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Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen
Journal Pre-proof Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen
Masumeh Mokhtarpour, Negar Basteholia, Hemayat Shekaari, Mohammed Taghi Zafarani-Moattar PII:
S0167-7322(19)35951-3
DOI:
https://doi.org/10.1016/j.molliq.2020.112504
Reference:
MOLLIQ 112504
To appear in:
Journal of Molecular Liquids
Received date:
27 October 2019
Revised date:
28 December 2019
Accepted date:
14 January 2020
Please cite this article as: M. Mokhtarpour, N. Basteholia, H. Shekaari, et al., Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen, Journal of Molecular Liquids(2018), https://doi.org/10.1016/j.molliq.2020.112504
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© 2018 Published by Elsevier.
Journal Pre-proof
Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen Masumeh Mokhtarpour, Negar Basteholia, Hemayat Shekaari, Mohammed Taghi ZafaraniMoattar Department of Physical Chemistry, University of Tabriz, Tabriz, Iran
Abstract A highly efficient and ecofriendly co-solvency method using choline-based ionic liquids (ILs) as novel green solvents was developed to enhance aqueous solubility of acetaminophen (ACP).
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ACP is a drug that is widely used as an antipyretic analgesic in clinical practice and its paediatric
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use is common. In this study the solubility of ACP in aqueous choline lactate (ChLa) and choline bitartrate (ChBi) solutions were measured at different temperatures for the first time. The
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temperature and solvent composition dependence of ACP solubility was analyzed through the
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some important semi-empirical and activity coefficient models acquiring the average relative deviation percent as e-NRTL (0.39%) < Wilson (1.40%) < Apelblat (1.86%) < λh (Buchowski)
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(2.34%) < Yalkowsky (4.39%) for correlative investigations. We also examined the intermolecular interaction between ACP and co-solvents using thermodynamic properties
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including volumetric and compressibility properties based on density and speed of sound measurements at experimental temperatures. Thermodynamic parameters results show that there
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obtained solubility data.
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are strong interactions between ACP and ILs. Finally these results were further confirmed by the
Keywords: Choline-based ionic liquids; Solubility; Acetaminophen; Volumetric properties; Compressibility properties.
Corresponding author. Tel.: +98-41-33393094. Fax: +98-41-33340191.
E-mail address: [email protected] (H. Shekaari).
Journal Pre-proof 1. Introduction The level of interest in green technology in pharmaceutical science has improved in recent years because of its unique properties and environmental impacts [1, 2]. One of the most important issues for sustainable and green chemical practices is the use of environmentally friendly solvents having lowest impact on environment [3]. In this respect, a new generation of green solvents has been recently introduced which has applications in many fields of science [4,
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5]. These components were named ionic liquids (ILs) which are the organic salts that are liquids
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at ambient temperature due to their low melting point. They are chemically synthesized, non-
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volatile, and thermally stable and recyclable. The high cost, low biodegradability, bio-
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compatibility and sustainability are the difficulties of the traditional ILs. There is therefore a
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general need for introducing new ILs which can overcome drawbacks. In this regard, choline chloride (ChCl) based ILs are one of the most important and water soluble, biodegradable and in-
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expensive organic compounds. Researches on choline based ILs have attracted more and more
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attentions in recent decades as they possess many attractive benefits and properties and they have
sciences [6].
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been extensively used in many chemical processes including as solvents in pharmaceutical
Acetaminophen (ACP, Fig.1) has been used as an analgesic for pain relief and as an antipyretic agent by all age groups, because of its lesser harmful effects on human body [7, 8]. However, this drug exhibits low solubility in water (14 g∙L-1 at 298.15 K [9]), which affects many physicochemical properties and should be increased toward new formulations. There are various methodological approaches to increase the solubility of drugs including pH adjustment, co-solvency, surfactants and etc. Hence, solubilization using co-solvents is the most common
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Journal Pre-proof technique used in the pharmaceutical industry and these new ILs can be applied as sustainable co-solvents. A key aim of this work is to evaluate ACP solubility in the presence of two choline-based ILs + water at T = (298.15 to 313.15) K. The experimentally measured values were correlated using the e-NRTL [10], Wilson [11], Yalkowsky [12, 13] , λh (Buchowski) [14] and Modified Apelblat [15, 16] models. In next step, physicochemical and thermodynamic tests should be
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simultaneously conducted to better and deep understand the interactions between the drug and
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solvents and development of ILs applications in pharmaceutical sciences. Therefore, the density
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and speed of sound of the solutions containing ACP + water + IL were measured at (298.15 to
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313.15) K and applied to calculate some thermodynamic parameters such as the apparent molar volume, V , standard partial molar volume, V0 , apparent molar isentropic compressibility, κφ, and
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infinite dilution apparent molar isentropic compressibility, 0 values. The corresponding
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parameters obtained from the volumetric and compressibility calculations are useful in
2.1. Chemicals
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2. Experimental
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theoretical studies of solute-solvents interactions.
Acetaminophen used in this work was obtained from Zahravi pharmaceutical company (Tabriz, Iran), all chemicals and regents in analytical reagent grade used for ILs preparation were purchased from Merck (Germany) and Sigma-Aldrich. The choline chloride were dried then stored in desiccator before use. Deionized water was obtained by a Milli-Q water purification system (Millipore, Billerica, MA). The description of the material has been comprehensively reported in Table 1. Finally, we note that choline lactate was synthesized and then used in this study, but choline bitartrate was purchased from Sigma-Aldrich. 3
Journal Pre-proof 2.2. Preparation of the choline lactate The ILs was prepared as following: this synthesis is generally involves (1:1 mole ratio) choline hydroxide neutralization reaction and the second component (lactic acid). The dehydrating reaction is conducted at reduced pressure and high temperature (343.15 K) to obtain the pure salt. For example, a certain amount of ChLa was prepared by a slowly addition of lactic acid to 45% methanolic choline hydroxide solution in an ice bath. The reaction mixture was
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stirred overnight at room temperature then evaporated under reduced pressure [17].
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2.3. Apparatus and procedure
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2.3.1. Solubility measurement
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The commonly used methods for solubility measurements are available in literature [18]. The saturation shake-flask method [19] was applied in this work. The experimental data were
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measured at weight fractions ranging from 0.00 to 0.15 for used ILs. For this purpose, the solvent
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mixtures were prepared by combination of the appropriate masses of the pure solvents (water and ILs). Then, excess amounts of ACP were added to the solvents in glass vials under permanent
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stirring in a system with thermostat (ED, Julabo Co., Germany T = ±0.1 K). Initial experiments
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showed that an equilibrium period of 72 h was appropriate for measuring the solubility of the drug at temperature ranges (298.15 to 313.15) K. After this time the supernatant solutions were filtered through a 0.45 μm membrane (Durapore® membrane filters, type HV, 0.45 µm, Millipore, MA). Finally the absorbance of diluted solutions was recorded at 248 nm using a UV– Vis spectrophotometer (Biotech-Ultraspec 2000, England). Each data point shown is the average of at least three independent experiments. 2.3.2. Density measurement procedure
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Journal Pre-proof The binary solutions were prepared in water + IL mixtures with different concentrations based on ACP molal solubility (molkg–1). The solvent mixtures were obtained by weighting with the analytical balance (AW 220, GR220, Shimadzu, Japan) and the solutions were kept in sealed glass vials protected using parafilm. A vibrating tube densimeter (Anton Paar, DSA 5000 densimeter and speed of sound analyzer, Austria) was used to measure the densities of mixtures (ACP (1) + water (2) + IL (3)). Periodically between uses, the densimeter was calibrated to the
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correct reading by using ultra-pure water and dry air. Additionally, the solutions speed of sound
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is measured using a propagation time technique. In the precision each measurement, density and
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speed of sound and temperature were ± 3×10-3 kg∙m-3, ±0.01 m∙s-1 and ±10−3 K, respectively.
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3. Thermodynamic modeling
Attempts at modeling the solubility of solid solutes in solvent mixtures for the purpose of
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correlation or prediction have followed experimental studies. The purpose of this work is to
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present results of improvement of ACP solubility for pharmaceutical research and industries. The co-solvency models could be divided into three types including theoretical [20, 21], semi-
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empirical [22, 23] and empirical [24] ones. It has been shown that some of the proper co-
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solvency models to define the experimental solubility in solvent mixtures at different temperatures are the Apelblat [15, 16], λh [14], Yalkowsky [25], Wilson [11] and e-NRTL [26] models which provide adequate and suitable correlations for ACP in aqueous ILs solutions. The general properties of the used models are discussed in more detail as following. 3.1. Modified Apelblat equation The modified Apelblat equation is known as a semi-empirical model having three parameters. This model was used in this study to fit the experimental solubility data [29].
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Journal Pre-proof According to this model, the solubility of the drug can potentially change by variations in temperature and the Eq. (1) shows this [27]:
ln x1 A
(1)
B C ln T / K T/K
where A, B, and C are empirical constants. The values of A and B represent the variation the activity coefficient of the solutions components and the C value reveals the temperature impact
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on fusion enthalpy.
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3.2. λh (Buchowski) equation
Buchowski et al. [28] expressed the solubility behavior of solid component in liquid
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solvents as the Buchowski equation. This equation provided a good explanation for many solid –
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liquid systems using two adjustable parameters, λ and h, as reported in previous studies [30, 31].
1 x1 1 1 ) h ( ) x1 T / K Tm1 / K
(2)
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ln(1
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This equation can be written as:
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where λ and h are two parameters and Tm1 is the melting temperature of ACP. The value of λ is recognized as the approximate mean association number of solute molecules, which shows the
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non-ideality of the solution system, and h estimates the excess mixing enthalpy of solution [28]. 3.3. Yalkowsky equation
The log-linear equation defines an exponential increase in drugs solubility with a linear increase in co-solvent amount in the solutions. This relationship is described algebraically by: ln x1mix ln x1 water w3
(3)
where x1-mix and x1-water are the total solute solubilities in the cos-olvent−water mixture and in water, respectively, σ is the co-solvent solubilization power for the particular co-solvent − solute system, and w3 is the weight fraction of the co-solvent in the aqueous mixture. 6
Journal Pre-proof 3. 4. Local composition models The next equation is used to express a solid-liquid equilibrium (SLE) framework [27]: ln x1
fus H 1 1 ( ) ln 1 R T T fus
(4)
where T fus , fusH , T , x1 and 1 are: fusion temperature and enthalpy for the pure drug, the experimental temperature, equilibrium mole fraction, and the activity coefficient of the ACP in
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the saturated solutions, respectively. Moreover, the fusion enthalpy appears to be temperature
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independent. To correlate the solubility data of the present drug, the molar excess Gibbs energy,
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Gex, is identified as sum of two contributions in order to generalize the e-NRTL and Wilson for a
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multi component aqueous solution containing electrolytes,
(5)
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G ex* G ex*,LR G ex*,SR RT RT RT
where superscript *, LR and SR, represent the asymmetric convention, long-range
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and short-range interactions, respectively. The extended version of the Pitzer–Debye–Hückel
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model, Gex*,PDH, proposed by Pitzer [28] can be used for the long-range contribution term. Also,
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in this study, the activity coefficient models e-NRTL [10] and Wilson [11] were applied for representing short-range interactions, Gex*SR. 3. 4. 1. The Pitzer–Debye–Hückel (PDH) equation The PDH equation for excess Gibbs energy, Gex*LR, can be written as [28]: 1/ 2
G ex*,PDH 1000 x j ( ) RT Ms j
4 A I x
(6)
ln(1 I x0.5 )
where MS is the molar mass of the solvent. The parameter ρ in Eq. (6) is related to the e closest approach parameter of ions in solution. The value of ρ = 14.9 has been commonly applied for aqueous electrolyte solutions [29]. Ix is the ionic strength on a mole fraction basis 7
Journal Pre-proof ( Ix
1 xi Z i2 ), Z is the charge number of ions in the solution, x is the mole fraction of ions 2
and Aφ signifies the usual Debye-Huckel parameter for the osmotic coefficient, which is stated by:
1 2N A 1/ 2 e2 A ( ) ( )3 / 2 3 VS 4DS kT
(7)
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VS is the molar volume, NA is Avogadro’s number, e is the charge of an electron, ε is the average
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dielectric constant of the solvent, k is the Boltzmann constant, and T is the temperature in Kelvin. 3. 4. 2. Electrolyte-NRTL model
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In thermodynamics, commonly considered models are based on activity coefficient for
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industrial systems such as electrolyte-NRTL model (e-NRTL) introduced by Chen (1982) [10]
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and Chen and Evans (1986) [30]. For each component, the activity coefficient is defined as the
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sum of the NRTL and the PDH contributions [10].
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3. 4. 3. Wilson model
(8)
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ln( i* ) ln( i*PDH ) ln( i* NRTL )
A non-linear model, known as the Wilson model is used to represent the solubility values of drugs in the binary solvents at experimental temperatures. The equation for this model in a solution with n-component was shown in terms of the activity coefficient as [11]:
n n x ln i 1 ln x j ij nk ki j 1 k 1 j 1x j kj
(9)
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Journal Pre-proof where ij is the interaction parameters between two components, which is related to the molar volumes of the pure components, , and to characteristic energy, , differences by: ij
j ij ii exp i RT
(10)
Interaction parameters were determined by minimized the value of the objective function as: n
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OF (ln iexp ln ical ) 2
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i 1
(11)
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where n is the experimental points, and ln iexp and ln ical are expressing the experimental and calculated activity coefficients.
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To evaluate the goodness of fit between the experimental and correlated solubility data,
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the average relative deviation percent (ARD%) is used. This parameter for comparison of the
xiexp xical
i 1
xiexp
% ARD 100 (
N
)
(12)
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N
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models can be calculated using the following equation:
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where xiexp , xical and N are experimental and calculated solubility mole fraction and the total number of experimental measurements, respectively. 4. Results and discussion 4.1. Solubility measurement results The mole fraction solubility of ACP (x1) in the two mixtures is obtained with Eq. (13):
w1 M1 x1 w w1 w 2 3 M1 M 2 M 3
(13)
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Journal Pre-proof where Mi and wi are the molar mass and weight fractions of i component in the saturated solution, respectively [31]. The experimental values of ACP solubility in the binary solvent mixtures with different concentration of co-solvent at various temperatures (298.15 to 313.15 K) are reported in Table 2. The ACP solubility in the presence of these ILs is 2 times more than its solubility in neat water at 313.15 K. On the other hand, there are some reports on solubility of ACP in co-solvent systems. In methanol + water co-solvent with methanol weight fraction of 0.1
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obtained at the same temperature and weight fraction for solubility of
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The value of 3.44 × 10
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and 298.15 K, the value of 2.65×10-3 (mole fraction) has been reported by Muñoza et al.[32].
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ACP in co-solvent system containing ChLa indicate that there is an improvement in the solubility
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of this drug using this IL. According to Jiménez et al. [33] solubility of ACP in propylene glycol + water co-solvent mixtures at 298.15 K and weight fraction of 0.1 for propylene glycol, is
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2.37×10-3, this value is lower than solubility we found in the presence of ChLa and ChBi. There
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are some co-solvent systems like ethanol + water, dioxin and deep eutectic solvent + water in which slightly higher solubility of ACP have been reported [34-36].
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The relationship between mole fraction solubility of ACP, x1, versus the weight fraction
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of IL (w3) in aqueous ILs solutions at 298.15 and 313.15 K is shown in Fig. 2. It can be understood from this figures that the solubility of ACP rises when temperature and weight fraction of ILs increases. Fig. 2 further illustrates that the efficiency order of studied ILs in the increasing of ACP solubility is: ChLa > ChBi. The levels of solubility observed for drugs in the presence of studied ILs could be due to solute−solvent interactions. Interactions such as Hbonds, van der Waals forces, ion-dipole and dipole-dipole between solute−solvent can be responsible for the solubilization of hydrophobic drugs in a solvent [37, 38]. At the atomic level, ACP molecules and ILs can interact with each other mainly via H-bonds interactions. ACP has
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Journal Pre-proof ability to act as HBDs or HBAs, forming H-bonds with ILs. The H-bond is formed between the NH and hydroxyl groups of the drug and the hydroxyl groups of the ILs. The solvating power of ILs is remarkable rather than water, because, there are H-bonds and dipole-dipole interactions in water + drug system. But in IL + drug systems, there are strong ion-dipole interactions in addition to H-bonds and dipole – dipole interactions. These interactions caused significant increase in the solubility of ACP in the presence of ILs. Some interactions in ILs + drug systems
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are shown in Fig. 3. On the other hand, it should also be noted that the ability of any IL as a
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powerful solubilizing agent for a drug is different. ChBi with stronger intermolecular interactions
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have much less interaction with the ACP. However, it seems that ChLa weak intermolecular
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interactions between the hydroxyl groups of the IL causing strong interactions of ChLa-ACP. 4. 2. Modeling results
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In the next step, all the solubility data were satisfactorily correlated to several
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thermodynamic equations. The modeling results are collected in Tables 2, 3 and 4. Also, the corresponding ARD% values for the used models are summarized in Table 5. Thus, ARD%
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values confirm that the used models performance were very good and can be ordered as e-NRTL
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(0.39%) Wilson (1.40%) Apelblat (1.86%) λh (Buchowski) (2.34%) Yalkowsky (4.39%) for the investigated systems. The models applied in this study are in two groups: semiempirical (Apelblat, λh (Buchowski) and Yalkowsky) and activity coefficient models (Wilson and NRTL). It can be noticed that the good fit between the activity coefficient models and the experimental data is probably due in part to the interactions parameters present in these models. But in semi-empirical models the interaction parameters aren’t considered. However, the empirical models are also suitable for correlating ACP solubility in selected co-solvents. 4.3. Volumetric properties
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Journal Pre-proof The measured densities, d, for ACP in the aqueous IL solutions (w3 = 0.05, 0.10 and 0.15 w/w) are reported in Table 6. The apparent molar volume, V , of drug can be stated as a function of the molality b of that solute and of the densities of the solution and solvent: V
M (d d 0 ) d mdd 0
(14)
where m is the molality of the ACP in the solvents (water + IL), M is represented the molar mass
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of the drug and d0, d are the solvent and solutions densities, respectively. The values of V for
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the investigated systems are given in Table 6. The obtained values for V describe the interaction
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of solvent with molecules of ACP. It was clearly observed that the V values decreased as the
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drug concentration enhanced. The values of apparent molar volumes at infinite dilution (standard
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partial molar volume), V0 , can be calculated using next relation: (15)
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V V 0 S v m
where S v (experimental slope) reflects the interactions between solute−solute and m is the
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molality of the ACP in binary solvent (water + IL) mixtures. In contrast, the values of V 0
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provide deep insight of solute-solvent interactions and also illustrates how different solvents interact differently with the same solute. Table 7 shows the values of V 0 and S v together and the observed trend indicates strong interactions between solute and solvent. Subsequently, these results were further strengthened with increasing the concentration of ILs in the solutions. The values of S v for ACP are currently being negative in the investigated solutions at experimental temperature. The negative values of S v represent weak interactions between drug molecules in the presence of ILs in the aqueous solutions. The values of S v are negative and less than V0 values indicate the weak solute-solute and stronger solute-solvent interactions. The comparison 12
Journal Pre-proof of V0 values for ACP in aqueous IL solutions are graphically shown in Fig. 4. It can be seen that the corresponding values for ACP in the ChLa solutions were higher than its values in ChBi solutions. 4.4. Compressibility properties The apparent molar isentropic compressibility, , for ACP in IL aqueous solutions at
0 M s s d s d 0 ) d mdd 0
(16)
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(
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various temperatures was obtained using next equation:
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where m shows the ACP molality in the aqueous IL solutions, M is the molar mass of the drug
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and d and d0 are the densities of the solutions containing (ACP + water + DES) and (water + IL)
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solutions, respectively. The s 0 and s are the isentropic compressibility of pure solvent and
1 u 2d
(17)
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s
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solution, respectively, which calculated using:
values for
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where u and d are speed of sound and the density of the solution. The obtained
ACP in aqueous IL solutions at the studied temperature are presented in Table 8. This parameter values increase by rising IL concentration. The positive values of show that the co-solvent species around the drug molecules are significantly compressible [39] which revealing strong interaction between ACP and co-solvent. Eq. (18) shows the variation of with molal concentration:
0 S .m
(18)
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Journal Pre-proof where 0 is infinite dilution apparent molar isentropic compressibility, and S is an empirical slope revealing the interactions between solute and solute. The value of 0 and S together are collected in Table 9. The positive values of 0 for the drug reveal strong attractive interactions of ACP-ILs [40]. The values of 0 for the ILs employed in this study are plotted versus temperatures for aqueous IL solutions of ACP in Fig. 5. The maximum values are observed with
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IL ChLa.
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5. Conclusions
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This work involved two main steps. An important step in this process was the acetaminophen aqueous solubility measurements in the presence of two choline-based ionic
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liquids (ChLa and ChBi) in water under normal pressure and at temperatures 298.15 K, 303.15
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K, 308.15 K and 313.15 K. By increasing the co-solvent concentration and temperatures, the
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higher solubility of acetaminophen is obtained. Some semi-empirical and activity coefficient models were applied to fit the obtained solubility data and their performance was as e-NRTL
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(4.39%).
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(0.39%) Wilson (1.40%) Apelblat (1.86%) λh (Buchowski) (2.34%) Yalkowsky
In second step, using the density and speed of sound data it is possible to determine the standard partial molar volumes, V0 , and isentropic compressibility, 0 , of acetaminophen. The resulting behavior shows that their values have raised by increasing the concentration of ionic liquids. These prominent thermodynamic properties prove that strong solvent-solute (acetaminophen-ionic liquid) interactions make the process of solvation more favorable. Additionally, it is concluded that the interactions of the ionic liquids with drug become stronger
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Journal Pre-proof by raising the concentration of co-solvent in the aqueous solutions. The work also provided data clearly showing that ChLa has high efficiency for solubility enhancement of acetaminophen in this investigation and the thermodynamic studies containing compressibility and volumetric properties also confirm it. Acknowledgment
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The authors wish to thank University of Tabriz for the financial support.
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[34] D.R. Delgado, M.Á. Peña, F. Martínez, Revista Colombiana de Ciencias Químico-Farmacéuticas 42
[35] P. Bustamante, S. Romero, A. Peña, B. Escalera, A. Reillo, J. Pharm. Sci. 87 (1998) 1590. [36] H. Shekaari, M.T. Zafarani-Moattar, A. Shayanfar, M. Mokhtarpour, J. Mol. Liq. 249 (2018) 1222. [37] H. Wang, S. Liu, Y. Zhao, J. Wang, Z. Yu, ACS Sustain. Chem. Eng. 7 (2019) 7760. [38] D. Shah, U. Mansurov, F.S. Mjalli, Phys. Chem. Chem. Phys. 21 (2019) 17200. [39] R. Sadeghi, A. Gholamireza, J. Chem. Thermodyn. 43 (2011) 200. [40] M.T. Zafarani-Moattar, S. Sarmad, J. Chem. Thermodyn. 42 (2010) 1213.
17
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Table1 Description of the material used in this study. Provenance Zahravi (Tabriz, Iran) Merck Merck Merck Sigma-Aldrich
CAS No. 67-48-1 50-21-5 67-56-1 87-67-2
Mass fraction (purity) >0.98 >0.99 ≥ 0.95 >0.99 >0.98
Jo
ur
na
lP
re
-p
ro
of
Chemical name Acetaminophen Choline Chloride Lactic acid Methanol Choline bitartrate
18
Journal Pre-proof
Table 2 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous IL solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based Apelblat, λh and Yalkowsky models. 10 3 x1exp
λh equation
Apelblat equation
10 3 x1cal
100
x1exp x1cal x1exp
10 3 x1cal
ro
ACP (1) + water (2) + ChLa (3) w3=0.0000 0.63 -1.81 1.83 -0.63
w3=0.0200 298.15 303.15 308.15 313.15
2.0681 2.6657 3.2737 3.8022
2.0674 2.6701 3.2685 3.8047
0.03 -0.16 0.15 -0.06
w3=0.0500 298.15 303.15 308.15 313.15
2.2342 3.1922 3.6624 4.3881
2.2620 3.0723 3.8073 4.3293
w3=0.0700 298.15 303.15 308.15 313.15
3.0586 3.3805 4.2911 5.0299
w3=0.1000 298.15 303.15 308.15 313.15
w3=0.1500 298.15 303.15 308.15 313.15
1.7579 2.1019 2.4986 2.9540
10 3 x1cal
100
x1exp x1cal x1exp
1.89 -3.23 0.29 -0.03
1.8180 2.2228 2.7422 3.2438
-1.46 -9.16 -9.43 -9.86
2.1217 2.6074 3.1828 3.8606
-2.59 2.18 2.77 -1.53
2.0481 2.5134 3.0758 3.6546
0.96 5.71 6.04 3.90
-1.24 3.75 -3.95 1.34
2.4543 3.0035 3.6516 4.4119
-9.85 5.91 0.29 -0.54
2.4491 3.0223 3.6539 4.3702
-9.61 5.32 0.23 0.39
3.0261 3.4901 4.1531 5.0884
1.06 -3.24 3.21 -1.16
2.9452 3.5456 4.2428 5.0481
3.70 -4.88 1.12 -0.36
2.7590 3.4175 4.0985 4.9235
9.79 -1.09 4.48 2.15
3.4409 4.1883 5.0342 6.7550
3.4621 4.1125 5.1341 6.7143
-0.61 1.81 -1.98 0.60
3.3572 4.2318 5.2942 6.5762
2.43 -1.03 -5.16 2.64
3.2991 4.1093 4.8688 5.8876
4.12 1.88 3.28 12.88
4.2436 5.4040 6.1560 7.1220
4.2700 5.3059 6.2720 7.0746
-0.62 1.81 -1.88 0.66
4.4234 5.2184 6.1234 7.1488
-4.23 3.43 0.53 -0.37
4.4442 5.5874 6.4877 7.9320
-4.72 -3.39 -5.38 -11.37
-p
1.7804 2.0729 2.4600 2.9716
re
1.7918 2.0361 2.5059 2.9529
Jo
ur
na
lP
298.15 303.15 308.15 313.15
Yalkowsky model x exp x cal 100 1 exp 1 x1
of
T/K
19
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ACP (1) + water (2) + ChBi(3)
1.7918 2.0361 2.5059 2.9529
1.7804 2.0729 2.4600 2.9716
0.63 -1.80 1.83 -0.63
1.7506 2.1023 2.5097 2.9792
2.29 -3.25 -0.15 -0.89
1.8035 2.1335 2.5288 2.9147
-0.65 -4.78 -0.91 1.29
w3=0.0200 298.15 303.15 308.15 313.15
1.8525 2.3217 2.8149 3.2466
1.8513 2.3288 2.8069 3.2500
0.06 -0.30 0.28 -0.10
1.9792 2.3315 2.7268 3.1665
-6.84 -0.42 3.131 2.466
1.9792 2.3327 2.8182 3.2520
-6.83 -0.47 -0.11 -0.16
w3=0.0500 298.15 303.15 308.15 313.15
2.2508 2.6405 3.3089 3.6024
2.2291 2.7236 3.2055 3.6423
0.96 -3.14 3.12 -1.10
2.2507 2.6768 3.1657 3.7239
0.004 -1.37 4.32 -3.37
2.2753 2.6669 3.3157 3.8325
-1.08 -1.00 -0.20 -6.38
w3=0.0700 298.15 303.15 308.15 313.15
2.7608 3.1587 3.6088 4.4789
2.7728 3.1180 3.6569 4.4610
-0.43 1.28 -1.33 0.40
2.7825 3.2326 3.7371 4.3005
-0.78 -2.34 -3.55 3.98
2.4969 2.9159 3.6951 4.2759
9.55 7.68 -2.39 4.53
w3=0.1000 298.15 303.15 308.15 313.15
3.0209 3.4721 4.6786 5.0972
2.9675 3.6694 4.4205 5.1966
1.76 -5.68 5.5 -1.95
3.0892 3.6631 4.3196 5.0670
-2.26 -5.50 7.67 0.59
2.8704 3.3336 4.3473 5.0392
4.98 3.98 6.63 1.14
w3=0.1500 298.15 303.15 308.15 313.15
3.3797 3.9190 5.4926 6.5642
3.3230 4.1268 5.2115 6.6844
1.67 -5.30 5.12 -1.83
3.3301 4.2047 5.2688 6.5549
1.46 -7.29 4.07 0.14
3.6212 4.1670 5.6999 6.6260
-7.14 -6.32 -3.77 -0.94
Jo
ur
na
lP
re
-p
ro
of
w3=0.0000 298.15 303.15 308.15 313.15
20
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Table 3 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous ChLa solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based e-NRTL and Wilson models. 10 3 x1exp
NRTL model 3
Wilson model xexp xcal 100 1 exp 1 x1
cal 1
10 x
w3=0.0000
2.0681 2.6657 3.2737 3.8022
2.0550 2.6351 3.2423 3.7649
w3=0.0500 298.15 303.15 308.15 313.15
2.2342 3.1922 3.6624 4.3881
w3=0.0700 298.15 303.15 308.15 313.15
3.0586 3.3805 4.2911 5.0299
w3=0.1500 298.15 303.15 308.15 313.15
x1exp x1cal x1exp
0.06 -0.91 0.10 0.04
0.63 1.15 0.96 0.97
2.0566 2.6602 3.2381 3.7642
0.56 -0.31 1.09 1.00
2.2351 3.1730 3.6552 4.3709
-0.03 0.60 0.20 0.38
2.2257 3.1653 3.6126 4.3294
0.38 0.84 1.36 1.34
3.0421 3.3819 4.2872 5.0230
0.54 -0.04 0.09 0.13
3.0224 3.3463 4.2134 4.9444
1.18 1.01 1.81 1.70
3.4409 4.1883 5.0342 6.7550
3.4371 4.1990 5.0519 6.7659
0.11 -0.25 -0.35 -0.16
3.3897 4.1133 4.9207 6.5641
1.48 1.79 2.25 2.83
4.2436 5.4040 6.1560 7.1220
4.2471 5.4231 6.1879 7.1738
-0.08 -0.35 -0.51 -0.73
4.1226 5.2521 5.9879 6.9461
2.85 2.81 2.73 2.47
na
ur
Jo
w3=0.1000 298.15 303.15 308.15 313.15
100
1.7907 2.0546 2.5034 2.9516
ro
w3=0.0200 298.15 303.15 308.15 313.15
-0.12 -0.78 -0.84 -0.95
cal 1
10 x
-p
1.7941 2.0519 2.5269 2.9811
re
1.7918 2.0361 2.5059 2.9529
lP
298.15 303.15 308.15 313.15
3
of
T/K
21
Journal Pre-proof
Table 4 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous ChBi solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based e-NRTL and Wilson models. 10 3 x1exp
NRTL model 3
Wilson model xexp xcal 100 1 exp 1 x1
cal 1
10 x
w3=0.0000
1.8525 2.3217 2.8149 3.2466
1.8530 2.3112 2.8051 3.2423
w3=0.0500 298.15 303.15 308.15 313.15
2.2508 2.6405 3.3089 3.6024
w3=0.0700 298.15 303.15 308.15 313.15
2.7608 3.1587 3.6088 4.4789
w3=0.1500 298.15 303.15 308.15 313.15
x1exp x1cal x1exp
0.18 0.17 0.05 -0.03
-0.02 0.46 0.35 0.14
1.8401 2.3023 2.791 3.2167
0.67 0.84 0.85 0.92
2.2370 2.6278 3.2991 3.6148
0.61 0.47 0.29 -0.35
2.2222 2.6071 3.2622 3.5551
1.27 1.27 1.41 1.31
2.7441 3.1389 3.6111 4.4531
0.60 0.62 -0.06 0.58
2.7096 3.1009 3.5516 4.3953
1.86 1.83 1.59 1.87
3.0209 3.4721 4.6786 5.0972
3.0160 3.4683 4.6579 5.0926
0.16 0.11 0.44 0.08
2.9577 3.3991 4.5730 4.9971
2.09 2.10 2.26 1.96
3.3797 3.919 5.4926 6.5642
3.3889 3.9391 5.5042 6.5860
-0.27 -0.51 -0.20 -0.33
3.3014 3.8248 5.3660 6.4059
2.32 2.40 2.30 2.41
na
ur
Jo
w3=0.1000 298.15 303.15 308.15 313.15
100
1.7886 2.0326 2.5047 2.9537
ro
w3=0.0200 298.15 303.15 308.15 313.15
0.04 -0.48 -0.16 -0.13
cal 1
10 x
-p
1.7911 2.0460 2.5101 2.9572
re
1.7918 2.0361 2.5059 2.9529
lP
298.15 303.15 308.15 313.15
3
of
T/K
22
Journal Pre-proof
Table 5 The calculated average relative deviation percent (ARD%) for the solubility of the ACP in the aqueous IL solutions at several temperatures from different models. λh equation ARD% ChLa ChBi
Apelblat equation ARD% ChLa ChBi
w
ACP (1) + water (2) + IL (3) 1.81 3.29 2.01 2.31 1.69 2.22
of
0.18 2.11 0.85 3.70 3.49 2.07
ro
0.93 2.61 2.20 1.29 1.19 1.64
2.60 1.81 2.09 3.19 2.59 2.46
-p
0.02 0.05 0.07 0.10 0.15 Average
e-NRTL
ARD% Wilson
re
T/K
Yalkowsky model
na
0.26 0.53 0.50 0.56 0.46
ur
298.15 303.15 308.15 313.15 Average
lP
ACP (1) + water (2) + ChLa (3)
Jo
298.15 303.15 308.15 313.15 Average
0.28 0.44 0.26 0.27 0.31
1.10 1.26 1.56 1.61 1.38
5.12 4.46 4.81 6.77 5.29
ACP (1) + water (2) + ChBi (3) 1.41 1.43 1.41 1.40 1.41
23
5.05 4.04 2.40 2.41 3.48
Jo
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lP
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-p
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Journal Pre-proof
24
Journal Pre-proof Table 6 The values of density, d, and apparent molar volume, Vφ , for ACP in the aqueous IL solutions at different temperatures. a b
m / mol∙kg-1 T/K
106 V / m3∙mol-1
10-3 d / kg∙m-3 298.15
303.15
308.15
313.15
298.15
303.15
308.15
313.15
ACP in aqueous solution of ChLa (0.05w/w) 1.004475
1.002954
1.001023
0.999347
125.707
126.345
127.029
127.691
0.0102
1.004610
1.003087
1.001153
0.999475
125.451
126.046
126.761
127.379
0.0201
1.004955
1.003422
1.001485
0.999800
124.888
125.638
126.208
126.869
0.0310
1.005340
1.003802
1.001859
1.000169
124.497
125.158
125.741
126.351
0.0400
1.005669
1.004127
1.002183
1.000488
124.736
125.248
125.853
0.0503
1.006073
1.004520
1.002573
1.000872
124.12
124.61
125.213
0.0600
1.006454
1.004900
1.002942
1.001228
122.951
123.562
124.141
124.839
0.0706
1.006877
1.005318
1.003366
1.001655
122.504
123.099
123.552
124.136
of
0.0062
124.115
-p
ro
123.433
ACP in aqueous solution of ChLa (0.10 w/w) 1.011776
1.010180
1.008306
1.006241
126.732
127.391
128.207
128.799
0.0102
1.011907
1.010308
1.008432
1.006365
126.571
127.244
127.949
128.533
0.0200
1.012219
1.010617
1.008734
1.006657
126.198
126.731
127.446
128.223
0.0314
1.012589
1.010984
1.009091
1.007004
125.808
126.278
127.041
127.853
0.0404
1.012894
1.011288
1.009390
1.007290
125.453
125.871
126.597
127.516
0.0500
1.013056
1.011438
1.009544
1.007442
125.190
125.781
126.386
127.265
0.0609
1.013627
1.012002
1.010090
1.007979
124.495
125.056
125.772
126.586
0.0705
1.013974
1.012350
1.010429
1.008307
124.118
124.614
125.354
126.204
ur
na
lP
re
0.0060
ACP in aqueous solution of ChLa (0.15 w/w)
1.019115
1.017350
1.015452
1.013296
127.937
128.367
129.058
130.027
0.0102
1.019237
1.017470
1.015570
1.013410
127.616
128.088
128.721
129.674
0.0204
1.019540
1.017765
1.015859
1.013696
127.112
127.727
128.359
129.058
0.0309
1.019872
1.018081
1.016169
1.014009
126.435
127.281
127.908
128.374
0.0407
1.020184
1.018388
1.016471
1.014305
126.066
126.842
127.455
127.971
0.0502
1.020496
1.018698
1.016789
1.014617
125.696
126.387
126.802
127.349
0.0606
1.020860
1.019053
1.017130
1.014946
125.125
125.837
126.383
127.02
0.0706
1.021214
1.019406
1.017479
1.015292
124.666
125.312
125.849
126.457
Jo
0.0060
ACP in aqueous solution of ChBi (0.05 w/w) 0.0062
1.012258
1.010673
1.008891
1.006948
125.337
125.878
126.634
127.411
0.0105
1.012347
1.010761
1.008976
1.007032
125.151
125.648
126.507
127.161
0.0204
1.012556
1.010966
1.009180
1.007230
124.758
125.322
125.909
126.691
0.0303
1.012768
1.011176
1.009387
1.007429
124.490
124.999
125.569
126.475
25
Journal Pre-proof
0.0402
1.012990
1.011397
1.009599
1.007640
124.022
124.473
125.212
125.972
0.0501
1.013214
1.011608
1.009818
1.007854
123.715
124.415
124.852
125.618
0.0606
1.013452
1.011855
1.010057
1.008089
123.47
123.898
124.446
125.191
0.0701
1.013680
1.012076
1.010281
1.008313
123.091
123.599
124.044
124.713
ACP in aqueous solution of ChBi (0.1 w/w) 1.027624
1.025897
1.024008
1.021955
125.954
126.701
127.355
127.915
0.0104
1.027748
1.026018
1.024125
1.022071
125.745
126.473
127.223
127.716
0.0206
1.028064
1.026324
1.024422
1.022366
125.285
126.089
126.878
127.303
0.0302
1.028378
1.026631
1.024710
1.022647
124.720
125.489
126.543
127.068
0.0403
1.028710
1.026964
1.025033
1.022958
124.333
124.935
125.952
126.614
0.0502
1.029053
1.027302
1.025366
1.023278
123.884
124.471
125.396
126.156
0.0605
1.029397
1.027644
1.025696
1.023609
123.697
124.237
125.180
125.833
0.0702
1.029744
1.027986
1.026039
1.023938
123.325
123.864
124.692
125.427
127.337
127.872
128.666
129.475
ro
of
0.0063
1.043382
1.041557
1.039491
0.0102
1.043487
1.041661
1.039592
1.037426
127.223
127.689
128.457
129.310
0.0209
1.043780
1.041941
1.039869
1.037697
126.480
127.238
127.824
128.560
0.0301
1.044052
1.042212
1.040125
1.037943
125.781
126.386
127.207
128.020
0.0411
1.044397
1.042530
1.040440
1.038258
124.996
125.948
126.657
127.311
0.0508
1.044712
1.042839
lP
1.037329
1.040719
1.038544
124.431
125.318
126.346
126.820
0.0602
1.044971
1.043097
1.041002
1.038801
124.231
125.030
125.643
126.390
0.0773
1.045373
1.043505
1.041352
1.039162
123.547
124.184
125.310
125.860
na
re
0.0061
ur
Standard uncertainties u are, u (T) = ± 0.001 K and the estimated uncertainty uc (V ) = 0.05 10-6 m3.mol-1.
Jo
a
-p
ACP in aqueous solution of ChBi (0.15 w/w)
26
Journal Pre-proof Table 7 Standard partial molar volumes, V0 and experimental slopes,
S v for ACP in aqueous IL solutions at different
temperatures. T/K
106Sv(m3.Kg.mol-2)
10V0φ(m3.mol-1.pa-1)
ACP in aqueous solution of ChLa (0.05w/w) -42.002 -37.942 -40.390 -40.687
125.506 126.646 127.336 127.980
of
298.15 303.15 308.15 313.15
-30.804 -32.335 -32.947 -29.847
-p
298.15 303.15 308.15 313.15
ro
ACP in aqueous solution of ChLa (0.10 w/w)
127.018 127.640 128.392 129.024
-37.542 -34.935 -36.947 -41.088
na
lP
298.15 303.15 308.15 313.15
re
ACP in aqueous solution of ChLa (0.15 w/w) 128.129 128.652 129.335 130.208
ACP in aqueous solution of ChBi (0.05 w/w) 125.397 126.041 126.840 127.620
ur
-39.613 -42.343 -48.445 -49.199
Jo
298.15 303.15 308.15 313.15
ACP in aqueous solution of ChBi (0.10 w/w)
298.15 303.15 308.15 313.15
-31.417 -34.512 -32.235 -30.138
126.117 126.929 127.691 128.229
ACP in aqueous solution of ChBi (0.15 w/w) 298.15 303.15 308.15 313.15
-45.965 -43.018 -40.243 -43.440
127.699 128.263 128.936 129.794
27
Journal Pre-proof Table 8 The values of speed of sound, u, and apparent molar isentropic compressibility,
, for ACP in the aqueous IL
solutions at different temperatures.
T/K
1014 (m3∙mol-1∙Pa-1)
u (m∙s-1)
m / mol∙kg-1 298.15
303.15
308.15
313.15
298.15
303.15
308.15
313.15
ACP in aqueous solution of ChLa (0.05w/w) 1529.64
1540.36
1549.23
1556.86
0.779
0.965
1.144
1.319
0.0102
1529.96
1540.67
1549.52
1557.14
0.815
0.985
1.195
1.354
0.0201
1530.72
1541.39
1550.22
1557.78
0.886
1.09
1.248
1.471
0.0310
1531.51
1542.11
1550.90
1558.43
0.954
1.192
1.359
1.553
0.0400
1531.10
1542.68
1551.40
1558.90
1.030
1.241
1.444
1.631
0.0503
1532.66
1543.16
1551.93
1559.38
1.146
1.392
1.514
1.709
0.0600
1533.15
1543.63
1552.30
1559.76
1.236
1.456
1.637
1.806
0.0706
1533.65
1544.08
1552.68
1560.11
1.323
1.542
1.73
1.886
0.0060 0.0102 0.0200 0.0314 0.0404 0.0500 0.0609 0.0705
1563.42 1563.73 1564.44 1565.16 1565.63 1565.80 1566.36 1566.67
1572.15 1572.45 1573.08 1573.69 1574.13 1574.31 1574.81 1575.01
ACP in aqueous solution of ChLa (0.10 w/w) 1579.80 1585.98 1.11 1580.07 1586.23 1.197 1580.66 1586.80 1.262 1581.22 1587.35 1.389 1581.59 1587.70 1.523 1581.80 1587.82 1.616 1582.17 1588.18 1.847 1582.39 1588.31 1.937
1.346 1.392 1.523 1.695 1.788 1.861 2.068 2.185
1.524 1.62 1.735 1.907 2.024 2.041 2.296 2.377
1.743 1.833 1.91 2.048 2.17 2.249 2.462 2.576
1.71 1.748 1.892 2.014 2.111 2.258 2.72 2.503
1.913 1.981 2.121 2.243 2.372 2.48 2.605 2.717
2.116 2.219 2.304 2.437 2.576 2.693 2.82 2.898
0.803 0.839 0.999 1.166 1.283 1.457 1.558
0.965 1.029 1.23 1.374 1.461 1.647 1.748
1.123 1.194 1.345 1.519 1.62 1.756 1.927
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na
lP
re
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ro
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0.0062
ACP in aqueous solution of ChLa (0.15 w/w)
0.0060 0.0102 0.0204 0.0309 0.0407 0.0502 0.0606 0.0706
1597.72 1597.99 1598.61 1599.20 1599.65 1599.95 1600.16 1600.32
1605.02 1605.29 1605.87 1606.38 1606.79 1607.04 1607.24 1607.37
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b
1610.93 1611.17 1611.69 1612.14 1612.46 1612.68 1612.85 1612.92
1615.63 1615.84 1616.33 1616.71 1616.97 1617.13 1617.25 1617.33
1.513 1.622 1.739 1.795 1.905 2.056 2.213 2.335
ACP in aqueous solution of ChBi (0.05 w/w) 0.0062 0.0105 0.0204 0.0303 0.0402 0.0501 0.0606
1523.81 1524.04 1524.52 1524.94 1525.34 1525.68 1525.98
1534.35 1534.57 1535.03 1535.43 1535.79 1536.09 1536.39
1543.49 1543.70 1544.12 1544.50 1544.86 1545.11 1545.39
1551.44 1551.64 1552.06 1552.42 1552.75 1553.02 1553.22
28
0.634 0.672 0.815 0.998 1.088 1.224 1.383
Journal Pre-proof 0.0701
1526.22
1536.60
1545.54
1553.36
1.496
1.684
1.897
2.059
1.001 1.061 1.144 1.325 1.475 1.579 1.682 1.869
1.282 1.363 1.433 1.644 1.727 1.883 1.999 2.118
1.489 1.531 1.703 1.779 1.927 2.049 2.196 2.324
1.241 1.327 1.459 1.617 1.778 1.918 2.073 2.215
1.515 1.575 1.77 1.892 2.083 2.256 2.333 2.503
1.786 1.859 2.039 2.175 2.364 2.522 2.624 2.752
ACP in aqueous solution of ChBi (0.10 w/w)
1580.28 1580.63 1581.46 1582.08 1582.61 1583.02 1583.39 1583.69
1588.55 1588.87 1589.65 1590.17 1590.72 1591.08 1591.28 1591.49
1595.49 1595.79 1596.46 1596.95 1597.38 1597.65 1597.86 1598.01
1601.02 1601.29 1601.89 1602.31 1602.65 1602.85 1602.99 1603.11
lP na ur Jo 29
1.037 1.095 1.229 1.340 1.560 1.703 1.789 1.939
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0.0061 0.0102 0.0209 0.0301 0.0411 0.0508 0.0602 0.0773
1568.82 1575.30 0.825 1569.12 1575.59 0.899 1569.85 1576.22 0.976 1570.37 1576.79 1.109 1570.91 1577.24 1.259 1571.28 1577.62 1.371 1571.67 1577.91 1.477 1571.91 1578.10 1.567 ACP in aqueous solution of ChBi (0.15 w/w)
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1560.53 1560.86 1561.65 1562.24 1562.78 1563.28 1563.76 1563.96
-p
1551.13 1551.47 1552.29 1552.95 1553.55 1554.09 1554.62 1555.05
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0.0063 0.0104 0.0206 0.0302 0.0403 0.0502 0.0605 0.0702
Journal Pre-proof Table 9 The values of S and
T/K
0 for ACP in aqueous IL solutions at different temperatures. 1014 0 (m3.mol-1.pa-1)
1014Sk(Kg.m3.mol-2.pa-1)
ACP in aqueous solution of ChLa (0.05w/w) 6.419 6.967 6.810 6.630
298.15 303.15 308.15 313.15
9.817 9.943 9.973 9.702
0.715 0.901 1.084 1.275
of
298.15 303.15 308.15 313.15
-p
ro
ACP in aqueous solution of ChLa (0.10 w/w)
1.024 1.265 1.472 1.668
9.175 9.399 9.244 8.830
lP
298.15 303.15 308.15 313.15
re
ACP in aqueous solution of ChLa (0.15 w/w) 1.458 1.629 1.865 2.098
298.15 303.15 308.15 313.15
ur
16.367 17.080 17.334 17.511
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298.15 303.15 308.15 313.15
na
ACP in aqueous solution of ChBi (0.05 w/w) 0.554 0.715 0.902 1.046
ACP in aqueous solution of ChBi (0.10 w/w)
8.935 10.098 9.918 9.759
0.759 0.910 1.208 1.412 ACP in aqueous solution of ChBi (0.15 w/w)
298.15 303.15 308.15 313.15
10.846 11.442 11.712 11.578
0.943 1.157 1.431 1.712
30
Journal Pre-proof
Figure captions Fig. 1. Chemical structure of acetaminophen Fig. 2. The relationship between solubility of ACP, mole fraction x1, versus weight fraction of IL, w3, in aqueous solutions at 29815 and 313.15 K, the solid lines obtained from e-NRTL model.
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Fig. 3. Solvent-solute interactions between the ACP and ILs (H-bonding interactions).
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Fig. 4. The comparison of the standard apparent molar volume, V0 , of ACP in aqueous IL solutions at experimental temperatures.
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Fig. 5. The comparison of the standard apparent molar isentropic compressibility, 0 , of ACP in
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na
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aqueous IL solutions at experimental temperatures.
31
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Fig. 1. Chemical structure of acetaminophen
32
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Fig. 2. The relationship between solubility of ACP, mole fraction x1, versus weight fraction of IL, w3, in aqueous solutions at 29815 and 313.15 K, the solid lines obtained from e-NRTL model.
33
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Fig. 3. Solvent-solute interactions between the ACP and ILs (H-bonding interactions).
34
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Fig. 4. The comparison of the standard apparent molar volume, V0 , of ACP in aqueous IL solutions at experimental
Jo
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temperatures.
35
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solutions at experimental temperatures.
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Fig. 5. The comparison of the standard apparent molar isentropic compressibility, , of ACP in aqueous IL
36
0
Journal Pre-proof Highlights
Solubility of acetaminophen in two aqueous choline-based ionic liquids solutions was measured.
Solubility data were correlated by using some empirical and activity coefficient models.
ChLa Ionic liquid was the most effective co-solvent.
Density and speed of sound behavior of acetaminophen in aqueous ILs solutions is
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na
lP
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ro
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reported.
37
Masumeh Mokhtarpour, Negar Basteholia, Hemayat Shekaari, Mohammed Taghi Zafarani-Moattar PII:
S0167-7322(19)35951-3
DOI:
https://doi.org/10.1016/j.molliq.2020.112504
Reference:
MOLLIQ 112504
To appear in:
Journal of Molecular Liquids
Received date:
27 October 2019
Revised date:
28 December 2019
Accepted date:
14 January 2020
Please cite this article as: M. Mokhtarpour, N. Basteholia, H. Shekaari, et al., Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen, Journal of Molecular Liquids(2018), https://doi.org/10.1016/j.molliq.2020.112504
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
© 2018 Published by Elsevier.
Journal Pre-proof
Effect of choline-based ionic liquids as novel green solvents on the aqueous solubility enhancement and thermodynamic properties of acetaminophen Masumeh Mokhtarpour, Negar Basteholia, Hemayat Shekaari, Mohammed Taghi ZafaraniMoattar Department of Physical Chemistry, University of Tabriz, Tabriz, Iran
Abstract A highly efficient and ecofriendly co-solvency method using choline-based ionic liquids (ILs) as novel green solvents was developed to enhance aqueous solubility of acetaminophen (ACP).
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ACP is a drug that is widely used as an antipyretic analgesic in clinical practice and its paediatric
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use is common. In this study the solubility of ACP in aqueous choline lactate (ChLa) and choline bitartrate (ChBi) solutions were measured at different temperatures for the first time. The
-p
temperature and solvent composition dependence of ACP solubility was analyzed through the
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some important semi-empirical and activity coefficient models acquiring the average relative deviation percent as e-NRTL (0.39%) < Wilson (1.40%) < Apelblat (1.86%) < λh (Buchowski)
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(2.34%) < Yalkowsky (4.39%) for correlative investigations. We also examined the intermolecular interaction between ACP and co-solvents using thermodynamic properties
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including volumetric and compressibility properties based on density and speed of sound measurements at experimental temperatures. Thermodynamic parameters results show that there
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obtained solubility data.
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are strong interactions between ACP and ILs. Finally these results were further confirmed by the
Keywords: Choline-based ionic liquids; Solubility; Acetaminophen; Volumetric properties; Compressibility properties.
Corresponding author. Tel.: +98-41-33393094. Fax: +98-41-33340191.
E-mail address: [email protected] (H. Shekaari).
Journal Pre-proof 1. Introduction The level of interest in green technology in pharmaceutical science has improved in recent years because of its unique properties and environmental impacts [1, 2]. One of the most important issues for sustainable and green chemical practices is the use of environmentally friendly solvents having lowest impact on environment [3]. In this respect, a new generation of green solvents has been recently introduced which has applications in many fields of science [4,
of
5]. These components were named ionic liquids (ILs) which are the organic salts that are liquids
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at ambient temperature due to their low melting point. They are chemically synthesized, non-
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volatile, and thermally stable and recyclable. The high cost, low biodegradability, bio-
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compatibility and sustainability are the difficulties of the traditional ILs. There is therefore a
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general need for introducing new ILs which can overcome drawbacks. In this regard, choline chloride (ChCl) based ILs are one of the most important and water soluble, biodegradable and in-
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expensive organic compounds. Researches on choline based ILs have attracted more and more
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attentions in recent decades as they possess many attractive benefits and properties and they have
sciences [6].
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been extensively used in many chemical processes including as solvents in pharmaceutical
Acetaminophen (ACP, Fig.1) has been used as an analgesic for pain relief and as an antipyretic agent by all age groups, because of its lesser harmful effects on human body [7, 8]. However, this drug exhibits low solubility in water (14 g∙L-1 at 298.15 K [9]), which affects many physicochemical properties and should be increased toward new formulations. There are various methodological approaches to increase the solubility of drugs including pH adjustment, co-solvency, surfactants and etc. Hence, solubilization using co-solvents is the most common
2
Journal Pre-proof technique used in the pharmaceutical industry and these new ILs can be applied as sustainable co-solvents. A key aim of this work is to evaluate ACP solubility in the presence of two choline-based ILs + water at T = (298.15 to 313.15) K. The experimentally measured values were correlated using the e-NRTL [10], Wilson [11], Yalkowsky [12, 13] , λh (Buchowski) [14] and Modified Apelblat [15, 16] models. In next step, physicochemical and thermodynamic tests should be
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simultaneously conducted to better and deep understand the interactions between the drug and
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solvents and development of ILs applications in pharmaceutical sciences. Therefore, the density
-p
and speed of sound of the solutions containing ACP + water + IL were measured at (298.15 to
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313.15) K and applied to calculate some thermodynamic parameters such as the apparent molar volume, V , standard partial molar volume, V0 , apparent molar isentropic compressibility, κφ, and
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infinite dilution apparent molar isentropic compressibility, 0 values. The corresponding
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parameters obtained from the volumetric and compressibility calculations are useful in
2.1. Chemicals
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2. Experimental
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theoretical studies of solute-solvents interactions.
Acetaminophen used in this work was obtained from Zahravi pharmaceutical company (Tabriz, Iran), all chemicals and regents in analytical reagent grade used for ILs preparation were purchased from Merck (Germany) and Sigma-Aldrich. The choline chloride were dried then stored in desiccator before use. Deionized water was obtained by a Milli-Q water purification system (Millipore, Billerica, MA). The description of the material has been comprehensively reported in Table 1. Finally, we note that choline lactate was synthesized and then used in this study, but choline bitartrate was purchased from Sigma-Aldrich. 3
Journal Pre-proof 2.2. Preparation of the choline lactate The ILs was prepared as following: this synthesis is generally involves (1:1 mole ratio) choline hydroxide neutralization reaction and the second component (lactic acid). The dehydrating reaction is conducted at reduced pressure and high temperature (343.15 K) to obtain the pure salt. For example, a certain amount of ChLa was prepared by a slowly addition of lactic acid to 45% methanolic choline hydroxide solution in an ice bath. The reaction mixture was
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stirred overnight at room temperature then evaporated under reduced pressure [17].
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2.3. Apparatus and procedure
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2.3.1. Solubility measurement
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The commonly used methods for solubility measurements are available in literature [18]. The saturation shake-flask method [19] was applied in this work. The experimental data were
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measured at weight fractions ranging from 0.00 to 0.15 for used ILs. For this purpose, the solvent
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mixtures were prepared by combination of the appropriate masses of the pure solvents (water and ILs). Then, excess amounts of ACP were added to the solvents in glass vials under permanent
ur
stirring in a system with thermostat (ED, Julabo Co., Germany T = ±0.1 K). Initial experiments
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showed that an equilibrium period of 72 h was appropriate for measuring the solubility of the drug at temperature ranges (298.15 to 313.15) K. After this time the supernatant solutions were filtered through a 0.45 μm membrane (Durapore® membrane filters, type HV, 0.45 µm, Millipore, MA). Finally the absorbance of diluted solutions was recorded at 248 nm using a UV– Vis spectrophotometer (Biotech-Ultraspec 2000, England). Each data point shown is the average of at least three independent experiments. 2.3.2. Density measurement procedure
4
Journal Pre-proof The binary solutions were prepared in water + IL mixtures with different concentrations based on ACP molal solubility (molkg–1). The solvent mixtures were obtained by weighting with the analytical balance (AW 220, GR220, Shimadzu, Japan) and the solutions were kept in sealed glass vials protected using parafilm. A vibrating tube densimeter (Anton Paar, DSA 5000 densimeter and speed of sound analyzer, Austria) was used to measure the densities of mixtures (ACP (1) + water (2) + IL (3)). Periodically between uses, the densimeter was calibrated to the
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correct reading by using ultra-pure water and dry air. Additionally, the solutions speed of sound
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is measured using a propagation time technique. In the precision each measurement, density and
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speed of sound and temperature were ± 3×10-3 kg∙m-3, ±0.01 m∙s-1 and ±10−3 K, respectively.
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3. Thermodynamic modeling
Attempts at modeling the solubility of solid solutes in solvent mixtures for the purpose of
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correlation or prediction have followed experimental studies. The purpose of this work is to
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present results of improvement of ACP solubility for pharmaceutical research and industries. The co-solvency models could be divided into three types including theoretical [20, 21], semi-
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empirical [22, 23] and empirical [24] ones. It has been shown that some of the proper co-
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solvency models to define the experimental solubility in solvent mixtures at different temperatures are the Apelblat [15, 16], λh [14], Yalkowsky [25], Wilson [11] and e-NRTL [26] models which provide adequate and suitable correlations for ACP in aqueous ILs solutions. The general properties of the used models are discussed in more detail as following. 3.1. Modified Apelblat equation The modified Apelblat equation is known as a semi-empirical model having three parameters. This model was used in this study to fit the experimental solubility data [29].
5
Journal Pre-proof According to this model, the solubility of the drug can potentially change by variations in temperature and the Eq. (1) shows this [27]:
ln x1 A
(1)
B C ln T / K T/K
where A, B, and C are empirical constants. The values of A and B represent the variation the activity coefficient of the solutions components and the C value reveals the temperature impact
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on fusion enthalpy.
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3.2. λh (Buchowski) equation
Buchowski et al. [28] expressed the solubility behavior of solid component in liquid
-p
solvents as the Buchowski equation. This equation provided a good explanation for many solid –
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liquid systems using two adjustable parameters, λ and h, as reported in previous studies [30, 31].
1 x1 1 1 ) h ( ) x1 T / K Tm1 / K
(2)
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ln(1
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This equation can be written as:
ur
where λ and h are two parameters and Tm1 is the melting temperature of ACP. The value of λ is recognized as the approximate mean association number of solute molecules, which shows the
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non-ideality of the solution system, and h estimates the excess mixing enthalpy of solution [28]. 3.3. Yalkowsky equation
The log-linear equation defines an exponential increase in drugs solubility with a linear increase in co-solvent amount in the solutions. This relationship is described algebraically by: ln x1mix ln x1 water w3
(3)
where x1-mix and x1-water are the total solute solubilities in the cos-olvent−water mixture and in water, respectively, σ is the co-solvent solubilization power for the particular co-solvent − solute system, and w3 is the weight fraction of the co-solvent in the aqueous mixture. 6
Journal Pre-proof 3. 4. Local composition models The next equation is used to express a solid-liquid equilibrium (SLE) framework [27]: ln x1
fus H 1 1 ( ) ln 1 R T T fus
(4)
where T fus , fusH , T , x1 and 1 are: fusion temperature and enthalpy for the pure drug, the experimental temperature, equilibrium mole fraction, and the activity coefficient of the ACP in
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the saturated solutions, respectively. Moreover, the fusion enthalpy appears to be temperature
ro
independent. To correlate the solubility data of the present drug, the molar excess Gibbs energy,
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Gex, is identified as sum of two contributions in order to generalize the e-NRTL and Wilson for a
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multi component aqueous solution containing electrolytes,
(5)
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G ex* G ex*,LR G ex*,SR RT RT RT
where superscript *, LR and SR, represent the asymmetric convention, long-range
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and short-range interactions, respectively. The extended version of the Pitzer–Debye–Hückel
ur
model, Gex*,PDH, proposed by Pitzer [28] can be used for the long-range contribution term. Also,
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in this study, the activity coefficient models e-NRTL [10] and Wilson [11] were applied for representing short-range interactions, Gex*SR. 3. 4. 1. The Pitzer–Debye–Hückel (PDH) equation The PDH equation for excess Gibbs energy, Gex*LR, can be written as [28]: 1/ 2
G ex*,PDH 1000 x j ( ) RT Ms j
4 A I x
(6)
ln(1 I x0.5 )
where MS is the molar mass of the solvent. The parameter ρ in Eq. (6) is related to the e closest approach parameter of ions in solution. The value of ρ = 14.9 has been commonly applied for aqueous electrolyte solutions [29]. Ix is the ionic strength on a mole fraction basis 7
Journal Pre-proof ( Ix
1 xi Z i2 ), Z is the charge number of ions in the solution, x is the mole fraction of ions 2
and Aφ signifies the usual Debye-Huckel parameter for the osmotic coefficient, which is stated by:
1 2N A 1/ 2 e2 A ( ) ( )3 / 2 3 VS 4DS kT
(7)
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VS is the molar volume, NA is Avogadro’s number, e is the charge of an electron, ε is the average
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dielectric constant of the solvent, k is the Boltzmann constant, and T is the temperature in Kelvin. 3. 4. 2. Electrolyte-NRTL model
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In thermodynamics, commonly considered models are based on activity coefficient for
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industrial systems such as electrolyte-NRTL model (e-NRTL) introduced by Chen (1982) [10]
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and Chen and Evans (1986) [30]. For each component, the activity coefficient is defined as the
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sum of the NRTL and the PDH contributions [10].
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3. 4. 3. Wilson model
(8)
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ln( i* ) ln( i*PDH ) ln( i* NRTL )
A non-linear model, known as the Wilson model is used to represent the solubility values of drugs in the binary solvents at experimental temperatures. The equation for this model in a solution with n-component was shown in terms of the activity coefficient as [11]:
n n x ln i 1 ln x j ij nk ki j 1 k 1 j 1x j kj
(9)
8
Journal Pre-proof where ij is the interaction parameters between two components, which is related to the molar volumes of the pure components, , and to characteristic energy, , differences by: ij
j ij ii exp i RT
(10)
Interaction parameters were determined by minimized the value of the objective function as: n
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OF (ln iexp ln ical ) 2
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i 1
(11)
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where n is the experimental points, and ln iexp and ln ical are expressing the experimental and calculated activity coefficients.
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To evaluate the goodness of fit between the experimental and correlated solubility data,
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the average relative deviation percent (ARD%) is used. This parameter for comparison of the
xiexp xical
i 1
xiexp
% ARD 100 (
N
)
(12)
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N
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models can be calculated using the following equation:
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where xiexp , xical and N are experimental and calculated solubility mole fraction and the total number of experimental measurements, respectively. 4. Results and discussion 4.1. Solubility measurement results The mole fraction solubility of ACP (x1) in the two mixtures is obtained with Eq. (13):
w1 M1 x1 w w1 w 2 3 M1 M 2 M 3
(13)
9
Journal Pre-proof where Mi and wi are the molar mass and weight fractions of i component in the saturated solution, respectively [31]. The experimental values of ACP solubility in the binary solvent mixtures with different concentration of co-solvent at various temperatures (298.15 to 313.15 K) are reported in Table 2. The ACP solubility in the presence of these ILs is 2 times more than its solubility in neat water at 313.15 K. On the other hand, there are some reports on solubility of ACP in co-solvent systems. In methanol + water co-solvent with methanol weight fraction of 0.1
-3
obtained at the same temperature and weight fraction for solubility of
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The value of 3.44 × 10
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and 298.15 K, the value of 2.65×10-3 (mole fraction) has been reported by Muñoza et al.[32].
-p
ACP in co-solvent system containing ChLa indicate that there is an improvement in the solubility
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of this drug using this IL. According to Jiménez et al. [33] solubility of ACP in propylene glycol + water co-solvent mixtures at 298.15 K and weight fraction of 0.1 for propylene glycol, is
lP
2.37×10-3, this value is lower than solubility we found in the presence of ChLa and ChBi. There
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are some co-solvent systems like ethanol + water, dioxin and deep eutectic solvent + water in which slightly higher solubility of ACP have been reported [34-36].
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The relationship between mole fraction solubility of ACP, x1, versus the weight fraction
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of IL (w3) in aqueous ILs solutions at 298.15 and 313.15 K is shown in Fig. 2. It can be understood from this figures that the solubility of ACP rises when temperature and weight fraction of ILs increases. Fig. 2 further illustrates that the efficiency order of studied ILs in the increasing of ACP solubility is: ChLa > ChBi. The levels of solubility observed for drugs in the presence of studied ILs could be due to solute−solvent interactions. Interactions such as Hbonds, van der Waals forces, ion-dipole and dipole-dipole between solute−solvent can be responsible for the solubilization of hydrophobic drugs in a solvent [37, 38]. At the atomic level, ACP molecules and ILs can interact with each other mainly via H-bonds interactions. ACP has
10
Journal Pre-proof ability to act as HBDs or HBAs, forming H-bonds with ILs. The H-bond is formed between the NH and hydroxyl groups of the drug and the hydroxyl groups of the ILs. The solvating power of ILs is remarkable rather than water, because, there are H-bonds and dipole-dipole interactions in water + drug system. But in IL + drug systems, there are strong ion-dipole interactions in addition to H-bonds and dipole – dipole interactions. These interactions caused significant increase in the solubility of ACP in the presence of ILs. Some interactions in ILs + drug systems
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are shown in Fig. 3. On the other hand, it should also be noted that the ability of any IL as a
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powerful solubilizing agent for a drug is different. ChBi with stronger intermolecular interactions
-p
have much less interaction with the ACP. However, it seems that ChLa weak intermolecular
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interactions between the hydroxyl groups of the IL causing strong interactions of ChLa-ACP. 4. 2. Modeling results
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In the next step, all the solubility data were satisfactorily correlated to several
na
thermodynamic equations. The modeling results are collected in Tables 2, 3 and 4. Also, the corresponding ARD% values for the used models are summarized in Table 5. Thus, ARD%
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values confirm that the used models performance were very good and can be ordered as e-NRTL
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(0.39%) Wilson (1.40%) Apelblat (1.86%) λh (Buchowski) (2.34%) Yalkowsky (4.39%) for the investigated systems. The models applied in this study are in two groups: semiempirical (Apelblat, λh (Buchowski) and Yalkowsky) and activity coefficient models (Wilson and NRTL). It can be noticed that the good fit between the activity coefficient models and the experimental data is probably due in part to the interactions parameters present in these models. But in semi-empirical models the interaction parameters aren’t considered. However, the empirical models are also suitable for correlating ACP solubility in selected co-solvents. 4.3. Volumetric properties
11
Journal Pre-proof The measured densities, d, for ACP in the aqueous IL solutions (w3 = 0.05, 0.10 and 0.15 w/w) are reported in Table 6. The apparent molar volume, V , of drug can be stated as a function of the molality b of that solute and of the densities of the solution and solvent: V
M (d d 0 ) d mdd 0
(14)
where m is the molality of the ACP in the solvents (water + IL), M is represented the molar mass
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of the drug and d0, d are the solvent and solutions densities, respectively. The values of V for
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the investigated systems are given in Table 6. The obtained values for V describe the interaction
-p
of solvent with molecules of ACP. It was clearly observed that the V values decreased as the
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drug concentration enhanced. The values of apparent molar volumes at infinite dilution (standard
lP
partial molar volume), V0 , can be calculated using next relation: (15)
na
V V 0 S v m
where S v (experimental slope) reflects the interactions between solute−solute and m is the
ur
molality of the ACP in binary solvent (water + IL) mixtures. In contrast, the values of V 0
Jo
provide deep insight of solute-solvent interactions and also illustrates how different solvents interact differently with the same solute. Table 7 shows the values of V 0 and S v together and the observed trend indicates strong interactions between solute and solvent. Subsequently, these results were further strengthened with increasing the concentration of ILs in the solutions. The values of S v for ACP are currently being negative in the investigated solutions at experimental temperature. The negative values of S v represent weak interactions between drug molecules in the presence of ILs in the aqueous solutions. The values of S v are negative and less than V0 values indicate the weak solute-solute and stronger solute-solvent interactions. The comparison 12
Journal Pre-proof of V0 values for ACP in aqueous IL solutions are graphically shown in Fig. 4. It can be seen that the corresponding values for ACP in the ChLa solutions were higher than its values in ChBi solutions. 4.4. Compressibility properties The apparent molar isentropic compressibility, , for ACP in IL aqueous solutions at
0 M s s d s d 0 ) d mdd 0
(16)
ro
(
of
various temperatures was obtained using next equation:
-p
where m shows the ACP molality in the aqueous IL solutions, M is the molar mass of the drug
re
and d and d0 are the densities of the solutions containing (ACP + water + DES) and (water + IL)
lP
solutions, respectively. The s 0 and s are the isentropic compressibility of pure solvent and
1 u 2d
(17)
ur
s
na
solution, respectively, which calculated using:
values for
Jo
where u and d are speed of sound and the density of the solution. The obtained
ACP in aqueous IL solutions at the studied temperature are presented in Table 8. This parameter values increase by rising IL concentration. The positive values of show that the co-solvent species around the drug molecules are significantly compressible [39] which revealing strong interaction between ACP and co-solvent. Eq. (18) shows the variation of with molal concentration:
0 S .m
(18)
13
Journal Pre-proof where 0 is infinite dilution apparent molar isentropic compressibility, and S is an empirical slope revealing the interactions between solute and solute. The value of 0 and S together are collected in Table 9. The positive values of 0 for the drug reveal strong attractive interactions of ACP-ILs [40]. The values of 0 for the ILs employed in this study are plotted versus temperatures for aqueous IL solutions of ACP in Fig. 5. The maximum values are observed with
of
IL ChLa.
ro
5. Conclusions
-p
This work involved two main steps. An important step in this process was the acetaminophen aqueous solubility measurements in the presence of two choline-based ionic
re
liquids (ChLa and ChBi) in water under normal pressure and at temperatures 298.15 K, 303.15
lP
K, 308.15 K and 313.15 K. By increasing the co-solvent concentration and temperatures, the
na
higher solubility of acetaminophen is obtained. Some semi-empirical and activity coefficient models were applied to fit the obtained solubility data and their performance was as e-NRTL
Jo
(4.39%).
ur
(0.39%) Wilson (1.40%) Apelblat (1.86%) λh (Buchowski) (2.34%) Yalkowsky
In second step, using the density and speed of sound data it is possible to determine the standard partial molar volumes, V0 , and isentropic compressibility, 0 , of acetaminophen. The resulting behavior shows that their values have raised by increasing the concentration of ionic liquids. These prominent thermodynamic properties prove that strong solvent-solute (acetaminophen-ionic liquid) interactions make the process of solvation more favorable. Additionally, it is concluded that the interactions of the ionic liquids with drug become stronger
14
Journal Pre-proof by raising the concentration of co-solvent in the aqueous solutions. The work also provided data clearly showing that ChLa has high efficiency for solubility enhancement of acetaminophen in this investigation and the thermodynamic studies containing compressibility and volumetric properties also confirm it. Acknowledgment
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The authors wish to thank University of Tabriz for the financial support.
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References [1] E. Rahimpour, M. Barzegar-Jalali, A. Shayanfar, A. Jouyban, J. Mol. Liq. 254 (2018) 34. [2] M. Barzegar-Jalali, A. Jouyban, F. Martinez, H. Shekaari, S.N. Mirheydari, Chin. J. Chem. Eng. (2019). [3] P. Gupta, A. Mahajan, RSC Adv. 5 (2015) 26686.
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[4] A. Sindhu, N.K. Mogha, P. Venkatesu, Int. J. Biol. Macromol. 126 (2019) 1.
ro
[5] P.K. Kumar, M. Bisht, P. Venkatesu, I. Bahadur, E.E. Ebenso, J. Phys. Chem B. 122 (2018) 10435. [6] B.L. Gadilohar, G.S. Shankarling, J. Mol. Liq. 227 (2017) 234.
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[7] W. Zhang, A. Jones, M. Doherty, Ann. Rheum. Dis. 63 (2004) 901.
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[8] J.G. Hardman, L.E. Limbird, Chapter 27 (2001) 712.
lP
[9] S.H. Yalkowsky, R.M. Dannenfelser, College of Pharmacy, University of Arizona, Tucson, AZ (1992).
na
[10] C.C. Chen, H.I. Britt, J. Boston, L. Evans, AIChE J. 28 (1982) 588. [11] G.M. Wilson, J. Am. Chem. Soc. 86 (1964) 127.
ur
[12] S.H. Yalkowsky, T.J. Roseman, (1981).
Jo
[13] S.H. Yalkowsky, Solubility and solubilization in aqueous media. Am. Chem. Soc. 1999. [14] H. Buchowski, A. Ksiazczak, S. Pietrzyk, The J. Phys. Chem. 84 (1980) 975. [15] A. Apelblat, E. Manzurola, J. Chem. Thermodyn. 31 (1999) 85. [16] A. Apelblat, E. Manzurola, J. Chem. Thermodyn. 19 (1987) 317. [17] S. Montes, I. Azcune, G. Cabañero, H.-J. Grande, I. Odriozola, J. Labidi, Materials 9 (2016) 499. [18] A. Jouyban, M.A. Fakhree, Toxicity and drug testing, IntechOpen, 2012. [19] V. Jouyban, M. Khoubnasabjafari, F. Martinez, A. Peña, A. Jouyban, J. Drug. Deliv. Sci. Technol. 22 (2012) 545. [20] W.E. Acree Jr, Thermochim. Acta 198 (1992) 71.
16
Journal Pre-proof [21] A. Jouyban-Gharamaleki, W. Acree Jr, Int. J. Pharm. 167 (1998) 177. [22] A. Jouyban-Gharamaleki, Chem. Pharm. Bull. 46 (1998) 1058. [23] A. Jouyban, A. Shayanfar, V. Panahi‐Azar, J. Soleymani, B.H. Yousefi, W.E. Acree, P. York, J. Pharm. Sci. 100 (2011) 4368. [24] M. Barzegar-Jalali, J. Hanaee, Int. J. Pharm. 109 (1994) 291. [25] J.T. Rubino, S.H. Yalkowsky, Pharm. Res. 4 (1987) 231.
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[26] C.C. Chen, Y. Song, AIChE J. 50 (2004) 1928. [27] J.M. Prausnitz, R.N. Lichtenthaler, E.G. de Azevedo, Molecular thermodynamics of fluid-phase
ro
equilibria. Pearson Education, 1998.
-p
[28] K.S. Pitzer, J. Am. Chem. Soc. 102 (1980) 2902.
re
[29] J.M. Simonson, K.S. Pitzer, J. Am. Chem. Soc. 90 (1986) 3009. [30] C.C. Chen, L.B. Evans, AIChE J. 32 (1986) 444.
lP
[31] A. Forte, C.I. Melo, R. Bogel-Łukasik, E. Bogel-Łukasik, Fluid Phase Equilib. 318 (2012) 89.
na
[32] M.M. Muñoz, A. Jouyban, F. Martínez, Phys. Chem. Liq. 54 (2016) 515. [33] J.A. Jiménez, F. Martínez, J. Braz. Chem. Soc. 17 (2006) 125.
Jo
(2013) 298.
ur
[34] D.R. Delgado, M.Á. Peña, F. Martínez, Revista Colombiana de Ciencias Químico-Farmacéuticas 42
[35] P. Bustamante, S. Romero, A. Peña, B. Escalera, A. Reillo, J. Pharm. Sci. 87 (1998) 1590. [36] H. Shekaari, M.T. Zafarani-Moattar, A. Shayanfar, M. Mokhtarpour, J. Mol. Liq. 249 (2018) 1222. [37] H. Wang, S. Liu, Y. Zhao, J. Wang, Z. Yu, ACS Sustain. Chem. Eng. 7 (2019) 7760. [38] D. Shah, U. Mansurov, F.S. Mjalli, Phys. Chem. Chem. Phys. 21 (2019) 17200. [39] R. Sadeghi, A. Gholamireza, J. Chem. Thermodyn. 43 (2011) 200. [40] M.T. Zafarani-Moattar, S. Sarmad, J. Chem. Thermodyn. 42 (2010) 1213.
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Table1 Description of the material used in this study. Provenance Zahravi (Tabriz, Iran) Merck Merck Merck Sigma-Aldrich
CAS No. 67-48-1 50-21-5 67-56-1 87-67-2
Mass fraction (purity) >0.98 >0.99 ≥ 0.95 >0.99 >0.98
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Chemical name Acetaminophen Choline Chloride Lactic acid Methanol Choline bitartrate
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Table 2 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous IL solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based Apelblat, λh and Yalkowsky models. 10 3 x1exp
λh equation
Apelblat equation
10 3 x1cal
100
x1exp x1cal x1exp
10 3 x1cal
ro
ACP (1) + water (2) + ChLa (3) w3=0.0000 0.63 -1.81 1.83 -0.63
w3=0.0200 298.15 303.15 308.15 313.15
2.0681 2.6657 3.2737 3.8022
2.0674 2.6701 3.2685 3.8047
0.03 -0.16 0.15 -0.06
w3=0.0500 298.15 303.15 308.15 313.15
2.2342 3.1922 3.6624 4.3881
2.2620 3.0723 3.8073 4.3293
w3=0.0700 298.15 303.15 308.15 313.15
3.0586 3.3805 4.2911 5.0299
w3=0.1000 298.15 303.15 308.15 313.15
w3=0.1500 298.15 303.15 308.15 313.15
1.7579 2.1019 2.4986 2.9540
10 3 x1cal
100
x1exp x1cal x1exp
1.89 -3.23 0.29 -0.03
1.8180 2.2228 2.7422 3.2438
-1.46 -9.16 -9.43 -9.86
2.1217 2.6074 3.1828 3.8606
-2.59 2.18 2.77 -1.53
2.0481 2.5134 3.0758 3.6546
0.96 5.71 6.04 3.90
-1.24 3.75 -3.95 1.34
2.4543 3.0035 3.6516 4.4119
-9.85 5.91 0.29 -0.54
2.4491 3.0223 3.6539 4.3702
-9.61 5.32 0.23 0.39
3.0261 3.4901 4.1531 5.0884
1.06 -3.24 3.21 -1.16
2.9452 3.5456 4.2428 5.0481
3.70 -4.88 1.12 -0.36
2.7590 3.4175 4.0985 4.9235
9.79 -1.09 4.48 2.15
3.4409 4.1883 5.0342 6.7550
3.4621 4.1125 5.1341 6.7143
-0.61 1.81 -1.98 0.60
3.3572 4.2318 5.2942 6.5762
2.43 -1.03 -5.16 2.64
3.2991 4.1093 4.8688 5.8876
4.12 1.88 3.28 12.88
4.2436 5.4040 6.1560 7.1220
4.2700 5.3059 6.2720 7.0746
-0.62 1.81 -1.88 0.66
4.4234 5.2184 6.1234 7.1488
-4.23 3.43 0.53 -0.37
4.4442 5.5874 6.4877 7.9320
-4.72 -3.39 -5.38 -11.37
-p
1.7804 2.0729 2.4600 2.9716
re
1.7918 2.0361 2.5059 2.9529
Jo
ur
na
lP
298.15 303.15 308.15 313.15
Yalkowsky model x exp x cal 100 1 exp 1 x1
of
T/K
19
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ACP (1) + water (2) + ChBi(3)
1.7918 2.0361 2.5059 2.9529
1.7804 2.0729 2.4600 2.9716
0.63 -1.80 1.83 -0.63
1.7506 2.1023 2.5097 2.9792
2.29 -3.25 -0.15 -0.89
1.8035 2.1335 2.5288 2.9147
-0.65 -4.78 -0.91 1.29
w3=0.0200 298.15 303.15 308.15 313.15
1.8525 2.3217 2.8149 3.2466
1.8513 2.3288 2.8069 3.2500
0.06 -0.30 0.28 -0.10
1.9792 2.3315 2.7268 3.1665
-6.84 -0.42 3.131 2.466
1.9792 2.3327 2.8182 3.2520
-6.83 -0.47 -0.11 -0.16
w3=0.0500 298.15 303.15 308.15 313.15
2.2508 2.6405 3.3089 3.6024
2.2291 2.7236 3.2055 3.6423
0.96 -3.14 3.12 -1.10
2.2507 2.6768 3.1657 3.7239
0.004 -1.37 4.32 -3.37
2.2753 2.6669 3.3157 3.8325
-1.08 -1.00 -0.20 -6.38
w3=0.0700 298.15 303.15 308.15 313.15
2.7608 3.1587 3.6088 4.4789
2.7728 3.1180 3.6569 4.4610
-0.43 1.28 -1.33 0.40
2.7825 3.2326 3.7371 4.3005
-0.78 -2.34 -3.55 3.98
2.4969 2.9159 3.6951 4.2759
9.55 7.68 -2.39 4.53
w3=0.1000 298.15 303.15 308.15 313.15
3.0209 3.4721 4.6786 5.0972
2.9675 3.6694 4.4205 5.1966
1.76 -5.68 5.5 -1.95
3.0892 3.6631 4.3196 5.0670
-2.26 -5.50 7.67 0.59
2.8704 3.3336 4.3473 5.0392
4.98 3.98 6.63 1.14
w3=0.1500 298.15 303.15 308.15 313.15
3.3797 3.9190 5.4926 6.5642
3.3230 4.1268 5.2115 6.6844
1.67 -5.30 5.12 -1.83
3.3301 4.2047 5.2688 6.5549
1.46 -7.29 4.07 0.14
3.6212 4.1670 5.6999 6.6260
-7.14 -6.32 -3.77 -0.94
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w3=0.0000 298.15 303.15 308.15 313.15
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Table 3 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous ChLa solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based e-NRTL and Wilson models. 10 3 x1exp
NRTL model 3
Wilson model xexp xcal 100 1 exp 1 x1
cal 1
10 x
w3=0.0000
2.0681 2.6657 3.2737 3.8022
2.0550 2.6351 3.2423 3.7649
w3=0.0500 298.15 303.15 308.15 313.15
2.2342 3.1922 3.6624 4.3881
w3=0.0700 298.15 303.15 308.15 313.15
3.0586 3.3805 4.2911 5.0299
w3=0.1500 298.15 303.15 308.15 313.15
x1exp x1cal x1exp
0.06 -0.91 0.10 0.04
0.63 1.15 0.96 0.97
2.0566 2.6602 3.2381 3.7642
0.56 -0.31 1.09 1.00
2.2351 3.1730 3.6552 4.3709
-0.03 0.60 0.20 0.38
2.2257 3.1653 3.6126 4.3294
0.38 0.84 1.36 1.34
3.0421 3.3819 4.2872 5.0230
0.54 -0.04 0.09 0.13
3.0224 3.3463 4.2134 4.9444
1.18 1.01 1.81 1.70
3.4409 4.1883 5.0342 6.7550
3.4371 4.1990 5.0519 6.7659
0.11 -0.25 -0.35 -0.16
3.3897 4.1133 4.9207 6.5641
1.48 1.79 2.25 2.83
4.2436 5.4040 6.1560 7.1220
4.2471 5.4231 6.1879 7.1738
-0.08 -0.35 -0.51 -0.73
4.1226 5.2521 5.9879 6.9461
2.85 2.81 2.73 2.47
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w3=0.1000 298.15 303.15 308.15 313.15
100
1.7907 2.0546 2.5034 2.9516
ro
w3=0.0200 298.15 303.15 308.15 313.15
-0.12 -0.78 -0.84 -0.95
cal 1
10 x
-p
1.7941 2.0519 2.5269 2.9811
re
1.7918 2.0361 2.5059 2.9529
lP
298.15 303.15 308.15 313.15
3
of
T/K
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Table 4 Experimental (xexp1 )a and calculated (xcal1 ) solubility of ACP in the aqueous ChBi solutions at different temperatures (T)b and weight fractions of IL (w3 )c-based e-NRTL and Wilson models. 10 3 x1exp
NRTL model 3
Wilson model xexp xcal 100 1 exp 1 x1
cal 1
10 x
w3=0.0000
1.8525 2.3217 2.8149 3.2466
1.8530 2.3112 2.8051 3.2423
w3=0.0500 298.15 303.15 308.15 313.15
2.2508 2.6405 3.3089 3.6024
w3=0.0700 298.15 303.15 308.15 313.15
2.7608 3.1587 3.6088 4.4789
w3=0.1500 298.15 303.15 308.15 313.15
x1exp x1cal x1exp
0.18 0.17 0.05 -0.03
-0.02 0.46 0.35 0.14
1.8401 2.3023 2.791 3.2167
0.67 0.84 0.85 0.92
2.2370 2.6278 3.2991 3.6148
0.61 0.47 0.29 -0.35
2.2222 2.6071 3.2622 3.5551
1.27 1.27 1.41 1.31
2.7441 3.1389 3.6111 4.4531
0.60 0.62 -0.06 0.58
2.7096 3.1009 3.5516 4.3953
1.86 1.83 1.59 1.87
3.0209 3.4721 4.6786 5.0972
3.0160 3.4683 4.6579 5.0926
0.16 0.11 0.44 0.08
2.9577 3.3991 4.5730 4.9971
2.09 2.10 2.26 1.96
3.3797 3.919 5.4926 6.5642
3.3889 3.9391 5.5042 6.5860
-0.27 -0.51 -0.20 -0.33
3.3014 3.8248 5.3660 6.4059
2.32 2.40 2.30 2.41
na
ur
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w3=0.1000 298.15 303.15 308.15 313.15
100
1.7886 2.0326 2.5047 2.9537
ro
w3=0.0200 298.15 303.15 308.15 313.15
0.04 -0.48 -0.16 -0.13
cal 1
10 x
-p
1.7911 2.0460 2.5101 2.9572
re
1.7918 2.0361 2.5059 2.9529
lP
298.15 303.15 308.15 313.15
3
of
T/K
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Table 5 The calculated average relative deviation percent (ARD%) for the solubility of the ACP in the aqueous IL solutions at several temperatures from different models. λh equation ARD% ChLa ChBi
Apelblat equation ARD% ChLa ChBi
w
ACP (1) + water (2) + IL (3) 1.81 3.29 2.01 2.31 1.69 2.22
of
0.18 2.11 0.85 3.70 3.49 2.07
ro
0.93 2.61 2.20 1.29 1.19 1.64
2.60 1.81 2.09 3.19 2.59 2.46
-p
0.02 0.05 0.07 0.10 0.15 Average
e-NRTL
ARD% Wilson
re
T/K
Yalkowsky model
na
0.26 0.53 0.50 0.56 0.46
ur
298.15 303.15 308.15 313.15 Average
lP
ACP (1) + water (2) + ChLa (3)
Jo
298.15 303.15 308.15 313.15 Average
0.28 0.44 0.26 0.27 0.31
1.10 1.26 1.56 1.61 1.38
5.12 4.46 4.81 6.77 5.29
ACP (1) + water (2) + ChBi (3) 1.41 1.43 1.41 1.40 1.41
23
5.05 4.04 2.40 2.41 3.48
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24
Journal Pre-proof Table 6 The values of density, d, and apparent molar volume, Vφ , for ACP in the aqueous IL solutions at different temperatures. a b
m / mol∙kg-1 T/K
106 V / m3∙mol-1
10-3 d / kg∙m-3 298.15
303.15
308.15
313.15
298.15
303.15
308.15
313.15
ACP in aqueous solution of ChLa (0.05w/w) 1.004475
1.002954
1.001023
0.999347
125.707
126.345
127.029
127.691
0.0102
1.004610
1.003087
1.001153
0.999475
125.451
126.046
126.761
127.379
0.0201
1.004955
1.003422
1.001485
0.999800
124.888
125.638
126.208
126.869
0.0310
1.005340
1.003802
1.001859
1.000169
124.497
125.158
125.741
126.351
0.0400
1.005669
1.004127
1.002183
1.000488
124.736
125.248
125.853
0.0503
1.006073
1.004520
1.002573
1.000872
124.12
124.61
125.213
0.0600
1.006454
1.004900
1.002942
1.001228
122.951
123.562
124.141
124.839
0.0706
1.006877
1.005318
1.003366
1.001655
122.504
123.099
123.552
124.136
of
0.0062
124.115
-p
ro
123.433
ACP in aqueous solution of ChLa (0.10 w/w) 1.011776
1.010180
1.008306
1.006241
126.732
127.391
128.207
128.799
0.0102
1.011907
1.010308
1.008432
1.006365
126.571
127.244
127.949
128.533
0.0200
1.012219
1.010617
1.008734
1.006657
126.198
126.731
127.446
128.223
0.0314
1.012589
1.010984
1.009091
1.007004
125.808
126.278
127.041
127.853
0.0404
1.012894
1.011288
1.009390
1.007290
125.453
125.871
126.597
127.516
0.0500
1.013056
1.011438
1.009544
1.007442
125.190
125.781
126.386
127.265
0.0609
1.013627
1.012002
1.010090
1.007979
124.495
125.056
125.772
126.586
0.0705
1.013974
1.012350
1.010429
1.008307
124.118
124.614
125.354
126.204
ur
na
lP
re
0.0060
ACP in aqueous solution of ChLa (0.15 w/w)
1.019115
1.017350
1.015452
1.013296
127.937
128.367
129.058
130.027
0.0102
1.019237
1.017470
1.015570
1.013410
127.616
128.088
128.721
129.674
0.0204
1.019540
1.017765
1.015859
1.013696
127.112
127.727
128.359
129.058
0.0309
1.019872
1.018081
1.016169
1.014009
126.435
127.281
127.908
128.374
0.0407
1.020184
1.018388
1.016471
1.014305
126.066
126.842
127.455
127.971
0.0502
1.020496
1.018698
1.016789
1.014617
125.696
126.387
126.802
127.349
0.0606
1.020860
1.019053
1.017130
1.014946
125.125
125.837
126.383
127.02
0.0706
1.021214
1.019406
1.017479
1.015292
124.666
125.312
125.849
126.457
Jo
0.0060
ACP in aqueous solution of ChBi (0.05 w/w) 0.0062
1.012258
1.010673
1.008891
1.006948
125.337
125.878
126.634
127.411
0.0105
1.012347
1.010761
1.008976
1.007032
125.151
125.648
126.507
127.161
0.0204
1.012556
1.010966
1.009180
1.007230
124.758
125.322
125.909
126.691
0.0303
1.012768
1.011176
1.009387
1.007429
124.490
124.999
125.569
126.475
25
Journal Pre-proof
0.0402
1.012990
1.011397
1.009599
1.007640
124.022
124.473
125.212
125.972
0.0501
1.013214
1.011608
1.009818
1.007854
123.715
124.415
124.852
125.618
0.0606
1.013452
1.011855
1.010057
1.008089
123.47
123.898
124.446
125.191
0.0701
1.013680
1.012076
1.010281
1.008313
123.091
123.599
124.044
124.713
ACP in aqueous solution of ChBi (0.1 w/w) 1.027624
1.025897
1.024008
1.021955
125.954
126.701
127.355
127.915
0.0104
1.027748
1.026018
1.024125
1.022071
125.745
126.473
127.223
127.716
0.0206
1.028064
1.026324
1.024422
1.022366
125.285
126.089
126.878
127.303
0.0302
1.028378
1.026631
1.024710
1.022647
124.720
125.489
126.543
127.068
0.0403
1.028710
1.026964
1.025033
1.022958
124.333
124.935
125.952
126.614
0.0502
1.029053
1.027302
1.025366
1.023278
123.884
124.471
125.396
126.156
0.0605
1.029397
1.027644
1.025696
1.023609
123.697
124.237
125.180
125.833
0.0702
1.029744
1.027986
1.026039
1.023938
123.325
123.864
124.692
125.427
127.337
127.872
128.666
129.475
ro
of
0.0063
1.043382
1.041557
1.039491
0.0102
1.043487
1.041661
1.039592
1.037426
127.223
127.689
128.457
129.310
0.0209
1.043780
1.041941
1.039869
1.037697
126.480
127.238
127.824
128.560
0.0301
1.044052
1.042212
1.040125
1.037943
125.781
126.386
127.207
128.020
0.0411
1.044397
1.042530
1.040440
1.038258
124.996
125.948
126.657
127.311
0.0508
1.044712
1.042839
lP
1.037329
1.040719
1.038544
124.431
125.318
126.346
126.820
0.0602
1.044971
1.043097
1.041002
1.038801
124.231
125.030
125.643
126.390
0.0773
1.045373
1.043505
1.041352
1.039162
123.547
124.184
125.310
125.860
na
re
0.0061
ur
Standard uncertainties u are, u (T) = ± 0.001 K and the estimated uncertainty uc (V ) = 0.05 10-6 m3.mol-1.
Jo
a
-p
ACP in aqueous solution of ChBi (0.15 w/w)
26
Journal Pre-proof Table 7 Standard partial molar volumes, V0 and experimental slopes,
S v for ACP in aqueous IL solutions at different
temperatures. T/K
106Sv(m3.Kg.mol-2)
10V0φ(m3.mol-1.pa-1)
ACP in aqueous solution of ChLa (0.05w/w) -42.002 -37.942 -40.390 -40.687
125.506 126.646 127.336 127.980
of
298.15 303.15 308.15 313.15
-30.804 -32.335 -32.947 -29.847
-p
298.15 303.15 308.15 313.15
ro
ACP in aqueous solution of ChLa (0.10 w/w)
127.018 127.640 128.392 129.024
-37.542 -34.935 -36.947 -41.088
na
lP
298.15 303.15 308.15 313.15
re
ACP in aqueous solution of ChLa (0.15 w/w) 128.129 128.652 129.335 130.208
ACP in aqueous solution of ChBi (0.05 w/w) 125.397 126.041 126.840 127.620
ur
-39.613 -42.343 -48.445 -49.199
Jo
298.15 303.15 308.15 313.15
ACP in aqueous solution of ChBi (0.10 w/w)
298.15 303.15 308.15 313.15
-31.417 -34.512 -32.235 -30.138
126.117 126.929 127.691 128.229
ACP in aqueous solution of ChBi (0.15 w/w) 298.15 303.15 308.15 313.15
-45.965 -43.018 -40.243 -43.440
127.699 128.263 128.936 129.794
27
Journal Pre-proof Table 8 The values of speed of sound, u, and apparent molar isentropic compressibility,
, for ACP in the aqueous IL
solutions at different temperatures.
T/K
1014 (m3∙mol-1∙Pa-1)
u (m∙s-1)
m / mol∙kg-1 298.15
303.15
308.15
313.15
298.15
303.15
308.15
313.15
ACP in aqueous solution of ChLa (0.05w/w) 1529.64
1540.36
1549.23
1556.86
0.779
0.965
1.144
1.319
0.0102
1529.96
1540.67
1549.52
1557.14
0.815
0.985
1.195
1.354
0.0201
1530.72
1541.39
1550.22
1557.78
0.886
1.09
1.248
1.471
0.0310
1531.51
1542.11
1550.90
1558.43
0.954
1.192
1.359
1.553
0.0400
1531.10
1542.68
1551.40
1558.90
1.030
1.241
1.444
1.631
0.0503
1532.66
1543.16
1551.93
1559.38
1.146
1.392
1.514
1.709
0.0600
1533.15
1543.63
1552.30
1559.76
1.236
1.456
1.637
1.806
0.0706
1533.65
1544.08
1552.68
1560.11
1.323
1.542
1.73
1.886
0.0060 0.0102 0.0200 0.0314 0.0404 0.0500 0.0609 0.0705
1563.42 1563.73 1564.44 1565.16 1565.63 1565.80 1566.36 1566.67
1572.15 1572.45 1573.08 1573.69 1574.13 1574.31 1574.81 1575.01
ACP in aqueous solution of ChLa (0.10 w/w) 1579.80 1585.98 1.11 1580.07 1586.23 1.197 1580.66 1586.80 1.262 1581.22 1587.35 1.389 1581.59 1587.70 1.523 1581.80 1587.82 1.616 1582.17 1588.18 1.847 1582.39 1588.31 1.937
1.346 1.392 1.523 1.695 1.788 1.861 2.068 2.185
1.524 1.62 1.735 1.907 2.024 2.041 2.296 2.377
1.743 1.833 1.91 2.048 2.17 2.249 2.462 2.576
1.71 1.748 1.892 2.014 2.111 2.258 2.72 2.503
1.913 1.981 2.121 2.243 2.372 2.48 2.605 2.717
2.116 2.219 2.304 2.437 2.576 2.693 2.82 2.898
0.803 0.839 0.999 1.166 1.283 1.457 1.558
0.965 1.029 1.23 1.374 1.461 1.647 1.748
1.123 1.194 1.345 1.519 1.62 1.756 1.927
ur
na
lP
re
-p
ro
of
0.0062
ACP in aqueous solution of ChLa (0.15 w/w)
0.0060 0.0102 0.0204 0.0309 0.0407 0.0502 0.0606 0.0706
1597.72 1597.99 1598.61 1599.20 1599.65 1599.95 1600.16 1600.32
1605.02 1605.29 1605.87 1606.38 1606.79 1607.04 1607.24 1607.37
Jo
b
1610.93 1611.17 1611.69 1612.14 1612.46 1612.68 1612.85 1612.92
1615.63 1615.84 1616.33 1616.71 1616.97 1617.13 1617.25 1617.33
1.513 1.622 1.739 1.795 1.905 2.056 2.213 2.335
ACP in aqueous solution of ChBi (0.05 w/w) 0.0062 0.0105 0.0204 0.0303 0.0402 0.0501 0.0606
1523.81 1524.04 1524.52 1524.94 1525.34 1525.68 1525.98
1534.35 1534.57 1535.03 1535.43 1535.79 1536.09 1536.39
1543.49 1543.70 1544.12 1544.50 1544.86 1545.11 1545.39
1551.44 1551.64 1552.06 1552.42 1552.75 1553.02 1553.22
28
0.634 0.672 0.815 0.998 1.088 1.224 1.383
Journal Pre-proof 0.0701
1526.22
1536.60
1545.54
1553.36
1.496
1.684
1.897
2.059
1.001 1.061 1.144 1.325 1.475 1.579 1.682 1.869
1.282 1.363 1.433 1.644 1.727 1.883 1.999 2.118
1.489 1.531 1.703 1.779 1.927 2.049 2.196 2.324
1.241 1.327 1.459 1.617 1.778 1.918 2.073 2.215
1.515 1.575 1.77 1.892 2.083 2.256 2.333 2.503
1.786 1.859 2.039 2.175 2.364 2.522 2.624 2.752
ACP in aqueous solution of ChBi (0.10 w/w)
1580.28 1580.63 1581.46 1582.08 1582.61 1583.02 1583.39 1583.69
1588.55 1588.87 1589.65 1590.17 1590.72 1591.08 1591.28 1591.49
1595.49 1595.79 1596.46 1596.95 1597.38 1597.65 1597.86 1598.01
1601.02 1601.29 1601.89 1602.31 1602.65 1602.85 1602.99 1603.11
lP na ur Jo 29
1.037 1.095 1.229 1.340 1.560 1.703 1.789 1.939
of
0.0061 0.0102 0.0209 0.0301 0.0411 0.0508 0.0602 0.0773
1568.82 1575.30 0.825 1569.12 1575.59 0.899 1569.85 1576.22 0.976 1570.37 1576.79 1.109 1570.91 1577.24 1.259 1571.28 1577.62 1.371 1571.67 1577.91 1.477 1571.91 1578.10 1.567 ACP in aqueous solution of ChBi (0.15 w/w)
ro
1560.53 1560.86 1561.65 1562.24 1562.78 1563.28 1563.76 1563.96
-p
1551.13 1551.47 1552.29 1552.95 1553.55 1554.09 1554.62 1555.05
re
0.0063 0.0104 0.0206 0.0302 0.0403 0.0502 0.0605 0.0702
Journal Pre-proof Table 9 The values of S and
T/K
0 for ACP in aqueous IL solutions at different temperatures. 1014 0 (m3.mol-1.pa-1)
1014Sk(Kg.m3.mol-2.pa-1)
ACP in aqueous solution of ChLa (0.05w/w) 6.419 6.967 6.810 6.630
298.15 303.15 308.15 313.15
9.817 9.943 9.973 9.702
0.715 0.901 1.084 1.275
of
298.15 303.15 308.15 313.15
-p
ro
ACP in aqueous solution of ChLa (0.10 w/w)
1.024 1.265 1.472 1.668
9.175 9.399 9.244 8.830
lP
298.15 303.15 308.15 313.15
re
ACP in aqueous solution of ChLa (0.15 w/w) 1.458 1.629 1.865 2.098
298.15 303.15 308.15 313.15
ur
16.367 17.080 17.334 17.511
Jo
298.15 303.15 308.15 313.15
na
ACP in aqueous solution of ChBi (0.05 w/w) 0.554 0.715 0.902 1.046
ACP in aqueous solution of ChBi (0.10 w/w)
8.935 10.098 9.918 9.759
0.759 0.910 1.208 1.412 ACP in aqueous solution of ChBi (0.15 w/w)
298.15 303.15 308.15 313.15
10.846 11.442 11.712 11.578
0.943 1.157 1.431 1.712
30
Journal Pre-proof
Figure captions Fig. 1. Chemical structure of acetaminophen Fig. 2. The relationship between solubility of ACP, mole fraction x1, versus weight fraction of IL, w3, in aqueous solutions at 29815 and 313.15 K, the solid lines obtained from e-NRTL model.
of
Fig. 3. Solvent-solute interactions between the ACP and ILs (H-bonding interactions).
ro
Fig. 4. The comparison of the standard apparent molar volume, V0 , of ACP in aqueous IL solutions at experimental temperatures.
-p
Fig. 5. The comparison of the standard apparent molar isentropic compressibility, 0 , of ACP in
Jo
ur
na
lP
re
aqueous IL solutions at experimental temperatures.
31
lP
re
-p
ro
of
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Jo
ur
na
Fig. 1. Chemical structure of acetaminophen
32
lP
re
-p
ro
of
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Jo
ur
na
Fig. 2. The relationship between solubility of ACP, mole fraction x1, versus weight fraction of IL, w3, in aqueous solutions at 29815 and 313.15 K, the solid lines obtained from e-NRTL model.
33
ur
na
lP
re
-p
ro
of
Journal Pre-proof
Jo
Fig. 3. Solvent-solute interactions between the ACP and ILs (H-bonding interactions).
34
-p
ro
of
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Fig. 4. The comparison of the standard apparent molar volume, V0 , of ACP in aqueous IL solutions at experimental
Jo
ur
na
lP
re
temperatures.
35
re
-p
ro
of
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Jo
ur
na
solutions at experimental temperatures.
lP
Fig. 5. The comparison of the standard apparent molar isentropic compressibility, , of ACP in aqueous IL
36
0
Journal Pre-proof Highlights
Solubility of acetaminophen in two aqueous choline-based ionic liquids solutions was measured.
Solubility data were correlated by using some empirical and activity coefficient models.
ChLa Ionic liquid was the most effective co-solvent.
Density and speed of sound behavior of acetaminophen in aqueous ILs solutions is
Jo
ur
na
lP
re
-p
ro
of
reported.
37