculated
values are satisfactory agreement with the experimental data. The thermodynamic
aspects of the solubility process of salicylamide in binary mixtures were studied
in order to select the best solvent and optimize its solubility.
ACKNOWLEDGMENT:
The authors express their sincere thanks to
the Dr. Apoorva P. Hiray, co-coordinator M.G. Vidyamandir, Malegaon camp and
Dr. D.F. Shirude Principal, M.S.G. College, Malegaon camp, for providing
laboratory facility and encouragement.
REFERENCES:
1. Di L, Fish PV, Mano T. Bridging solubility
between drug discovery and development. Drug Discovery Today. 2012; 17:
486-495.
2. Strickley RG. Solubility excipients in oral
and injectable formulations. Pharm Res. 2004; 21: 201-230.
3. Alsenz J, Kansy M, High throughput
solubility measurement in drug discovery and development. Adv. Drug Delivery
Rev. 2007; 59: 546-567.
4. Ullmann F. Encyclopedia of industrial
chemistry, Vol. A23, VCH: weinheim, Germany. 1993; 477-483.
5. Fredrik L N and Ake CR. Solubility and
melting properties of salicylamide. J. Chem. Eng. Data. 2006; 51: 1775-1777.
6. Pawar RR, Aher CS, Pagar JD, Nikam SL, and
Hasan M. Solubility, density and solution thermodynamics of NaI in different
pure solvents and binary mixtures. J. Chem. Eng. Data. 2012; 57: 3563-3572.
7. Pawar RR, Nahire SB, Hasan M, Solubility and
density of potassium iodide in binary water-ethanol solvent mixtures at298.15,
303.15, 308.15, and 313.15) K. J. Chem. Eng. Data. 2009; 54: 1935−37.
8. Pawar RR, Golait SM, Hasan M, Sawant AB.
Solubility and density of potassium iodide in binary water-propan-1-ol solvent
mixtures at (298.15,303.15,308.15 and313.15) K. J. Chem. Eng. Data. 2010; 55:
1314−16.
9. Apelblat A, Manzurola E. Solubilities of
L-aspartic, DL-aspartic, DL-glutamic, p-hydroxybenzoic, o-anisic, p-anisic and
itaconic acid in water from T= 278 K to T=345 K. J. Chem. Thermodyn. 1997; 29:
1527-1533.
10. Apelblat A, Manzurola E. Solubilities of
o-acetylsalicylic, 4-aminosalicylic, 3-5-dinitrosalicylic and p-toluic acid and
magnesium in water from T= (278 to 348) K. J. Chem. Thermodyn. 1999; 31: 85-91.
11. Wei T, Wang C, Du S. Measurement and
correlation of the solubility of penicillin V potassium in ethanol + water and
1-butyl alcohol + water system. J. Chem. Eng. Data. 2015; 60: 112-117.
12. Vehdati S, Shyanfar A, Hanaee J. Solubility
of carvedilol in ethanol + propylene glycol mixtures at various temperatures.
Ind. Eng. Chem. Res. 2013; 52: 16630-16636.