Solubility and Data Correlation of Isoniazid in Different Pure and

Article Cite This: J. Chem. Eng. Data XXXX, XXX, XXX−XXX

pubs.acs.org/jced

Solubility and Data Correlation of Isoniazid in Different Pure and Binary Mixed Solvent Systems from 283.15 K to 323.15 K Tingting Gong, Dandan Han, Yifu Chen, Shuo Wang, and Weiwei Tang* State Key Laboratory of Chemical Engineering, The Co-Innovation Center of Chemistry and Chemical Engineering of Tianjin, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People’s Republic of China

J. Chem. Eng. Data Downloaded from pubs.acs.org by UNIV OF RHODE ISLAND on 11/29/18. For personal use only.

S Supporting Information *

ABSTRACT: The solubility of isoniazid (INH) in eight pure solvents (water, methanol, ethanol, n-propanol, isopropyl alcohol, DMF, ethyl acetate, and acetonitrile) and three binary solvent mixtures of methanol−water, ethanol−water, and isopropyl alcohol−water were experimentally determined by gravimetric method at temperatures ranging from (283.15 to 323.15) K. Expectedly, the solubility displays temperature dependence, and the most remarkable change was found in water. In all three binary solvent mixtures, INH solubility bears a maximum at 0.2−0.4 mole fraction of alcohols, and the maximum solubility values were found varying with temperature. The experimental solubility data were well correlated by the modified Apelblat, van’t Hoff, CNIBS/R−K, and Apel−JA equations. Among these models, the modified Apelblat model produces the best fitting results.

1. INTRODUCTION Isoniazid (INH) (pyridine-4-carbohydrazide, C6 H7N 3O, CASRN 54-85-3, Figure 1), is a synthetic bactericide and used

Solution crystallization is a key step for control of the product quality attributes such as purity, size, and size distribution, and flowability in the manufacturing of INH.8 To select the appropriate solvent and design the optimal crystallization technique, systematically determining physicochemical data such as solubility and dissolution enthalpy of INH in different solvent systems is of critical importance.9 Few available literature works10,11 reported the solubility of INH in several pure solvents and ionic liquids at different temperatures. However, these limited data could not meet the requirements of solvent selection and the development of a crystallization technique. Therefore, a thorough determination of the solubility of INH in different solvent systems is desirable and important. In this presentation, the solubility of INH in eight commonly used solvents, water, methanol, ethanol, n-propanol, isopropyl alcohol, N,N-dimethylformamide (DMF), ethyl acetate, and acetonitrile, and three binary mixed solvents (methanol−water, ethanol−water, isopropyl alcohol−water) at different temperatures was reported. The solubility behavior of INH in both pure

Figure 1. Chemical formula (left) and 3D structure with surface added (right) of INH.

as a first-line drug against human tuberculosis (TB) worldwide.1,2 TB, one of the biggest causes of death worldwide, is caused by infection with Mycobacterium tuberculosis bacilli, transmitted mainly through the respiratory tract.3 Although new drugs for clinical treatment have been developed by researchers over the past decades, INH is still widely utilized in the actual treatment because of its superior characteristics such as low price, strong bactericidal ability, and slight side effects.4,5 Recently, there has been growing interest in crystallization and cocrystallization of INH with other active pharmaceutical ingredients (APIs) for development of anti-TB drugs.6,7 © XXXX American Chemical Society

Received: September 1, 2018 Accepted: November 16, 2018

A

DOI: 10.1021/acs.jced.8b00785 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Description of Materials Used in the Experiments chemical name

CASRN

source

mass fraction purity

analysis method

isoniazid methanol ethanol n-propanol isopropyl alcohol DMF ethyl acetate acetonitrile

54-85-3 67-56-1 64-17-5 71-23-8 67-63-0 68-12-2 141-78-6 75-05-8

Wuhan Dongkangyuan Technology Co., Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd. Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd.

≥0.990 ≥0.995 ≥0.995 ≥0.995 ≥0.995 ≥0.995 ≥0.995 ≥0.995

HPLCa GCb GCb GCb GCb GCb GCb GCb

a

High performance liquid chromatography. bGas chromatography.

and binary mixed solvents was investigated. Furthermore, the solubility data were correlated by the modified Apelblat equation, van’t Hoff equation, CNIBS/R-K equation, and Apel-JA equation to extend the application of crystallization process design.

2. MATERIALS AND METHODS 2.1. Materials. The INH (≥0.990 mass fraction) was purchased from Wuhan Dongkangyuan Technology Co., Ltd., China. The organic solvents used in the experiment including methanol, ethanol, n-propanol, isopropyl alcohol, DMF, ethyl acetate, and acetonitrile, are of analytical grade (≥0.995 mass fraction) purchased from Rionlon Bohua (Tianjin) Pharmaceutical & Chemical Co. Ltd., China. All materials were used as received. Ultrapure water (18.2 MΩ·cm resistivity) was prepared in our laboratory and used throughout the measurement process. The detailed information on chemicals was listed in Table 1. 2.2. Powder X-ray Diffraction Analysis. Powder X-ray diffraction (PXRD) was used to identify the crystal form of samples to ensure no polymorphic transformation during solubility measurements. The PXRD patterns were obtained by using the D/MAX-2500 (Rigaku, Japan) with Cu Kα radiation (1.5406 Å) at 100 mA and 40 kV, and the measurements were carried out at 2θ degrees from 2° to 40° with a scanning rate of 8°/min. 2.3. Differential Thermal Analysis. Differential scanning calorimeter (DSC 1/500, Mettler Toledo, Switzerland), calibrated by standard indium and zinc under a nitrogen atmosphere, was employed to perform thermal analysis of INH samples. About 5−10 mg of INH was put into a crucible, and the measurements were carried out at a heating rate of 10 K/min under nitrogen atmosphere. 2.4. Solubility Determination. The gravimetric method was used to determine the solubility of INH in different solvent systems. In the experiments, all mass was measured by an analytic balance (AB204-N, Mettler-Toledo, Switzerland) with a precision of ±0.0001 g. Excess INH solids were added in the 50 mL stoppered conical flask containing 30 mL of each given solvent. Subsequently, the suspension solution of INH was transferred into a thermostatic shaker (Tianjin Ounuo Instrument Co., Ltd., China) with an accuracy of ±0.01 K and shaken at 220 rpm for about 12 h which is long enough to reach solid−liquid equilibrium from preliminary experiments. Then, the shaker was stopped and the solution was kept still for at least 2 h until the appearance of clear saturated supernatant. A preheated/cooled disposable syringe equipped with a 0.22 μm filter was used to pipet out approximately 5 mL of saturated supernatant from each flask. The samples were poured into glass dishes weighed beforehand and the total weight was measured immediately. After that, the glass dishes were placed in a vacuum drying oven

Figure 2. Powder X-ray diffraction patterns of INH in solvents: (a) raw material; (b) water; (c) methanol; (d) ethanol; (e) n-propanol; (f) isopropyl alcohol; (g) DMF; (h) ethyl acetate; and (i) acetonitrile.

Figure 3. DSC curve of INH.

(DZ-1BCII, Yichuan Appearance of Bearing Co., Ltd., China) to evaporate the solutions at T = 323.15 K for about 12 h until the weight remained constant. Taking account of experimental errors, each measurement was repeated three times under the same condition and the average value was given. The mole fraction solubility (x1) of INH in pure solvents was calculated by x1 = B

m1/M1 m1/M1 + m2 /M 2

(1) DOI: 10.1021/acs.jced.8b00785 J. Chem. Eng. Data XXXX, XXX, XXX−XXX


Article

Table 2. Experimental and Correlated Mole Solubility of INH in Eight Pure Solvents from 283.15 K to 323.15 K (p = 0.1 MPa)a T/K

103xexp 1

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

10.582 13.397 15.923 19.794 24.012 29.615 35.416 42.142 51.677

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

5.741 6.702 7.966 9.609 11.175 13.142 15.139 17.920 21.118

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.665 3.177 3.838 4.647 5.494 6.460 7.538 8.705 9.964

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.191 2.636 3.292 4.189 4.953 5.901 7.052 8.403 9.833

103xcal A

103xcal v

T/K

10.712 13.180 16.160 19.748 24.057 29.216 35.374 42.707 51.415

10.347 12.943 16.068 19.802 24.237 29.471 35.613 42.779 51.097

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

5.746 6.790 8.013 9.444 11.115 13.063 15.333 17.973 21.039

5.540 6.671 7.983 9.495 11.229 13.208 15.455 17.996 20.856

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.622 3.204 3.873 4.636 5.496 6.458 7.525 8.696 9.975

2.708 3.255 3.887 4.615 5.448 6.397 7.473 8.687 10.051

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

2.162 2.698 3.333 4.078 4.944 5.942 7.083 8.377 9.834

2.216 2.732 3.346 4.068 4.916 5.903 7.048 8.368 9.882

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

Water

Methanol

Ethanol

n-Propanol

103xexp 1

103xcal A

Isopropyl Alcohol 2.102 2.091 2.534 2.551 3.145 3.104 3.727 3.767 4.533 4.558 5.578 5.501 6.513 6.621 8.044 7.950 9.491 9.522 DMF 22.998 23.225 27.019 26.896 31.015 30.957 34.962 35.423 41.180 40.310 45.849 45.633 51.141 51.401 56.705 57.627 64.910 64.318 Ethyl Acetate 0.976 0.954 1.198 1.154 1.360 1.387 1.602 1.659 1.946 1.975 2.342 2.339 2.788 2.759 3.306 3.239 3.736 3.786 Acetonitrile 0.725 0.716 0.912 0.903 1.090 1.126 1.409 1.385 1.690 1.685 2.004 2.027 2.406 2.413 2.881 2.845 3.308 3.324

103xcal v 2.016 2.504 3.087 3.779 4.595 5.552 6.669 7.963 9.457 23.422 26.996 30.964 35.353 40.188 45.494 51.298 57.624 64.498 0.946 1.149 1.386 1.661 1.979 2.345 2.763 3.240 3.779 0.750 0.926 1.134 1.379 1.667 2.002 2.391 2.840 3.354

a

xexp 1 refers to the experimental mole solubility of INH; xcal A and xcal v are the calculated mole solubility by the modified Apelblat equation and van’t Hoff equation, respectively. The standard uncertainty of temperature is u(T) = 0.05 K. The relative standard uncertainty of the solubility measurement is ur(x) = 0.02. The relative uncertainty of pressure is ur(p) = 0.05.

3. RESULTS AND DISCUSSION

where m1 is the mass of INH in the saturated solution; m2 is the mass of the pure solvent. M1 and M2 are the molecular mass of INH and the corresponding pure solvent. For a binary solvent mixture, the initial mole fraction (x20) in the solvent mixture and the mole fraction solubility (x1) of INH in the mixed solvent were calculated by x2 0 =

x1 =

m2 /M 2 m2 /M 2 + m3 /M3

m1/M1 m1/M1 + m2 /M 2 + m3 /M3

3.1. Physical Properties of INH. The INH solid phase was equilibrated to be the same crystal form with the solution in all studied pure and binary mixed solvents, according to PXRD and DSC data. As can be seen in Figure 2, the PXRD patterns of equilibrated INH crystal phase were found to be same in all studied solvent systems, which demonstrates the absence of crystal phase transformation during solubility measurements. The characteristic peaks of the PXRD pattern match well with those reported in the literature,12 suggesting the same crystal form of INH. The thermal analysis data by DSC confirms the only one crystal form of INH equilibrated with the solution, and a typical DSC curve was plotted in Figure 3. The onset point of the endothermic peak in the DSC result was considered as the melting temperature of INH, Tm, which was determined to be

(2)

(3)

where m1, m2, and m3 are the mass of INH, organic solvent, and water, respectively; M1, M2, and M3 represent their corresponding molecular mass. C



Article

446.04 K with an accuracy of ±0.5 K, and the enthalpy of fusion (ΔfusH) was 28.13 kJ·mol−1 (the uncertainty is 1.41 kJ·mol−1 at 0.95 level of confidence). These data were in excellent agreement with the reported values 445.84 ± 0.5 K and 27.912 ± 0.28 kJ·mol−1 in the literature.11 The entropy of INH fusion (ΔfusS) was calculated to be 63.07 J·K−1·mol−1 by eq 4. ΔfusS = ΔfusH /Tm

(4)

3.2. Experimental Solubility Data of INH in Pure and Binary Mixed Solvents. The mole fraction solubility (x1) data of INH in eight pure solvents at temperatures from (283.15 to 323.15) K are tabulated in Table 2 and plotted in Figure 4.

Figure 5. Mole fraction solubility (x1) of isoniazid in methanol, ethanol, and ethyl acetate in this paper compared to the literature.10

At a given temperature, the order of solubility in pure solvents follows DMF > water > methanol > ethanol > n-propanol > isopropyl alcohol > ethyl acetate > acetonitrile. To understand this solubility behavior, the correlation between solubility values and solvent properties, for example solvent polarity, was examined. According to the literature,13 the polarity rank of eight solvents utilized in this work is water (100) > methanol (76.2) > ethanol (65.4) > n-propanol (61.7) > isopropyl alcohol (54.6) > acetonitrile (46) > DMF (40.4) > ethyl acetate.23 Evidently, the order of solubility in eight pure solvents is not strictly consistent with the rank of solvent polarity, and thus is not in compliance to the principle of “like dissolves like”.14,15 This is not unexpected given lots of other factors such as steric hindrance, surface tension, or even solvent−solvent interactions affecting the solubility rank.16−18 On the basis of the above solubility data in pure solvents, water could be a potential solvent for purification of INH using the crystallization technique. Nevertheless, the remarkably high solubility of INH in water limits the crystallization yield. Antisolvent crystallization is a desirable and commonly applied approach to improve the yield of INH crystallization. Therefore, the solubility of INH in a binary solvent mixture of water + alcohols (methanol, ethanol, and isopropyl alcohol) was experimentally determined. The mole fraction solubility (x1) data of INH in binary mixed solvents at temperatures ranging from 283.15 to 323.15 K was summarized in Tables 3−5 and demonstrated in Figure 6. It can be intuitively seen that for all selected binary solvent systems, when the composition of the solution is given, the solubility and temperature are positively correlated. As shown in Figure 6, at a given temperature, INH solubility curves all display a maximum value at 0.2−0.4 solute-free mole fraction of alcohols in binary solvent mixtures of methanol− water, ethanol−water, and isopropyl alcohol−water. The phenomenon is referred to as cosolvency and was reported in many other systems,19,20 likely due to complex intermolecular interactions among solute, solvent, and antisolvent molecules. Moreover, the maximum solubility values were found to vary with temperature and toward the direction of decreasing water content as the temperature increases. 3.3. Correlation of Solubility Data. To expand the application scope of solubility data, the modified Apelblat equation, van’t Hoff equation, CNIBS/R-K equation, and Apel-JA

Figure 4. Experimental mole solubility of INH in eight pure solvents from 283.15 to 323.15 K (p = 0.1 MPa).

The comparison of solubility data determined in this study from the literature values10 is shown in Figure 5. The agreement is generally acceptable, and the average deviation of solubility data of isoniazid in methanol, ethanol, and ethyl acetate is 9.5% possibly due to factors such as filtering ways, equilibration time, and impurity types. It can be seen in Figure 4 that as expected the solubility of INH increases with increasing temperature, but the extent (or slope) of temperature-dependence of INH solubility shows large discrepancies in different solvents. Among eight solvent systems, the solubility of INH in water displays the largest temperaturedependence with a five times increase in solubility values when the temperature increases from 283.15 K to 323.15 K. Consequently, these data suggest that the purification of INH by cooling crystallization in water could be the best suitable option. D



Article

Table 3. Experimental and Correlated Mole Solubility of INH (x1) in Methanol (x20) + Water Binary Mixed Solvent from 283.15 K to 323.15 K (p = 0.1 MPa)a x20

103xexp 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

10.582 11.164 12.479 14.295 15.115 14.550 13.247 11.007 8.816 7.068 5.741

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

13.397 13.986 15.415 17.388 17.806 17.211 15.473 13.143 10.434 8.313 6.702

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

15.923 16.988 19.266 21.316 21.809 20.694 18.394 15.470 12.481 9.922 7.966

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

19.794 21.585 24.147 26.010 26.292 24.815 22.001 18.662 15.206 11.903 9.609

0 0.1 0.2 0.3 0.4 0.5

24.012 26.411 29.313 30.962 30.771 28.592

103xcal A T = 283.15 10.712 11.089 12.444 14.202 15.122 14.525 13.137 10.975 8.857 7.142 5.746 T = 288.15 13.180 13.920 15.599 17.482 18.159 17.359 15.582 13.117 10.550 8.414 6.790 T = 293.15 16.160 17.354 19.392 21.359 21.729 20.661 18.422 15.606 12.539 9.921 8.013 T = 298.15 19.748 21.492 23.916 25.909 25.912 24.492 21.712 18.485 14.875 11.704 9.444 T = 303.15 24.057 26.451 29.275 31.218 30.800 28.922

103xcal R

103xcal v

x20

103xexp 1

10.526 11.223 12.637 14.123 14.989 14.714 13.250 11.052 8.775 6.942 5.829

10.347 10.999 12.522 14.256 14.771 14.293 12.858 10.841 8.563 6.766 5.540

0.6 0.7 0.8 0.9 1

25.441 21.523 17.582 13.922 11.175

13.318 14.104 15.591 17.066 17.809 17.321 15.580 13.055 10.423 8.229 6.773

12.943 13.860 15.650 17.515 17.949 17.224 15.422 13.040 10.376 8.195 6.671

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

29.615 32.903 35.889 37.424 36.671 33.992 29.035 25.726 20.902 16.573 13.142

15.769 17.290 19.314 21.047 21.710 20.842 18.555 15.466 12.348 9.790 8.097

16.068 17.329 19.412 21.370 21.667 20.625 18.382 15.586 12.491 9.861 7.983

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

35.416 39.049 42.797 45.094 43.236 40.307 35.638 30.291 24.426 18.703 15.139

19.673 21.832 24.145 25.833 26.201 24.918 22.183 18.631 15.015 11.923 9.668

19.802 21.503 23.905 25.899 25.991 24.548 21.782 18.518 14.943 11.793 9.495

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

42.142 47.447 51.094 51.930 49.969 46.198 40.830 34.576 28.674 22.811 17.920

23.872 26.717 29.262 30.768 30.668 28.809

24.237 26.495 29.236 31.190 30.990 29.051

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

51.677 57.443 61.632 62.098 60.048 54.428 47.088 40.692 34.122 26.984 21.118

K

K

K

K

K

103xcal A T = 303.15 25.512 21.802 17.611 13.815 11.115 T = 308.15 29.216 32.361 35.578 37.374 36.494 34.029 29.889 25.611 20.811 16.312 13.063 T = 313.15 35.374 39.365 42.946 44.471 43.110 39.895 34.920 29.969 24.546 19.264 15.333 T = 318.15 42.707 47.626 51.505 52.609 50.775 46.615 40.686 34.938 28.898 22.755 17.973 T = 323.15 51.415 57.321 61.391 61.892 59.633 54.290 47.281 40.587 33.961 26.879 21.039

103xcal R

103xcal v

25.525 21.489 17.435 13.919 11.238

25.667 21.876 17.772 14.020 11.229

29.446 33.198 35.985 37.184 36.454 33.876 29.924 25.294 20.673 16.572 13.265

29.471 32.424 35.523 37.336 36.742 34.192 30.084 25.705 21.018 16.574 13.208

35.222 39.492 42.818 44.367 43.613 40.553 35.720 29.977 24.217 19.109 15.010

35.613 39.426 42.895 44.437 43.324 40.034 35.083 30.048 24.724 19.490 15.455

42.079 47.612 51.003 51.826 50.084 46.184 40.798 34.687 28.535 22.851 17.932

42.779 47.645 51.490 52.600 50.821 46.642 40.716 34.953 28.936 22.802 17.996

51.441 57.902 61.572 62.053 59.493 54.493 47.915 40.661 33.497 26.959 21.345

51.097 57.242 61.459 61.939 59.322 54.085 47.036 40.469 33.700 26.547 20.856

K

K

K

K

K

a

cal cal cal x20 is the initial mole fraction of methanol in the mixed solvent; xexp 1 refers to the experimental mole solubility of INH; xA , xR , and xv are the calculated mole solubility by the modified Apelblat equation, CNIBS/R−K equation, and van’t Hoff equation, respectively. The standard uncertainty of temperature is u(T) = 0.05 K. The relative standard uncertainty of the solubility measurement is ur(x) = 0.02. The relative uncertainty of pressure is ur(p) = 0.05. The relative standard uncertainty in mole fraction of methanol in the solvent mixtures is ur(x20) = 0.005.

E



Article

Table 4. Experimental and Correlated Mole Solubility of INH (x1) in Ethanol (x20) + Water Binary Mixed Solvent from 283.15 K to 323.15 K (p = 0.1 MPa)a x20

103xexp 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

10.582 14.155 18.663 20.717 19.877 17.157 14.173 10.376 6.837 4.295 2.665

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

13.397 17.230 22.423 24.468 23.442 20.281 16.557 12.102 8.284 5.198 3.177

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

15.923 21.043 26.840 28.428 26.693 23.221 18.440 13.669 9.412 5.995 3.838

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

19.794 26.235 32.229 33.445 31.102 26.830 21.465 15.982 11.079 7.289 4.647

0 0.1 0.2 0.3 0.4 0.5

24.012 32.667 38.659 39.656 36.491 31.413

103xcal A T = 283.15 10.712 13.793 18.293 20.487 19.722 16.951 14.092 10.305 6.792 4.292 2.622 T = 288.15 13.180 17.291 22.372 24.349 23.140 20.013 16.295 11.985 8.103 5.139 3.204 T = 293.15 16.160 21.483 27.092 28.765 27.041 23.452 18.813 13.916 9.602 6.134 3.873 T = 298.15 19.748 26.466 32.503 33.789 31.474 27.288 21.689 16.130 11.306 7.298 4.636 T = 303.15 24.057 32.342 38.652 39.474 36.498 31.540

103xcal R

103xcal v

x20

103xexp 1

10.297 14.728 18.453 20.379 19.986 17.564 13.973 10.183 6.885 4.383 2.668

10.347 13.958 18.775 20.510 19.511 17.194 13.719 10.030 6.830 4.188 2.708

0.6 0.7 0.8 0.9 1

25.078 18.809 13.252 8.787 5.494

13.037 17.987 22.083 24.134 23.555 20.659 16.430 11.992 8.154 5.257 3.281

12.943 17.399 22.661 24.362 23.025 20.144 16.096 11.836 8.124 5.078 3.255

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

29.615 39.859 45.209 46.031 42.213 36.174 28.973 21.621 15.609 10.284 6.460

15.615 21.750 26.383 28.224 26.965 23.299 18.438 13.532 9.326 6.112 3.857

16.068 21.525 27.176 28.768 27.019 23.474 18.782 13.889 9.607 6.116 3.887

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

35.416 46.005 53.580 53.004 48.836 41.717 32.604 25.043 17.914 11.938 7.538

19.556 26.813 31.807 33.309 31.347 26.922 21.379 15.866 11.097 7.358 4.642

19.802 26.441 32.392 33.782 31.536 27.214 21.803 16.210 11.296 7.321 4.615

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

42.142 57.395 62.684 61.314 55.931 47.395 38.150 28.404 20.393 14.213 8.705

23.927 32.890 38.477 39.567 36.713 31.363

24.237 32.260 38.387 39.461 36.621 31.397

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

51.677 66.785 70.916 69.824 63.540 52.598 43.031 32.980 23.534 16.656 9.964

K

K

K

K

K

103xcal A T = 303.15 24.967 18.664 13.233 8.655 5.496 T = 308.15 29.216 39.222 45.582 45.878 42.173 36.225 28.698 21.561 15.401 10.235 6.458 T = 313.15 35.374 47.222 53.331 53.060 48.562 41.355 32.940 24.867 17.826 12.069 7.525 T = 318.15 42.707 56.462 61.932 61.078 55.736 46.943 37.756 28.635 20.526 14.191 8.696 T = 323.15 51.415 67.069 71.411 69.994 63.768 52.999 43.216 32.922 23.520 16.642 9.975

103xcal R

103xcal v

25.015 18.778 13.291 8.833 5.456

25.185 18.823 13.212 8.712 5.448

29.700 39.657 45.377 45.968 42.313 36.080 28.865 21.799 15.531 10.364 6.389

29.471 39.106 45.241 45.862 42.320 36.055 28.957 21.752 15.374 10.308 6.397

35.223 46.559 52.928 53.343 48.855 41.445 33.009 24.874 17.774 12.001 7.588

35.613 47.114 53.040 53.046 48.680 41.221 33.145 25.021 17.804 12.131 7.473

42.601 56.467 62.985 61.970 55.751 47.023 37.709 28.836 20.861 14.009 8.473

42.779 56.431 61.873 61.076 55.751 46.930 37.778 28.654 20.523 14.205 8.687

51.996 65.891 71.767 69.915 62.803 53.121 42.799 32.914 23.984 16.282 10.032

51.097 67.213 71.834 70.015 63.582 53.215 42.886 32.678 23.554 16.551 10.051

K

K

K

K

K

a 0 cal cal cal x2 is the initial mole fraction of ethanol in the mixed solvent; xexp 1 refers to the experimental mole solubility of INH; xA , xR , and xv are the calculated mole solubility by the modified Apelblat equation, CNIBS/R-K equation and van’t Hoff equation, respectively. The standard uncertainty of temperature is u(T) = 0.05 K. The relative standard uncertainty of the solubility measurement is ur(x) = 0.03. The relative uncertainty of pressure is ur(p) = 0.05. The relative standard uncertainty in mole fraction of ethanol in the solvent mixtures is ur(x20) = 0.005.

F



Article

Table 5. Experimental and Correlated Mole Solubility of INH (x1) in I-propanol (x20) + Water Binary Mixed Solvent from 283.15 to 323.15 K (p = 0.1 MPa)a x20

103xexp 1

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

10.582 17.095 21.169 21.580 20.234 17.522 13.634 10.256 6.950 4.265 2.102

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

13.397 20.835 25.553 25.426 23.231 20.384 15.947 11.980 7.937 5.134 2.534

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

15.923 25.806 30.610 29.837 26.968 23.145 17.750 13.403 9.338 5.982 3.145

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

19.794 31.199 35.757 34.443 30.823 26.890 20.514 15.233 10.916 6.984 3.727

0 0.1 0.2 0.3 0.4 0.5

24.012 39.621 43.757 41.029 36.429 31.211

103xcal A T = 283.15 10.712 16.632 21.006 21.360 20.045 17.407 13.479 10.197 6.839 4.227 2.091 T = 288.15 13.180 20.986 25.511 25.377 23.314 20.243 15.667 11.791 8.022 5.068 2.551 T = 293.15 16.160 26.090 30.653 29.924 27.034 23.446 18.129 13.601 9.389 6.047 3.104 T = 298.15 19.748 31.984 36.460 35.034 31.257 27.050 20.887 15.655 10.964 7.181 3.767 T = 303.15 24.057 38.696 42.956 40.739 36.040 31.091

103xcal R

103xcal v

x20

103xexp 1

10.676 16.992 21.039 21.878 20.219 17.229 13.767 10.286 7.024 4.201 2.067

10.347 17.703 21.730 21.647 19.713 17.266 13.415 9.992 6.663 4.182 2.016

0.6 0.7 0.8 0.9 1

24.041 18.255 12.874 8.531 4.533

13.458 20.868 25.224 25.735 23.494 19.924 15.951 11.997 8.260 4.967 2.436

12.943 21.660 25.930 25.536 23.136 20.169 15.633 11.682 7.924 5.042 2.504

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

29.615 46.010 49.572 46.957 41.462 35.763 27.487 20.903 14.778 10.218 5.578

16.166 25.481 30.472 30.364 27.031 22.500 17.891 13.553 9.523 5.898 2.987

16.068 26.320 30.755 29.955 27.005 23.436 18.124 13.586 9.367 6.040 3.087

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

35.416 55.054 58.660 54.548 47.682 40.416 31.418 23.296 17.289 11.653 6.513

20.180 30.605 35.709 35.094 31.058 25.842 20.608 15.681 11.068 6.879 3.490

19.802 31.775 36.269 34.950 31.359 27.094 20.907 15.720 11.012 7.192 3.779

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

42.142 63.302 66.408 61.543 54.178 46.571 35.509 27.039 20.030 13.605 8.044

24.765 38.353 44.045 42.077 36.365 29.973

24.237 38.122 42.541 40.571 36.235 31.175

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

51.677 73.820 75.996 70.031 62.109 52.280 39.848 30.593 23.043 15.935 9.491

K

K

K

K

K

103xcal A T = 303.15 23.967 17.980 12.776 8.489 4.558 T = 308.15 29.216 46.238 50.155 47.072 41.443 35.609 27.394 20.607 14.858 9.993 5.501 T = 313.15 35.374 54.605 58.063 54.058 47.532 40.645 31.194 23.569 17.243 11.714 6.621 T = 318.15 42.707 63.775 66.678 61.725 54.381 46.242 35.396 26.904 19.973 13.677 7.950 T = 323.15 51.415 73.707 75.988 70.093 62.066 52.445 40.027 30.651 23.089 15.910 9.522

103xcal R

103xcal v

24.078 18.676 13.432 8.339 4.033

24.005 18.102 12.876 8.514 4.595

30.419 44.510 50.130 47.852 41.553 34.344 27.556 21.341 15.460 9.898 5.158

29.471 45.468 49.639 46.869 41.674 35.707 27.438 20.749 14.980 10.024 5.552

36.353 53.301 59.326 55.679 47.601 38.949 31.172 24.252 17.732 11.455 5.979

35.613 53.925 57.637 53.896 47.715 40.722 31.229 23.681 17.344 11.740 6.669

43.247 61.169 67.193 63.014 54.098 44.469 35.710 27.879 20.543 13.529 7.355

42.779 63.612 66.609 61.705 54.400 46.248 35.399 26.914 19.988 13.682 7.963

52.780 71.504 77.022 71.712 61.409 50.368 40.335 31.465 23.347 15.750 9.037

51.097 74.658 76.635 70.350 61.771 52.319 39.970 30.468 22.934 15.871 9.457

K

K

K

K

K

a

cal cal cal x20 is the initial mole fraction of isopropyl alcohol in the mixed solvent; xexp 1 refers to the experimental mole solubility of INH; xA , xR , and xv are the calculated mole solubility by the modified Apelblat equation, CNIBS/R−K equation, and van’t Hoff equation, respectively. The standard uncertainty of temperature is u(T) = 0.05 K. The relative standard uncertainty of the solubility measurement is ur(x) = 0.05. The relative uncertainty of pressure is ur(p) = 0.05. The relative standard uncertainty in mole fraction of isopropyl alcohol in the solvent mixtures is ur(x20) = 0.005.

G



Article

Table 7. Parameters of the van’t Hoff Equation for INH in Eight Pure Solvents solvent

a

b

102ARD

104RMSD

water methanol ethanol n-propanol isopropyl alcohol DMF ethyl acetate acetonitrile

−3653.202 −3032.593 −2999.894 −3420.049 −3535.446 −2317.143 −3168.585 −3425.670

8.331 5.514 4.683 5.966 6.280 4.429 4.227 4.903

1.241 1.125 1.087 1.223 1.563 0.996 2.070 1.772

3.551 1.624 0.573 0.598 0.751 5.256 0.414 0.302

Modified Apelblat Equation. The modified Apelblat equation, based on Clausius−Clapeyron equation, is a semiempirical expression which is widely used for the correlation of the solid−liquid equilibrium data.21,22 The relationship between the solubility of INH and temperature is expressed as follows: B ln x1 = A + + C ln(T /K ) (5) T /K where x1 is the mole fraction solubility; T refers to the absolute experimental temperature; A, B, and C are the empirical constants. The values of A and B represent the variations in the solution activity coefficient, and the value of C represents the effect of temperature on the fusion enthalpy.23,24 van’t Hoff Equation. The equation describes the relationship between the mole fraction solubility and the absolute temperature and can be empirically expressed by the following correlation a ln x1 = +b (6) T /K where a and b are model constants.25−27 For ideal mixtures or solutions with activity coefficients near 1, the parameters of eq 6 can be interpreted as enthalpy and entropy parameters. However, for the present systems the activity coefficients are unknown. The van’t Hoff equation used in this study was hence considered merely as an empirical correlation. CNIBS/R−K Equation. The (CNIBS)/Redlich−Kister equation, proposed by Acree et al.,28 expresses the correlation between the mole fraction solubility and solvent composition in binary solvent mixtures at a given temperature by N

ln x1 = x 2 ln X 2 + x3 ln X3 + x 2x3 ∑ Si(x 2 − x3)i i=0

(7)

where x1 is the mole fraction solubility of INH; x2 and x3 are the solute-free mole fraction of alcohol and water, respectively, satisfying x2 + x3 = 1; X2 and X3 represent the saturated solubility of INH in corresponding pure solvents, and Si denotes the equation parameter.29 For a binary solvent mixture, N = 2, eq 7 can be simplified as

Figure 6. Experimental mole solubility of INH in binary mixed solvent from 283.15 to 323.15 K (p = 0.1 MPa): (a) methanol + water; (b) ethanol + water; and (c) isopropyl alcohol + water.

equation were applied to correlate the solubility of INH in pure and binary mixed solvents.

Table 6. Parameters of the Apelblat Equation for INH in Eight Pure Solvents Solvent

A

B

C

102ARD

104RMSD

water methanol ethanol n-propanol isopropyl alcohol DMF ethyl acetate acetonitrile

−74.9996 −93.2445 91.2488 67.2753 −82.3291 15.6055 −17.6145 120.7154

155.1013 1469.1684 −6946.3799 −6219.7256 512.4465 −2954.4194 −2172.0179 −8715.0672

12.3832 14.6824 −12.8694 −9.1120 13.1685 −1.8273 3.2466 −17.2120

0.897 0.755 0.450 1.023 0.965 0.954 1.949 1.180

2.736 1.022 0.218 0.494 0.596 5.116 0.412 0.213

H



Article

Table 8. Parameters of the Apelblat Equation for INH in Binary Mixed Solvents 0

x2

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

A −74.9996 −10.3417 23.4013 17.0253 −54.5045 −36.6285 −52.1848 −26.7645 −83.3175 −137.9583 −93.2445

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

−74.9996 37.0361 75.3800 9.1908 −25.0659 46.3655 −73.3578 −72.4906 20.3247 −58.6014 91.2488

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

−74.9996 164.9408 99.2342 43.7604 −43.2922 −19.0781 −9.6080 −55.5568 −67.7062 −22.7927 −82.3291

B

C

Methanol + Water 155.1013 12.3832 −2897.2083 2.8466 −4321.4950 −2.2185 −3789.8232 −1.3984 −374.2661 9.1454 −1077.8568 6.4122 −309.1503 8.6689 −1514.1279 4.8884 953.0691 13.3236 3439.1711 21.4082 1469.1684 14.6824 Ethanol + Water 155.1013 12.3832 −4902.9554 −4.2515 −6194.1039 −10.1852 −2952.4632 −0.4696 −1305.7988 4.5610 −4464.1857 −6.1419 955.2522 11.6405 823.3035 11.5140 −3529.3813 −2.2763 −214.2065 9.5478 −6946.3799 −12.8694 Isopropyl Alcohol + Water 155.1013 12.3832 −10474.8384 −23.3872 −7115.3916 −13.8094 −4429.4889 −5.6612 −401.1652 7.2262 −1445.1355 3.5655 −1855.1869 2.0994 177.7176 8.9167 483.2498 10.8067 −1769.8958 4.1759 512.4465 13.1685

2

10 ARD

ln x1 = ln X3 + (ln X 2 − ln X3 + S0 − S1 + S2)x 2 + ( −S0 + 3S1 − 5S2)x 2 2 + ( −2S1 + 8S2)x 2 3

4

10 RMSD

0.897 0.769 0.649 0.640 0.779 0.661 1.001 0.714 0.730 1.103 0.755

+ ( −4S2)x 2 4

2.736 2.571 2.241 3.314 3.565 2.585 3.969 2.077 1.592 2.272 1.022

0.897 1.464 0.801 0.593 0.662 0.929 1.012 0.791 1.066 0.775 0.450

2.736 6.077 3.786 2.219 2.454 3.150 2.698 1.540 1.461 0.820 0.218

0.897 1.288 0.831 0.605 0.535 0.628 0.997 1.243 0.632 1.112 0.965

2.736 5.032 4.637 2.946 2.242 2.043 2.343 2.395 0.728 1.110 0.596

(8)

Equation 8 can be further simplified as ln x1 = B0 + B1x 2 + B2 x 2 2 + B3x 2 3 + B4 x 2 4

(9)

where B0, B1, B2, B3, and B4 are the equation constants and regressed from solubility data by nonlinear least-squares method.30,31 Apel−JA Equation. The Jouyban−Acree equation describes the effects of both solvent composition and temperature on solubility in binary mixed solvent systems, defined as follows: N

ln x1 = x 2 ln X 2 + x3 ln X3 + x 2x3 ∑ i=0

Ji T

(x 2 − x3)i

(10)

32,33

where Ji is the adjust equation parameter. By combining with the modified Apelblat equation, the Jouyban−Acree equation can be further simplified to be eq 11, the so-called Apel−JA equation. Ax A x2 A1 + A 2 ln T + A3x 2 + 4 2 + 5 2 T T T A 7 x 24 A 6x 23 + + + A8x 2 ln T (11) T T where A0−A8 are adjustable parameters and obtained by leastsquares analysis.34,35 The values of the above model parameters were optimized by minimizing the following objective function with experimental solubility data: ln x1 = A 0 +

N

Fobj =

∑ (ln x1,expi − ln x1,cali )

(12)

i=1

xexp 1,i

xcal 1,i

in which and represent the experimental and calculated solubility of INP, respectively; N is the number of data points. The optimization procedure was carried out by a nonlinear regression method (lsqnonlin function) in MATLAB software.

Table 9. Parameters of the CNIBS/R−K Equation for INH in Binary Mixed Solvents T/K

B0

B1

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

−4.554 −4.319 −4.150 −3.929 −3.735 −3.525 −3.346 −3.168 −2.967

0.116 0.145 0.650 0.936 1.153 1.358 1.262 1.514 1.477

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

−4.576 −4.340 −4.160 −3.934 −3.733 −3.517 −3.346 −3.156 −2.957

4.259 3.797 4.048 3.953 4.111 3.788 3.660 3.864 3.282

B2

B3

Methanol + Water 6.656 −14.832 5.479 −12.568 3.705 −10.537 1.738 −7.278 0.188 −4.874 −1.366 −2.369 −0.891 −3.054 −2.802 0.152 −2.981 0.404 Ethanol + Water −6.871 0.695 −5.724 −0.661 −7.547 2.110 −8.356 3.949 −9.955 6.900 −9.653 7.092 −9.318 6.474 −11.480 10.585 −9.998 9.008 I

102ARD

104RMSD

7.469 6.268 5.516 3.893 2.780 1.579 1.830 0.283 0.220

0.882 0.783 0.945 0.567 0.505 0.918 0.906 0.205 0.664

1.093 1.344 1.653 1.350 1.494 3.422 3.433 0.942 3.946

0.567 1.208 −0.009 −0.984 −2.533 −2.763 −2.351 −4.584 −3.937

1.684 1.810 1.222 0.782 0.403 0.487 0.745 1.313 1.001

2.751 3.226 2.965 2.489 1.204 1.204 3.270 4.731 5.092

B4



Article

Table 9. continued T/K

B0

B1

283.15 288.15 293.15 298.15 303.15 308.15 313.15 318.15 323.15

−4.540 −4.308 −4.125 −3.903 −3.698 −3.493 −3.314 −3.141 −2.942

6.207 5.950 6.304 5.837 6.330 5.500 5.624 5.109 4.515

B2

Isopropyl Alcohol + Water −17.285 17.706 −17.397 18.529 −19.603 21.659 −18.730 21.043 −22.124 26.931 −19.071 22.430 −20.303 24.450 −18.511 21.989 −16.624 19.287

x20

methanol + water ethanol + water isopropyl alcohol + water

A0 A1 A2 A3 A4 A5 A6 A7 A8 102ARD 104RMSD

−3.564 −3179.972 1.808 −70.497 4329.182 332.359 −1820.212 974.967 9.999 1.616 6.403

−29.773 −1753.448 5.570 8.707 1618.021 −2486.732 1301.008 −399.657 −1.804 2.531 10.784

45.074 −4989.140 −5.656 −141.297 8785.197 −5465.433 5928.085 −2686.450 20.643 3.449 14.859

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

The average relative deviation (ARD) and absolute root-meansquare deviation (RMSD) are applied to evaluate complementarily the fitting accuracy of solubility of INH by the above four models, which are calculated as follows: ARD% =

100 N

N

∑

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

cal x1,exp i − x1, i

x1,exp i

ÄÅ ÉÑ1/2 ÅÅ cal y2 Ñ Ñ ÅÅ 1 N ijj x1,exp x − z i 1, i zz ÑÑÑÑ RMSD = ÅÅÅÅ ∑ jjj z exp zz ÑÑÑ ÅÅÅ N i = 1 jk x1, i { ÑÑÑÖ (14) ÅÇ Tables 6 and 7 listed the optimized correlation parameters of the modified Apelblat equation and van’t Hoff equation together with their ARD and RMSD values. The overall fitting ARD and 104×RMSD deviations for modified Apelblat equation are respectively 1.022% and 1.351, and 1.385% and 1.634 for van’t Hoff equation. Thus, the Apelblat equation obtains the slightly better correlation performance. The optimization parameters, ARDs and RMSDs of solubility of INH in binary mixed solvents by four equations, were tabulated in Tables 8−11. It was found that the modified Apelblat equation again fits best among the four equations and achieves the smallest overall values of ARD (0.845%) and 104×RMSD (2.482). i=1

102ARD

104RMSD

−8.270 −8.791 −10.049 −9.904 −12.952 −10.634 −11.576 −10.358 −8.942

0.975 1.623 1.668 2.108 3.069 2.801 2.745 2.690 2.285

1.480 2.397 2.998 4.654 7.179 7.962 9.209 11.469 12.035

Table 11. Parameters of the van’t Hoff Equation for INH in Binary Mixed Solvents

Table 10. Parameters of the Apel-JA Equation for INH in Binary Mixed Solvents parameters

B4

B3

(13)

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1

a

b

102ARD

Methanol + Water 8.331 1.241 8.816 0.919 8.472 0.688 7.617 0.629 7.017 0.988 6.503 0.858 6.124 1.198 6.117 0.886 6.308 1.140 6.048 1.537 5.514 1.125 Ethanol + Water −3653.202 8.331 1.241 −3595.479 8.426 1.480 −3069.452 6.865 0.865 −2808.587 6.032 0.582 −2702.379 5.607 0.839 −2584.415 5.064 0.793 −2607.192 4.919 1.430 −2701.901 4.940 1.237 −2831.927 5.015 1.023 −3143.543 5.626 1.187 −2999.894 4.683 1.087 Isopropyl Alcohol + Water −3653.202 8.331 1.241 −3292.193 7.593 2.221 −2883.037 6.353 1.315 −2696.038 5.689 0.647 −2612.693 5.301 0.770 −2535.986 4.897 0.703 −2497.425 4.509 1.016 −2550.405 4.401 1.524 −2827.473 4.975 0.875 −3050.643 5.297 1.278 −3535.446 6.280 1.563 −3653.202 −3773.263 −3639.197 −3360.310 −3180.387 −3044.256 −2966.770 −3013.051 −3134.082 −3127.143 −3032.593

104RMSD 3.551 2.632 2.293 3.330 4.167 2.949 4.319 2.231 2.410 3.234 1.624 3.551 6.163 4.803 2.223 2.768 3.478 3.517 2.266 1.479 1.036 0.573 3.551 8.340 6.429 3.428 3.012 2.214 2.375 2.697 1.291 1.142 0.751

solvents displays temperature dependence, but it bears the largest slope in water. It was further found the solubility order of INH in different solvents could not completely match the rank of solvent polarity, indicting the involvement of other influencing factors. At a given temperature, the solubility of INH exhibits a maximum in all studied binary solvent mixtures, and the maximum solubility values were found varying with temperature. Experimental solubility data was well correlated by the modified Apelblat, van’t Hoff, CNIBS/R−K, and Apel−JA models in which the modified Apelblat equation shows the best

4. CONCLUSIONS The solubility of INH in eight pure solvents (water, methanol, ethanol, n-propanol, isopropyl alcohol, DMF, ethyl acetate, and acetonitrile) and three binary mixed solvents (methanol−water, ethanol−water, and isopropyl alcohol−water) were experimentally determined by gravimetric method from (283.15 to 323.15) K. X-ray diffraction patterns and thermal analyses demonstrate the absence of crystal phase transformation during solubility measurements. The solubility of INH in all pure J



Article

fitting results. The determined solubility data and correlated equations presented in this paper could be of great importance in the design and optimization of the process of INH purification in industry.

■

(11) Forte, A.; Melo, C. I.; Bogel-Łukasik, R.; Bogel-Łukasik, E. A favourable solubility of isoniazid, an antitubercular antibiotic drug, in alternative solvents. Fluid Phase Equilib. 2012, 318, 89−95. (12) Lemmerer, A. Covalent assistance to supramolecular synthesis: modifying the drug functionality of the antituberculosis API isoniazid in situ during co-crystallization with GRAS and API compounds. CrystEngComm 2012, 14, 2465−2478. (13) Smallwood, I. M. Handbook of Organic Solvent Properties; Halsted: New York, 1996. (14) Gantiva, M.; Martínez, F. Thermodynamic analysis of the solubility of ketoprofen in some propylene glycol + water cosolvent mixtures. Fluid Phase Equilib. 2010, 293, 242−250. (15) Wang, S.; Zhang, Y.; Wang, J. Solubility Measurement and Modeling for Betaine in Different Pure Solvents. J. Chem. Eng. Data 2014, 59, 2511−2516. (16) Zhao, K.; Lin, L.; Li, C.; Du, S.; Huang, C.; Qin, Y.; Yang, P.; Li, K.; Gong, J. Measurement and Correlation of Solubility of γAminobutyric Acid in Different Binary Solvents. J. Chem. Eng. Data 2016, 61, 1210−1220. (17) Zhang, T.; Li, Z.; Wang, Y.; Li, C.; Yu, B.; Zheng, X.; Jiang, L.; Gong, J. Determination and correlation of solubility and thermodynamic properties of l-methionine in binary solvents of water + (methanol, ethanol, acetone). J. Chem. Thermodyn. 2016, 96, 82−92. (18) Tang, W.; Dai, H.; Feng, Y.; Wu, S.; Bao, Y.; Wang, J.; Gong, J. Solubility of tridecanedioic acid in pure solvent systems: An experimental and computational study. J. Chem. Thermodyn. 2015, 90, 28−38. (19) Domanska, U. Solubility of benzoyl-substituted naphthols in mixtures of hexane and 1-butanol. Ind. Eng. Chem. Res. 1990, 29, 470− 475. (20) Jouyban, A. Review of the cosolvency models for predicting solubility of drugs in water-cosolvent mixtures. J. Pharm. Pharm. Sci. 2008, 11, 32−58. (21) Apelblat, A.; Manzurola, E. Solubilities of L-aspartic, DL-aspartic, DL-glutamic, p-hydroxybenzoic, o-anisic, p-anisic, and itaconic acids in water from T = 278 K to T = 345 K. J. Chem. Thermodyn. 1997, 29, 1527−1533. (22) Manzurola, E.; Apelblat, A. Solubilities of L-glutamic acid, 3nitrobenzoic acid, p-toluic acid, calcium-L-lactate, calcium gluconate, magnesium-DL-aspartate, and magnesium-L-lactate in water. J. Chem. Thermodyn. 2002, 34, 1127−1136. (23) Zhu, L.; Wang, L. Y.; Li, X. C.; Sha, Z. L.; Wang, Y. F.; Yang, L. B. Experimental determination and correlation of the solubility of 4hydroxy-2,5-dimethyl-3(2H)-furanone (DMHF) in six different solvents. J. Chem. Thermodyn. 2015, 91, 369−377. (24) Shakeel, F.; Haq, N.; Alshehri, S.; Ibrahim, M. A.; Elzayat, E. M.; Altamimi, M. A.; Mohsin, K.; Alanazi, F. K.; Alsarra, I. A. Solubility, thermodynamic properties and solute-solvent molecular interactions of luteolin in various pure solvents. J. Mol. Liq. 2018, 255, 43−50. (25) Nordström, F. L.; Rasmuson, A. C. Prediction of solubility curves and melting properties of organic and pharmaceutical compounds. Eur. J. Pharm. Sci. 2009, 36, 330−344. (26) Fan, J. P.; Cao, Y. H.; Zhang, X. H.; Jiang, D. Q.; Yu, J. X. Determination and Modeling of the Solubilities of Oleanolic Acid and Ursolic Acid in Ethanol + Sodium Hydroxide + Water Mixed Solvents from T = 283.2 to 323.2 K. J. Chem. Eng. Data 2017, 62, 3991−3997. (27) Shakeel, F.; Haq, N.; Siddiqui, N. A.; Alanazi, F. K.; Alsarra, I. A. Thermodynamics of the solubility of reserpine in {{2-(2ethoxyethoxy)ethanol + water}} mixed solvent systems at different temperatures. J. Chem. Thermodyn. 2015, 85, 57−60. (28) Acree, W. E., Jr.; Zvaigzne, A. I. Thermodynamic properties of non-electrolyte solutions: Part 4. Estimation and mathematical representation of solute activity coefficients and solubilities in binary solvents using the NIBS and Modified Wilson equations. Thermochim. Acta 1991, 178, 151−167. (29) Barzegar-Jalali, M.; Jouyban-Gharamaleki, A. A general model from theoretical cosolvency models. Int. J. Pharm. 1997, 152, 247−250. (30) Wang, L. Y.; Li, X. C.; Zhu, L.; Sha, Z. L.; Wang, Y. F.; Yang, L. B. Experimental determination and correlation of the solubility of 4-

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.8b00785. Experimental method utilized in this study for solubility determination was verified by measuring the reported solubility data of theophylline that was previously determined using HPLC method in the literature. Data comparisons and discussions between the two methods were presented in Figure S1 and Table S1 (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Tel: 86-22-27405754. Fax: 86-2227374971. ORCID

Yifu Chen: 0000-0003-4674-5705 Weiwei Tang: 0000-0002-7998-4350 Funding

The authors are grateful for the financial support of National Natural Science Foundation of China (NNSFC 21808159, NNSFC 21676179, and NNSFC 91634117), the open foundation of State Key Laboratory of Chemical Engineering (No. SKL-ChE-18B04), and Innovative Group Project 21621004. Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) Ramaswamy, S.; Musser, J. M. Molecular genetic basis of antimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tuber. Lung Dis. 1998, 79, 3−29. (2) Lang, M. Q.; Jiang, L.; Huang, J. S. Review of Anti-tuberculosis Drug Treatment. J. Clin. Pulm. Med. 2010, 15, 1153−1154. (3) World Health Organization (WHO). Global Tuberculosis Report 2017; WHO: Geneva; 2017; http://www.who.int/tb/publications/ global_report/en/. (4) Raviglione, M.; Marais, B.; Floyd, K.; Lönnroth, K.; Getahun, H.; Migliori, G. B.; Harries, A. D.; Nunn, P.; Lienhardt, C.; Graham, S.; Chakaya, J.; Weyer, K.; Cole, S.; Kaufmann, S. H.; Zumla, A. Scaling up interventions to achieve global tuberculosis control: progress and new developments. Lancet 2012, 379, 1902−1913. (5) Zumla, A.; Nahid, P.; Cole, S. T. Advances in the development of new tuberculosis drugs and treatment regimens. Nat. Rev. Drug Discovery 2013, 12, 388−404. (6) Aitipamula, S.; Wong, A. B.; Chow, P. S.; Tan, R. B. Novel solid forms of the anti-tuberculosis drug, Isoniazid: ternary and polymorphic cocrystals. CrystEngComm 2013, 15, 5877−5887. (7) Liu, F.; Song, Y.; Liu, Y. N.; Li, Y. T.; Wu, Z. Y.; Yan, C. W. DrugBridge-Drug Ternary Cocrystallization Strategy for Antituberculosis Drugs Combination. Cryst. Growth Des. 2018, 18, 1283−1286. (8) Torregrosa, H. A.; Fernandez, I. M.; Garcia, S. M. Mixtures of mono- and disodium salts of fosfomycin. Eur. Patent 0213704, 1987. (9) Tung, H. H.; Paul, E. L.; Midler, M.; Mccauley, J. A. Crystallization of Organic Compounds: An Industrial Perspective; Wiley: New York, 2009. (10) Heryanto, R.; Hasan, M.; Abdullah, E. C. Solubility of Isoniazid in Various Organic Solvents from (301 to 313) K. J. Chem. Eng. Data 2015, 53, 1962−1964. K



Article

hydroxy-2,5-dimethyl-3(2H)-furanone (DMHF) in binary (ethanol +water) solvent mixtures. J. Mol. Liq. 2015, 208, 211−218. (31) Fan, J. P.; Zheng, B.; Liao, D. D.; Yu, J. X.; Cao, Y. H.; Zhang, X. H.; Zhu, J. H. Determination and modeling of the solubility of (limonin in methanol or acetone + water) binary solvent mixtures at T = 283.2 to 318.2 K. J. Chem. Thermodyn. 2016, 98, 353−360. (32) Jouyban-Gharamaleki, A.; Acree, W. E., Jr Comparison of models for describing multiple peaks in solubility profiles. Int. J. Pharm. 1998, 167, 177−182. (33) Jouyban, A. In silico prediction of drug solubility in water-ethanol mixtures using Jouyban-Acree model. J. Pharm. Pharm. Sci. 2006, 9, 262−269. (34) Wang, S.; Qin, L.; Zhou, Z.; Wang, J. Solubility and Solution Thermodynamics of Betaine in Different Pure Solvents and Binary Mixtures. J. Chem. Eng. Data 2012, 57, 2128−2135. (35) Ding, Z.; Zhang, H.; Han, D.; Zhu, P.; Yang, P.; Jin, S.; Li, M.; Gong, J. Solubility Measurement and Correlation of Fosfomycin Sodium in Six Organic Solvents and Different Binary Solvents at Temperatures between 283.15 and 323.15 K. J. Chem. Eng. Data 2017, 62, 3929−3937.

L


Solubility and Data Correlation of Isoniazid in Different Pure and

Recommend Documents