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Solubility Data as a Response for a Challenge for Formulation Chemists: Imidazolium-Based Ionic Liquids and Antitubercular Antibiotic Medicines Ricardo A. M. Faria,†,‡ Tiago F. M. Vieira,† Catarina I. Melo,† and Ewa Bogel-Łukasik*,† †

LAQV, REQUIMTE, Departamento de Química, Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, 2829-516 Caparica, Portugal ‡ Faculty of Science, Plant and Environmental Sciences, University of Copenhagen, Thorvaldsensvej 40, DK-1871 Frederiksberg C, Denmark S Supporting Information *

ABSTRACT: The evolution of technology is directed to reduce industrial waste from chemical processes to zero. In the past decade interest in ionic liquids (ILs) has grown, and they have been recognized as potential substitutes for volatile organic solvents used in certain chemical processes, including those in the pharmaceutical industry. Following this increasing interest and because ILs can have a great potential for the pharmaceutical industry, we tested the solubility of two antitubercular medicines, pyrazinecarboxamide and isoniazid, in imidazolium ionic liquids, namely [C4mim][BF4], [C4mim][PF6], [C4mim][OTf], and [C8mim][OTf], in the range of 279.98 to 417.05 K. Both drugs exhibited an improved solubility in [C4mim][BF4] than in the other studied ILs. The solutes had an enhanced solubility in more hydrophilic ILs, such as [C4mim][BF4] and [C4mim][PF6]. The solubility decreased in ILs containing the hydrophobic anion trifluoromethanesulfonate and with the increasing alkyl chain length in the cation. The solid−liquid phase equilibria of all investigated systems were described using six different correlation equations. The satisfactory results which revealed a good description with an acceptable standard deviation temperature range were collected for isoniazid or pyrazinecarboxamide in [C4mim][PF6], [C4mim][OTf] and [C8mim][OTf]. Comparison to solubility in NTf2 and [C10mim][OTf] was provided. industries, such as oil refining or the bulk or fine chemicals sectors.5 Ionic liquids (ILs) have been proposed as a green alternative for VOCs in the pharmaceutical industry,6−8 mainly due to being sufficient, nonflammable, and thermally stable solvents, with insignificant vapor pressure9 for many groups of compounds.10 The use of volatile classical solvents in operations such as granulation, blending, compounding, and drying creates flammable or explosive atmospheres. Flammable solvents require a specific engineering design, and certain features of pharmaceutical facilities and process equipment,11 that can be overcome by use of ionic liquids due to their nonflammability and negligible vapor pressure. These properties can be considered as beneficial compared to those represented by common pharmaceutical solvents. Ionic liquids with a short alkyl chain appended in the imidazolium cation and with hydrophilic anions exhibit low toxicity on Daphnia magna, algae, bacteria, fish, and humans.12,13 The [C4mim] and [C6mim] cations are nontoxic toward Caco-2 cells, and the [C8mim] cation has a slightly higher toxicity.14

1. INTRODUCTION Tuberculosis (TB) is a disease that kills three times more people within a minute than other diseases together in the World. In 2013 there were 9 million new cases of TB, and 0.6 million people were provided with isoniazid as a preventive therapy.1 The value of the total Global Fund financed purchases for 2012 for antitubercular medicines was $54,259 for rifampicin, $134,548 for pyrazine-2-carboxamide, and $185,856 for isoniazid.2 In pharmacology, solubility is recognized as the anticipated concentration of drug in the system and focuses on obtaining a homogeneous solution due to dissolution of solute in the solvent. Formulation chemists and scientists need solubility data to design new products from conception to commercialization. The drug must exhibit an absorption feature to be absorbed.3 Volatile organic solvents, VOCs, frequently used in pharmaceutical industries and chemical processes, amount up to 350 million tons of hazardous and toxic waste, per year, in the United States of America. These compounds are generally dangerous for the environment and, as a consequence, it is expensive to safely dispose of them.4 In the pharmaceutical industry the Sheldon E-factor of 25−100, defined as the mass ratio of waste to desired product, is the highest among other © XXXX American Chemical Society

Received: March 6, 2016 Accepted: July 20, 2016

A

DOI: 10.1021/acs.jced.6b00201 J. Chem. Eng. Data XXXX, XXX, XXX−XXX

Journal of Chemical & Engineering Data

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the pharmaceutical industry due to their ability to perform liquid−liquid extractions,24 to increase chemeo- and enantioselectivity,25,26 and to increase yield.27 The best known large scale application of an imidazolium based IL is its use in BASF’s BASIL process in the synthesis of alkoxyphenylphosphines.28−30 The solubility of TB medicines, such as pyrazinecarboxamide (IUPAC name: pyrazine-2-carboxamide) and isoniazid (IUPAC name: isonicotinohydrazide) have been reported for ammonium,31 phosphonium,32,33 and some imidazolium7,34,35 ILs. This work aimed to provide more solubility data on two antibiotic medicines used in the treatment of TB, namely pyrazinecarboxamide and isoniazid, in several ILs composed by imidazolium cations, to see the effect of the anion (tetrafluoroborate [BF4], hexafluorophosphate [PF6], trifluoromethanesulfonate [OTf]), as well as influence of the alkyl chain length of the cation by investigating 1-alkyl-3methylimidazolium trifluoromethanesulfonate [C n mim] [OTf], (n = 4, 8) and comparison with n = 10.7,35 The molecular structures for the antitubercular compounds and the ionic liquids that were used in this work are presented in Figure 1.

Figure 1. Structure of the solvents and solutes used in this work: (a) 1butyl-3-methylimidazolium cation with hexafluorophosphate, tetrafluoroborate, or trifluoromethanesulfonate (from left to right); (b) 1octyl-3-methylimidazolium trifluoromethanesulfonate; (c) 1-decyl-3methylimidazolium trifluoromethanesulfonate; (d) pyrazinecarboxamide; (e) isoniazid.

2. EXPERIMENTAL PROCEDURE 2.1. Solid−Liquid Equilibria Measurement. Solid−liquid equilibria (SLE) of the studied systems were performed at 0.1 MPa and at a temperature range from 279.98 to 417.05 K, using a dynamic method.36−38 The solutions containing the ionic liquids and TB drugs (presented in Table 1) were weighted with an accuracy of 10−4 g and placed into a Pyrex glass cell which was capped with a Teflon valve at the end of a capillarythin (inner diameter of 0.1 mm) neck. The cell was placed in a temperature-controlled bath with water (293−333 K) with 10% methanol (267−293 K) or silicon (333−416 K). The prepared mixture of solute and solvent was stirred and heated slowly with a maximum heating rate of 2 K·h−1 near the equilibrium temperature. The measurement cell was placed in a thermostatic bath. The experimental solubility point was detected at the temperature where the last crystal was dissolved in the solution forming homogeneous system. A calibrated DOSTMANN electronic P600 thermometer with a Pt 100 probe placed in the thermostatic bath was used in this study. The standard uncertainty of the temperature measurements was 0.03 K and of the mole fraction was 0.0005. The reliability of the experimental SLE solubility curves was validated by using six different correlation equations, namely Wilson, universal quasichemical (UNIQUAC), UNIQUAC

Taking into consideration that pharmaceutical excipients, such as the nonionic surfactants (e.g., polysorbate 80), exhibit similar toxicities to several ILs,15 these could compete with common solvents in pharmaceutical processes. Following the classification of solvents according to their volatility, ionic liquids definitely can be recognized as green solvents because they offer “safer” manufacturing processes11,16 and are suitable for pharmaceutical processing.6,8 Although some ILs have a high toxicity, this does not exclude them from having pharmaceutical applications, due to benefits based on their nonflammability and negligible volatility as compared to that of volatile organic solvents. Ionic liquids have been claimed as “green” solvents because they prevent the emissions of volatile compounds. Furthermore, IL properties can be tuned for specific applications, such as media for processes,17−19 and separation,20 API,21 or catalysts,17 by exchanging the anion or cation. Therefore, it is essential to study various solvents to optimize solvent dependency (solubility, polymorphism, crystallinity, and crystal habit of pharmaceutical compounds).6,22,23 Imidazolium-based ILs are of great interest to Table 1. Characteristics of Chemicals Used in This Study

chemical name [C4mim][BF4]a [C4mim][PF6]b [C4mim][OTf]c [C8mim][OTf]d Isoniazid Pyrazine-2-Carboxamide (pyrazinecarboxamide)

source

initial mass fraction purity

Iolitec, Germany

>95 mol %

Fluka SigmaAldrich

≥99 mol % ≥98 mass%

purification method degassed, dried, and freed from residues of volatile compounds by 0.1 Pa vacuum at T = 333.15 K for minimum 48 h prior to experiments

final mass fraction purity ≥99 mol %

water content in the final sample/ppm 120 110 130 130

analysis method NMR and Coulometric Karl Fischer titration

none

a

1-Butyl-3-methylimidazolium tetrafluoroborate. b1-Butyl-3-methylimidazolium hexafluorophosphate. c1-Butyl-3-methylimidazolium trifluoromethanesulfonate. d1-Octyl-3-methylimidazolium trifluoromethanesulfonate. B



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Table 2. Thermophysical Properties of Compoundsa value solute isoniazid pyrazinecarboxamide (pyrazine-2carboxamide) [C4mim][BF4]

[C4mim][OTf]

[C4mim][PF6]

parameter

in this work

melting point, Tfus, (K) enthalpy of fusion, ΔfusH (kJ·mol−1) melting point, Tfus,(K) enthalpy of fusion, ΔfusH (kJ·mol−1) glass transition temperature, Tg (K)

189.86 ± 0.50

melting point, Tfus, (K) enthalpy of fusion, ΔfusH (kJ·mol−1) temperature of freezing, Tfr (K) melting point, Tfus, (K)

249.60 ± 0.50 291.46 ± 0.50

enthalpy of fusion, ΔfusH (kJ·mol−1) entropy of crystal-to-crystal transition, ΔfusSm (J·K−1·mol−1) phase transition temperature Tr (K) glass transition temperature, Tg (K) (α-phase)77

20.18 ± 0.20

melting point, Tfus, (K) (γ-phase)77

286.46 ± 0.50

enthalpy of fusion, ΔfusH (kJ·mol−1) (γ-phase)77

11.43 ± 0.11

198.87 ± 0.50

solid−solid transition temperature, Tsol−sol (K) [C8mim][OTf]

glass transition temperature, Tg (K) melting point, Tfus, (K)

198.21 ± 0.5 285.98 ± 0.50

enthalpy of fusion, ΔfusH (kJ·mol−1) enthalpy of solid−solid transition Δsol−solH (kJ·mol−1) solid−solid transition temperature, Tsol−sol (K)

16.54 ± 0.17 3.06 ± 0.03 215.65 ± 0.50

literature 445.84 ± 0.0535 27.91 ± 0.2835 461.42 ± 0.507 28.14 ± 0.287 185.75 ± 2.4067 188.15 ± 0.3068,69 176.1539b 190.1570b 188.00 ± 1.0071 186.30 ± 0.4072 190.41 ± 0.37(calculated)73 181.00 ± 1.0074 281.83 ± 0.56(calculated)73 20.67 ± 0.04(calculated)73 254.15 ± 0.3068 290.98 ± 0.0175 286.15 ± 0.3068 290.15 ± 0.0170b 289.00 ± 1.0076 19.43 ± 0.0275 66.8 ± 0.1075 120 ± 1.0075 196.5640,78 197.1568 193.1539b 196.1570b 196.15 ± 0.1879 190.6 ± 0.180 276.43 ± 0.0140,78 284.15 ± 0.3068 277.1539b 283.51 ± 0.0180 285.00 ± 0.0181 283.1570b 283.03 ± 0.1082 281.83 ± 0.5683 19.88 ± 0.0540,78 19.60 ± 0.0267 19.91 ± 0.2082 20.67 ± 0.0483 (calculated) 257.95/196.56 ± 0.05 (glass)40,78 193.15 ± 1.0065 284.1443b 278.15 ± 1.0065

264.2443b

Melting point, Tfus; enthalpy of fusion, ΔfusH; glass transition temperature, Tg; and temperature of freezing, Tfr were acquired using differential scanning calorimetry (DSC) in this study at p = 0.1 MPa. bUncertainties not reported. a

associated-solution model (ASM), nonrandom two liquid (NRTL), NRTL1, and NRTL2. 2.2. Differential Scanning Calorimetry. Differential scanning calorimetry (DSC) measurements were carried out on a Setaram Instrumentation, DSC-131, scanning calorimeter equipped with a thermal analysis data system. Samples of up to 5 mg were encapsulated in 30 μL aluminum crucibles and scanned in a range of 143 to 573 K at a 10 K/min heating rate.

The DSC instrument was calibrated using 99.9999 mol % purity indium and zinc. Using zinc allowed us to calibrate the apparatus to detect the high melting points of the compounds investigated in this work with a calorimetric standard uncertainty of 1%. The measured values are provided with a 0.5 K standard uncertainty. Measurements were carried out under a nitrogen atmosphere with a flow rate of around 20 mL C



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Table 3. Experimental Solubility of Isoniazid (1) in Studied Ionic Liquids (2) at T = 298. 15 K and p = 0.1 MPa. γ1 Is the Activity Coefficient of the Solutea isoniazid [C4mim][BF4]

a

[C4mim][OTf]

[C4mim][PF6]

[C10mim][OTf]35

[C8mim][OTf]

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

0.0409 0.0422 0.0450 0.0612 0.0747 0.1135 0.1269 0.1428 0.1461 0.1544 0.1599 0.1692 0.1815 0.1855 0.2082 0.2123 0.2442 0.2535 0.2754 0.3299 0.3374 0.4058 0.4067 0.4213 0.4525 0.4681 0.4740 0.4981 0.5280 0.5610 0.5812 0.6095 0.6377 0.6925 0.7299 0.7477 0.7859 0.8107 0.8286 0.8665 0.8944 0.9246 0.9529 1.0000

293.68 294.68 296.73 306.59 312.93 326.34 329.91 333.68 334.42 336.20 337.31 339.13 341.37 342.06 345.75 346.38 350.86 352.06 354.71 360.49 361.21 367.12 367.19 368.32 370.61 371.69 372.09 373.68 375.55 377.48 378.62 380.14 381.59 384.23 385.91 386.68 388.28 389.27 389.97 391.40 392.42 393.48 394.45 445.84

0.49 0.50 0.51 0.53 0.55 0.56 0.56 0.56 0.56 0.56 0.55 0.55 0.55 0.55 0.54 0.54 0.53 0.53 0.52 0.51 0.51 0.49 0.49 0.49 0.48 0.48 0.47 0.47 0.46 0.46 0.45 0.45 0.44 0.43 0.43 0.42 0.42 0.41 0.41 0.40 0.40 0.40 0.39 1.00

0.0213 0.0239 0.0264 0.0347 0.0496 0.0742 0.1024 0.1286 0.1678 0.1692 0.1764 0.1919 0.1945 0.2092 0.2188 0.2514 0.2640 0.2824 0.3244 0.3439 0.3981 0.4239 0.4805 0.4979 0.5217 0.5350 0.5536 0.5606 0.5879 0.5912 1.0000

301.45 302.02 305.46 315.28 327.94 342.24 353.69 361.79 371.25 371.55 373.01 376.01 376.49 379.08 380.68 386.11 387.36 389.75 394.68 396.75 401.96 404.19 408.64 409.91 411.56 412.46 413.67 414.12 415.81 416.01 445.84

1.27 1.16 1.19 1.27 1.35 1.38 1.37 1.35 1.31 1.31 1.30 1.29 1.28 1.27 1.26 1.24 1.22 1.20 1.16 1.15 1.10 1.09 1.05 1.04 1.02 1.02 1.01 1.00 0.99 0.99 1.00

0.0245 0.0256 0.0323 0.0347 0.0566 0.0809 0.1282 0.1505 0.1687 0.1764 0.1829 0.1894 0.1946 0.2004 0.2150 0.2206 0.2368 0.2665 0.2805 0.3003 0.3461 0.3995 0.4258 0.4816 0.4989 0.5226 0.5359 0.5544 0.5614 0.5886 0.6253 0.6883 0.7218 0.7353 1.0000

290.37 295.46 297.68 300.39 318.75 332.16 349.44 355.47 359.76 361.42 362.78 364.09 365.11 366.22 368.84 369.81 372.46 376.82 378.82 381.38 386.71 392.10 394.49 399.11 400.43 402.18 403.11 404.39 404.86 406.63 408.9 412.5 414.29 414.98 445.84

0.72 0.85 0.73 0.75 0.88 0.94 0.98 0.98 0.98 0.98 0.98 0.97 0.97 0.97 0.97 0.96 0.96 0.94 0.94 0.93 0.91 0.89 0.88 0.86 0.85 0.84 0.84 0.83 0.83 0.82 0.81 0.79 0.78 0.78 1.00

0.0223 0.0251 0.0259 0.0289 0.0312 0.0328 0.0376 0.0485 0.0501 0.0787 0.1058 0.1395 0.1723 0.1801 0.2148 0.2313 0.2478 0.2626 0.2734 0.3258 0.3294 0.3354 0.3678 0.4124 0.4476 0.4680 0.4999 0.5126 0.5189 1.0000

297.84 302.24 303.48 307.54 310.52 312.30 317.43 327.02 328.24 345.21 356.33 366.75 374.69 376.34 382.98 385.76 388.35 390.54 392.04 398.64 399.06 399.73 403.20 407.5 410.59 412.26 414.74 415.68 416.15 445.84

1.06 1.11 1.13 1.17 1.20 1.22 1.26 1.34 1.34 1.42 1.43 1.41 1.39 1.38 1.35 1.34 1.32 1.31 1.30 1.26 1.26 1.25 1.23 1.19 1.17 1.16 1.14 1.13 1.13 1.00

0.0062 0.0079 0.0203 0.0272 0.0407 0.0582 0.0746 0.1004 0.1206 0.1448 0.1678 0.2048 0.2431 0.2997 0.3500 1.0000

314.17 320.70 333.76 341.20 352.01 360.91 366.64 374.02 378.94 383.79 387.83 391.69 396.11 401.69 406.42 445.84

6.93 6.70 3.94 3.66 3.31 2.92 2.64 2.35 2.20 2.05 1.93 1.73 1.60 1.46 1.38 1.00

Standard uncertainties u are u(T) = 1.00 K, ur(x) = 0.0005.

min−1. The mass balances were performed using a Mettler Toledo AT21 comparator with the precision of ±1 μg.

and other published values can be attributed to differences in the scanning rates, impurities (such as water content) and at what point the transition temperature is extracted (peak vs transition onset).39,40 In our study, all temperatures were extracted from the apex of the peaks. It is however worthy to mention that two exothermic changes were detected for [C8mim][OTf] (Figure 4). In the first cooling run the IL crystallizes with an onset temperature of 240.15 K, as revealed by the detection of a broad exothermal event. The respective melting is observed in the subsequent heating (from −183.15 to 423.15 K) covering a relative wide temperature range from

3. RESULTS AND DISCUSSION 3.1. Differential Scanning Calorimetry. The thermophysical properties of the solutes and solvents used in this study are collected in Table 2. These data are accompanied by the data of various literature reports. The physicochemical properties obtained in this study are in good agreement with previously reported values. Discrepancies between our reported D



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Table 4. Experimental Solubility of Pyrazinecarboxamide (1) in Studied Ionic Liquids (2) at T = 298.15 K and p = 0.1 MPa. γ1 Is the Activity Coefficient of the Solutea pyrazinecarboxamide [C4mim][BF4]

a

[C4mim][OTf]

[C4mim][PF6]

[C10mim][OTf]7

[C8mim][OTf]

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

x1

T/K

γ1

0.0410 0.0423 0.0451 0.0614 0.0748 0.1137 0.1272 0.1430 0.1464 0.1548 0.1602 0.1696 0.1819 0.1859 0.2086 0.2127 0.2447 0.2540 0.2759 0.3305 0.3380 0.4066 0.4075 0.4221 0.4534 0.4691 0.475 0.4991 0.5290 0.5621 0.5823 0.6107 0.6390 0.6939 0.7314 0.7492 0.7875 0.8123 0.8302 0.8683 0.8962 0.9264 0.9548 1.0000

283.74 284.74 286.79 296.65 302.99 316.40 319.98 323.74 324.49 326.26 327.37 329.19 331.43 332.12 335.81 336.45 340.92 342.12 344.77 350.55 351.27 357.18 357.25 358.38 360.67 361.76 362.16 363.75 365.61 367.55 368.68 370.21 371.65 374.29 375.98 376.75 378.34 379.34 380.03 381.47 382.48 383.54 384.51 461.42

0.20 0.20 0.21 0.23 0.24 0.26 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.27 0.26 0.26 0.26 0.26 0.26 0.26 0.25 0.25 0.25 0.25 0.24 0.24 0.24 0.24 0.24 0.24 0.23 0.23 0.23 1.00

0.0249 0.0294 0.0355 0.0626 0.0874 0.1177 0.1496 0.1678 0.1724 0.1823 0.1888 0.1935 0.1999 0.2145 0.2223 0.2456 0.2657 0.2890 0.3261 0.3456 0.3998 0.4256 0.4822 0.4996 0.5234 0.5367 0.5530 0.5623 0.5896 0.6259 1.0000

300.48 306.29 313.00 333.21 345.07 355.63 364.16 368.25 369.21 371.19 372.44 373.31 374.47 376.97 378.24 381.79 384.58 387.57 391.86 393.93 399.10 401.33 405.77 407.03 408.68 409.57 410.78 411.23 412.91 415.04 461.42

0.66 0.70 0.74 0.84 0.87 0.88 0.88 0.87 0.87 0.87 0.86 0.86 0.86 0.85 0.85 0.84 0.83 0.82 0.81 0.80 0.78 0.77 0.75 0.74 0.73 0.73 0.72 0.72 0.71 0.70 1.00

0.0263 0.0313 0.0368 0.0645 0.0888 0.1196 0.1509 0.1697 0.1737 0.1836 0.1901 0.1954 0.2012 0.2158 0.2236 0.2475 0.2670 0.2903 0.3274 0.3475 0.4011 0.4275 0.4835 0.5009 0.5247 0.5380 0.5566 0.5636 0.5909 0.6278 0.6910 0.7247 0.7583 0.7689 0.8234 0.8890 1.0000

279.98 286.50 292.62 313.68 325.66 336.83 345.57 349.98 350.85 352.93 354.24 355.26 356.37 358.99 360.33 364.13 366.98 370.12 374.63 376.86 382.25 384.64 389.26 390.58 392.33 393.26 394.54 395.01 396.78 399.05 402.65 404.44 406.14 406.66 409.23 412.11 461.42

0.26 0.29 0.32 0.42 0.46 0.49 0.51 0.52 0.52 0.52 0.52 0.53 0.53 0.53 0.53 0.53 0.53 0.53 0.53 0.53 0.52 0.52 0.51 0.51 0.51 0.50 0.50 0.50 0.50 0.49 0.49 0.48 0.48 0.48 0.47 0.46 1.00

0.0235 0.0289 0.0326 0.0398 0.0446 0.0492 0.0784 0.1128 0.1147 0.1323 0.1569 0.1884 0.2031 0.2245 0.2447 0.2687 0.3158 0.3254 0.3689 0.3878 0.4257 0.4567 0.4998 0.5099 0.5555 0.5623 1.0000

295.76 303.54 308.02 315.56 319.82 323.55 341.07 354.77 355.38 360.75 367.16 374.04 376.88 380.64 383.87 387.39 393.47 394.60 399.32 401.20 404.70 407.35 410.74 411.49 414.71 417.05 461.42

0.57 0.64 0.67 0.73 0.75 0.78 0.86 0.90 0.90 0.90 0.91 0.90 0.90 0.89 0.89 0.88 0.86 0.86 0.85 0.84 0.83 0.81 0.80 0.80 0.78 0.81 1.00

0.0076 0.0116 0.0239 0.0388 0.0525 0.0660 0.0927 0.1121 0.1358 0.1833 0.2536 0.3542 0.4867 1.0000

290.40 306.78 323.02 335.33 346.88 353.06 364.38 369.27 374.77 382.72 391.93 403.04 417.42 461.42

1.43 1.81 1.58 1.46 1.54 1.46 1.43 1.34 1.28 1.16 1.04 0.96 0.95 1.00

Standard uncertainties u are u(T) = 1.00 K, ur(x) = 0.0005.

∼250.15 K to ∼287.15 K, also exhibiting multiple exothermic peaks. In the second cooling run, crystallization is avoided and the liquid vitrifies. The signature of the glass transition is observed by the typical heat flux discontinuity in the following heating run, with a midpoint of 198.15 K. Interestingly, upon further heating, the ionic liquid undergoes cold crystallization41 followed by melting according to two phase transitions, solid− solid phase transition (Tsol−sol) and Tfus (Figure 4 and Table 2). This latter behavior is observed upon a new cooling/heating scan. The third heating run was carried out at a lower rate (5 K· min−1) to deconvolute the crystallization peak which allowed its

resolution in two subpeaks. This behavior together with the detection of two well resolved phase transition peaks is coherent with the possibility of polymorphism;42 however, to verify this hypothesis X-ray analysis will be necessary. The Tsol−sol reported in this study is lower than previously reported.43 The author did not provide information about the heating scanning rate. In our study the deconvolution of the two phase transition peaks was only possible with a slow scan, as previously mentioned. The DSC curves for the other ILs can be found in the Supporting Information. E



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The commonly discovered result is confirmed in this study, namely a slight increase of temperature leads to a slight increase of solubility.7,31−34 The presented phase diagrams are theoretical solid−liquid phase envelopes. The experimental method did not allow a determination of the eutectic points. The trend of solubilities presented in Figures 2 and 3 indicates that the eutectic point lies below the values of the solute’s mole fraction investigated as a consequence of the high melting points and enthalpies of fusion of the studied compounds. Pyrazinecarboxamide was slightly more soluble than isoniazid; this is in agreement with previous reported studies with the same solutes and similar ILs.7,35 The fact that isoniazid has a lower melting point, enthalpy of melting and more proton donor groups than pyrazinecarboxamide, should make it more soluble in the solvents. This contradictory effect may be explained by the fact that the hydrazine group in isoniazid, that has a basic character (pKb = 5.9044), lowers the acidity of the protons in this molecule, making them less available for solvent interactions. As observed in Figures 2 and 3, the anion of the ionic liquid had a higher impact on the solubility of the compounds than the cation’s alkyl chain. The hydrogen bond acidity, one of the Kamlet−Taft parameters,45−48 is determined by the C-2 proton in the imidazolium ring. By increasing its acidity, solute−solvent interactions can be increased. Thus, higher alkyl chain length drives a less acidic character, and in turn the interactions are diminished. The hydrogen bond basicity (β), another Kamlet−Taft parameter, contrary to the hydrogen bond acidity, is controlled by the nature of the anion. The β values are diverse and depend on the IL. For [C4mim][PF6] and [C4mim][BF4] these values are among the lowest in ILs. The average β for [C4mim][PF6] is 0.205 (reported values: 0.17,49 0.19,50 0.207,51 0.21,52 and 0.24653), for [C4mim][BF4] equals to 0.393 (reported values: 0.37651 and 0.4150) and for [C4mim][OTf] is 0.464.51 Hence, it is expected that the BF4 anion will form stronger hydrogen bonds then PF6. Another important factor controlling the solubility is the IL polarity. It is expected that hydrophilic compounds will exhibit a lower solubility in hydrophobic solvents. The polarity of ILs is based on the ENT scale determined versus Reichardt’s dye and present the solvating power of many ILs.54 The ENT values reported in the literature, for three of the studied ILs, are 0.670 ([C4mim][BF4]), 0.669 ([C4mim][PF6]), and 0.656 ([C4mim][OTf]).51 This increase of ENT is coherent with the solubility trend observed in this work ([C4mim][BF4] < [C4mim][PF6] < [C4mim][OTf]). Because of the higher capacity of BF4 to form stronger hydrogen bonds and higher hydrophilicity, the investigated TB medicines exhibited a higher solubility in this IL. In summary, we can state that the major factors controlling the solubility in this work, are the IL polarity and their capacity to form hydrogen bonds. Comparison of the solubility trend obtained for ([C4mim] ILs with data reported7,35 allows to underline that among imidazolium ILs the solubility of TB antibiotic drugs is the highest for [BF4]. The solubilities of both medicines follows the increasing trend [BF4] > [PF6] > [OTf] > [NTf2], as seen in other studies.7,35 Considering the dependence of the alkyl chain length of the [OTf] ILs on the solubility, it can be stated that the shortest alkyl chain, namely butyl, has an increased solvent power as compared to other longer alkyl chains investigated. The similar trend was observed in the case of [NTf2] ILs, where the ethyl substituent was a better solvent among others.7,35

Figure 2. Comparison of the solubility of isoniazid in [C4mim][BF4] (■, dash-dotted), [C4mim][PF6] (⊞, short-dashed), [C4mim][OTf] (□, solid), [C8mim][OTf] (●, dotted) and [C10mim][OTf] (▲, dashed).35 Lines represent the solubility data calculated by the models with the lowest deviation, which are mentioned in Table 5.

Figure 3. Comparison of the solubility of pyrazinecarboxamide in [C4mim][BF4] (■, dash-dotted), [C4mim][PF6] (⊞, short-dashed), [C 4 mim][OTf] ( □ , solid), [C 8 mim][OTf] ( ● , dotted) and [C10mim][OTf] (▲, dashed).35 Lines represent the solubility data calculated by the models with the lowest deviation, which are mentioned in Table 5.

3.2. Solid−Liquid Equilibrium (SLE). Imidazolium ionic liquids and TB drugs isoniazid and pyrazinecarboxamide were selected for the study of solid−liquid phase envelopes. The solid−liquid phase diagrams were measured within 279.98 and 417.05 K by a dynamic (synthetic) method. The experimental solubilities of TB medicines in the abovementioned ionic liquids are collected in Tables 3 and 4 and Figures 2 and 3. In Figures 2 and 3, the solubilities of isoniazid and pyrazinecarboxamide, respectively, and the comparison between the different ionic liquids are presented. Tables 3 and 4 show the solid−liquid equilibria results, temperatures, T, versus x1 (mole fraction of the solute), for the studied systems. F



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Figure 4. (a) First cooling curve of [C8mim][OTf]; (b) second cooling curve of [C8mim][OTf]; (c) third cooling curve of [C8mim][OTf]; (d) first heating curve of [C8mim][OTf]; (e) second heating curve of [C8mim][OTf]; (f) third heating curve of [C8mim][OTf].

Table 5. Correlation Results, Obtained by Different Models, Of the Solubility Data, SLE, of the Solutes (1) + Studied Ionic Liquids (2) with the Lowest Standard Deviation isoniazid solvent [C4mim] [BF4] [C4mim] [OTf] [C4mim] [PF6] [C8mim] [OTf] [C10mim] [OTf]7,35 a

model NRTL1 NRTL UNIQUAC ASM NRTL Wilson

parameters/J·mol−1 −1036.89 −7820.53 −3124.67 −12984.66 9872.92

pyrazinecarboxamide deviations σT/Ka

−3698.27 10131.68 4350.44 17097.11 −4355.54

b

9.12 0.66c 1.18 0.33d 3.02

model

parameters/J·mol−1

deviations σT/Ka

NRTL NRTL2 NRTL2 NRTL NRTL2

4651.80 −7592.67 −8336.56 11382.66 −31313.76−1954.10 −68866.98−4503.75 −2047.72 3200.41

15.32e 1.10f 6.21g 2.66h 1.58i

According to the equation

⎡ i = 1 (T exp − T cal)2 ⎤1/2 i ⎥ σT = ⎢∑ i ⎢⎣ n ⎥⎦ n−2 Calculated with the third nonrandomness parameter α = 0.99. cCalculated with the third nonrandomness parameter α = 0.20. dCalculated with the third nonrandomness parameter α = 0.10. eCalculated with the third nonrandomness parameter α = 0.85. fCalculated with the third nonrandomness parameter α = 0.15. gCalculated with the third nonrandomness parameter α = 0.90. hCalculated with the third nonrandomness parameter α = 0.40. i Calculated with the third nonrandomness parameter α = 0.95. b

3.3. Correlation Equations of SLE. A detailed version of the calculations performed are described in previous papers.7,18,32 Like in previous studies, six equations were provided to derive the solute activity coefficients γ1 from the so-called correlation equations that describe the Gibbs excess energy (G E), the Wilson, 55 UNIQUAC, 56 UNIQUAC ASM,57 NRTL,58 NRTL159 and NRTL259 according to the mathematical equations described already in detail.60 The γ1 present in Tables 3 and 4 were calculated by the models with the lowest standard deviation, which are present in Table 5. For the correlations, the molar volume of solute and ILs Vm1 (298.15 K) was calculated by the group contribution method:61 110.10 cm 3 ·mol −1 for isoniazid, 35 94.5 cm 3 ·mol −1 for pyrazinecarboxamide,7 187.57 cm3·mol−1 for [C4mim][BF4],62 204.10 cm3·mol−1 for [C4mim][PF6],63 223.60 cm3·mol−1 for [C4mim][OTf],64 and 288.64 cm3·mol−1 for [C8mim][OTf].65 The coordination number Z and the bulk factor li for the cyclic molecule were assumed to be 10 and 1, respectively. Data set of association K= 12.5 and − Δhh = 9.29 kJ mol−1 at 313.15 K for both solutes,7,35 and the Kretschmer−Wiebe model of association were used.66 Values of the parameter α, (0.05 up to 0.99), a proportionality constant similar to the nonrandom-

ness constant of the UNIQUAC ASM, NRTL, NRTL1, and NRTL2 equations were used in calculations for different binary systems. The experimental data of SLE and activity coefficients for systems of isoniazid or pyrazinecarboxamide in the different ILs investigated in these works are collected in Tables 3 and 4. The analysis of the obtained results shown in Table 3 and Figure 2 shows that systems consisting of isoniazid plus [C4mim][OTf] and [C8mim][OTf] exhibit positive deviations from ideality, while negative deviations are observed for [C4mim][BF4], [C4mim][PF6]. Positive deviations from ideality were reported as well for [C10mim][OTf].35 This indicates a general trend of imidazolium triflate-based ionic liquids to have a lower solubility than ideality in systems with isoniazid. For pyrazinecarboxamide negative deviations are observed for all investigated ionic liquids: [C4mim][BF4], [C4mim][PF6], [C4mim][OTf], and [C8mim][OTf] as presented in Table 4. Negative deviations from ideality were reported as well for [C10mim][OTf] for x1 > 0.35 with pyrazinecarboxamide being responsible for stronger interactions between the medicine and the IL. This resulted in a higher solubility of pyrazine-2carboxamide in all examined imidazolium ILs.7 In Figures 1 and 2 of the Supporting Information it is possible to see a G



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pharmaceutical formulation and development. From these and other published results we can conclude that ionic liquids can compete with volatile flammable solvents to compete with the safety and “greenness” of the future designed pharmaceutical processes.

comparison of the experimental, ideal, and calculated phase diagrams. Because of the diverse nature of ILs, these can have several potential interactions with the compounds, namely Coulombic, dispersive, hydrogen bonding, π−π, n−π, dipolar, and ionic/charge−charge. Nevertheless, in previous studies it has been concluded that the major factors affecting the solubility are the polarity of the ionic liquids and their ability to form hydrogen bonds.7,31−35 Isoniazid being a more hydrophilic compound exhibits enhanced solubility in hydrophilic ILs, that is, negative deviations from ideality, while pyrazinecarboxamide, being slightly less hydrophilic than isoniazid, exhibits enhanced solubility even in slightly more hydrophobic ILs, such as the ones with trifluoromethanesulfonate, but not for highly hydrophobic ILs, such as [C10mim][OTf].35 In this work, the experimental solubility data provided for pharmaceutical and bioactive compounds are described by correlation equations with an adequate σT. The correlation parameters, obtained by the different models and with the lowest standard deviation, can be found in Table 5. Tables 1 and 2 in the Supporting Information contain all the correlation parameters and standard deviations for all the models used. As shown in Table 5 for isoniazid, Wilson’s equation had the lowest standard deviation (σT = 3.02) for [C10mim][OTf].35 NRTL1 equation best described the system with [C4mim][BF4] (σT = 9.12), and NRTL σT = 0.66 and σT = 0.33 were obtained for [C4mim][OTf] and [C8mim][OTf], respectively. UNIQUAC ASM gave a standard deviation equal to 1.18 for [C4mim][PF6]. For pyrazinecarboxamide, it can be concluded that the best standard deviations were obtained for [C4mim][BF4] (σT = 15.32) and [C8mim][OTf] (σT = 2.66) with NRTL, for [C4mim][OTf] (σT = 1.10), [C4mim][PF6] (σT = 6.21) and [C10mim][OTf] (σT = 1.58)7 with NRTL2. Summarizing, the best standard deviation for systems with isoniazid in [C8mim][OTf] (0.33 K) was received using the NRTL equation. For pyrazinecarboxamide the best standard deviation (1.10 K) was obtained using the NRTL2 equation, in [C4mim][OTf]. The average standard deviation (σT), received in the correlation of the experimental results ranges from 0.33 to 22.20 K in isoniazid and 1.10 to 29.94 K in pyrazinecarboxamide.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.jced.6b00201. Comparison of the experimental, ideal and calculated solubility of the solutes in the different ILs, all the correlation data for the various models used, and the DSC curves (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. Funding

This work was supported by Fundaçaõ para a Ciência e Tecnologia (PEst-C/EQB/LA0006/2013 and IF/01643/ 2013). The work was supported by COST Actions: CM 1304: “Emergence and Evolution of Complex Chemical Systems” and FPS COST Action FP1306: “Valorisation of lignocellulosic biomass side streams for sustainable production of chemicals, materials & fuels using low environmental impact technologies”. Notes

The authors declare no competing financial interest.

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4. CONCLUSION Solubility data for formulation scientists are collected in this work for two TB medicines and several imidazolium ILs. The solubility decreased when the hydrophobicity of the ILs increased ([C4mim][BF4] < [C4mim][PF6] < [C4mim][OTf] < [C8mim][OTf] < [C10mim][OTf]). As expected, the solubility increased with the capability of the solvent to form hydrogen interactions with the solute. Thus, both solutes exhibited an enhanced solubility in the most hydrophilic IL with the highest ability to interact with the solute, that is, [C4mim][BF4]. The solubility trend decreased with the increase in the alkyl chain length of the cation. The solid− liquid phase equilibria for isoniazid was best described by NRTL1 in [C4mim][BF4], UNIQUAC ASM in [C4mim][PF6], NRTL in [C4mim][OTf], and [C8mim][OTf]. The Wilson equation was reported earlier to give the best standard deviation in [C10mim][OTf]. For pyrazinecarboxamide, the solubility was best described by NRTL1 in [C4mim][BF4], NRTL2 in [C4mim][PF6] and [C4mim][OTf], and NRTL in [C8mim][OTf], contrary to NRTL1 in [C10mim][OTf]. Generally, [C4mim][BF4] can be recommended as the best solvent for both drug manufacturing and sufficient for H

NOMENCLATURE IL = ionic liquid TB = tuberculosis [C4mim] = 1-butyl-3-methylimidazolium [C8mim] = 1-octyl-3-methylimidazolium [C10mim] = 1-decyl-3-methylimidazolium [BF4] = tetrafluoroborate [PF6] = hexafluorophosphate [OTf] = trifluoromethanesulfonate [NTf2] = bis[(trifluoromethyl)sulfonyl]imide DSC = differential scanning calorimetry SLE = solid−liquid equilibrium T = temperature g12−g22, g21−g11 = adjustable parameters of Wilson GE = Gibbs excess energy K = association constant li = bulk factor n = number of experimental points q = pure component surface parameter P1, P2 = model parameters resulting from the minimization procedure r = pure component volume parameter R = ideal gas constant SLE = solid−liquid equilibrium T = temperature Texpi = experimental equilibrium temperature Tcali = calculated equilibrium temperature Tfus,1 = melting temperature of solute Tg = glass transition temperature Tfr = temperature of freezing Tsol−sol = solid−solid transition temperature Tr = phase transition temperature DOI: 10.1021/acs.jced.6b00201 J. Chem. Eng. Data XXXX, XXX, XXX−XXX


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(16) Pareek, S.; Rajsharad, C.; Kirkinde, Safer alternatives to organic solvents. R. Express Pharma 2008. (17) Parvulescu, V. I.; Hardacre, C. Catalysis in Ionic Liquids. Chem. Rev. 2007, 107, 2615−2665. (18) Melo, C. I.; Bogel-Lukasik, R.; Bogel-Lukasik, E. Combination of supercritical carbon dioxide and ionic liquid in a novel assembly of carvacrol. J. Supercrit. Fluids 2012, 61, 191−198. (19) Bogel-Lukasik, E.; Santos, S.; Bogel-Lukasik, R.; Nunes da Ponte, M. Selectivity enhancement in the catalytic heterogeneous hydrogenation of limonene in supercritical carbon dioxide by an ionic liquid. J. Supercrit. Fluids 2010, 54, 210−217. (20) Arce, A.; Earle, M. J.; Katdare, S. P.; Rodríguez, H.; Seddon, K. R. Phase equilibria of mixtures of mutually immiscible ionic liquids. Fluid Phase Equilib. 2007, 261, 427−433. (21) Hough, W. L.; Smiglak, M.; Rodriguez, H.; Swatloski, R. P.; Spear, S. K.; Daly, D. T.; Pernak, J.; Grisel, J. E.; Carliss, R. D.; Soutullo, M. D.; et al. The third evolution of ionic liquids: active pharmaceutical ingredients. New J. Chem. 2007, 31, 1429−1436. (22) Neves, C. M. S. S.; Batista, M. L. S.; Claudio, A. F. M.; Santos, L. M. N. B. F.; Marrucho, I. M.; Freire, M. G.; Coutinho, J. A. P. Thermophysical Properties and Water Saturation of [PF6]-Based Ionic Liquids. J. Chem. Eng. Data 2010, 55, 5065−5073. (23) Lee, T.; Kuo, C. S.; Chen, Y. H. Solubility, polymorphism, crystallinity, and crystal habit of acetaminophen and ibuprofen by initial solvent screening. Pharm. Technol. 2006, 30, 72−92. (24) Cull, S. G.; Holbrey, J. D.; Vargas-Mora, V.; Seddon, K. R.; Lye, G. J. Room-Temperature Ionic Liquids as Replacements for Organic Solvents in Multiphase Bioprocess Operations. Biotechnol. Bioeng. 2000, 69, 227−233. (25) Sarkar, A.; Roy, S. R.; Parikh, N.; Chakraborti, A. K. Nonsolvent Application of Ionic Liquids: Organo-Catalysis by 1-Alkyl-3-methylimidazolium Cation Based Room-Temperature Ionic Liquids for Chemoselective N-tert-Butyloxycarbonylation of Amines and the Influence of the C-2 Hydrogen on Catalytic Efficiency. J. Org. Chem. 2011, 76, 7132−7140. (26) Choi, H. K.; Uhm, K. N.; Kim, H. K. Production of chiral compound using recombinant Escherichia coli cells co-expressing reductase and glucose dehydrogenase in an ionic liquid/water two phase system. J. Mol. Catal. B: Enzym. 2011, 70, 114−118. (27) Earle, M. J.; McCormac, P. B.; Seddon, K. R. The first high yield green route to a pharmaceutical in a room temperature ionic liquid. Green Chem. 2000, 2, 261−262. (28) BASF SE. Method for the Separation of Acids from Chemical Reaction Mixtures by Means of Ionic Fluids. World Patent WO/2003/ 062171, Jul. 31, 2003. (29) BASF SE. Method for the Separation of Acids from Chemical Reaction Mixtures by Means of Ionic Fluids. World Patent WO/2003/ 062251, Jul. 31, 2003. (30) BASF SE. Method for Isolating Acids from Chemical Reaction Mixtures by Using 1-Alkylimidazoles. World Patent WO2005/061416, Jul. 7, 2005. (31) Melo, C. I.; Bogel-Łukasik, R.; Nunes da Ponte, M.; BogelŁukasik, E. Ammonium ionic liquids as green solvents for drugs. Fluid Phase Equilib. 2013, 338, 209−216. (32) Faria, R. A.; Nunes da Ponte, M.; Bogel-Łukasik, E. Solubility studies on the system of trihexyl(tetradecyl)phosphonium bis[(trifluoromethyl)sulfonyl]amide) ionic liquid and pharmaceutical and bioactive compounds. Fluid Phase Equilib. 2015, 385, 1−9. (33) Faria, R. A.; Bogel-Łukasik, E. Solubilities of pharmaceutical and bioactive compounds in trihexyl(tetradecyl)phosphonium chloride ionic liquid. Fluid Phase Equilib. 2015, 397, 18−25. (34) Santos, A. D.; Morais, A. R. C.; Melo, C.; Bogel-Łukasik, R.; Bogel-Łukasik, E. Solubility of pharmaceutical compounds in ionic liquids. Fluid Phase Equilib. 2013, 356, 18−29. (35) Forte, A.; Melo, C.; 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.

u = standard uncertainty of measurement Vm = molar volume of pure compound at 298.15 K x1 = mole fraction of solute Z = coordination number α = constant of the NRTL, NRTL1, and NRTL2 equations γ1 = activity coefficient of solute ΔCp,g = heat capacity at glass transition temperature ΔfusCp = heat capacity between the solid and liquid at the melting temperature Δg12, Δg21 = adjustable parameters of NRTL, NRTL1, and NRTL2 equations ΔfusH1 = enthalpy of fusion of solute Δsol−solH = enthalpy of solid−solid transition Δhh = enthalpy of association Δu12, Δu21 = adjustable parameters of UNIQUAC and UNIQUAC ASM equations σT = root-mean-square deviation of temperature Ω = objective function

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REFERENCES

(1) Global Tuberculosis Report; World Health Organization: 2014; http://www.who.int/tb/publications/factsheet_global.pdf (accessed on January, 2016). (2) Smith, L.; Yadav, P.; Analysis of the Global Fund Financed Market for TB Medicines; William Davidson Institute: January 2014. (3) Savjani, K. T.; Gajjar, A. K.; Savjani, J. K. Drug solubility: importance and enhancement techniques. ISRN Pharm. 2012, 2012, 195727. (4) Patel, D. D.; Lee, J. Applications of Ionic Liquids. Chem. Rec. 2012, 12, 329−355. (5) Sheldon, R. A. The E Factor: fifteen years on. Green Chem. 2007, 9, 1273−128. (6) Smith, K. B.; Bridson, R. H.; Leeke, G. A. Solubilities of Pharmaceutical Compounds in Ionic Liquids. J. Chem. Eng. Data 2011, 56, 2039−2043. (7) Lourenço, C.; Melo, C. I.; Bogel-Łukasik, R.; Bogel-Łukasik, E. Solubility Advantage of Pyrazine-2-carboxamide: Application of Alternative Solvents on the Way to the Future Pharmaceutical Development. J. Chem. Eng. Data 2012, 57, 1525−1533. (8) Mizuuchi, H.; Jaitely, V.; Murdan, S.; Florence, A. T. Room temperature ionic liquids and their mixtures: potential pharmaceutical solvents. Eur. J. Pharm. Sci. 2008, 33, 326−331. (9) Bogel-Lukasik, R.; Matkowska, D.; Zakrzewska, M. E.; BogelLukasik, E.; Hofman, T. The phase envelopes of alternative solvents (ionic liquid, CO2) and building blocks of biomass origin (lactic acid, propionic acid). Fluid Phase Equilib. 2010, 295, 177−185. (10) Domanska, U.; Bogel-Lukasik, R. Physicochemical Properties and Solubility of Alkyl-(2-hydroxyethyl)-dimethylammonium Bromide. J. Phys. Chem. B 2005, 109, 12124−12132. (11) Tait, K. D. Pharmaceutical industry, Encyclopedia of Occupational Health and Safety: Chemical, Industries and Occupations; Stellman, J. M., Ed.; International Labour Office: 1998; p 64. (12) Stolte, S.; Matzke, M.; Arning, J.; Boschen, A.; Pitner, W. R.; Welz-Biermann, U.; Jastorff, B.; Ranke, J. Effects of different head groups and functionalised side chains on the aquatic toxicity of ionic liquids. Green Chem. 2007, 9, 1170−1179. (13) Stolte, S.; Arning, J.; Bottin-Weber, U.; Muller, A.; Pitner, W. R.; Welz-Biermann, U.; Jastorff, B.; Ranke, J. Effects of different head groups and functionalised side chains on the cytotoxicity of ionic liquids. Green Chem. 2007, 9, 760−767. (14) Jaitely, V.; Karatas, A.; Florence, A. T. Water-immiscible room temperature ionic liquids (RTILs) as drug reservoirs for controlled release. Int. J. Pharm. 2008, 354, 168−173. (15) Moniruzzaman, M.; Tamura, M.; Tahara, Y.; Kamiya, N.; Goto, M. Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: Characterization and cytotoxicity evaluation. Int. J. Pharm. 2010, 400, 243−250. I



Article

(36) Domanska, U. Vapour-liquid-solid equilibrium of eicosanoic acid in one- and two-component solvents. Fluid Phase Equilib. 1986, 26, 201−220. (37) Domanska, U.; Bogel-Lukasik, E. Solid−liquid equilibria for systems containing 1-butyl-3-methylimidazolium chloride. Fluid Phase Equilib. 2004, 218, 123−129. (38) Pobudkowska, A.; Domanska, U.; Jurkowska, B. A.; Dymczuk, K. Solubility of pharmaceuticals in water and alcohols. Fluid Phase Equilib. 2015, 392, 56−64. (39) Huddleston, J. G.; Visser, A. E.; Reichert, W. M.; Willauer, H. D.; Broker, G. A.; Rogers, R. D. Characterization and comparison of hydrophilic and hydrophobic room temperature ionic liquids incorporating the imidazolium cation. Green Chem. 2001, 3, 156−164. (40) Domanska, U.; Marciniak, A. Solubility of 1-Alkyl-3-methylimidazolium Hexafluorophosphate in Hydrocarbons. J. Chem. Eng. Data 2003, 48, 451−456. (41) Menczel, J. D.; Prime, R. B. Thermal Analysis of Polymers: Fundamentals and Applications; John Wiley & Sons, Inc.: NJ, 2009. (42) An, J.; Kim, J.; Chang, S.; Kim, W. Application of Ionic Liquid to Polymorphic Design of Pharmaceutical Ingredients. Cryst. Growth Des. 2010, 10, 3044−3050. (43) Vieira, N. S. M. Biomedical Applications Using Ionic Liquids. Master thesis, Universidade de Coimbra, 2014; https://estudogeral. sib.uc.pt/jspui/handle/10316/28129. (44) Hall, H. K. Correlation of the Base Strengths of Amines. J. Am. Chem. Soc. 1957, 79, 5441−5444. (45) Kamlet, M. J.; Taft, R. W. The solvatochromic comparison method. 1. The beta-scale of solvent hydrogen-bond acceptor (HBA) basicities. J. Am. Chem. Soc. 1976, 98, 377−383. (46) Taft, R. W.; Kamlet, M. J. The solvatochromic comparison method. 2. The alpha-scale of solvent hydrogen-bond donor (HBD) acidities. J. Am. Chem. Soc. 1976, 98, 2886−2894. (47) Yokoyama, T.; Taft, R. W.; Kamlet, M. J. The solvatochromic comparison method. 3. Hydrogen bonding by some 2-nitroaniline derivatives. J. Am. Chem. Soc. 1976, 98, 3233−3237. (48) Kamlet, M. J.; Abboud, J. L.; Taft, R. W. The solvatochromic comparison method. 6. The pi* scale of solvent polarities. J. Am. Chem. Soc. 1977, 99, 6027−6038. (49) Fletcher, K. A.; Pandey, S. Solvatochromic Probe Behavior Within Binary Room-Temperature Ionic Liquid 1-Butyl-3-Methyl Imidazolium Hexafluorophosphate Plus Ethanol Solutions. Appl. Spectrosc. 2002, 56, 1498−1503. (50) Fredlake, C. P.; Muldoon, M. J.; Aki, S. N. V. K.; Welton, T.; Brennecke, J. F. Solvent strength of ionic liquid/CO2 mixtures. Phys. Chem. Chem. Phys. 2004, 6, 3280−3285. (51) Crowhurst, L.; Mawdsley, P. R.; Perez-Arlandis, J. M.; Salter, P. A.; Welton, T. Solvent−solute interactions in ionic liquids. Phys. Chem. Chem. Phys. 2003, 5, 2790−2794. (52) Baker, S. N.; Baker, G. A.; Bright, F. V. Temperature-dependent microscopic solvent properties of ‘dry’ and ‘wet’ 1-butyl-3-methylimidazolium hexafluorophosphate: correlation with ET(30) and Kamlet−Taft polarity scales. Green Chem. 2002, 4, 165−169. (53) Chiappe, C.; Pieraccini, D. J. Determination of Ionic Liquids Solvent Properties Using an Unusual Probe: The Electron Donor− Acceptor Complex between 4,4‘-bis(Dimethylamino)-benzophenone and Tetracyanoethene. J. Phys. Chem. A 2006, 110, 4937−4941. (54) Bogel-Łukasik, R.; Gonçalves, L. M. N.; Bogel-Łukasik, E. Phase equilibrium phenomena in solutions involving tannins, flavonoids and ionic liquids. Green Chem. 2010, 12, 1947−1953. (55) Wilson, G. M. Vapor-Liquid Equilibrium. XI. A New Expression for the Excess Free Energy of Mixing. J. Am. Chem. Soc. 1964, 86, 127−130. (56) Abrams, D. S.; Prausnitz, J. M. Statistical thermodynamics of liquid mixtures: A new expression for the excess Gibbs energy of partly or completely miscible systems. AIChE J. 1975, 21, 116−128. (57) Nagata, I. On the thermodynamics of alcohol solutions. Phase equilibria of binary and ternary mixtures containing any number of alcohols. Fluid Phase Equilib. 1985, 19, 153−174.

(58) Renon, H.; Prausnitz, J. M. Local compositions in thermodynamic excess functions for liquid mixtures. AIChE J. 1968, 14, 135−144. (59) Nagata, I.; Nakamiya, Y.; Katoh, K.; Koyabu, J. Ternary liquid liquid equilibria and their representation by modified NRTL equations. Thermochim. Acta 1981, 45, 153−165. (60) Domanska, U.; Rolinska, J. Measurement and correlation of the solubility of n-alkanols (C18, C20) in n-alkanes (C7−C16). Fluid Phase Equilib. 1993, 86, 233−250. (61) Barton, A. F. M. CRC Handbook of Solubility Parameters; CRC Press: Boca Raton, FL, 1985; p 64. (62) Matkowska, D.; Hofman, T. High-pressure volumetric properties of ionic liquids: 1-butyl-3-methylimidazolium tetrafluoroborate, [C4mim][BF4], 1-butyl-3-methylimidazolium methylsulfate [C4mim][MeSO4] and 1-ethyl-3-methylimidazolium ethylsulfate, [C2mim][EtSO4]. J. Mol. Liq. 2012, 165, 161−167. (63) Navia, P.; Troncoso, J.; Romaní, L. Critical Point Measurements for n-Alkyl Benzoates (C8 to C13). J. Chem. Eng. Data 2007, 52, 1369−1374. (64) Vercher, E.; Miguel, P. J.; Llopis, F. J.; Orchilles, A. V.; MartínezAndreu, A. Volumetric and Acoustic Properties of Aqueous Solutions of Trifluoromethanesulfonate-Based Ionic Liquids at Several Temperatures. J. Chem. Eng. Data 2012, 57, 1953−1963. (65) Papaiconomou, N.; Yakelis, N.; Salminen, J.; Bergman, R.; Prausnitz, J. M. Synthesis and Properties of Seven Ionic Liquids Containing 1-Methyl-3-octylimidazolium or 1-Butyl-4-methylpyridinium Cations. J. Chem. Eng. Data 2006, 51, 1389−1393. (66) Kretschmer, C. B.; Wiebe, R. Thermodynamics of AlcoholHydrocarbon Mixtures. J. Chem. Phys. 1954, 22, 1697−1701. (67) Van Valkenburg, M. E.; Vaughn, R. L.; Williams, M.; Wilkes, J. S. Thermochemistry of ionic liquid heat-transfer fluids. Thermochim. Acta 2005, 425, 181−188. (68) Fredlake, C. P.; Crosthwaite, J. M.; Hert, D. G.; Aki, S. N. V. K.; Brennecke, J. F. Thermophysical Properties of Imidazolium-Based Ionic Liquids. J. Chem. Eng. Data 2004, 49, 954−964. (69) Nishida, T.; Tashiro, Y.; Yamamoto, M. Physical and electrochemical properties of 1-alkyl-3-methylimidazolium tetrafluoroborate for electrolyte. J. Fluorine Chem. 2003, 120, 135−141. (70) Tokuda, H.; Tsuzuki, S.; Susan, M. A. B. H.; Hayamizu, K.; Watanabe, M. How Ionic Are Room-Temperature Ionic Liquids? An Indicator of the Physicochemical Properties. J. Phys. Chem. B 2006, 110, 19593−19600. (71) Nakata, Y.; Kohara, K.; Matsumoto, K.; Hagiwara, R. Thermal Properties of Ionic Liquid + Water Binary Systems Applied to Heat Pipes. J. Chem. Eng. Data 2011, 56, 1840−1846. (72) Shirota, H.; Mandai, T.; Fukazawa, H.; Kato, T. Comparison between dicationic and monocationic ionic liquids: liquid density, thermal properties, surface tension, and shear viscosity. J. Chem. Eng. Data 2011, 56, 2453−2459. (73) Zhang, Z. H.; Tan, Z. C.; Li, Y. S.; Sun, L. X. Thermodynamic investigation of room temperature ionic liquid. J. Therm. Anal. Calorim. 2006, 85, 551−557. (74) Paulechka, Y. U.; Blokhin, A. V.; Kabo, G. J. Evaluation of thermodynamic properties for non-crystallizable ionic liquids. Thermochim. Acta 2015, 604, 122−128. (75) Paulechka, Y. U.; Kohut, S. V.; Blokhin, A. V.; Kabo, G. J. Thermodynamic properties of 1-butyl-3-methylimidazolium trifluoromethanesulfonate ionic liquid in the condensed state. Thermochim. Acta 2010, 511, 119−123. (76) Calvar, N.; Gomez, E.; Macedo, E. A.; Dominguez, A. Thermal analysis and heat capacities of pyridinium and imidazolium ionic liquids. Thermochim. Acta 2013, 565, 178−182. (77) Saouane, S.; Norman, S. E.; Hardacre, C.; Fabbiani, F. P. A. Pinning down the solid-state polymorphism of the ionic liquid [bmim][PF6]. Chem. Sci. 2013, 4, 1270−1280. (78) Domanska, U.; Mazurowska, L. Solubility of 1,3-dialkylimidazolium chloride or hexafluorophosphate or methylsulfonate in organic solvents: effect of the anions on solubility. Fluid Phase Equilib. 2004, 221, 73−82. J



Article

(79) Dzyuba, S. V.; Bartsch, R. A. Influence of Structural Variations in 1-Alkyl(aralkyl)-3-Methylimidazolium Hexafluorophosphates and Bis(trifluromethylsulfonyl)imides on Physical Properties of the Ionic Liquids. ChemPhysChem 2002, 3, 161−166. (80) Kabo, G. J.; Blokhin, A. V.; Paulechka, Y. U.; Kabo, A. G.; Shymanovich, M. P.; Magee, J. W. Thermodynamic Properties of 1Butyl-3-methylimidazolium Hexafluorophosphate in the Condensed State. J. Chem. Eng. Data 2004, 49, 453−461. (81) Gomes de Azevedo, R.; Esperanca, J. M. S. S.; Najdanovic-Visak, V.; Visak, Z. P.; Guedes, H. J. R.; Nunes da Ponte, M.; Rebelo, L. P. N. Thermophysical and Thermodynamic Properties of 1-Butyl-3methylimidazolium Tetrafluoroborate and 1-Butyl-3-methylimidazolium Hexafluorophosphate over an Extended Pressure Range. J. Chem. Eng. Data 2005, 50, 997−1008. (82) Troncoso, J.; Cerdeirina, C. A.; Sanmamed, Y. A.; Romani, L.; Rebelo, L. P. N. Thermodynamic Properties of Imidazolium-Based Ionic Liquids: Densities, Heat Capacities, and Enthalpies of Fusion of [bmim][PF6] and [bmim][NTf2]. J. Chem. Eng. Data 2006, 51, 1856−1859. (83) Zhang, Z. H.; Cui, T.; Zhang, J. I.; Xiong, H.; Li, G. P.; Sun, L. X.; Xu, F.; Cao, Z.; Li, F.; Zhao, J. J. Thermodynamic investigation of room temperature ionic liquid - The heat capacity and thermodynamic functions of BMIPF6. J. Therm. Anal. Calorim. 2010, 101, 1143−1148.

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