INTRODUCTION:
Knowing the solubility in different solvents is crucial for determining optimal solvents and designing an effective production process.The enhancement of solubility and dissolution rate of poorly water soluble drug by using modified guar gum is studied by vipul v. jambukiya et. al1. The novel methods to enhance solubility of water insoluble drugs was investigated by tawaret. al2. In addition to the general solubility enhancement techniques, microcrystals preparation and characterization of tinidazole for improvement in solubility and dissolution is carried out by reddy et.al3. Asija rajesh4 studied solubility enhancement of nebivolol by solid dispersion technique.
Pimelic acid is utilised as a starting
material in the production of 1,7-Heptanediol, an essential chemical used in
the production of medicines, surfactants, flavours, and cosmetics5.
The solubilities of pimelic acid in pure water, methanol, and their binary
mixtures over various compositions were determined at various temperatures in
these studies. The Apelblat model was used to correlate the experimental
solubility data. The solutions' thermodynamic properties (
,
%ζH, %ζTS) were computed using
the van't Hoff equation.
Experimental:
Materials and Apparatus:
Pimelic Acid (99%) was obtained from Sigma Aldrich. Ethanol (99.8%) was supplied by Merck. They were utilised without being purified in any way. Throughout all of these investigations, triple distilled water was used. Earlier method of determining solubility has been applied6-10.
In this study, an excess of Pimelic acid was added to
binary solvent mixtures made by weight (Shimadzu, Auxzzo) in a specifically built
100mL double jacketed flask with an uncertainty of 0.1mg. Water was flowed
between the flask's outer and inner sides at a constant temperature. The
temperature of the circulating water was controlled by thermostat to within
(±0.1)K. The solution was agitated constantly with a magnetic stirrer for a
long period (approximately 1 h) to ensure equilibrium, then left to stand for 1
h. Then, using a pipette that was hotter than the solution, a defined amount of
the supernatant liquid was taken from the flask and placed in a weighing
bottle. The sample's weight was taken, and it was stored in an oven at 343K
until all of the solvent had evaporated. This was confirmed by weighing two or
three times until a constant weight was obtained. The solubility has been calculated
using weight of solute and weight of solution. Each experimental value of
solubility is an average of at least three different measurements. The
saturated mole fraction solubility (Xb), initial the mole fraction
of ethanol (
), and initial the mole fraction of water (
) were calculated using usual Eq. 1 and 2:
mb/Mb
Xb = ------------------------------------ (1)
ma/Ma+mb/Mb + mc/Mc
(2)
Where mb, ma, and mc are the mass of solute, water andethanol respectively, and Mb, Ma, and Mc are the molecular weight of the solute, water, and ethanol respectively.
RESULTS AND DISCUSSION:
Solubility of Pimelic Acid (PA):
The values of mole fraction solubility (Xb) of PA in pure water and ethanol within the range of temperature 293.15 K to 313.15 K are presented in Table 1 and depicted graphically in Figure 1. It can be shown that the solubility of PA in pure solvents increases as the temperature rises.In comparison to water, ethanol has a higher solubility.
Table 2 summarises the measured mole fraction
solubilities (Xb) of PA in water + ethanol, as well as estimated
solubilities using the Apelblat correlating model. Figures 2 and 3 shows the
relationship between PA solubility and the initial mole fraction of ethanol and
temperature, respectively. As a results from Tables 2 and Fig. 2 and 3 that
solubility of PA in studied binary system found to be increase with the initial
mole fraction of ethanol (
) and temperature.
Table 1: - Experimental Xbvalue of mole fraction solubility of PA in pure water and ethanol at T = (293.15 - 303.15 K).
|
T/K |
Xb |
|
|
Water |
Ethanol |
|
|
293.15 |
0.0044 |
0.1129 |
|
296.15 |
0.0053 |
0.1236 |
|
298.15 |
0.0058 |
0.1349 |
|
300.15 |
0.0066 |
0.1390 |
|
303.15 |
0.0077 |
0.1503 |
Fig.1. Mole fraction solubility (Xb) variation with temperatures for water (), methanol (),
Solubility Correlation:
The modified semi-empirical Apelblat model7 with three parameters (Eq. 3) is an appropriate method for correlating solubility data with temperature. The equation, which is based on solid-liquid equilibrium theory, yields excellent agreement between experimental and calculated solubility values.
(3)
A, B, and C are the model parameters and T is temperature in Kelvin. A andB reflects non-idealities of solutions, C represents temperature influence on fusion enthalpy11,12. A, B, and C parameters are obtained from non-linear least square fitting.Eq.3 was used to calculate the solute's solubility in water, ethanol, and their binary mixtures. Table 2 shows the experimental mole fraction solubility, which was correlated with equation 3, and Table 3 shows the A, B, and C parameter values.
Thermodynamic parameters of dissolution
Van't Hoff analysis is used to investigate
the thermodynamic dissolution of pimelic acid in pure and binary solvent
mixtures at temperatures ranging from 293.15 to 313.15 K. The van't Hoff
equation13, 15 is used to compute the standard molar enthalpy change
of solution, standard molar entropy change
, and standard molar Gibbs energy change 
for the solution process (Table 4).
= (4)
(5)
(6)
In Eq. 4, Tmean is the mean harmonic temperature i.e. Tmean= 303.03 K. In addition, the relative contribution of enthalpy (%ζH) and entropy (%ζTS) were calculated by using following Eq. 7. The effects of enthalpy and entropy on Gibbs energy in the solution process could be evaluated using %ζH and %ζTS.
% and (7)
The thermodynamic parameters (, %ζH, and % ζTS) in pure and
binary solvents mixtures are given in Table 4.
Table 2 Experimental (Xb) and
calculated mole fraction solubility of PA in various initial mole fraction 
of ethanol at T= 293.15 to 313.15 K
|
T/K |
|
|
|
T/K |
|
|
|
293.15 |
0.0000 |
0.0044 |
0.0043 |
296.15 |
0.0053 |
0.0053 |
|
0.0416 |
0.0071 |
0.0073 |
0.0085 |
0.0084 |
||
|
0.0891 |
0.0136 |
0.0133 |
0.0158 |
0.0174 |
||
|
0.1435 |
0.0209 |
0.0234 |
0.0366 |
0.0335 |
||
|
0.2068 |
0.0344 |
0.0263 |
0.0425 |
0.0407 |
||
|
0.2811 |
0.0645 |
0.0643 |
0.0729 |
0.0727 |
||
|
0.3697 |
0.0742 |
0.0771 |
0.0927 |
0.0889 |
||
|
0.4771 |
0.0965 |
0.0968 |
0.1058 |
0.1064 |
||
|
0.6100 |
0.1090 |
0.1094 |
0.1179 |
0.1198 |
||
|
0.7787 |
0.1140 |
0.1144 |
0.1240 |
0.1243 |
||
|
1.0000 |
0.1129 |
0.1137 |
0.1236 |
0.1242 |
||
|
298.15 |
0.0000 |
0.0058 |
0.0059 |
300.15
|
0.0066 |
0.0067 |
|
0.0416 |
0.0096 |
0.0095 |
0.0116 |
0.0111 |
||
|
0.0891 |
0.0215 |
0.0208 |
0.0255 |
0.0246 |
||
|
0.1435 |
0.0453 |
0.0414 |
0.0527 |
0.0500 |
||
|
0.2068 |
0.0558 |
0.0522 |
0.0703 |
0.0649 |
||
|
0.2811 |
0.0790 |
0.0790 |
0.0839 |
0.0860 |
||
|
0.3697 |
0.0989 |
0.0972 |
0.1079 |
0.1058 |
||
|
0.4771 |
0.1148 |
0.1134 |
0.1209 |
0.1207 |
||
|
0.6100 |
0.1294 |
0.1271 |
0.1374 |
0.1347 |
||
|
0.7787 |
0.1333 |
0.1312 |
0.1377 |
0.1384 |
||
|
1.0000 |
0.1349 |
0.1315 |
0.1503 |
0.1390 |
||
|
303.15 |
0.0000 |
0.0077 |
0.0078 |
|
||
|
0.0416 |
0.0147 |
0.0144 |
||||
|
0.0891 |
0.0345 |
0.0316 |
||||
|
0.1435 |
0.0614 |
0.0636 |
||||
|
0.2068 |
0.0816 |
0.0846 |
||||
|
0.2811 |
0.0992 |
0.0976 |
||||
|
0.3697 |
0.1174 |
0.1192 |
||||
|
0.4771 |
0.1326 |
0.1326 |
||||
|
0.6100 |
0.1455 |
0.1466 |
||||
|
0.7787 |
0.1494 |
0.1498 |
||||
|
1.0000 |
0.1503 |
0.1508 |
||||
Fig. 2 Mole fraction solubility (Xb) variation with Initial mole fraction ( of ethanol, at various temperatures (◆T=293.15 K, ■T=296.15 K; ▲T=298.15 K; ×T=300.15 K; ×T=303.15K..
Fig. 3 Mole fraction solubility (Xb)
variation with temperature at initial mole fraction (
of methanol (◆ = wt. fraction 0.0; ■ = 0.1; ▲= 0.2; × = 0.3; × =
0.4; ● = 0.5; + = 0.6; - = 0.7; ▬ = 0.8 and ◇= 0.9; □ =1)
The values for PA dissolution in all mixtures
are all positive; illustrating that PA dissolution is endothermic process
throughout all cases. The value in pure water is 39.0425 KJK-1mol-1and
in ethanol is 20.2579KJK-1mol-1. This demonstrates that
the dissolution of PA in water needs more energy than the dissolution of PA in
ethanol. The dissolution process occurs with an increase in entropy and is
non-spontaneous because the value of ΔG0soln and ΔS0soln
are positive. Table 4 reveals that for all examined mixtures, the percent
enthalpy is greater than the percent TS, implying that enthalpy is the dominant
contributing force to the Gibbs free energy for PA dissolution. Overall,PA
dissolving is an enthalpy-driven endothermic process in all binary solvent
combinations.
Table 3 Model parameters and correlation coefficient of the Apelblat equation.
|
Solvent |
|
Parameters |
R2 |
100*RAD |
100*RMSD |
||
|
A |
B |
C |
|||||
|
Ethanol |
0.0000 |
780.3133 |
-39429.2 |
-114.644 |
0.9915 |
2.3042 |
0.0262 |
|
0.0416 |
-3493 |
150098 |
523.89 |
0.9938 |
3.9936 |
0.1174 |
|
|
0.0891 |
302.1983 |
-20176.6 |
-41.8423 |
0.9832 |
5.9826 |
0.2893 |
|
|
0.1435 |
2971.62 |
-139975 |
-439.716 |
0.9761 |
6.8257 |
0.4462 |
|
|
0.2068 |
4441.523 |
-206652 |
-658.411 |
0.987 |
5.3475 |
0.4489 |
|
|
0.2811 |
-268.048 |
8660.254 |
41.50236 |
0.9979 |
0.9577 |
0.1227 |
|
|
0.3697 |
500.7225 |
-25680.5 |
-73.1748 |
0.9895 |
2.2532 |
0.2684 |
|
|
0.4771 |
-84.3126 |
1277.11 |
13.664 |
0.9987 |
0.5293 |
0.0949 |
|
|
0.6100 |
57.26061 |
-4857.15 |
-7.55277 |
0.9953 |
1.0777 |
0.1705 |
|
|
0.7787 |
15.87518 |
-2832.78 |
-1.47517 |
0.9983 |
0.5417 |
0.0957 |
|
|
1.0000 |
100.3608 |
-6688.27 |
-14.0334 |
0.9962 |
0.7063 |
0.1434 |
|
Table 4 Thermodynamic parameters relative to solution process of PA atThm= 303.03K
|
|
∆H0sol KJK-1 mol-1 |
∆G0sol KJK-1 mol-1 |
∆S0sol KJK-1 mol-1 |
∆S0sol JK-1 mol-1 |
T∆S0sol KJK-1 mol-1 |
ζH%
|
ζTS% |
|
PA + Water+ Ethanol |
|||||||
|
0.0000 |
39.0425 |
12.2990 |
0.0883 |
88.2511 |
26.7435 |
59.3477 |
40.6523 |
|
0.0416 |
71.6925 |
10.4288 |
0.2022 |
202.164 |
61.2636 |
53.9219 |
46.0781 |
|
0.0891 |
62.3533 |
8.7501 |
0.1769 |
176.886 |
53.6032 |
53.7730 |
46.2270 |
|
0.1435 |
56.1710 |
7.2019 |
0.1616 |
161.594 |
48.9692 |
53.4249 |
46.5751 |
|
0.2068 |
59.6530 |
6.6070 |
0.1750 |
175.046 |
53.0459 |
52.9313 |
47.0687 |
|
0.2811 |
32.5368 |
5.8507 |
0.0881 |
88.0617 |
26.6861 |
54.9396 |
45.0604 |
|
0.3697 |
29.1896 |
5.4103 |
0.0785 |
78.4695 |
23.7793 |
55.1071 |
44.8929 |
|
0.4771 |
23.7997 |
5.0921 |
0.0617 |
61.7332 |
18.7076 |
55.9897 |
44.0103 |
|
0.6100 |
21.3578 |
4.8492 |
0.0545 |
54.4769 |
16.5086 |
56.4031 |
43.5969 |
|
0.7787 |
19.8359 |
4.7918 |
0.0496 |
49.6441 |
15.0441 |
56.8689 |
43.1311 |
|
1.0000 |
20.2579 |
4.7822 |
0.0511 |
51.0683 |
15.4757 |
56.6915 |
43.3085 |
CONCLUSION:
The solubility of PA in pure liquids was
shown to rise as the experimental temperature was raised. Ethanol seems to have
a higher solubility than water, according to measurements. The initial mole fraction
of ethanol () and temperature enhance PA solubilities
in all binary systems investigated. The measured solubilities of PA are well
correlated with temperature by Apelblat model. PA dissolving in all binary
solvent mixtures is an enthalpy driven endothermic process, according to a
thermodynamic analysis based on observed solubilities. The results of ζH
suggest that enthalpy is the main contributing force to the Gibbs free energy
for the dissolution of PA.
ACKNOWLEDGEMENTS:
The author is thankful to Principal of MSG Arts, Science and Commerce College Malegaon for providing laboratory facilities. The authors also express their sincere thanks to Dr ApoorvaHiray (Co-ordinator M.G. Vidyamandir Malegaon).
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Received on 16.05.2022 Modified on 22.07.2022 Accepted on 26.09.2022 ©A&V Publications All right reserved Research J. Science and Tech. 2022; 14(4):233-237. DOI: 10.52711/2349-2988.2022.00038 |
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