Kirkwood Buff Integrals Method Research Articles

Solubility, Hansen solubility parameter, solvent effect and preferential solvation of benorilate in aqueous mixtures of isopropanol, N,N-dimethylformamide, ethanol and N-methyl-2-pyrrolidinone

• Benorilate solubility in four aqueous co-solvent mixtures of cosolvents was determined and correlated. • Preferential solvation of benorilate in mixtures were derived via IKBIs method. • Solubility parameter and dipolarity-polarizability of solvents mainly control solubility variation. • Solubility data was analyzed by using Hildebrand and Hansen solubility parameters. This contribution was devoted to the equilibrium solubility profile, solute–solvent and solvent–solvent interactions and solvation behavior of benorilate in aqueous binary mixtures of the cosolvent (i.e. ethanol, N -methyl-2-pyrrolidinone (NMP), isopropanol and N , N -dimethylformamide (DMF)) together with several mathematical associations. All experiments were conducted by a shake-flask method under ambient pressure of 101.2 kPa from 278.15 to 318.15 K. The maximum scale of equilibrium benorilate solubility in neat cosolvent at T = 318.15 K; while the minimum one was observed in pure water at 278.15 K. The equilibrium benorilate solubility was analyzed by using the Hildebrand and Hansen solubility parameters. Various solubility models including Jouyban–Acree–van’t Hoff, modified Wilson, Jouyban–Acree and mixture response surface (MRS) were employed to fit the mole fraction solubility data, attaining the average relative deviations ( RAD ) of no more than 9.62%. The relative significance of molecular interactions of solvent–solvent and solute–solvent species upon the equilibrium solubility of benorilate at 298.15 K analyzed through the linear solvation energy relationships specified that the dominant contributions to solubility variation were observed as solubility parameter and dipolarity-polarizability of systems. The solubility data was investigated by means of the extended Hildebrand solubility approach gaining relative average deviation values of no higher than 3.71%. In terms of solution properties, a quantitative analysis on preferential solvation of benorilate was conducted by inverse Kirkwood–Buff integrals method. The preferential solvation parameters for neat cosolvent were recorded as positive in cosolvent-rich and intermediate regions in solutions, suggesting that benorilate was preferentially solvated by the cosolvents. In the above composition regions, it is conjectured that benorilate is performing as a Lewis acid with the cosolvent molecules.

Dissolution behavior and preferential solvation of diacerein in mixtures of (ethyl acetate/acetonitrile + ethanol) at several temperatures

• Research the solid liquid equilibrium phase diagram of diacerein in two mixtures. • Preferential solvation parameters were evaluated by using the inverse Kirkwood-Buff integrals method. • The solubility was correlated by Jouyban-Acree model. • The apparent thermodynamic properties in dissolution process were evaluated. Because the chemical structure of diacerein is plane structure, the solubility of diacerein is poor, and most of the products crystallized by solvent contain solvate, so it is difficult to get a large amount of diacerein without solvate. The present work demonstrates cosolvent as a successful technique to improve the dissolution property of diacerein. The solid liquid equilibrium phase diagram of diacerein in mixtures of (ethyl acetate/acetonitrile + ethanol) within the temperature range from (273.15 to 313.15) K was studied and represented using Jouyban-Acree model. The solubility profile of diacerein in two mixtures increased at first and then decreased with the increasing mass fraction of ethyl acetate/acetonitrile. In (ethyl acetate + ethanol) and (acetonitrile + ethanol) mixtures, the minimum mole solubility was obtained in pure ethanol, 5.085 × 10 −5 , and the maximum data in (ethyl acetate + ethanol) mixtures was 2.568 × 10 −4 at the composition of w (ethyl acetate) = 0.8 (mass fraction), and 1.727 × 10 −4 for (acetonitrile + ethanol) systems at w (acetonitrile) = 0.6, respectively. Preferential solvation parameters ( δx 1,3 ) of diacerein in two mixtures were evaluated by using the inverse Kirkwood-Buff integrals method, and it was all negative in ethanol-rich mixtures but positive at the mole compositions of ethyl acetate from 0.37 to 0.61, and with the range from 0.53 to 0.61 for acetonitrile. However, it should be noted that the positive preferential solvation parameters in acetonitrile + ethanol mixtures are lower than 0.01, near 0.002, and thus, a consequence of uncertainties propagation in IKBI calculations must be taken into account here. Moreover, the corresponding relative average deviations ( RAD ) of solubility correlation are 4.96% and 5.74%, respectively. The values of Δ H sol o were from 22.68 to 36.45 kJ·mol −1 . The analysis of apparent thermodynamic properties shows that the dissolution process in all investigated solvent mixtures is an endothermic and entropy driven process.

Thermodynamic analysis and preferential solvation of sulfanilamide in different cosolvent mixtures

ABSTRACT The thermodynamic analysis and preferential solvation of the solubility of sulphanilamide (SA) in five cosolvent mixtures (ethanol + water; 1,4-dioxane + water, acetonitrile + water, dimethyl-sulphoxide + water, and dimethylsulphoxide + water) are presented. The thermodynamic functions are calculated employing the Gibbs and van´t Hoff equations, and the analysis of preferential solvation is developed by inverse Kirkwood–Buff integrals method. The solubility process is endothermic, with entropic favouring in all cases. Finally, according to the solvation parameter, SA is solvated preferentially by water in more polar mixtures, and in DMF + W, and DMSO + W mixtures it is solvated by organic solvent. In the other mixtures (EtOH + W, DIOX + W, and MeCN + W) the SA is solvated by the organic solvent in intermediate mixtures and by water in the less polar mixtures.

Evodiamine in several binary aqueous co-solvents: Solubility measurement and modeling, Hansen solubility parameter, preferential solvation and apparent dissolution and transfer properties

Abstract Equilibrium solubilities of evodiamine were determined in four aqueous mixtures of methanol, isopropanol, acetone and ethanol over their full mass fraction range via the shake-flask approach covering from 283.15 to 323.15 K. The solubility profiles showed maxima in the neat cosolvents. The temperature and the mixture composition dependence of evodiamine solubility in mole fraction scale was well described by using five well-known models involving NRTL, Jouyban-Acree, van't Hoff-Jouyban-Acree, UNIQUAC and Wilson. The means of the relative deviations were recorded as 5.40%, 0.98% and 0.48% for the Wilson, UNIQUAC and NRTL models, respectively. The Jouyban-Acree and van't Hoff-Jouyban-Acree models resulted in the calculated relative average and root-mean-square deviations lower than 6.83% and 9.19 × 10−6, respectively. Hansen solubility parameter was utilized to disclose the solubility behavior of evodiamine. We also employed the linear solvation energy relationships to detect which intermolecular interactions were mainly responsible for the observed solvent effect upon solubility behavior. This analysis revealed the highlighted role of cavity term and dipolarity-polarizability of solvent in solubility variation of evodiamine. Solubility data was further examined by using the inverse Kirkwood-Buff integrals method in order to analysis the preferential solvation of evodiamine in the mixtures. Results showed the selective solvation of evodiamine by organic solvent in intermediate and organic solvent-rich compositions, and by water in water-rich compositions. The thermodynamic quantities including the apparent molar dissolution enthalpy, molar dissolution entropy and molar Gibbs energy, and the relative contribution of dissolution enthalpy and dissolution entropy to the dissolution Gibbs energy change for dissolution of evodiamine were calculated in each binary mixture. Moreover, the transfer properties were derived and discussed.

Antisolvent effect on the crystallization of fosfomycin phenylethylamine by acetone: Solubility measurement and thermodynamic mechanism analysis

AbstractAntisolvent crystallization of fosfomycin phenylethylamin (FPEA) by acetone is demonstrated by measuring its solubility in binary solvents of (ethanol + acetone) and (water + acetone) at 293.15 K. The solubility (g/g) of FPEA always decreased with the increase of acetone composition and correlations were proposed to sufficiently represent the data. Excess solubilities (mole fraction) of FPEA were always positive with maximum and well correlated by the simplified‐modified‐Wilson equation. Effects of various solvent properties on the solubility were analyzed by the solvatochromic KAT linear solvation energy relationship, which revealed the decrease of solvent's hydrogen bond donation ability should be the most essential characteristics of the antisolvent. Finally, by analyzing its surrounding solvent composition using the inverse Kirkwood–Buff integrals method, we found FPEA was preferentially solvated by water in acetone–water due to the strong acidic behavior of water, while, because of different competing interactions in acetone–ethanol, FPEA was preferentially solvated by acetone in ethanol‐rich region while by ethanol in acetone‐rich region.

Solubility of sulphadiazine in some {Carbitol® (1) + water (2)} mixtures: determination, correlation, and preferential solvation

ABSTRACT The mole fraction solubility of sulphadiazine (SD) in {Carbitol® (1) + water (2)} binary solvent mixtures at different temperatures from (278.15 to 313.15) K was determined. Solubility values were correlated with the combined nearly ideal binary solvent/Redlich-Kister, modified Wilson and Jouyban-Acree models. Preferential solvation parameters of SD by Carbitol® (δx 1,3) were derived from their thermodynamic solution properties using the inverse Kirkwood-Buff integrals method. δx 1,3 values are negative in water-rich mixtures but positive in Carbitol® mole fractions higher than 0.12. In the former case is conjecturable that hydrophobic hydration around non-polar groups of SD plays a relevant role in drug solvation.

Thermodynamic analysis and preferential solvation of gatifloxacin in DMF + methanol cosolvent mixtures

This paper presents the thermodynamic analysis of solubility of gatifloxacin in the N,N-Dimethylformamide (DMF) + methanol (MeOH) cosolvent system at 10 temperatures. From the solubility 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 inverse Kirkwood-Buff integral (IKBI) method. The result of the performed calculations indicates that the gatifloxacin solution process is endothermic with entropic favor, where the addition of DMF has a positive cosolvent effect in all cases. Regarding preferential solvation, the results are not entirely conclusive, since in all cases the values of the preferential solvation parameter are less than 0.01, so that, negligible preferential solvation takes place.

Equilibrium solubility of 7-amino-4-methylcoumarin in several aqueous co-solvent mixtures revisited: Transfer property, solute-solvent and solvent-solvent interactions and preferential solvation

The preferential solvation analysis was carried out by the inverse Kirkwood–Buff integrals method on available solubility data of 7-amino-4-methylcoumarin in four aqueous co-solvent mixtures of ethylene glycol (EG, 1) + water (2), isopropanol (1) + water (2), ethanol (1) + water (2) and DMF (1) + water (2). Results show that the drug is preferentially surrounded by water in water-rich regions, and by organic solvents in other composition ranges. Among these binary mixtures, the highest preferential solvation magnitude was recorded for isopropanol solutions. Selective solvation of the drug by organic solvents may be owing to the higher basicity of solvents that facilitates interactions with the Lewis acidic groups of 7-amino-4-methylcoumarin. A solvent effect analysis was performed by using the linear solvation energy relationships to unravel the relative importance of solute-solvent and solvent-solvent interactions on the solubility variation. In addition, the transfer properties, e.g. transfer Gibbs free energy (ΔtrGo), transfer enthalpy (ΔtrHo) and transfer entropy (ΔtrSo) were derived in terms of the accessible solubility data, indicating more favorable solubilization ability in the intermediate compositions of co-solvents.

Rutaecarpine dissolved in binary aqueous solutions of methanol, ethanol, isopropanol and acetone: Solubility determination, solute-solvent and solvent-solvent interactions and preferential solvation study

Abstract The main objective of this work was to report the mole fraction solubility of rutaecarpine in four binary solutions of methanol (1) + water (2), isopropanol (1) + water (2), acetone (1) + water (2) and ethanol (1) + water (2) acquired through the saturation shake-flask technique. All experiments were conducted at temperatures from 283.15 K to 323.15 K. The maximum solubility was observed in the pure solvent of methanol/ethanol/isopropanol/acetone for each solution. The achieved rutaecarpine solubility in mole fraction was mathematically described by two common co-solvency models, namely Jouyban-Acree model and van’t Hoff-Jouyban-Acree model. The calculated relative average deviations were no more than 6.78%; and root-mean-square deviations, no more than 23.69 × 10−6. The linear solvation energy relationships suggested by Kamlet and Taft was used to examine the effect of solvent descriptors on the behaviour of rutaecarpine solubility. The Hildebrand solubility parameter and dipolarity-polarizability were predominant contributors to solvent effect for the four mixtures studied. The local mole fractions of methanol (acetone, isopropanol or ethanol) and water nearby the solute rutaecarpine were quantitatively analyzed through an Inverse Kirkwood–Buff integrals method. For these mixtures within intermediate and methanol/ethanol/isopropanol/acetone-rich compositions, rutaecarpine was preferentially solvated by the methanol/ethanol/isopropanol/acetone; while within water-rich compositions, by the water.

Griseofulvin dissolved in binary aqueous co-solvent mixtures of N,N-dimethylformamide, methanol, ethanol, acetonitrile and N-methylpyrrolidone: Solubility determination and thermodynamic studies

• Solubility of griseofulvin in five aqueous mixtures was determined and correlated. • Preferential solvation of griseofulvin were derived via IKBIs method applied to solubility. • Solvent effect upon solubility variation was investigated by KAT-LSER model. The equilibrium solubility of griseofulvin in five co-solvent mixtures of N , N -dimethylformamide (DMF) + water (2), methanol (1) + water (2) , ethanol (1) + water (2), acetonitrile (1) + water (2) and N -methylpyrrolidone (NMP) (1) + water (2) were acquired through experiment at temperatures covering from 278.15 K to 323.15 K by the saturation shake-flask technique. The maximum solubility appeared in the neat co-solvents of DMF/methanol/ethanol/acetonitrile/NMP for each mixture. The mole fraction solubility of griseofulvin in the five mixtures was well correlated via van’t Hoff–Jouyban-Acree model and Jouyban-Acree model acquiring values of relative average deviations<9.41% and root-mean-square deviations<10.30 × 10 -4 . The cavity term and KAT parameters correlated the mole fraction solubility in terms of the linear solvation energy relationships. The significant effect to the solubility variation was the cavity term and dipolarity-polarizability term in aqueous DMF/methanol/ethanol/acetonitrile/NMP mixtures. What's more, the quantitative magnitudes for local mole fractions of DMF/methanol/ethanol/acetonitrile/NMP and water around the drug griseofulvin were evaluated by using the Inverse Kirkwood–Buff integrals method applied to griseofulvin solubility. In the methanol (1) + water (2) mixture with compositions 0.31 < x 1 < 1, ethanol (1) + water (2) mixture with compositions 0.25 < x 1 < 1, DMF (1) + water (2) mixture with compositions 0.20 < x 1 < 1, NMP (1) + water (2) mixture with compositions 0.16 < x 1 < 1 and acetonitrile (1) + water (2) mixture with compositions 0.253 < x 1 < 1, griseofulvin was preferentially solvated by DMF/methanol/ethanol/acetonitrile/NMP.

Bezafibrate in several aqueous mixtures of low alcohols: Solubility, solvent effect and preferential solvation

Abstract By using the saturation shake-flask method, the saturated solubility of bezafibrate in neat water, methanol, ethanol, n-propanol and isopropanol and aqueous co-solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and n-propanol (1) + water (2) was experimentally acquired at temperatures from 283.15 Kto 323.15 K and local atmospheric pressure. The maximum solubility magnitudes in mole fraction were recorded in the neat solvents of methanol/ethanol/n-propanol/isopropanol for corresponding solutions. The mole fraction solubility was described mathematically by using the van’t Hoff-Jouyban-Acree and Jouyban-Acree models. The largest value of relative average deviations was 6.23%; and, root-mean-square deviations, 8.92 × 10−5. The local mole fractions of water and co-solvent (methanol, ethanol, n-propanol or isopropanol) around the drug bezafibrate were quantitatively investigated by the use of Inverse Kirkwood–Buff integrals method. Results indicated that the bezafibrate was preferentially solvated by methanol (ethanol, n-propanol or isopropanol) in alcohol-rich and intermediate compositions in the alcohol mixtures; while in water-rich compositions, bezafibrate was preferentially solvated by water. The main factors relating to solvent effect were inspected through Kamlet and Taft linear solvation energy relationships, demonstrating that the cavity formation energy and dipolarity-polarizability in methanol solutions, cavity formation energy and basicity in ethanol solutions, and cavity formation energy in n-propanol (isopropanol) solutions played the principal role upon the bezafibrate solubility variation.

Biapenem in binary aqueous mixtures of N,N-dimethylformamide, N-methyl-2-pyrrolidone, isopropanol and ethanol: Solute-solvent and solvent-solvent interactions, solubility determination and preferential solvation

Abstract This work mainly aimed to study the mole fraction solubility of biapenem in four binary solutions of N,N-dimethylformamide (DMF, 1) + water (2), isopropanol (1) + water (2), N-methyl-2-pyrrolidone (NMP, 1) + water (2) and ethanol (1) + water (2). Experiments were performed through a common static equilibrium method at temperatures from 283.15 to 323.15 K. The maximum solubility magnitudes were observed in pure solvent of DMF/NMP/isopropanol/ethanol for each solution. The achieved biapenem solubility was mathematically described by using two famous co-solvency models, Jouyban-Acree and van’t Hoff-Jouyban-Acree. The calculated relative average deviations were not greater than 4.20%; and root-mean-square deviations, not greater than 7.45 × 10−6. The linear solvation energy relationships method put forward by Kamlet and Taft was employed to examine the influence of solvent descriptors upon biapenem solubility behaviour. The principal contributors to solvent effect was hydrogen bond acidity for DMF/NMP mixtures; and hydrogen bond acidity and non-specific dipolarity-polarizability for isopropanol/ethanol mixtures. Quantitative local mole fractions of DMF (NMP, isopropanol or ethanol) and water nearby the biapenem were analyzed through Inverse Kirkwood–Buff integrals method. For the isopropanol/ethanol + water mixtures within water-rich compositions, biapenem was preferentially solvated by isopropanol/ethanol; while within intermediate and co-solvent-rich compositions, by water. However, for the DMF/NMP mixture within entire composition ranges, the absolute δx1,3 values were all smaller than 1.0 × 10−2, consequently biapenem was not preferentially solvated by DMF/NMP or water.

Risperidone (I) in some aqueous mixtures of low alcohols: Solubility, preferential solvation and solvent effect analysis

Abstract Using the saturation shake-flask technique, the equilibrium solubility of risperidone (I) in co-solvent mixtures of methanol (1) + water (2), ethanol (1) + water (2), isopropanol (1) + water (2) and n-propanol (1) + water (2) was obtained at the temperatures from 283.15 K to 328.15 K. The solubility values in mole fraction were maximum in the neat solvents of methanol/ethanol/n-propanol/isopropanol for the four mixtures. At the same alcohol compositions and temperature, the risperidone solubility was greater in (methanol + water) mixture than in the other alcohol mixtures. They were mathematically correlated by the van’t Hoff-Jouyban-Acree and Jouyban-Acree models, obtaining relative average deviations smaller than 6.39% and root-mean-square deviations smaller than 9.74 × 10−5, respectively. The local mole fractions of methanol (ethanol, n-propanol or isopropanol) and water around the risperidone (I) were quantitatively studied with the help of Inverse Kirkwood–Buff integrals method in terms of the solubility data determined. Risperidone (I) was preferentially solvated by methanol (ethanol, n-propanol or isopropanol) in the mixtures studied in alcohol-rich and intermediate compositions; while in water-rich compositions, risperidone (I) was preferentially solvated by water. The main factors describing solvent effect were examined through by Kamlet and Taft linear solvation energy relationships applied to the experimental solubility data, indicating that the change in cavity formation energy and dipolarity-polarizability of the solvents played the chief role upon the variation of risperidone (I) solubility.

6-Phenyl-3(2H)-pyridazinone dissolved in some aqueous co-solvent mixtures of alcohols: Equilibrium solubility, solvent effect and preferential solvation

Abstract The saturated solubility of 6-phenyl-3(2H)-pyridazinone in aqueous co-solvent mixtures of methanol, ethanol, isopropanol and ethylene glycol (EG) was determined through experiment by employing the saturation shake-flask method at temperatures from 278.15 to 318.15 K and local atmospheric pressure. For all the co-solvent mixtures, the maximum value of solubility was observed in neat methanol (ethanol, isopropanol or EG). The 6-phenyl-3(2H)-pyridazinone solubility in mole fraction scale was well correlated by using the Jouyban-Acree model and van’t Hoff-Jouyban-Acree model, obtaining the values of relative average deviations smaller than 3.98%; and root-mean-square deviation, lower than 7.81 × 10−5. The local mole fractions of methanol (ethanol, isopropanol or EG) and water nearby the 6-phenyl-3(2H)-pyridazinone were quantitatively calculated by means of the Inverse Kirkwood-Buff integrals method. 6-Phenyl-3(2H)-pyridazinone was preferentially solvated by the solvent of water in water-rich compositions; while within the regions of co-solvent-rich and intermediate compositions, 6-phenyl-3(2H)-pyridazinone was preferentially solvated by the solvent of methanol (ethanol, isopropanol or EG). The mole fraction solubility was fitted by using the Kamlet and Taft linear solvation energy relationships to inspect the key factors describing solvent effect. The variation in cavity formation energy and hydrogen-bond acidity played the chief role upon the 6-phenyl-3(2H)-pyridazinone solubility in aqueous solutions of methanol and ethanol; and the hydrogen bond acidity and dipolarity/polarizability term, in the aqueous of mixtures isopropanol and EG .

Further numerical analyses on the solubility of diazepam in aqueous tert-butanol mixtures

ABSTRACT The mole fraction equilibrium solubility of diazepam in some {tert-butanol (1) + water (2)} mixtures at several temperatures has been correlated by means of the Jouyban–Acree model and also to evaluate the preferential solvation of this compound by the mixtures components. By using the inverse Kirkwood-Buff integrals method apparently is observed that diazepam is preferentially solvated by water in water-rich and tert-butanol-rich mixtures but preferentially solvated by tert-butanol in mixtures of similar proportions of both solvents.

Preferential solvation of 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxybenzoyl)-3,4-dihydropyrimidin-2(1H)-one in {PEG 400 (1) + water (2)} mixtures

ABSTRACT The reported equilibrium mole fraction solubility of 4-(4-ethoxyphenyl)-5-(3,4,5-trimethoxybenzoyl)-3,4-dihydropyrimidin-2(1H)-one (DHP-5) in some {polyethylene glycol (PEG 400 (1) + water (2)} mixtures at 298.2 K has been used to evaluate the preferential solvation of this compound by the mixture components. First, molar volume and Hildebrand solubility parameter of DHP-5 were calculated as 277.7 cm3 mol–1 and 25.11 MPa1/2, respectively, by means of Fedors’ method. In this way, by using the inverse Kirkwood–Buff integrals method, it is observed that this compound is preferentially solvated by PEG molecules in all the mixtures. Thus, maximum preferential solvation parameter by PEG was observed in the mixture x 1 = 0.15 being 1.55 × 10–2.

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

Abstract 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

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

Abstract 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.

Solubility and thermodynamic properties of mesalazine in {2-propanol + water} mixtures at various temperatures

Abstract The solubility of mesalazine in presence of 2-propanol as cosolvent in aqueous media was reported at T = (293.2 to 313.2) K. It was observed that the solubility of mesalazine is maximal in the 0.4 weight fraction of 2-propanol in the binary solvents. The performances of mathematical models of Jouyban-Acree, Apelblat-Jouyban-Acree, Jouyban-Acree-van't Hoff, modified Wilson, combined nearly ideal binary solvent/Redlich-Kister, UNIQUAC, NRTL and Wilson models in the solubility data representation were investigated. Two versions of Yalkowsky model were employed to estimate the solubility data. Dissolution and mixing apparent thermodynamic functions for mesalazine in studied solvents were also evaluated. Moreover, by means of inverse Kirkwood-Buff integrals method it is demonstrated that this drug is preferentially solvated by water in all the 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

Abstract 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