Solubility of p-Aminobenzoic Acid Potassium in Organic Solvents and

Article pubs.acs.org/jced

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

Solubility of p‑Aminobenzoic Acid Potassium in Organic Solvents and Binary (Water + Isopropyl Alcohol) Mixture at Temperatures from (283.15 to 318.15) K Min Su,*,† Qing Lu,† Hua Sun,*,‡,§ and Jingkang Wang§ †

School of Chemical Engineering, Hebei University of Technology, Tianjin 300130, China College of Chemical and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, Hebei 050018, China § School of Chemical Engineering, Tianjin University, Tianjin 300130, China ‡

ABSTRACT: The solid−liquid equilibrium behavior of p-aminobenzoic acid potassium (KPAB) in pure organic solvents and binary (water + isopropyl alcohol) solvents were determined over the temperature range (283.15−318.15) K using a laser dynamic method. It was found that KPAB is easily dissolved in water, polyhydroxy alcohols and amides; slightly soluble in ethyl acetate, isopropyl alcohol, and n-propanol. The solubility of KPAB in both the mono- and binary mixed solvents increases with the increasing temperature, whereas it decreases with the rise of mole fraction of isopropyl alcohol in binary (water + isopropyl alcohol) mixed solvents. The solubility in pure solvents was correlated by the modified Apelblat equation, and the solubility in binary mixed solvents was correlated with the modified Apelblat equation and Combined Nearly Ideal Binary Solvent/ Redlich−Kister (CNIBS/R-K) model. All the models give satisfactory correlation results with an average relative deviation (ARD) less than 2.5%, which provide basic data for the design of KPAB crystallization process and equipment.

1. INTRODUCTION p-Amino-benzoic acid potassium (KPAB/Potaba, C7H6KNO2, CAS No.138-84-1, Figure 1), a white crystal compound, is an

acetone mole fraction in binary solvents was 0.4 and at 312.05 K. Liu and Sun5 using the Apelblat equation, the CNIBA/R-K equation, and modified Jouyban−Acree equation correlate the solubility data of disodium 5′-guanylate heptahydrate in the water− ethanol mixture solvents, the results show that the Apelblat and CNIBA/R-K equation were more suitable applied in this binary solvent system. The solubility of potassium clavulanate in different organic solvents were determined by Liu,6 and the results were correlated with semiempirical equation such as the modified Apelblat equation. Up to now, there was no report about the solubility of KPAB, thus, there remains a strong need to determine the solid−liquid equilibrium and associated thermodynamic properties of KPAB in solvent systems within a wide temperature range. In this paper, the solubility of KPAB in pure solvents and in binary (water + isopropyl alcohol) solvent mixtures with different compositions was determined using a laser dynamic method from 278.15 to 338.15 K. The modified Apelblat equation and CNIBS/R-K model were used to correlate the experimental results.

Figure 1. Molecular structure of KPAB (MW = 175.23).

important fiber softening drug used to cure scleroderma, pulmonary fibrosis, and skin atrophy diseases.1 In the pharmaceutical industry, crystallization is a basic unit operation for purification and obtaining crystals with specific bioavailability.2 The measurement and correlation of the solubility of drugs will give aid to the design and improvement of their crystallization processes. In recent years, there are a lot of studies about the solubility measurement and correlation of the solubility data for different kinds of pharmaceutical salts. The solubility of sodium phenytoin in propylene glycol and water mixture solvents were measured by Fathi-Azarjbayjani3 and the results were correlated with the Jouyban−Acree model. Dun4 measured the solubility of ibuprofen sodium dehydrate in acetone + water mixtures and the solubility data were correlated with modified Apelblat equation, van’t Hoff equation, and CNIBS/R-K equation, it was found that the solubility of ibuprofen sodium dehydrate increasing with the temperature increasing and the maximum mole fraction solubility is 0.059575 when the © XXXX American Chemical Society

2. SOLID−LIQUID PHASE EQUILIBRIUM MODELS To select a suitable model to describe the solute solubility in solvent (x), in this work, the modified Apelblat equation was Received: November 9, 2017 Accepted: May 29, 2018

A

DOI: 10.1021/acs.jced.7b00978 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

Article

Table 1. Sources and Mass Purity of Materials chemical name

source

CAS No.

molar mass (g/mol)

mass purity (mass %)

purification method

KPAB potassium chloride ethylene glycol formamide ethanol DMF n-propanol isopropyl alcohol ethyl acetate

Zhongdan International Pharmaceutical Industry Co., Ltd. Tianjin Fengchun Chemical Reagent Technologies Co., Ltd. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co. Tianjin Chemical Reagent Co.

138-84-1 7447-40-7 107-21-1 75-12-7 64-17-5 68-12-2 71-23-8 67-63-0 141-78-6

175.23 74.55 62.07 45.04 46.07 73.09 60.10 60.10 88.11

>99 >99.5 >99.5 >99.5 >99.7 >99.5 >99.8 >99.7 >99.5

none none none none none none none none none

3. EXPERIMENTAL SECTION 3.1. Materials and Apparatus. KPAB crystals were supplied by Zhongdan International Pharmaceutical Industry Co., Ltd. (Jiangsu, China) with USP27 Standard.14 Organic solvents with analytical grade (ethylene glycol, formamide, ethanol, N,N-dimethylformamide (DMF), n-propanol, isopropyl alcohol, ethyl acetate) were purchased from Tianjin Chemical Reagent Co. (Tianjin, China). All materials above were used without further treatment and detailed information about these chemicals is listed in Table 1. Distilled-deionized water was used for all experiments. The experimental apparatus consisted of a 150 mL jacketed glass vessel, a magnetic stirring system (CJJ85-2, Shanghai Sile Apparatus Co.) and a circulating water bath. The temperature of the dissolution system was regulated by using a thermostatic water bath (uncertainty 0.05 K, CS501, Chongqing Test Equipment Co., China) and was further corrected by a silver thermometer with an uncertainty of 0.05 K. A He−Ne laser generator used to monitor the particle dissolution was purchased from the Research Institute of Laser, Beijing University. An analytical balance (Mettler Toledo, type AB204-N) having a standard uncertainty of 0.0001 g was employed to determine the mass of the solvents and solute. 3.2. Solubility Determination. The solubility of KPAB was determined by the laser dynamic method on each set temperature. The solubility of potassium chloride in water has been measured using the same method to verify the reliability of the laser dynamic method. The experimental setup for the solubility determined was shown in Figure 2. A 150 mL jacked vessel was used to contain the solute and solvent. The temperature of the contents in the

employed to correlate the solubility data of KPAB in monoorganic solvent systems; the modified Apelblat equation and CNIBS/R-K equation were employed to correlate the binary solvents of (water + isopropyl alcohol). The reliability was compared for each type of solvent system. 2.1. Modified Apelblat Equation. The mole fraction solubility dependence on temperature T can be described by using the modified Apelblat equation,7,8 which is a semiempirical equation with three parameters as shown in eq 1. The derivation can also be found in literature.9 It is a rather accurate mathematical description for solid−liquid phase equilibrium, and has been widely employed to correlate the solute solubility in pure solvents and binary systems.9,10 ln x1 = A +

B + C ln T T

(1)

In which, x1 is the mole fraction solubility of KPAB in solvents at temperature T; A, B, and C are fit parameters which can be acquired by correlating the experimental solubility. 2.2. CNIBS/R-K Model. The CNIBS/R-K equation was proposed by Acree et al.11−13 and used to calculate the solubility of solid solute in binary solvents system. It is expressed as follows: N

ln x1 = f2 ln(x1)2 + f3 ln(x1)3 + f2 f3

∑ Si(f2 i=0

− f3 )i

(2)

In which, Si is the model parameter, f 2 and f 3 are the molar fraction of solvent isopropyl alcohol (2) and water (3) in the binary solvent mixture system on a solute free basis, respectively; (x1)2 and (x1)3 are the equilibrated mole fraction solubility of KPAB (1) in isopropyl alcohol (2) and water (3), respectively; N can be equal to 0, 1, 2, 3. Depending on the values of N, four equations can be obtained from eq 2. When N = 2 and f 2 + f 3 = 1, the equation can be further simplified to eq 3. ln x1 = B1 + B2 f2 + B3f22 + B4 f23 + B5f 24

(3)

B1, B2, B3, B4, and B5 are parameters of this model, which were obtained by least-squares analysis. The average relative deviation (ARD) was employed to test the applicability and accuracy of the models used in this study, and the equation was defined as follows: ARD =

xexp 1,i

1 K

K

∑ i=1

cal x1,exp i − x1, i

x1,exp i

Figure 2. Schematic experimental setup for the solubility determination (1) laser generator; (2) jacket glass vessel; (3) condenser; (4) solvent injector; (5) solute inlet; (6) light intensity recorder; (7) photoelectric transformer; (8) superthermostatic bath; (9) magnetic stirrer; (10) magnetic stirrer; (11) thermometer.

(4)

xcal 1,i

where is the experimental value, is the value calculated using the model, and K is the number of temperature points measured in each study system. B



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vessel was controlled to be constant through a thermostatic water bath. During experiments, the contents of the vessel were stirred continuously at a required temperature, and the in situ dissolution of the solute was monitored by the laser beam penetrating the vessel. To prevent loss of the solvent through evaporation, a condenser vessel was introduced. To begin with, a predetermined 100 g of solvent was added to the vessel and kept stable at the desired temperature using the water bath. At this moment, the solvent was clear and the intensity of laser penetrating the vessel could reach 2400 which was considered the maximum value for the dissolution process. Then, a predetermined mass of KPAB was put into the inner chamber of the vessel. In the early stage of the experiment, the laser beam was blocked by the undissolved particles of KPAB in the solution, so the intensity of laser beam penetrating the vessel was lower through the scattering effect by the particles. Along with the dissolution of the particles of KPAB, the intensity of laser beam increased gradually and nearly approached the maximum value finally. Then additional solute of known mass (1−5 mg) was introduced into the vessel. This procedure was repeated every 30 min until the penetrated laser intensity could not return 90% of the maximum value (about 2200), or in other words, the last addition of solute could not dissolve completely. The total amount of the solute consumed was recorded as the dissolved mass of KPAB in 100 g of solvent. The same solubility experiment was conducted three times, and the average values were used to calculate the mole fraction solubility x1 based on the eq 5: m1/M1 x1 = m1/M1 + m2 /M 2

Figure 3. DSC curve of KPAB crystals.

Figure 4. XRD patterns of KPAB crystals before and after solubility experiment. (5)

Table 2. Comparison of the Experimental Solubility of a Potassium Chloride in Water (xexp kcl ) (p = 0.1 MPa ) with the lit Literature Data (xkcl), and the Relative Error (σkcl) Was Calculated

The mole fraction solubility of KPAB x1 in binary solvents (water + isopropyl alcohol) was calculated from eq 6, and the molar fraction of solvent isopropyl alcohol f 2 in the binary solvent mixture system was calculated from eq 7. x1 =

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

(6)

f2 =

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

(7)

xlit kcl xexp kcl σkcl/%

T/K = 283.15

T/K = 293.15

T/K = 298.15

T/K = 303.15

T/K = 313.15

T/K = 333.15

0.0703 0.0702 0.1422

0.0766 0.0767 0.1305

0.0795 0.0794 0.1258

0.0826 0.0827 0.1211

0.0881 0.0883 0.2270

0.0988 0.0987 0.1012

a Standard uncertainties u are u(T) = 0.05 K for temperature, u(P) = 10 kPa for pressure, u(xexp kcl ) = 0.001.

where m1, m2, and m3 represent the mass of the solute KPAB, isopropyl alcohol (2), and water (3), respectively, and M1, M2, and M3 are the molecular weight of KPAB, isopropyl alcohol (2), and water (3), respectively. 3.3. Properties Determination. The melting temperature (Tm) was determined by differential scanning calorimetric (DSC 214, Netzsch) with the temperature from (300 to 750) K, and the heating rate was 10 K·min−1 under the protection of N2 with flow rate 40 mL/min. The melting temperature was determined as the first peak temperature Tm = 661.70 K with an uncertainty of 0.5 K, which was shown in Figure 3. The crystal form of KPAB before and after dissolution was analyzed by X-ray diffraction which was performed on SMART APEXII (Bruker, type D8 FOCUS) in the 2θ range of 3° to 50° with a scanning speed of 12°·min−1. The measured current is 40 mA and the voltage is 40 kV. In this experiment KPAB before and after dissolution was characterized using XRD, and the results are shown in Figure 4. The XRD patterns validate that there is no form transformation phenomenon in the dissolution process.

Figure 5. Mole fraction solubility of potassium chloride in water: experiments data; ●, literature data.

△,

4. RESULTS AND DISCUSSION 4.1. Method Dependability. The solubility of potassium chloride in water at different temperatures (295−370 K) has been determined using the laser dynamic method C



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cal Table 3. Experimental (xexp 1 ) and Correlated Mole Fraction Solubility (x1 ) of KPAB in Selected Pure Solvents from (278.15 to a 338.15) K at 0.1 MPa

T/K Water 278.15 288.15 298.15 308.15 318.15 328.15 338.15 Ethlene Glycol 283.15 293.15 303.15 313.15 323.15 333.15 Formamide 283.15 293.15 303.15 313.15 323.15 333.15 Ethanol 283.15 293.15 303.15 313.15 323.15 333.15 a

102xexp 1

102xcal 1 (Apelblat)

9.2013 10.9500 12.5100 14.4067 16.1400 17.6700 19.3800

9.2471 10.8841 12.5777 14.2995 16.0218 17.7188 19.3677

9.7312 11.5432 12.7412 14.5460 15.5660 17.2406

9.8881 11.3339 12.8051 14.2822 15.7472 17.1839

7.9400 9.2900 10.4000 11.2000 11.8600 12.5200

8.0575 9.1498 10.1614 11.0649 11.8403 12.4750

0.2240 0.2320 0.2380 0.2440 0.2503 0.2520

0.2239 0.2318 0.2386 0.2443 0.2490 0.2526

T/K DMF 283.15 293.15 303.15 313.15 323.15 333.15 n-Propanol 283.15 293.15 303.15 313.15 323.15 333.15 Isopropyl Alcohol 283.15 293.15 303.15 313.15 323.15 333.15 Ethyl Acetate 283.15 293.15 303.15 313.15 323.15

102xexp 1

102xcal 1 (Apelblat)

0.1427 0.1460 0.1526 0.1536 0.1585 0.1613

0.1425 0.1469 0.1510 0.1548 0.1582 0.1613

0.0852 0.0874 0.0884 0.0929 0.0952 0.0981

0.0851 0.0871 0.0895 0.0921 0.0951 0.0983

0.0366 0.0416 0.0486 0.0496 0.0520 0.0556

0.0370 0.0418 0.0461 0.0498 0.0528 0.0550

0.0198 0.0205 0.0211 0.0216 0.0219

0.0198 0.0205 0.0211 0.0216 0.0219

cal Standard uncertainties u are u(T) = 0.05 K for temperature, u(P) = 10 kPa for pressure, and u(x1) = 0.003, which was calculated as u(x1) = | xexp 1 − x1 |.

Figure 6. Mole fraction solubility of KPAB (x1) in different solvents at different temperatures: (a) the overall solubility figure, (b) local enlarged solubility figure. A, ethylene glycol; B, water; C, formamide; D, ethanol; E, DMF; F, n-propanol; G, isopropyl alcohol; H, ethyl acetate.

Table 4. Molecular Polarity, Dipole Moment (μ), Dielectric Constants (ε), and Hildebrand Solubility Parameters (δH) for the Selected Solvents solvent molecular polarity (water = 100) μ(D) ε δH ((J/cm3)1/2)

watera 100 1.87 79.7 11.4

ethylene glycola 79.0 2.31 37.7 7.1

formamide c

84.0 3.37b 109.6b 9.2b

ethanola

DMFa

n-propanola

isopropyl alcohola

ethyl acetatea

65.4 1.70 22.4 6.5

40.4 3.80 36.7 5.9

61.7 1.70 20.1 5.8

54.6 1.66 18.3 5.6

23.0 1.70 6.02 4.4

a Taken from ref 16. bTaken from ref 17. cTaken from ref 18. A ccomparison of the molecular polarity value of ethanol from ref 18 and the dipole moment value of water from ref 17 with that from ref 16 shows that the relative errors were both less than 2.67%. Therefore, the value for formamide in refs 17 and 18 can be used for comparison with the value in ref 16.

described in section 3.2. The experiments data (xexp kcl ) were 15 lit compared with the literature data (xkcl), and the results are

compared in Table 2 and Figure 5. The relative error was lit lit calculated as %σkcl = |xexp kcl − xkcl|/xkcl × 100 and was less D



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4.2. Solubility in Pure Solvents. The solubility of KPAB in eight solvents was measured: ethylene glycol, water,

than 0.25%, which verified that the laser method was dependable.

Table 5. Regression Parameters (A, B, C), Correlation Coefficient (R2) and Average Relative Deviation (ARD) of the Modified Apelblat Equation for Solubility of KPAB in Pure Solvents in the Temperature Range of 278.15−338.15 K modified Apelblat equation solvent

A

B

C

R2

102 ARD

ethylene glycol water formamide ethanol DMF n-propanol isopropyl alcohol ethyl acetate

38.40961 49.31574 87.94620 21.56999 6.47571 −30.09917 96.22632 28.22368

−2521.39057 −3112.18762 −4606.22642 −1242.93854 −580.25670 1031.99455 −5162.42800 −1643.39237

−4.81998 −6.37909 −12.32591 −3.30801 −1.12910 4.24921 −14.39792 −4.66567

0.9924 0.9993 0.9872 0.9923 0.9679 0.9748 0.9503 0.9990

1.1942 0.4941 1.1691 0.2185 0.4632 0.4671 1.6417 0.0732

cal Table 6. Experimental (xexp 1 ) and Correlated Mole Fraction Solubility (x1 ) of KPAB in (Water + Isopropyl Alcohol) Mixed a Solvents at 0.1 MPa

volume fraction of isopropyl alcohol (vol2 %) 278.15 0 10 20 30 40 50 60 70 80 90 288.15 0 10 20 30 40 50 60 70 80 90 298.15 0 10 20 30 40 50 60 70 80 90 308.15 0 10 20 30 40

f 2b

xexp 1

xcal 1 (Apelblat)

xcal 1 (R-K)

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.0920 0.0868 0.0849 0.0818 0.0741 0.0678 0.0555 0.0384 0.0233 0.0120

0.0921 0.0864 0.0850 0.0820 0.0751 0.0673 0.0552 0.0382 0.0234 0.0118

0.0906 0.0884 0.0854 0.0812 0.0752 0.0667 0.0547 0.0393 0.0230 0.0120

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.1095 0.1020 0.0993 0.0936 0.0891 0.0752 0.0594 0.0404 0.0256 0.0134

0.1089 0.1028 0.0993 0.0940 0.0884 0.0759 0.0597 0.0409 0.0255 0.0136

0.1064 0.1046 0.1011 0.0953 0.0865 0.0743 0.0589 0.0416 0.0252 0.0134

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.1251 0.1200 0.1143 0.1074 0.1029 0.0847 0.0643 0.0441 0.0276 0.0152

0.1262 0.1196 0.1139 0.1066 0.1018 0.0850 0.0649 0.0440 0.0277 0.0153

0.1225 0.1211 0.1172 0.1100 0.0989 0.0835 0.0648 0.0449 0.0273 0.0153

0 0.02555 0.05570 0.09183 0.13591

0.1441 0.1364 0.1281 0.1203 0.1151

0.1436 0.1365 0.1283 0.1196 0.1152

0.1403 0.1378 0.1325 0.1236 0.1105

volume fraction of isopropyl alcohol (vol2 %)

K

308.15 50 60 70 80 90 318.15 0 10 20 30 40 50 60 70 80 90 328.15 0 10 20 30 40 50 60 70 80 90 338.15 0 10 20 30 40 50 60 70 80 90

K

K

K

f 2b

xexp 1

xcal 1 (Apelblat)

xcal 1 (R-K)

0.19089 0.26139 0.35505 0.48553 0.67984

0.0953 0.0712 0.0481 0.0303 0.0167

0.0946 0.0708 0.0474 0.0299 0.0170

0.0929 0.0717 0.0494 0.0299 0.0167

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.1614 0.1530 0.1421 0.1326 0.1278 0.1045 0.0778 0.0509 0.0320 0.0191

0.1608 0.1531 0.1424 0.1331 0.1282 0.1047 0.0776 0.0512 0.0322 0.0187

0.1571 0.1539 0.1475 0.1372 0.1220 0.1019 0.0778 0.0527 0.0315 0.0192

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.1767 0.1695 0.1560 0.1458 0.1393 0.1154 0.0854 0.0549 0.0341 0.0204

0.1775 0.1691 0.1559 0.1469 0.1406 0.1152 0.0852 0.0554 0.0344 0.0202

0.1728 0.1691 0.1621 0.1508 0.1342 0.1119 0.0852 0.0571 0.0334 0.0204

0 0.02555 0.05570 0.09183 0.13591 0.19089 0.26139 0.35505 0.48553 0.67984

0.1938 0.1841 0.1686 0.1617 0.1530 0.1260 0.0936 0.0603 0.0368 0.0215

0.1935 0.1843 0.1686 0.1610 0.1521 0.1262 0.0938 0.0600 0.0366 0.0217

0.1886 0.1847 0.1772 0.1649 0.1470 0.1229 0.0935 0.0625 0.0361 0.0215

K

K

K

K

a

Standard uncertainties u are u(T) = 0.05 K for temperature, u(P) = 10 kPa for pressure, u(x1) = 0.01, and u( f 2) = 0.01. bf 2 is the molar fraction of solvent isopropyl alcohol (2) in the binary solvent mixture system on a solute free basis. E



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molecule and ethylene glycol molecule/DMF molecule. It is necessary to indicate that the molecular polarity is only the main factor to influence the dissolution behaviors. The dissolution behavior of organic solute in organic solvents is very complicated, it may be due to many factors, for example, solute−solvent interactions, solvent−solvent interactions, and molecular structure and sizes, which still needs further investigation. The modified Apelblat equation was used to correlate the solubility data in pure solvents (Table 5). The ability of the Apelblat model to represent mathematically the experimental solubility is summarized as well, in the form of regression parameters, correlation efficient R2 and ARD. From the correlation coefficient in Table 5, the modified Apelblat equation has a high accuracy. On the basis of the obtained values of parameters, the solubility of KPAB at different temperatures may be calculated. The calculated solubility data with the modified Apelblat model can be used as the basic data for design and scaling up of crystallization process of KPAB. 4.3. Solubility in (Water + Isopropyl Alcohol) Mixed Solvent. In the crystallization process of KPAB, water was chosen as the good solvent, and isopropyl alcohol was selected as the antisolvent. In this section, the solubility of KPAB in (water + isopropyl alcohol) mixture solvents at different temperatures and compositions were determined (Table 6 and Figure 7), which provided foundation for the design of the crystallization process. From Figure 7, it is illustrated that the solubility of KPAB is a function of solvent composition and temperature in (water + isopropyl alcohol) mixed solvents. The solubility of KPAB increases with increasing temperature from 278.15 to 338.15 K. The addition of antisolvent isopropyl alcohol depresses the solvation of KPAB in water, expressed by the decrease of solubility with the increase in the volume fraction of isopropyl alcohol in mixed solvent. It also can be seen that the depressing effect of isopropyl alcohol gets stronger when the volume fraction of isopropyl alcohol in mixed solvents exceeds 50%. This behavior can be explained by the molecular polarity of the solvent mixture. With the increase in composition of isopropyl alcohol, the polarities of the solvent mixture decrease, the solubility of KPAB decreases with the increase in volume fraction isopropyl alcohol. The mole fraction solubility of KPAB supplied a basic data for the selection of temperature and composition of the antisolvent in mixtures. The CNIBS/R-K equation and Apelblat equation were used to correlate the solubility of KPAB in a binary mixture solvent. The model parameters, correlation coefficients, and the ARD of the two models for the binary solvent systems are listed in Tables 7 and 8. It can be seen that the CNIBS/R-K model at N = 2 gives a correlation efficient higher than 0.997 and the ARD value less than 2.5%, and thus can accurately describe the solubility of KPAB in (water + isopropyl alcohol) mixtures.

Figure 7. Solubility of KPAB in (water + isopropyl alcohol) mixed solvents.

formamide, ethanol, DMF, n-propanol, isopropyl alcohol, and ethyl acetate. The solubility data of KPAB in selected solvents was listed in Table 3 and plotted in Figure 6. It was found that the solubility of KPAB in ethyl acetate, isopropyl alcohol, n-propanol, ethanol, and DMF are around 10−4 to 3 × 10−3 in mole fraction basis, with the following order: ethanol > DMF > n-propanol > isopropyl alcohol > ethyl acetate (Figure 6b). The solubility of KPAB in ethylene glycol, water, and formamide are much higher than that in the above solvents, around 10−2 in a molar fraction basis, with the following order: water > ethylene glycol > formamide. In respect to the effect of temperature, the molar solubility of KPAB in all solvents increases almost linearly with increasing temperature. The molecular polarity is generally an important factor to influence the solubility of KPAB in the studied solvents. The mole fraction solubility of KPAB generally increases with the increase in polarities, dielectric constants (ε), and Hildebrand solubility parameters (δH) of solvents. This behavior is perhaps due to the strong molecular polarity of the KPAB molecule. The polarities of water, ethylene glycol, and formamide are relatively much stronger compared to the rest of the solvents (Table 4), and as a result, the KPAB solubility in these solvents is relatively high (Figure 6a). For the same reason, the polarities of water and ethyl acetate are the strongest and the weakest (Table 4), so the KPAB solubility in water and ethyl acetate is the highest one and the lowest one among the studied solvents (Figure 6b). However, there are also exceptions. The solubility of KPAB in ethylene glycol exceeds that in formamide even though the molecular polarity value of ethylene glycol is smaller than formamide. A similar phenomenon was also found for DMF. This may be due to stronger H-bonds formed between the KPAB

Table 7. Parameters (B1, B2, B3, B4, B5), Correlation Coefficient (R2) and Average Relative Deviation (ARD) of CNIBS/R-K Model for Solubility of KPAB in Binary Water + Isopropyl Alcohol Solvent Mixtures T/K

B1

B2

B3

B4

B5

R2

102ARD

278.15 288.15 298.15 308.15 318.15 328.15 338.15

−2.40123 −2.24093 −2.09983 −1.96412 −1.85092 −1.75585 −1.66828

−0.90766 −0.41185 −0.11619 −0.40048 −0.51677 −0.55526 −0.55245

−2.43480 −9.47938 −13.03080 −12.03379 −11.68024 −11.11794 −10.77612

−8.62328 9.84990 17.80849 15.92327 13.70109 11.24053 10.01241

11.38301 −2.37517 −7.38128 −6.07075 −3.08848 −0.70215 0.18302

0.9991 0.9982 0.9984 0.9977 0.9971 0.9974 0.9974

1.2995 1.8583 1.6970 2.1530 2.3289 2.2864 2.2135

F



■

Table 8. Parameters (A, B, C), Correlation Coefficient (R2) and Average Relative Deviation (ARD) of Apelblat Equation for the Solubility of KPAB in Water + Isopropyl Alcohol vol2 %

A

B

C

R2

102ARD

0 10 20 30 40 50 60 70 80 90

53.39337 60.93349 52.12391 11.83233 58.71881 −4.72029 −58.37597 −47.17900 0.14449 45.41459

−3511.36929 −3877.47286 −3381.57036 −1536.28769 −3714.86404 −732.06437 1828.02334 1406.67256 −766.40229 −3068.01030

−7.66751 −8.78477 −7.53913 −1.56532 −8.52000 0.82681 8.68958 6.90412 −0.20353 −6.89832

0.9995 0.9998 0.9999 0.9990 0.9983 0.9992 0.9990 0.9951 0.9967 0.9918

0.4082 0.2817 0.1402 0.5130 0.7402 0.4813 0.4662 0.7900 0.5872 1.4155

NOMENCLATURE x1 = mole fraction of KPAB in the solution T = absolute temperature, K A, B, C = empirical parameters R = gas constant, J·mol−1·K−1 Tm = melting temperature, K Si = model parameters of (CNIBS)/Redlich−Kister equation f 2 = molar fraction of isopropyl alcohol f 3 = molar fraction of water B1, B2, B3, B4, B5 = model parameters of (CNIBS)/Redlich− Kister equation K = number of temperature points R2 = correlation coefficient

Greek Letters

σ = relative error μ = dipole moment ε = dielectric constants δ = solubility parameters

The correlation coefficient R2 of the Apelblat equation is higher than 0.990, and the ARD value is less than 1.5%, demonstrating that the Apelblat equation also gives a satisfactory description for the solubility of KPAB in binary solvents (water + isopropyl alcohol). It can be found that both the Apelblat model and the CNIBS/R−K model can provide accurate mathematical representation for the variation of the solubility of KPAB in the binary (isopropyl alcohol + water) solvent mixtures at different temperatures and solvent composition.

Superscripts

cal = calculated data exp = calculated value lit = literature data Subscripts

5. CONCLUSION The solubility of KPAB in pure organic solvents and binary (water + isopropyl alcohol) solvent mixtures within the temperature range from 278.15 to 338.15 K were measured using a laser dynamic method. The mole fraction solubility of KPAB in water, ethylene glycol, and formamide is on the order of 10−1, while in other pure organic solvents it is on the order of 10−3. Water and isopropyl alcohol can be selected as the good solvent and antisolvent, respectively, for crystallization of KPAB. The solubility of KPAB increases with the increase of temperature both in mono-sovents or binary solvents, while decreases with the increase of isopropyl alcohol content in the binary (water + isopropyl alcohol) solvent mixtures, which means that by cooling the solvent from 383.15 K to 278.15 K, and by adding the antisolvent isopropyl alcohol into the aqueous solution, the mole fraction solubility of KPAB in the binary solvents can decrease from 0.194 to 0.012. The modified Apelblat model can correlate the solubility of KPAB in pure solvents with acceptable error, while the modified Apelblat model and CNIBS/R−K model can reasonably match the experimental data in (water + isopropyl alcohol) binary solvents. All of these models showed satisfactory correlation results with the experimental values.

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m = melting p = pressure

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. Fax: 86-022-60204274. *E-mail: [email protected]. Fax: 86-0311-88632183. ORCID

Min Su: 0000-0002-4824-5651 Funding

This study was supported by the National Natural Science Foundation of China (No. 21406050), Natural Science Foundation of Hebei Province (No. B2015208106), and Hebei Food and Drug Administration (ZD2015026). Notes

The authors declare no competing financial interest. G



Article

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Solubility of p-Aminobenzoic Acid Potassium in Organic Solvents and

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