Preferential Solvation Parameters Research Articles

Thermodynamic solubility, solvent effect and preferential solvation analysis of rebamipide in aqueous co-solvent mixtures of propylene glycol, n-propanol, isopropanol and ethanol

Mole fraction solubility of rebamipide (R- and S-enantiomer mixtures with a mole ratio of 50:50) in mixtures of propylene glycol (PG, 1) + water (2), n-propanol (1) + water (2) , isopropanol (1) + water (2) and ethanol (1) + water (2) was reported at temperature range from (273.15 to 318.15) K. All experiments were made by the use of the isothermal saturation technique under ambient pressure of 101.2 kPa. At the same mass fraction proportions of PG, n-propanol, isopropanol or ethanol and temperature, the rebamipide solubility was highest in the PG (1) + water (2) mixture. The solubility data were correlated mathematically through the Jouyban-Acree model, attaining RAD values lower than 6.35% and RMSD values lower than 6.73 × 10−6. Quantitative values for local mole fraction of PG (n-propanol, isopropanol or ethanol) and water adjacent the rebamipide were determined by means of the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. The preferential solvation parameters were negative in the water-rich mixtures but positive in the co-solvent compositions from 0 to 0.20 in mole fraction of n-propanol/PG, and from 0 to 0.25 in mole fraction of ethanol/isopropanol, respectively. It was conjectured that the preference of rebamipide in water-rich mixtures could be the result from the higher basic behaviour of rebamipide molecules interacting with the proton-donor functional groups of the water. In addition, the solubility variation over the composition range was analysed by KAT-LSER model to distinguish the main factors that explained solvent effect on solubility of rebamipide in the PG (n-propanol, isopropanol or ethanol) + water mixtures. It was found that the rebamipide solubility variation was mainly due to the change in the hydrogen bond acidity and cavity term for the ethanol (isopropanol, n-propanol) mixtures and the cavity term for the PG + water mixture.

Solvatochromism in some cosolvent mixtures of sulfolane and aliphatic alcohols: a tool to predict preferential solvation

The phenomenon of solvatochromism for three indicator solutes, namely para-nitroaniline, N,N-dimethyl-p-nitroaniline, and the betaine dye 4-(2,4,6-triphenylpyridinium-1-yl)-2,6-diphenylphenolate, was studied at 303.15 ± 0.1 K by means of UV–vis absorption measurements. The spectral shifts of these dyes in different mole fractions (0.0–1.0) of binary mixtures of sulfolane with eight alcohols (methanol, ethanol, 1-propanol, 2-propanol, 1-butanol, 2-butanol, iso-butanol, tert-butanol) were analyzed to investigate preferential solvation of them in terms of both the solute–solvent and the solvent–solvent interactions. A modified theoretical model (solvent exchange model) was successfully employed to calculate preferential solvation parameters and to obtain information into the contribution of intermolecular interactions to the local and bulk mole fraction distribution of solvation species. It was found that the solvation shell of the dyes is mainly affected by the solvent–solvent interactions, and in all binary mixtures, the studied solvation behavior was non-ideal.

5-Nitrosalicylaldehyde in aqueous co-solvent mixtures of methanol, ethanol, isopropanol and acetonitrile: Solubility determination, solvent effect and preferential solvation analysis

The equilibrium 5-nitrosalicylaldehyde solubility in methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and acetonitrile (1) + water (2) mixtures was determined by a shake-flask method from 273.15 K to 313.15 K under local pressure of 101.2 kPa. At the same mass fraction of methanol (ethanol, isopropanol or acetonitrile) and temperature, the mole fraction solubility of 5-nitrosalicylaldehyde was greater in (acetonitrile + water) mixture than in ethanol (1) + water (2), isopropanol (1) + water (2) and methanol (1) + water (2) mixtures. The relative importance of solute–solvent and solvent–solvent interactions upon the solubility variation was valued by using the linear solvation energy relationship analysis of solvent effect. The method of inverse Kirkwood–Buff integrals was used to study the preferential solvation on the basis of thermodynamic solution properties. The preferential solvation parameters for methanol, ethanol, isopropanol and acetonitrile were positive in the four mixtures in co-solvent-rich and intermediate composition, indicating that 5-nitrosalicylaldehyde was solvated preferentially by the co-solvent. It is conjecturable that in these regions 5-nitrosalicylaldehyde acts as a Lewis acid with the alcohols’ molecules; while for the acetonitrile + water mixture, the preferential solvation could be attributed to polarization effects. Moreover, the drugs’ solubility was mathematically represented via the Jouyban-Acree model acquiring the average relative deviations<6.03%.

Thermodynamic analysis and preferential solvation of sulfamethazine in acetonitrile + water cosolvent mixtures

This paper presents the solubility of sulfamethazine (SMT) in the acetonitrile (MeCN) + water (W) cosolvent system at nine temperatures. From the solubility experimental data, the thermodynamic functions of solution, mixing, and transfers are calculated and analyzed using the Perlovich graphical method. On the other hand, an enthalpy−entropy compensation analysis is performed and the preferential solvation parameters are calculated using the Kirkwood-Buff (IKBI) inverse integral method. The result of the performed calculations indicates that the SMT solution process is endothermic with entropic favor, where the addition of MeCN has a positive cosolvent effect between pure water and the mixture with w1 = 0.90. As for the preferential solvation, the SMT molecule is preferentially surrounded by water in water- and MeCN-rich mixtures, and in intermediate mixtures, the SMT molecule tends to be surrounded by MeCN.

Preferential solvation in mixed solvents. 16. Mixtures of N,N-dimethylformamide or propylene carbonate with organic solvents

The preferential solvation parameters for the self-association and the mutual association of each of N,N-dimethylformamide and propylene carbonate with a co-solvent in their binary mixtures as well as the self-association of each of these components at infinite dilution in the other component as solvent have been calculated from previously reported experimental data, using the inverse Kirkwood-Buff integrals approach.

Domperidone Solubility in Aqueous Cosolvent Mixtures of N,N-Dimethylformamide, Isopropanol, Dimethyl Sulfoxide, and Ethanol: Thermodynamic Modeling and Preferential Solvation Analysis

The determination of solubility of domperidone in aqueous cosolvent mixtures of isopropanol, N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and ethanol was carried out by a shake-flask method over the temperatures from 293.15 to 333.15 K under local atmospheric pressure p = 101.1 kPa. It may be observed that the domperidone solubility increased and then decreased as the mass fractions of DMF (DMSO, isopropanol, or ethanol) increased. The maximum solubility data was found with the cosolvent composition of 0.8 in mass fraction. The determined solubility values were correlated using the Jouyban–Acree, van’t Hoff–Jouyban–Acree, and Apelblat–Jouyban–Acree models. The attained average relative deviations were smaller than 7.56%. Preferential solvation analysis of domperidone was performed by the inverse Kirkwood–Buff integral method. The preferential solvation parameters (δx1,3) by the cosolvent showed positive values in the composition regions of 0.20 < x1 < 0.50 for DMF, 0.24 < x1 < 0.55 for isopropa...

Solubility of sulfacetamide in (ethanol + water) mixtures: Measurement, correlation, thermodynamics, preferential solvation and volumetric contribution at saturation

The equilibrium solubility at temperatures from (278.15 to 313.15) K, dissolution thermodynamics, preferential solvation, and apparent specific volume at saturation of sulfacetamide (SCM) in {ethanol (1) + water (2)} mixtures is reported. Mole fraction solubility of SCM (x3) increases when temperature arises and also increases with the ethanol proportion increasing reaching maximum values in the mixture w1 = 0.80. It varies from 7.06 × 10−4 in neat water to 2.506 × 10−2 in the mixture w1 = 0.80 at 298.15 K. Solubility behavior was adequately correlated by various cosolvency models and the obtained mean percentage deviations (MPD) varied between 2.6 and 15.9%. Moreover, the trained Jouyban-Acree model using a minimum number of 7 data points is used for predicting the rest of data points with the MPD of ~14% (N = 81). In addition, the generally trained model (Jouyban-Acree-Abraham) was also used to predict the solubility data of SCM in {ethanol (1) + water (2)} mixtures and obtained MPD for prediction was 36.9%. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the mixtures and neat solvents. Based on the inverse Kirkwood-Buff integrals (IKBI) preferential solvation parameters were calculated. SCM is preferentially solvated by water molecules in water-rich mixtures and also in ethanol-rich mixtures. Further, from densities of the saturated solutions and those of the cosolvent mixtures free of drug, the apparent specific volumes at saturation were also calculated.

Solvent effect on solubility and preferential solvation analysis of buprofezin dissolved in aqueous co-solvent mixtures of N,N-dimethylformamide, ethanol, acetonitrile and isopropanol

The mole fraction solubility of buprofezin in aqueous co-solvent mixtures of N,N-dimethylformamide (DMF,1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and acetonitrile (1) + water (2) over the temperature range from (273.15 to 318.15) K was reported. At the same composition of DMF, ethanol, isopropanol or acetonitrile and temperature, the buprofezin solubility was highest in DMF (1) + water (2) mixtures. By using the Jouyban-Acree model, the buprofezin solubility was correlated obtaining RAD lower than 5.86% and RMSD lower than 15.60 × 10−4. Quantitative values for local mole fraction of DMF (ethanol, isopropanol or acetonitrile) and water nearby the buprofezin were calculated through the Inverse Kirkwood–Buff integrals method applied to the solubility. The values of preferential solvation parameters (δx1,3) were negative in water-rich mixtures but positive in co-solvent compositions from 0.19, 0.20 (0.25) or 0.25 to 1 in mole fraction of DMF, isopropanol, ethanol or acetonitrile, respectively. It was conjecturable that in water-rich mixtures, the hydrophobic hydration around the nonpolar methyl groups and aromatic ring group of buprofezin played a relevant important role in the solvation. The preference of buprofezin in water-rich mixtures could be explained in terms of the higher basic behaviour of buprofezin molecules interacting with the proton-donor functional groups of the water. In addition, solute-solvent and solvent-solvent interactions of buprofezin in the DMF (ethanol, isopropanol or acetonitrile) + water mixtures were investigated from the solubility data by using the linear solvation energy relationships concept. The variation of buprofezin solubility depended mainly upon the hydrogen bond acidity and cavity term for ethanol (isopropanol) + water mixtures, and the cavity term for DMF (acetonitrile) + water mixtures.

Solubility of 4-amino-2,6-dimethoxypyrimidine in aqueous co-solvent mixtures revisited: Solvent effect, transfer property and preferential solvation analysis

The preferential solvation parameters of 4-amino-2,6-dimethoxypyrimidine in four aqueous co-solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and DMF (1) + water (2) were derived from their available solubility data by using the inverse Kirkwood–Buff integrals method. In water-rich compositions for the four aqueous co-solvent mixtures, the value of δx1,3 was negative, which showed that the 4-amino-2,6-dimethoxypyrimidine was preferentially solvated by water. In intermediate composition and co-solvent-rich composition, 4-amino-2,6-dimethoxypyrimidine was preferentially solvated by the co-solvent (methanol, ethanol, isopropanol or DMF). The preferential solvation magnitude of 4-amino-2,6-dimethoxypyrimidine was highest in isopropanol mixtures than in the other three solvent mixtures. The higher solvation by co-solvents could be explained in terms of the higher basic behavior of the solvents interacting with the Lewis acidic groups of the 4-amino-2,6-dimethoxypyrimidine. The contributions from solute-solvent and solvent-solvent interactions to the solvent effect were studied by using the linear solvation energy relationships. Furthermore, transfer Gibbs free energy (ΔtrGo), enthalpy (ΔtrHo), and entropy (ΔtrSo) were derived, demonstrating that the solubilization capacity was more favorable in the intermediate concentration of co-solvents.

Solubility of acetaminophen in 1-propanol + water mixtures at T = 293.2–313.2 K

ABSTRACT The mole fraction solubilities of acetaminophen (ACP) were measured in the binary solvent mixtures of {1-propanol + water} at T = 293.2–313.2 K. The Jouyban–Acree, Jouyban–Acree–van’t Hoff, combined nearly ideal binary solvent/Redlich–Kister (CNIBS/R-K) and modified Wilson models as well as a non-linear model presented by Machatha et al. were used to correlate the measured equilibrium solubilities. Furthermore, the experimental data were predicted with five predictive models, i.e. Yalkowsky, extended Yalkowsky as well as trained versions of Yalkowsky, Jouyban–Acree and Jouyban–Acree–Hansen models. Moreover, the apparent standard molar Gibbs energy, enthalpy, and entropy of dissolution and mixing (, , , , , ) of ACP in {1-propanol (1) + water (2)} mixtures were calculated at mean harmonic temperature T hm = 303 K based on van’t Hoff and Gibbs free energy equations. Additionally, preferential solvation parameters of ACP in the mixtures were also analysed based on the inverse Kirkwood–Buff integrals.

Solute–Solvent and Solvent–Solvent Interactions and Preferential Solvation of 1,1-Diamino-2,2-dinitroethylene in Aqueous Co-solvent Mixtures of N,N-Dimethylformamide and Dimethyl Sulfoxide

The effects of solvent properties on 1,1-diamino-2,2-dinitroethylene (FOX-7) solubility were investigated from the solubility values in aqueous co-solvent mixtures of N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) in terms of the linear solvation energy relationships with use of mathCAD software. For both aqueous mixtures, the main effect of hydrogen bond basicity was observed based on the solubility variation of FOX-7. The preferential solvation (the difference in composition between the solvation shell of the solute and the bulk composition in a mixture) of FOX-7 in the two aqueous of co-solvent solutions were investigated by using the method of inverse Kirkwood–Buff integrals (IKBI). The values of the preferential solvation parameters (δx1,3) were negative in water-rich mixtures, which are − 3.103×10−2 to − 2.936 × 10−2 for DMF (1) + water (2) mixtures and − 4.470 × 10−2 to − 3.995 × 10−2 for DMSO (1) + water (2) mixtures. However, in the co-solvent compositions ranging from 0.19 or 0.21 to 1 in mole fraction of DMF or DMSO, positive values of δx1,3 were observed. The preference of FOX-7 in water-rich mixtures can be explained based on the higher acidic behavior of FOX-7 molecules, which interact with the proton–acceptor functional groups of DMF and DMSO. KAT-LSER analysis showed that only the hydrogen-bond acceptor basicity of solvents played an important role on the FOX-7 solubility owing to its two amino functional groups. The squared correlation coefficient and F-statistic values are 0.98 and 314 for DMF + water mixture, and 0.96 and 130 for DMSO + water mixture, respectively.

Lamotrigine solubility in 1-propanol + water mixtures at different temperatures: experimental data and mathematical modelling

ABSTRACT The solubility of lamotrigine (LTG) was determined in {1-propanol (1) + water (2)} mixtures over a temperature range of 293.15 to 313.15 K. The measured data were correlated to cosolvency models namely Jouyban-Acree, Jouyban-Acree-van’t Hoff, combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K), modified Wilson and Machatha models. Among the models, Jouyban-Acree with temperature and solvent composition dependencies has more accuracy rather than Jouyban-Acree-van’t Hoff model and CNIBS/R-K model with solvent composition dependency is more compatible with the experimental solubility data. Furthermore, the apparent standard molar Gibbs energy, entropy, and enthalpy of dissolution and mixing , , , , and for LTG in the studied binary mixtures were calculated based on the van’t Hoff and Gibbs free energy equations which suggest that the dissolution process is more favourable in 1-propanol-rich mixtures and proceeds entropically. Finally, preferential solvation parameters of LTG by 1-propanol were also calculated by means of the inverse Kirkwood-Buff integrals.

Preferential solvation in mixed solvents. 15. Mixtures of acetonitrile with organic solvents

The preferential solvation parameters for the mutual association of acetonitrile with a co-solvent in their binary mixtures and for the self-association of acetonitrile in these mixtures, and the self-association of each of these components at infinite dilution in the other component as solvent have been determined. The co-solvents studied include dichloromethane, acetone and nitromethane that form practically ideal mixtures with acetonitrile and 1,2-dichloroethane and chloroform that nearly do so, as well as benzene, toluene, chlorobenzene, tetrarchloromethane, methanol, ethanol, acetic acid, formamide, dimethylformamide, and dimethylacetamide, which show appreciable preferential solvation.

Solubility of sulphadiazine in (acetonitrile + water) mixtures: measurement, correlation, thermodynamics and preferential solvation

ABSTRACTThe equilibrium solubility at temperatures from (293.15 to 313.15) K, dissolution thermodynamics and preferential solvation of sulphadiazine (SD) in {acetonitrile (ACN) (1) + water (2)} mixtures is reported. Mole fraction solubility of SD (x3) increases when temperature arises and also increases with the ACN proportion increasing. It varies from 4.81 × 10–6 in neat water to 6.02 × 10–4 in neat ACN at 298.15 K. Solubility behaviour was adequately correlated by Jouyban-Acree, modified Wilson and non-linear (proposed by Machatha et al.) models and the obtained mean percentage deviations (MPD) are 4.1%, 2.3% and 2.3%, respectively. The comparison of the MPD shows that the prediction using Jouyban-Acree model is more accurate than Jouyban-Acree-Abraham equation for solubility prediction of SD in {ACN (1) + water (2)}. From the variation of solubility with temperature the apparent thermodynamic analysis of dissolution was performed in all the mixtures and neat solvents. Based on the inverse Kirkwood-Buff integrals preferential solvation parameters were calculated. SD is preferentially solvated by water in water-rich mixtures (0.00 < x1 < 0.26) but preferentially solvated by ACN in the interval (0.26 < x1 < 0.65). In ACN-rich mixtures the behaviour is not well defined.

Experimental and computational approaches for measuring minoxidil solubility in propylene glycol + water mixtures at different temperatures

Minoxidil solubility in binary mixtures of propylene glycol + water at different temperatures has been performed by shake-flask method followed by spectrophotometry method. Four cosolvency models including the modified Wilson model, the Yalkowsky model, Jouyban-Acree model and Jouyban-Acree-van't Hoff model were used to correlate the measured solubility data. The correlation and prediction abilities of these models were compared by computing mean relative deviations (MRD%). Apparent thermodynamic properties of minoxidil dissolution such as enthalpy, entropy and Gibbs free energy were investigated through van't Hoff and Gibbs equations. Furthermore, preferential solvation parameters of minoxidil were calculated by means of the inverse Kirkwood-Buff integrals.

Preferential Solvation of Vitamin C in Binary Solvent Mixtures Formed by Methanol, Ethanol, n-Propanol, Isopropanol and Water

The present work is an investigation of the preferential solvation of vitamin C in five solvent mixtures: ethanol (1) + methanol (2), isopropanol (1) + methanol (2), ethanol (1) + water (2), n-propanol (1) + water (2) and isopropanol (1) + water (2) from the reported solubility data by employing the method of inverse Kirkwood–Buff integrals. In the ethanol (1) + water (2) mixtures with compositions 0.25 < x1 < 1.00, and isopropanol (1) + water (2) and n-propanol (1) + water (2) mixtures with compositions 0.20 < x1 < 1.00, the local mole fractions of ethanol, isopropanol or n-propanol are smaller than those of the bulk solutions. Consequently, the values of preferential solvation parameter (δx1,3) are negative, which shows that vitamin C is preferentially solvated by water. Perhaps the structuring of water molecules near the vitamin C molecule contributes to lowering of the δx1,3 from the neat solvent water to negative values in the three solvent mixtures. Vitamin C acts as a Lewis base that interacts with the acidic hydrogen atoms of water. Nevertheless, in the ethanol (1) + methanol (2) and isopropanol (1) + methanol (2) mixtures, vitamin C is preferentially solvated neither by methanol nor by ethanol nor isopropanol.

Equilibrium solubility investigation and thermodynamic aspects of biologically active gimeracil (form P) dissolved in aqueous co-solvent mixtures of isopropanol, N,N-dimethylformamide, ethylene glycol and dimethylsulfoxide

Solubilities of gimeracil (form P) in aqueous co-solvent mixtures of isopropanol, N,N-dimethylformamide (DMF), ethylene glycol (EG) and dimethylsulfoxide (DMSO) were investigated via the isothermal dissolution equilibrium method at (283.15–328.15) K under ambient pressure p = 101.2 kPa. Experimental solubility was increased with increasing temperature and mass fraction of each co-solvent. The largest solubility was found in neat co-solvents. The solids equilibrated with liquid phase were characterized by X-ray power diffraction, indicating no polymorphic transformation, solvate formation or crystal transition according to the spectral data. The Jouyban-Acree model was adopted to correlate the obtained solubility. The highest RAD and RMSD values were, respectively, 2.61 × 10−2 and 14.96 × 10−4. Quantitative values for the local mole fraction of DMF (EG, DMSO or isopropanol) and water around gimeracil (form P) were acquired by using the Inverse Kirkwood–Buff integrals method. The preferential solvation parameters for isopropanol were positive in the isopropanol mixtures in intermediate and isopropanol-rich compositions, which indicated that gimeracil (form P) was preferentially solvated by isopropanol. Gimeracil (form P) could act mainly as a Lewis acid interacting with proton-acceptor functional group of isopropanol. Within the same region, gimeracil (form P) was not preferentially solvated by DMF, EG and DMSO. Furthermore, the method of linear solvation energy relationships was performed with a suitable combination of solvent polarity descriptors to explain the nature of intermolecular interactions resulting in the solubility variation in the co-solvent mixtures.

Equilibrium solubility determination, modelling and preferential solvation of bioactive iminodibenzyl in aqueous co-solvent mixtures at various temperatures

The mole fraction solubility of bioactive iminodibenzyl in aqueous co-solvent mixtures of ethanol, ethylene glycol (EG), dimethyl sulfoxide (DMSO) and isopropanol was examined by the saturation shake-flask method over the temperature range from 283.15 K to 328.15 K at pressure of 101.2 kPa. The experimental solubility increased with increasing temperature at a given co-solvent composition and decreased with the increasing mass fraction of water in each binary system. The maximum solubility was found in pure co-solvent. Given the same temperature and mass fraction of the co-solvent, the solubility of iminodibenzyl was greater in (DMSO + water) than in the other three co-solvent systems. The solid crystal examples of iminodibenzyl was tested by X-ray power diffraction showing no polymorphic transformation, solvate formation or crystaltransition during entire experiments. The Jouyban-Acree model was employed to correlate the measured solubility. The calculated data were in alignment to measured values and RAD and RMSD data were no more than 3.08% and 10.37 × 10−4, respectively. Furthermore, quantitative values for the local mole fraction of ethanol (EG, DMSO or isopropanol) and water around the iminodibenzyl were acquired by using the Inverse Kirkwood–Buff integrals method. The preferential solvation parameters for ethanol, EG, DMSO or isopropanol were positive in the four co-solvent mixtures in intermediate and co-solvent-rich compositions, which indicated that iminodibenzyl was preferentially solvated by the co-solvent. iminodibenzyl could act mainly as a Lewis acid interacting with proton-acceptor functional groups of the co-solvents.

Solvent effect and preferential solvation of cefpiramide in cosolvent plus water mixtures

The preferential solvation parameters (δx1,3) of cefpiramide in two cosolvent mixtures of ethanol (1) + water (2), and isopropanol (1) + water (2) were derived from their available solubility data by means of the inverse Kirkwood–Buff integrals method. For the studied systems, the values of δx1,3 were negative in the entire composition region for the isopropanol (1) + water (2) mixtures at 293.15 K and 298.15 K and for the ethanol (1) + water (2) mixtures at different temperatures studied, therefore the cefpiramide was preferentially solvated by water in the entire composition region. However in the isopropanol (1) + water (2) mixtures at 303.15 K with composition 0.45 < x1 < 0.62 and 0.85 < x1 < 1, the δx1,3 values were positive. The negative δx1,3 values indicated that cefpiramide was preferentially solvated by water. Probably the structuring of water molecules around the nonpolar aromatic group of cefpiramide (i.e. hydrophobic hydration of aromatic rings group) contributes to lowering of the net δx1,3 to negative values. Furthermore, linear solvation energy relationships concept was used to describe the variation in the solubility based on the solvent effect.

Experimental solubility evaluation and thermodynamic analysis of quinocetone in aqueous co-solvent solutions of ethanol, isopropanol, dimethyl sulfoxide and N,N-dimethylformamide

Experimental measurement of drug quinocetone solubility in water-co-solvent mixtures of ethanol, isopropanol, dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) were determined by the static equilibrium method at temperature range of (283.15–328.15) K under ambient condition (101.2 kPa). The solid phase equilibrated with liquor was examined by X-ray power diffraction, resulting in no polymorphic transformation, solvate formation or crystal transition compared to the raw material. Quantitative knowledge about the solvent effect on the solubility was obtained with the help of linear solvation energy relationships in the terms of dipolarity-polarizability, hydrogen-bond donor and acceptor ability, and cavity term of mixtures. The preferential solvation was investigated from their thermodynamic solution properties by means of the inverse Kirkwood-Buff integrals. The preferential solvation parameters (δx1,3) for ethanol, isopropanol, DMSO or DMF were negative in the four co-solvent mixtures with water-rich compositions, which indicated that quinocetone was preferentially solvated by water. Temperature has a little effect on the preferential solvation magnitudes for the ethanol and isopropanol mixtures. The higher solvation by water could be explained in terms of the higher acidic behavior of the solvents interacting with the Lewis basic groups of the quinocetone. In addition, thermodynamic co-solvency models including the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Modified Apelblat-Jouyban-Acree model were employed to describe the solubility of this drug obtaining average relative deviations lower than 2.14% and root-mean-square deviations lower than 1.75 × 10−4 for correlative studies. The standard dissolution enthalpies of quinocetone in the solvent mixtures were positive, demonstrating that the dissolution process of quinocetone was endothermic.