Aqueous Co-solvent Mixtures Research Articles

Phenformin in aqueous co-solvent mixtures of N,N-dimethylformamide, ethanol, N-methylpyrrolidone and dimethyl sulfoxide: Solubility, solvent effect and preferential solvation

The equilibrium mole fraction solubility of phenformin in four co-solvent mixtures of N,N-dimethylformamide (DMF) + water (2), ethanol (1) + water (2) and N-methylpyrrolidone (NMP, 1) + water (2) at temperatures from 278.15 K to 323.15 K and dimethyl sulfoxide (DMSO) (1) + water (2) at temperatures from 293.15 K to 323.15 K were determined via the saturation shake-flask technique. The maximum solubility values were observed in the neat co-solvents of DMF (DMSO, NMP and ethanol). Through the Jouyban-Acree model, the phenformin solubility in the four solvent mixtures was well correlated attaining RAD values less than 3.21% and RMSD values less than 4.84 × 10−4. To describe how solvent affect the solubility, the obtained solubility data were introduced into the linear solvation energy relationships model by taking the cavity term and KAT parameters as solvent’s descriptors. It was shown that the cavity term and hydrogen bond acidity of solvent play the key role on the solubility variation in aqueous DMF, DMSO, ethanol and NMP mixtures. What's more, the quantitative values for local mole fractions of DMSO (DMF, ethanol or NMP) and water around the drug phenformin were calculated by the Inverse Kirkwood–Buff integrals method based on solubility data. Phenformin was preferentially solvated by water in the DMSO/DMSO (1) + water (2) mixtures with compositions 0 < x1 < 0.20 and NMP (1) + water (2) mixture with compositions 0 < x1 < 0.16; while for the ethanol (1) + water (2) mixture with compositions 0.25 < x1 < 1, phenformin is preferentially solvated ethanol.

3-Methyl-6-nitroindazole in some aqueous co-solvent mixtures: Solubility determination, preferential solvation and solvent effect analysis

The equilibrium solubility of 3-methyl-6-nitroindazole in co-solvent mixtures of acetonitrile (1) + water (2), ethanol (1) + water (2) and n-propanol (1) + water (2) is reported. Experiments were performed by using the saturation shake-flask technique at temperature range from 278.15 to 328.15 K. The maximum solubility value was observed in neat acetonitrile (ethanol or n-propanol) for each co-solvent mixtures. By using the Jouyban-Acree model, the 3-methyl-6-nitroindazole solubility was well correlated obtaining RAD values smaller than 4.50% and RMSD values smaller than 3.36 × 10−4. Quantitative values for the local mole fraction of acetonitrile (ethanol, n-propanol, DMF or acetone) and water around the 3-methyl-6-nitroindazole were computed by using the Inverse Kirkwood–Buff integrals method applied to the solubility data. 3-Methyl-6-nitroindazole was preferentially solvated by water in water-rich compositions; while within co-solvent-rich and intermediate compositions, 3-methyl-6-nitroindazole is preferentially solvated by acetonitrile (ethanol, n-propanol, DMF or acetone) in the acetonitrile (ethanol, n-propanol, DMF or acetone) + water mixtures. The experimental solubility data were correlated by Kamlet and Taft linear solvation energy relationships to examine the main factors describing solvent effect. The results showed that the change in cavity formation energy over the composition played the main role on the solubility variation of 3-methyl-6-nitroindazole in all aqueous mixtures.

Maraviroc in aqueous co-solvent solutions of n-propanol, ethanol, dimethyl sulfoxide and N,N-dimethylformamide: Solubility determination, preferential solvation and solvent effect analysis

The liquid–solid equilibrium and solubility of maraviroc in co-solvent mixtures of n-propanol, ethanol, dimethyl sulfoxide (DMSO) and N,N-dimethylformamide (DMF) plus water was obtained via the saturation shake-flask technique between 278.15 K and 323.15 K under 101.2 kPa. For the four aqueous co-solvent mixtures investigated, the mole fraction solubility of maraviroc increased with the increase in the temperature and mass fraction of n-propanol, ethanol, DMSO and DMF. The maximum solubility values of maraviroc were observed in the neat co-solvents. The dependence of the maraviroc solubility on the solvent composition and temperature was mathematically correlated by means of the Jouyban-Acree model. The obtained values of relative average deviation (RAD) and root-mean-square deviation (RMSD) were no more than 4.16 × 10−2 and 49.13 × 10−6, respectively. KAT-LSER model was implemented to get quantitative information about solvent effect on the variation of solubility data. The variation in the maraviroc solubility was dependent upon the hydrogen-bond donation and cavity term in n-propanol + water and ethanol + water mixtures; and the cavity term was the dominant term in the (DMSO + water) and (DMF + water) mixtures. Quantitative study was made for the local mole fraction of ethanol (n-propanol, DMSO and DMF) and water around the maraviroc by the Inverse Kirkwood–Buff integrals method applied to the solubility data determined. Maraviroc was preferentially solvated by ethanol or n-propanol for the aqueous co-solvent mixtures of ethanol or n-propanol in intermediate and ethanol/n-propanol-rich compositions. It was conjecturable that maraviroc could act mainly as a Lewis acid in front to the ethanol or n-propanol molecules. However in the {n-propanol (1) + water (2)} mixture with compositions 0 < x1 < 0.20, ethanol (1) + water (2) mixture with compositions 0 < x1 < 0.25 and DMF/DMSO mixtures within entire compositions, maraviroc was preferentially solvated neither by co-solvent (1) nor by water.

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.

Experimental Determination and Thermodynamic Correlation of 7-Amino-4-Methylcoumarin Solubility in Various Cosolvency Mixtures at (278.15–323.15) K

Four solvents (ethanol, isopropanol, ethylene glycol (EG), and N,N-dimethylformamide (DMF)) that can be mixed with water in any ratio were selected to determine the dissolution performance of 7-amino-4-methylcoumarin by the classical shake-flask method. The measured temperature range began at 278.15 K and ended at 303.15 K, and the pressure environment was controlled at standard atmospheric pressure (101.1 kPa). Results reveal that with the addition of organic solvents, the solubilization effect of 7-amino-4-methylcoumarin was very significant and the larger the amount of addition, the more obvious was the effect of solubilization. Not only that, the temperature change had a non-negligible effect on the dispersion of 7-amino-4-methylcoumarin; the temperature increased monotonically, and the better was the dissolution. When the external conditions were kept constant, the addition of DMF made the solubilization effect of 7-amino-4-methylcoumarin most obvious among all organic solvents used. This study involved three models, including the Jouyban–Acree model and its two variants (van’t Hoff–Jouyban–Acree model and Apelblat–Jouyban–Acree model), which were used to correlate the solubility data of 7-amino-4-methylcoumarin in aqueous cosolvent mixtures. The relative average deviation (RAD) and root-mean-square deviation (RMSD) reaches to 3.47 × 10–2 and 1.79 × 10–3 rooting in the van’t Hoff–Jouyban–Acree model. The relevant parameters obtained through model calculation and experimental means are essential for product synthesis, separation, and purification processes.

Solubility of monobenzone in aqueous co-solvent mixtures of several alcohols: Determination, modelling and thermodynamic aspects analysis

Investigation upon the solubility of monobenzone in aqueous co-solvent mixtures of isopropanol, n-propanol, ethylene glycol (EG) and ethanol was performed via a saturation shake-flask technique at temperatures from 283.15 K to 328.15 K under pressure of p = 101.2 kPa. Experimental solubility magnitude presented positive dependence upon the mass fraction of each co-solvent and temperature. The greatest solubility value on the mole fraction scale was observed in the neat co-solvents. The equilibrated solids with corresponding co-solvent mixtures were characterized through an X-ray power diffraction (XRD) technique, demonstrating the absence of polymorphic transformation or solvate formation. The Jouyban-Acree model was adopted to mathematically describe the monobenzone solubility data. The maximum magnitudes of RAD and RMSD were 3.17 × 10−2 and 7.64 × 10−4, respectively. The local mole fractions of isopropanol (n-propanol, EG or ethanol) and water adjacent monobenzone were quantitatively studied by the Inverse Kirkwood–Buff integrals method. The parameters of preferential solvation for the isopropanol (n-propanol, EG or ethanol) were positive in the isopropanol (n-propanol, EG or ethanol) mixtures in intermediate and alcohol-rich compositions, indicating that monobenzone was preferentially solvated by the isopropanol (n-propanol, EG or ethanol). Monobenzone mainly acted as a Lewis acid which interacted with proton-acceptor functional group of the alcohols. Furthermore, the analysis of linear solvation energy relationships was made with a suitable combination of the solvent polarity descriptors to reveal the nature of intermolecular interactions bringing about the solubility variation in the co-solvent mixtures.

Equilibrium solubility, solvent effect and preferential solvation of 5-nitrofurazone (form γ) in aqueous co-solvent mixtures of isopropanol, N-methyl pyrrolidone, ethanol and dimethyl sulfoxide

Solubilities of 5-nitrofurazone (form γ) in aqueous co-solvents mixtures of isopropanol, N-methyl pyrrolidone (NMP), ethanol and dimethyl sulfoxide (DMSO) were experimentally investigated via the saturation shake-flask technique at temperatures from 278.15 K to 323.15 K under ambient pressure of p = 101.2 kPa. The solubility of 5-nitrofurazone increased to a maximum value with 100% mass fractions of NMP and DMSO in aqueous solutions of NMP and DMSO, while with 80% mass fractions of isopropanol and ethanol in aqueous solutions of isopropanol and ethanol. The solids equilibrated with liquor were characterized by X-ray power diffraction, indicating that no solvate formation or polymorphic transformation occurred. The Jouyban-Acree model was accepted to correlate the obtained solubility. The acquired highest relative average deviation and root-mean-square deviation values were, respectively, 5.62 × 10−2 and 11.18 × 10−4. Quantitative values for local mole fractions of NMP (ethanol, DMSO, DMF or isopropanol) and water nearby 5-nitrofurazone were obtained by the method of Inverse Kirkwood–Buff integrals. The parameters of preferential solvation were positive for isopropanol/ethanol in the isopropanol/ethanol mixtures in intermediate compositions, and for NMP/DMF/DMSO in the NMP/DMF/DMSO mixtures in intermediate and NMP/DMF/DMSO-rich compositions, which indicated that 5-nitrofurazone was preferentially solvated by the co-solvents. Linear solvation energy relationships were used to model the solvent effect through the analysis of correlations between solubility data and solvent polarity quantified by suitable descriptors.

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%.

Equilibrium solubility determination, solvent effect and preferential solvation of amoxicillin in aqueous co-solvent mixtures of N,N-dimethylformamide, isopropanol, N-methyl pyrrolidone and ethylene glycol

The mole fraction solubility of amoxicillin in four co-solvent mixtures of N,N-dimethylformamide (DMF) + water (2), isopropanol (1) + water (2), N-methyl pyrrolidone (NMP) (1) + water (2) and ethylene glycol (EG, 1) + water (2) at temperatures from 278.15 K to 328.15 K was determined by means of the shake-flask technique. At the same temperature and composition of DMF, isopropanol, NMP or EG, the solubility magnitude of amoxicillin was highest in the DMF (1) + water (2) mixture, and lowest in the isopropanol (1) + water (2) mixture. Through the Jouyban-Acree model, amoxicillin solubility was well correlated obtaining RAD lower than 4.55% and RMSD lower than 1.96 × 10-4. Quantitative values for the local mole fraction of DMF (isopropanol, NMP or EG) and water nearby the amoxicillin were computed by means of the Inverse Kirkwood–Buff integrals method. In the DMF (1) + water (2) mixture with compositions 0.20 < x1 < 1.00, NMP (1) + water (2) mixture with compositions 0.165 < x1 < 1.00 and EG/isopropanol (1) + water (2) mixtures with compositions 0.25 < x1 < 1.00, amoxicillin was solvated preferentially by the co-solvent. In addition, solvent effect was modeled by linear solvation energy relationships in terms of KAT solvent polarity descriptors to detect the main intermolecular interactions controlling the solubility variation in solvent mixtures. Results showed that the work for cavity formation in solvent for solute’s accommodation had the most significant effect on solubility variance over the entire composition range in all the mixed solvents.

Equilibrium solubility and apparent specific volume at saturation of sodium sulfadiazine in some aqueous cosolvent mixtures at 298.2 K

ABSTRACT The main objective of this research was to determine and correlate the equilibrium solubility of sodium sulfadiazine in several {cosolvent (1) + water (2)} mixtures at 298.2 K. Cosolvents were formamide, N-methylformamide, N,N-dimethylformamide, dimethyl sulphoxide, N-methyl-2-pyrrolidone, 1,4-dioxane, and methanol. Classical shake-flask method was used to determine isothermal solubility. Drug concentration measurements were performed by means of electrical conductivity determinations after adequate aqueous dilutions. Solubility of sodium sulfadiazine decreases non-linearly with the addition of cosolvent to water in almost all mixtures compositions. The Jouyban-Acree and Jouyban-Acree-Abraham models correlate the solubility values with the mixtures composition for all cosolvent systems. Furthermore, the apparent specific volume of this drug at saturation was also calculated from density and mixtures compositions.

Baicalin solubility in aqueous co-solvent mixtures of methanol, ethanol, isopropanol and n-propanol revisited: solvent–solvent and solvent–solute interactions and IKBI preferential solvation analysis

ABSTRACT The effect of solvent on the baicalin solubility was studied by making a correlation between the solubility values and solvent’s descriptors for solute–solvent and solvent–solvent interactions with the help of linear solvation energy relationship concept. The preferential solvation analysis of baicalin in the four aqueous co-solvent solutions of isopropanol, n-propanol, ethanol and methanol was carried out from solubility values through the method of inverse Kirkwood–Buff integrals. In intermediate and alcohol-rich compositions, the solvation of baicalin was preferred by the isopropanol, n-propanol, ethanol or methanol.

Solubility of chloroxine in aqueous co-solvent mixtures of N,N-dimethylformamide, dimethyl sulfoxide, N-methyl-2-pyrrolidone and 1,4-dioxane: Determination, solvent effect and preferential solvation analysis

The equilibrium solubility of amorphous chloroxine in four co-solvent mixtures of dimethyl sulfoxide (DMSO) (1) + water (2), N,N-dimethylformamide (DMF) (1) + water (2), N-methyl-2-pyrrolidone (NMP) (1) + water (2) and 1,4-dioxane (1) + water (2) is reported. Experiments were performed by using the saturation shake-flask technique over the temperature range from (293.15 to 333.15) K. The maximum solubility was observed in neat DMF (DMSO, NMP or 1,4-dioxane) for the four co-solvent mixtures. By using the Jouyban-Acree model, the chloroxine solubility was well correlated obtaining RAD values lower than 3.64% and RMSD values lower than 8.82 × 10−6. Quantitative values for the local mole fraction of DMSO (DMF, NMP or 1,4-dioxane) and water around the chloroxine were computed by using the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. Chloroxine was preferentially solvated by water for the studied mixtures in water-rich compositions; while within intermediate and co-solvent-rich compositions, chloroxine is preferentially solvated by DMSO (DMF, NMP or 1,4-dioxane) in DMSO (DMF, NMP or 1,4-dioxane) + water mixtures. Moreover, in the light of Kamlet and Taft linear solvation energy relationships model, the co-solvency effect was rationalized, and the relative importance of solvent-solute and solvent-solvent interactions was recognized. It was shown that the change in solvent-solvent interaction energy accounted by cavity term governed the solubility variation of chloroxine in all aqueous mixtures.

Solubility modelling and thermodynamic aspect of d-aspartic acid in aqueous co-solvent mixtures of N-methyl-2-pyrrolidone, N,N-dimethylformamide, dimethyl sulfoxide and 1.4-dioxane

The solubility of d-aspartic acid in co-solvent mixtures of dimethyl sulfoxide (DMSO) (1) + water (2), N,N-dimethylformamide (DMF) (1) + water (2), N-methyl-2-pyrrolidone (NMP) (1) + water (2) and 1,4-dioxane (1) + water (2) at the temperatures from (288.15/298.15 to 333.15) K was reported. Experiments were performed through the saturation shake-flask technique. The maximum solubility values were observed in the neat DMF (DMSO, NMP and 1,4-dioxane) for the four aqueous co-solvent mixtures. Through the Jouyban-Acree model, the d-aspartic acid solubility was well correlated attaining RAD values less than 2.55% and RMSD values less than 2.81 × 10−4. The local mole fractions of DMSO (DMF, NMP or 1,4-dioxane) and water nearby the d-aspartic acid were analyzed through the Inverse Kirkwood–Buff integrals method. d-Aspartic acid was preferentially solvated by water in water-rich compositions; while within intermediate and co-solvent-rich compositions, d-aspartic acid was preferentially solvated by DMF (NMP or 1,4-dioxane) in DMF (NMP or 1,4-dioxane) + water mixtures. In addition, the model of Kamlet and Taft linear solvation energy relationships was employed in order to rationalize the co-solvency effect and to identify its main components. It was found that the work needed for breaking solvent-solvent interactions presented by cavity term mainly controlled the solubility enhancement over the entire composition range in all the aqueous binary mixtures.

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...

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.

Thermodynamic solubility modelling, solvent effect and preferential solvation of p-nitrobenzamide in aqueous co-solvent mixtures of dimethyl sulfoxide, ethanol, isopropanol and ethylene glycol

The equilibrium p-nitrobenzamide solubility in mixtures of dimethyl sulfoxide (DMSO, 1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and ethylene glycol (EG, 1) + water (2) was determined with a shake-flask method from (293.15 to 328.15) K under atmospheric pressure (101.1 kPa). At the same temperature and mass fraction of DMSO (ethanol, isopropanol or EG), the mole fraction solubility of p-nitrobenzamide was greater in (DMSO + water) than in ethanol (1) + water (2), isopropanol (1) + water (2) and ethylene glycol (EG, 1) + water (2) mixtures. X-Ray power diffraction analysis of solid phase showed no polymorphic transformation or solvate formation in experiments. The degree of relative importance of solute–solvent and solvent–solvent interactions on the solubility variation was evaluated by the linear solvation energy relationship analysis of solvent effect. The inverse Kirkwood–Buff integrals was used to study the preferential solvation based on thermodynamic solution properties. The parameters of preferential solvation for ethanol and isopropanol were positive in the ethanol (1) + water (2) and isopropanol (1) + water (2) mixtures in co-solvent-rich and intermediate composition, indicating that p-nitrobenzamide was solvated preferentially by the co-solvent. p-Nitrobenzamide acted mainly as a Lewis acid interacting with proton-acceptor functional groups of the co-solvents. Moreover, the drugs’ solubility was represented mathematically via the Jouyban-Acree model attaining the average relative deviations smaller than 2.16%.

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.

Equilibrium solubility and apparent specific volume at saturation of sodium diclofenac in {formamide (1)/N-methylformamide (1)/or N,N,-dimethylformamide (1) + water (2)} mixtures at 298.2 K

ABSTRACT Sodium diclofenac is an analgesic drug commonly used in current therapeutics. Solubility data of this drug in aqueous cosolvent mixtures are not abundant. The main objective of this research was to determine and correlate the equilibrium solubility of sodium diclofenac in some {cosolvent (1) + water (2)} mixtures at 298.2 K. Cosolvents were formamide, N-methylformamide, and N,N-dimethylformamide. Classical shake-flask method was used to determine isothermal solubility. Drug concentration measurements were performed by means of electrical conductivity determinations after adequate aqueous dilutions. Solubility of sodium diclofenac increases non-linearly with the addition of cosolvent to water in almost all mixtures compositions. Higher solubility values were found in {N,N-dimethylformamide (1) + water (2)} mixtures. Jouyban-Acree model correlates solubility values with the mixtures composition for all cosolvent systems. Furthermore, the apparent specific volume of this drug was also calculated from density and mixtures compositions.

Solubility and preferential solvation of flubendazole dissolved in aqueous co-solvent mixtures of 1,4-dioxane, dimethyl sulfoxide, N,N-dimethylformamide and isopropanol

The equilibrium solubility of flubendazole in four co-solvent mixtures of dimethyl sulfoxide (DMSO,1) + water (2), N,N-dimethylformamide (DMF,1) + water (2), isopropanol (1) + water (2) and 1,4-dioxane (1) + water (2) at temperature range from (283.15 to 333.15) K was reported. At the same composition of DMSO, DMF, isopropanol or 1,4-dioxane and temperature, the mole fraction solubility of flubendazole was highest in DMSO (1) + water (2) mixtures, and lowest in isopropanol (1) + water (2) mixtures. By using the Jouyban-Acree model, van’t Hoff-Jouyban-Acree model and Apelblat-Jouyban-Acree model, flubendazole solubility was well correlated obtaining RAD lower than 5.08% and RMSD lower than 0.20 × 10−4. Quantitative values for the local mole fraction of DMSO (DMF, isopropanol or 1,4-dioxane) and water around the flubendazole were computed by using the Inverse Kirkwood–Buff integrals method applied to the determined solubility data. Flubendazole was preferentially solvated by water in water-rich compositions; while in intermediate and co-solvent-rich composition for DMF (DMSO, 1,4-dioxane) (1) + water (2) mixtures, flubendazole is preferentially solvated by the co-solvent. While for the isopropanol (1) + water (2) mixture, flubendazole was preferentially solvated by water in water-rich and co-solvent-rich compositions; and preferentially solvated by isopropanol in intermediate compositions. The preferential solvation magnitude of flubendazole was highest in 1,4-dioxane mixtures than in the other three co-solvent mixtures.