Preferential Solvation Parameters Research Articles

Spectroscopic investigation of preferential solvation of N-confused tetraphenylporphyrinin binary mixtures of dichloromethane with organic cosolvents

Spectroscopic behaviour of porphyrin is known to be sensitive to the choice of the solvent and has been used to probe solvation phenomena. The UV–visible spectra of N-confused tetraphenylporphyrin are observed in a series of binary solvent mixtures – (dichloromethane + diethyl ether), (dichloromethane + chlorobenzene) and (dichloromethane + ethyl acetate). The resulting ET scale for NCTPP solvation indicates nonlinear behaviour and preferential solvation by a solvent–solvent complex in all the three solvents – with the dichloromethane + ethyl acetate system showing the largest deviation from ideality. The data is fitted to the model based on solvent exchange equilibria for determining the preferential solvation parameters which are specific to the probe as well as the identity of solvents in the binary mixture. Further analysis using polarity parameters from literature indicate that the solvation of NCTPP in the (dichloromethane + ethyl acetate) mixture is dependent on the hydrogen bond accepting capacity and polarizability of the medium. Excess spectra derived from ATR-FTIR measurement of dichloromethane + ethyl acetate solutions lead to important inferences about the structure and role of solvent–solvent interactions responsible for the preferential solvation.

Preferential solvation of 5,7-dihydroxyflavone (chrysin) in aqueous co-solvent mixtures of methanol and ethanol

ABSTRACT The inverse Kirkwood-Buff integrals were used to calculate the preferential solvation parameters of the natural polyphenolic compound chrysin in binary mixtures of ethanol (1) + water (2) and methanol (1) + water (2) as a function of their thermodynamic properties. At temperatures between 298.15 K and 318.15 K, chrysin is extremely sensitive to specific solvation effects; therefore, the negative values of were found in the water-rich range of 0 < x1 < 0.30 for methanol (1) + water (2) and 0 < x1 < 0.25 for ethanol (1) + water (2) which suggested that water (2) preferentially dissolves chrysin (3). In co-solvent-rich regions, the values of were positive, and the co-solvents preferentially dissolve chrysin (3). The solvation of drugs in water-rich mixtures is likely to be facilitated by hydrophobic hydration around aromatic rings or groups.

Solid-liquid phase equilibrium of SOV-I2 in various pure and binary mixed solvents: Solubility determination, solvent effect, preferential solvation and model correlation

The solubility knowledge is important in the field of separation and purification of chemicals as well as quality control of drugs. In this work, the saturated phase equilibrium of SOV-I2 in ethanol, 1-butanol, acetone, methanol, 1-propanol, acetonitrile, toluene, 2-propanol, ethyl acetate, water, ethanol + water and acetone + water at a series of temperature of 278.15 K-318.15 K was constructed and the solubility data was measured by using isothermal saturation methods. The solvent effect evaluation, preferential solvation discussion and model correlation were used to explore the solubility behavior of SOV-I2. The solubility of SOV-I2 in mole fraction increased with the increasing of temperature. The experimental solubility data of SOV-I2 in mole fraction showed a subsequence in acetone > ethyl acetate > toluene > acetonitrile > methanol > ethanol > 1-propanol > 2-propanol > 1-butanol > water. For SOV-I2 + aqueous mixtures systems, the solubility data raised with the adding of co-solvents and no co-solvency phenomenon appeared in the dissolution process of SOV-I2 in two aqueous mixtures. The solvent effect was analyzed by KAT-LSER model which suggested that interaction of nonspecific dipolarity/polarizability played a dominant role in SOV-I2 dissolution. The solute–solvent interactions, accounted for>60%, were very important in dissolution of SOV-I2. Furthermore, the preferential solvation mechanism of SOV-I2 in two aqueous mixtures was discussed by IKBI method. The negative preferential solvation parameter (δx1,3) exhibited in the region of < x1 < 0.24 for ethanol (1) + water (2) mixtures and 0 < x1 < 0.21 for acetone (1) + water (2) mixtures. It suggested that SOV-I2 (3) was dissolved by water (2) preferentially in water-rich region. However, in other regions, the δx1,3 values were positive which indicated that SOV-I2 (3) was dissolved by co-solvents (1, ethanol or acetone) preferentially. In addition, the classical Apelblat, λh, Jouyban-Acree and Apelblat-Jouyban-Acree models were used to correlate the solubility data of SOV-I2. The correlation results showed that the greatest values of RAD and RMSD were 0.94% and 0.68 × 10-4 for pure solvent systems, and 2.10% and 2.14 × 10-4 for two aqueous mixtures systems, respectively. The evaluation indexes were quite small. In brief, these models showed a good applicability to experimental solubility data of SOV-I2.

Quantitative molecular surface analysis of doxofylline and its thermodynamic solubility behavior in aqueous solutions

The Hirshfeld surface, molecular surface electrostatic potential together with molecular surface average local ionization energy, were employed in this work to analyze the electrostatic characteristics of acidity and basicity of doxofylline at a microscopic level. H···H and O···H contacts present predomination among all contact interactions and doxofylline molecule can behave as a hydrogen-bonding donor with powerful ability. The nitrogen of -N = group and oxygen of >C=O group of doxofylline molecule are primary sites of electrophilic attack. The mole-fraction solubility of doxofylline in four blends of isopropanol + water, ethanol + water, acetone + water and methanol + water covering the temperature from 278.15 to 323.15 K was acquired by the use of saturation shake-flask method under atmospheric pressure of 101.2 kPa. For each aqueous solution, the solubility data firstly presented a peak at isopropanol (ethanol, acetone or methanol) composition of 0.7 and then decreased with the increasing mass fraction of organic solvents at a fixed temperature. No existence of crystaltransition and solvation was recorded in all experiments as indicated by X-ray power diffraction patterns. Solubility data were mathematically correlated by Jouyban-Acree, modified Wilson model, Apelblat and modified van’t Hoff-Jouyban–Acree models. Investigation on preferential solvation of crystalline doxofylline was performed by the inverse Kirkwood–Buff integrals over temperatures from 293.15 to 313.15 K. The preferential solvation parameters of isopropanol, acetone or acetonitrile presented positive values in blends with middle isopropanol/acetone/acetonitrile composition regions, demonstrating the preferential solvation of doxofylline by isopropanol/acetone/acetonitrile. In addition, the extended Hildebrand solubility approach was employed to quantitatively describe the solubility behavior at 298.15 K in isopropanol/ethanol/acetone/methanol + water blends studied in this paper and in acetonitrile + water blends previously reported, attaining the average relative deviations of < 7.80 %.

Quantitative surface analysis of paclobutrazol molecule and comprehensive insight into its solubility in aqueous co-solvent solutions

As powerful tools, the minimum negative surface electrostatic potential together with minimum surface average local ionization energy, were used herein to illustrate the electrostatic characteristics of acidity and basicity at a microscopic level, correspondingly. The groups of -N = and –OH of the paclobutrazol molecule are primary sites of electrophilic and nucleophilic attack. The mole-fraction solubility of paclobutrazol in three co-solvent blends of isopropanol + water, acetone + water and acetonitrile + water covering the temperature range from 278.15 to 318.15 K was experimentally acquired by the use of isothermal saturation method under 101.2 kPa. Under the identical experimental conditions, e.g. same temperature and mass composition of isopropanol (acetone or acetonitrile), the solubility of paclobutrazol in mole fraction was much larger in acetone + water blends than in isopropanol/acetonitrile + water blends. The minimal solubility was recorded in neat water solvent at 278.15 K; and the maximal one, in acetone/acetonitrile/isopropanol at T = 318.15 K. No appearance of crystaltransition as well as solvate formation was observed in experiments as indicated by X-ray power diffraction patterns. Solubility data were mathematically correlated by three models including Jouyban-Acree, Apelblat and modified van’t Hoff-Jouyban–Acree. Investigation on preferential solvation of crystalline paclobutrazol was performed by the powerful approach of inverse Kirkwood–Buff integrals at 298.15 K. The preferential solvation parameters of isopropanol, acetone or acetonitrile presented positive values in blends with middle and isopropanol/acetone/acetonitrile-rich composition regions, which indicated the preferential solvation of paclobutrazol by the co-solvents. In addition, the extended Hildebrand solubility approach was employed to quantitatively describe the solubility behavior at 298.15 K in isopropanol/acetone/acetonitrile + water blends studied in this paper and in ethanol/n-propanol/1,4-dioxane + water blends previously reported by us, attaining the average relative deviations < 7.61 %.

Solubility of tadalafil in aqueous mixtures of Transcutol® and PEG 400 revisited: correlation, thermodynamics and preferential solvation

ABSTRACT Mole fraction solubilities of tadalafil (3) in aqueous mixtures of Transcutol® and PEG 400 at temperatures from 298.15 to 333.15 K were analysed following Hildebrand solubility parameters. Cosolvency models for representing tadalafil solubility at various temperatures were also provided for correlation/prediction purposes. Apparent thermodynamic quantities for tadalafil dissolution processes were calculated based on van’t Hoff and Gibbs equations. Non-linear enthalpy–entropy compensation was observed for tadalafil transfer from more polar to less polar solvent systems. Preferential solvation parameters of tadalafil at 298.15 and 313.15 K were determined by means of the inverse Kirkwood-Buff integrals (IKBI). Tadalafil is preferentially solvated by water in water-rich mixtures of Transcutol® but preferentially solvated by Transcutol® in mixtures of 0.12 < x 1 < 1.00. In the former case, this result could be due to hydrophobic hydration around the non-polar moieties of tadalafil. Otherwise, tadalafil is preferentially solvated by PEG 400 in all the aqueous mixtures.

Investigation on co-solvency, solvent effect, Hansen solubility parameter and preferential solvation of fenbufen dissolution and models correlation

The solubility behavior as a significant molecular property in pharmaceuticals development is challenging in modern pharmaceutical industry. The high quality solubility is advantageous to crystal forms optimization, dosage forms design and product purification. In this work, the saturated solubility of fenbufen in 2-butanone, acetone, ethyl acetate, 1-propanol, 2-propanol, 1-butanol, methanol, ethanol, acetonitrile, water, cyclohexane, toluene and two mixtures (ethanol + water and acetone + water) at region of 278.15 K-318.15 K was measured by employing isothermal saturation method. The preferential solvation investigation, solvent effect analysis, Hansen solubility parameters discussion, models correlation and thermodynamics properties were explored. The molarity solubility of fenbufen present as a positive relation with temperature and enhance as the rise of temperature with a different rate of increase in different solvents. In view of mono-solvent systems, the tendency of molarity solubility was as 2-butanone > acetone > ethyl acetate > 1-butanol > 1-propanol > ethanol > methanol > 2-propanol > acetonitrile > toluene > water > cyclohexane. Solvent effect was analyzed by KAT-LSER model which indicated that the solute–solvent interactions came into prominence in solubility of fenbufen. In addition, the Hansen solubility parameter (HSP) was employed to discuss the dissolution ability of solvents to fenbufen. In view of mixtures systems, the co-solvency phenomenon appeared in acetone + water systems. The solubility of fenbufen in mixtures could be explained in depth by HSP. Moreover, the preferential solvation of fenbufen was investigated by IKBI method. The positive preferential solvation parameters (δx1,3) occurred at 0.24 < x1 < 1 for ethanol (1) + water (2) mixtures and 0.20 < x1 < 0.70 for acetone (1) + water (2) which indicated that ethanol/acetone solvated fenbufen preferentially. In other regions, the δx1,3 values were negative which indicated that water solvated fenbufen preferentially. What’s more, fenbufen solubility data was correlated by four famous models (Apelblat, Wilson, Jouyban-Acree and Apelblat-Jouyban-Acree models). The maximum relative average deviation (RAD) and root-mean-square deviation (RMSD) values were 1.99% and 3.35 × 10-4 for mono-solvents systems, 1.91% and 1.30 × 10-4 for mixtures systems, respectively. Finally, all positive values of these thermodynamics properties illustrated that the dissolution of fenbufen was an entropy increment and endothermic process.

Solubility of Sulfamethazine in the Binary Mixture of Acetonitrile + Methanol from 278.15 to 318.15 K: Measurement, Dissolution Thermodynamics, Preferential Solvation, and Correlation

Solubility of sulfamethazine (SMT) in acetonitrile (MeCN) + methanol (MeOH) cosolvents was determined at nine temperatures between 278.15 and 318.15 K. From the solubility data expressed in molar fraction, the thermodynamic functions of solution, transfer and mixing were calculated using the Gibbs and van ’t Hoff equations; on the other hand, the solubility data were modeled according to the Wilson models and NRTL. The solubility of SMT is thermo-dependent and is influenced by the solubility parameter of the cosolvent mixtures. In this case, the maximum solubility was achieved in the cosolvent mixture at 318.15 K and the minimum in pure MeOH at 278.15 K. According to the thermodynamic functions, the SMT solution process is endothermic in addition to being favored by the entropic factor, and as for the preferential solvation parameter, SMT tends to be preferentially solvated by MeOH in all cosolvent systems; however, , so the results are not conclusive. Finally, according to mean relative deviations (MRD%), the two models could be very useful tools for calculating the solubility of SMT in cosolvent mixtures and temperatures different from those reported in this research.

Thermodynamic study and preferential solvation of sulfamerazine in acetonitrile + methanol cosolvent mixtures at different temperatures

This paper discusses sulfamerazine (SMR) solubility in Acetonitrile (MeCN) + Methanol (MeOH) cosolvents at nine temperatures (278.15–318.15 K). Herein, the maximum SMR solubility was reached in a cosolvent mixture at the highest studied temperature, and the minimum SMR solubility was reached in neat methanol at the lowest studied temperature. Using experimental data, thermodynamic functions were calculated for both the solution and mixture using the Gibbs and van’t Hoff equations, thus determining that the solution process is endothermic with entropic favoring. In addition, the preferential solvation parameters (δx3,1), calculated using the inverse Kirkwood-Buff integrals (IKBI) method, are reported; SMR is preferentially solvated by MeOH in MeOH-rich mixtures, and in intermediate and MeCN-rich mixtures, the δx3,1 values indicate that SMR is not preferentially solvated by any of the two solvents in the mixture (MeCN + MeOH). Finally, eight models were assessed (Apelblat, van’t Hoff, Yaws, λh, Weibull, NRTL, Wilson, and Wilson modified), with all presenting mean relative deviation percentages (MRD%) under 6%, which indicates a good correlation with the experimental data.

Solubility, solvent effect, enthalpy–entropy compensation and solvation thermodynamics of 4-(bromomethyl)-2(1H)-quinolinone in several aqueous blends

The current study was mainly devoted to solubility for the systems formed by 4-(bromomethyl)-2(1H)-quinolinone (BMQ) and blended solvents of isopropanol, N-methyl-2-pyrrolidinone (NMP), ethanol and n-propanol with water. Experiments for solubility determination were conducted by employing the shake-flask equilibration method from 278.15 to 318.15 K under 101.2 kPa. For each aqueous cosolvent mixture, the minimum solubility was recorded in water at 278.15 K; and the maximum value, in neat organic solvents at 318.15 K. The solubility performance was illustrated by Hansen solubility parameters of water, BMQ and co-solvents. No occurrence of polymorphic transformation or solvation was observed after experiments based on the XRD spectra of raw BMQ and excess solids analyzed. The satisfactory correlation results for solubility data was obtained by modified Wilson model, mixture response surface model, modified van’t Hoff-Jouyban–Acree model and Jouyban–Acree model. The relative average deviations were calculated to be no more than 8.72 %. Investigation on the relative contributions from inter- and intra-molecular interactions to the solubility variation of BMQ at temperature of 298.15 K was quantitatively performed via the linear solvation energy relationships (LSER). The descriptors of solvent blends including solubility parameter, dipolarity-polarizability and hydrogen-bond basicity were primarily responsible for the solubility variation. As well, the preferential solvation of BMQ was researched quantitatively via the inverse Kirkwood–Buff integrals method on the basis of some obtainable properties of solvent blends. The positive preferential solvation parameters for BMQ in middle and cosolvent-rich blends strongly suggest that the crystalline solute of BMQ is preferentially solvated by cosolvents of isopropanol, NMP, ethanol and n-propanol. The transfer and apparent dissolution properties including apparent Gibbs energy change (298.15 K), dissolution enthalpy and dissolution entropy (298.15 K) were derived and discussed. Analysis of enthalpy–entropy compensation indicates the entropy-driven mechanism of BMQ dissolved in all blend solvents.

Preferential solvation and solute-solvent interactions of posaconazole in mixtures of (ethyl acetate + ethanol/isopropanol) at several temperatures

In this work, the dissolution process of stable crystalline form I in mixtures of (ethyl acetate + ethanol/isopropanol) at several temperatures was studied and represented by using Jouyban-Acree model, which was considered to be useful in the development of a pharmaceutical product. The influence of solvent properties of mixed solvents on the solubility of posaconazole was analyzed by KAT-LSER method. The solubility of posaconazole in mixture of ethyl acetate + isopropanol increased monotonically with the increasing mass fraction of ethyl acetate. However, it increased firstly and then decreased with the rising mass fraction of ethyl acetate in ethyl acetate + ethanol, and the maximum mole solubility was 4.871 × 10−4 when the mass fraction of ethyl acetate is w = 0.50 at T = 313.15 K. The co-solvency phenomenon was investigated by solubility parameters method. More importantly, preferential solvation parameters (δx1,3) of posaconazole in two mixtures were calculated by using the inverse Kirkwood-Buff integrals method, and it was all negative in ethyl acetate + ethanol system and ethanol-rich mixture in ethyl acetate + isopropanol, but positive at the mole compositions of ethyl acetate from 0.44 to 1.0 in ethyl acetate + isopropanol. Furthermore, some apparent thermodynamic properties including apparent molar standard dissolution enthalpy (ΔHsolo), apparent molar standard Gibbs energy (ΔGsolo), apparent molar standard dissolution entropy (ΔSsolo), the relative contributions by enthalpy (ζH) and by entropy (ζTS) toward to Gibbs energy were calculated by the van’t Hoff equation. Consequently, the experimental solubility and thermodynamic parameters could be used as the reference for simulation in the purification and separation of posaconazole.

Solubility of 6-phenyl-4,5-dihydropyridazin-3(2H)-one in aqueous mixtures of Transcutol and PEG 400 revisited: Correlation and preferential solvation

Reported equilibrium mole fraction solubility values of 6-phenyl-4,5-dihydropyridazin-3(2H)-one (PDP-6) (3) in {Transcutol (1) + water (2)} and {PEG 400 (1) + water (2)} mixtures at five temperatures from T = (293.15 to 313.15) K were analyzed based on the Hildebrand solubility parameter of the respective aqueous mixtures. Cosolvency models for representing the equilibrium solubility of PDP-6 in both binary solvent systems at various temperatures were also provided for correlation/prediction purposes. Moreover, the preferential solvation parameters of PDP-6 in these aqueous-cosolvent mixtures at T = (298.15 and 313.15) K were determined by means of the “inverse Kirkwood-Buff integrals” (IKBI). PDP-6 is preferentially solvated by water in water-rich mixtures of {Transcutol (1) + water (2)} system but preferentially solvated by Transcutol in mixtures of 0.13 < x1 < 1.00. In the former case this result could be due to hydrophobic hydration around the non-polar moieties of PDP-6. Otherwise, PDP-6 is preferentially solvated by PEG 400 in all the aqueous mixtures. Moreover, in the systems where preferentially solvation of PDP-6 by cosolvents are observed, these results could be due to the Lewis acidic behavior of PDP-6 in front of Transcutol or PEG 400 molecules because these cosolvents exhibit higher Lewis basic behavior than water.

Solubility, solvation thermodynamics and solvent effect of thiabendazole in several cosolvent blends

Equilibrium solubility determination and model correlation were performed in the present research for the systems formed by solid solute of thiabendazole and binary aqueous blends of acetonitrile, methanol, n-propanol and isopropanol. Experiments at temperatures ranging from 283.15 to 323.15 K were conducted by the use of the shake-flask saturation technique at 101.2 kPa. For the given binary solvent blends, the minimum mole fraction solubility was recorded in water at 283.15 K; and the maximum one, in neat organic solvent at 323.15 K. The generated equilibrium solubility was satisfactorily described by two models, modified van’t Hoff-Jouyban–Acree and Jouyban–Acree, with the relative average deviations (%) of no more than 6.08. Good prediction results of extend Hildebrand solubility approach (relative average deviations < 4.10%) were observed in terms of quartic polynomial for the four solution systems to correlate the interaction parameter (W) and solubility parameters of the solvents’ blends in the absence of thiabendazole (δ1+2). Analysis of the relative contributions from intra- and inter-molecular interactions to solubility variation of solid solute of thiabendazole (298.15 K) was quantitatively carried out via the linear solvation energy relationships (LSER). The descriptors of blended solvents comprising solubility parameter and hydrogen-bond basicity were principally responsible for the variation of determined solubility. Besides, the preferential solvation of thiabendazole was quantitatively researched via the inverse Kirkwood–Buff integrals method on the basis of some accessible properties for blended solvent systems. The positive preferential solvation parameters for thiabendazole in the middle and cosolvent-rich blends powerfully suggested that thiabendazole was preferentially solvated by cosolvents of isopropanol, acetonitrile, n-propanol, ethanol and methanol. The conjecture was reasonable that in above compositions, thiabendazole mainly served as Lewis acidic in terms of its interactions with alcohol molecules; while for the acetonitrile mixtures, this behavior was contributed by polarization effect. Besides, thiabendazole was preferentially solvated by ethanol (2) in ethyl acetate (1) + ethanol (2) solutions with ethyl acetate-rich compositions, and by water (2) solvent in aqueous blends with rich water compositions.

Equilibrium solubility, inter- and intra-molecular interactions and solvation performance of flutamide in some aqueous blended co-solvents

The current research was devoted to the solubility profile and its computational methodologies, partial Hansen solubility parameter, inter- and intra-molecular interactions, and solvation performance for the systems formed by crystalline flutamide dissolved in water and cosolvent, i.e. ethanol/isopropanol/acetonitrile/1,4-dioxane. All solubility experimentations were done via a common shake-flask saturation method at a pressure of atmosphere (p = 101.2 kPa) and the temperature range from 278.15 to 323.15 K. The solubility in magnitudes of flutamide were recorded as the lowest in pure water at 278.15 K; and the highest in pure co-solvent at 323.15 K. The three-dimensional Hansen solubility parameters were utilized here to illustrate the solubility profile. The quantifiable explanation of solvent effect was carried out via modelling the flutamide solubility using linear solvation energy relationships. Satisfactory outcomes for correlating the solubility magnitudes were realized by means of modified van’t Hoff–Jouyban–Acree, modified Wilson and Jouyban–Acree models with the relative average errors of < 6. 67 %. The observed solubility data at 298.15 K were further studied by the extended Hildebrand solubility approach, acquiring the relative average deviations of < 1.54 %. The preferential solvation investigation of flutamide was further performed through quantitation by inverse Kirkwood–Buff integrals. The positive values of preferential solvation parameters in co-solvent-rich and middle composition blends point to that the drug flutamide is preferentially solvated by the co-solvent. In these composition ranges, flutamide is possibly acting as Lewis acid performance with 1,4-dioxane/ethanol/isopropanol molecules; while for the aqueous acetonitrile solutions, the solvation behavior is responsible for the polarization effect.

Effect of temperature and polarity on the solubility and preferential solvation of sinapic acid in aqueous mixtures of DMSO and Carbitol

Reported equilibrium mole fraction solubilities of sinapic acid (3) in {DMSO (1) + water (2)} and {Carbitol (1) + water (2)} mixtures at several temperatures were analyzed in terms of the Hildebrand solubility parameter of these aqueous mixtures. Moreover, the preferential solvation parameters of sinapic acid in these aqueous saturated mixtures at (298.15 and 313.15) K were determined based on the inverse Kirkwood-Buff integrals (IKBI) as widely described in the literature. Sinapic acid is preferentially solvated by water in water-rich mixtures, i.e. (0.00 < x1 < 0.21 in {DMSO (1) + water (2)}) and (0.00 < x1 < 0.12 in {Carbitol (1) + water (2)}) but preferentially solvated by the cosolvents in the other mixtures composition. In the former cases these results could be interpreted as a consequence of hydrophobic hydration around the non-polar moieties of sinapic acid. Moreover, in the last cases, the observed trends could be due to the Lewis acidic behavior of sinapic acid in front of DMSO or Carbitol molecules because both cosolvents exhibit higher Lewis basic character than water, as indicated by the respective solvatochromic parameters. A single cosolvency model for representing the equilibrium solubility of sinapic acid in binary solvents at various temperatures was also provided based on a combination of Hansen solubility parameters and Jouyban-Acree model.

Solubility modeling, Hansen solubility parameter, solvation thermodynamics and enthalpy–entropy compensation of 5-chlorooxine (form I) in several aqueous cosolvent solutions

The current contribution was dedicated to solubility profile, solvation behavior, and inter- and intramolecular interactions for the binary systems formed by 5-chlorooxine (I) in aqueous solutions of ethanol, N-methyl-2-pyrrolidinone (NMP), isopropanol and N,N-dimethylformamide (DMF) together with numerous computational approach. A shake-flask method conducted all experiments under local pressure p = 101.2 kPa over temperatures ranging from 278.15 to 323.15 K. For each cosolvent system, the highest equilibrium solubility of 5-chlorooxine (I) was recorded in neat cosolvent at temperature of T = 323.15 K; and the lowest one, in neat solvent of water at 278.15 K. The solubility performance was investigated by the use of the Hansen solubility parameter and extended Hildebrand solubility approach. Numerous models, e.g. mixture response surface, Jouyban–Acree, modified Wilson and Jouyban–Acree–van’t Hoff acceptably correlated the obtained mole fraction solubility with relative average deviations (RAD) no greater than 7.25 %. The relative contribution of solute–solvent and solvent–solvent interactions to equilibrium solubility variation of 5-chlorooxine (I) at the temperature of 298.15 K was analyzed quantitatively by employing the linear solvation energy relationships, indicating that the dipolarity-polarizability and solubility parameter of solvent systems were predominantly responsible for the 5-chlorooxine (I) solubility. The solvation behavior was inspected by the extended Hildebrand solubility approach applied to the solubility data at 298.15 K, gaining RAD of no more than 3.15 %. In addition, preferential solvation of 5-chlorooxine (I) was quantitatively analyzed by the method of inverse Kirkwood–Buff integrals in terms of some available solution properties. The positive preferential solvation parameters for 5-chlorooxine (I) in intermediate and cosolvent-rich solutions suggests that the solute 5-chlorooxine (I) is preferentially solvated by cosolvents. It is speculated that 5-chlorooxine (I) performs as a Lewis acid behavior with cosolvent molecules in above composition districts. The dissolution of 5-chlorooxine (I) in all aqueous solution systems was entropy-driven and endothermic process.

Solubility, correlation, dissolution thermodynamics and preferential solvation of meloxicam in aqueous mixtures of 2-propanol

Background: Meloxicam is a powerful analgesic and anti-inflammatory drug widely prescribed by physicians in current therapeutics. Because of the very low aqueous equilibrium solubility of meloxicam, this property has been studied in {2-propanol + water} mixtures from (293.15 to 313.15) K to expand the solubility database about pharmaceutical compounds in mixed solvents useful for homogeneous liquid dosage forms design. Methods: Flask shaken method and UV-vis spectrophotometry were used for meloxicam solubility determinations. Jouyban-Acree model was challenged for solubility correlation. The van’t Hoff and Gibbs equations were employed here to calculate the respective apparent standard thermodynamic quantities for the dissolution and mixing processes, namely Gibbs energy, enthalpy, and entropy. In addition, the inverse Kirkwood-Buff integrals were employed to compute the preferential solvation parameters of meloxicam by 2-propanol in the mixtures. Results: Meloxicam solubility increases with temperature arising and maximum solubilities are observed in the mixture of x1 = 0.70 at all temperatures. Jouyban-Acree model correlates the meloxicam solubility very well. Dissolution processes were endothermic in all cases and entropy-driven in the interval 0.20 ≤ x1 ≤ 1.00. Non-linear enthalpy–entropy relationship was observed in the plot of enthalpy vs. Gibbs energy exhibiting negative but variant slopes in the composition region 0.00 &lt; x1 &lt; 0.40 and variant negative and positive slopes in the other mixtures. Meloxicam is preferentially solvated by water in water-rich mixtures, it is apparently solvated by water in 2-propanol-rich mixtures, but it is preferentially solvated by 2-propanol in the composition interval of 0.19 &lt; x1 &lt; 0.78. Conclusion: Solid-liquid equilibrium of meloxicam in {2-propanol + water} mixtures has been studied at several temperatures as a contribution to preformulation studies of homogeneous liquid pharmaceutical dosage forms based on this drug.

Solubility and thermodynamic aspects of etonogestrel in several aqueous co-solvent solutions

The current work was devoted to the investigation on equilibrium solubility, Hansen solubility parameter, solvation performance and dissolution thermodynamics of etonogestrel in binary aqueous blends of the cosolvents {n-propanol, N,N-dimethylformamide (DMF), ethanol or isopropanol} by experimentation and several mathematical relationships. The solubility determination was conducted under atmospheric pressure (101.2 kPa) from 278.15 to 323.15 K through the common shake-flask method. The maxima of etonogestrel solubility expressed in mole fraction scale at 323.2 K were observed as 8.713 × 10−3 for ethanol, 16.81 × 10−3 for n-propanol, 19.52 × 10−3 for isopropanol and 121.4 × 10−3 for DMF; while the minimum was 0.01477 × 10−3 for pure water at 278.15 K. The solubility performance of etonogestrel was deeply considered by means of Hansen solubility parameter concept. The obtained equilibrium solubility was computationally expressed by modified Jouyban–Acree–van’t Hoff model, mixture response surface (MRS) model, modified Wilson model and Jouyban–Acree model with the relative average deviations of no higher than 7.12%. The relative prominence of solvent–solvent and solute–solvent molecule interactions on etonogestrel solubility variation specified the dipolarity-polarizability and solubility parameter of solution descriptors that was studied in terms of the linear solvation energy relationships. The extended Hildebrand solubility approach was used to inspect the solubility data at 298.15 K acquiring the correlation coefficient of >0.9999. The quantitative investigation on preferential solvation of etonogestrel by solvent species in different solutions was made by the inverse Kirkwood–Buff integrals technique in terms of numerous solution properties. Positive preferential solvation parameters for cosolvents of isopropanol, DMF, ethanol and n-propanol in aqueous solutions with cosolvent-rich and intermediate scopes suggested the preferential solvation of etonogestrel by the cosolvents (isopropanol/DMF/ethanol/n-propanol). It was assumed that etonogestrel acted as a Lewis acid in these composition ranges with the isopropanol/DMF/ethanol/n-propanol molecules. Thermodynamic analysis of dissolution properties and enthalpy–entropy compensation demonstrated an entropy-driven mechanism and endothermic process for etonogestrel dissolved in different blended solvents.

Solubility of sulfamerazine in (ethylene glycol + water) mixtures: Measurement, correlation, dissolution thermodynamics and preferential solvation

The equilibrium solubility of sulfamerazine (SMR) in neat ethylene glycol (EG) and nineteen {(EG) (1) + water (2)} mixtures is reported at temperatures from (278.15 to 318.15) K. Mole fraction solubility of SMR (x3) increases with temperature arising and also increases with the EG proportion increasing. It varies from 1.71 × 10−5 in neat water to 7.78 × 10−4 in neat EG at 298.15 K. Solubility behavior was correlated by the extended log-linear model of Yalkowsky, the Jouyban-Acree model, and Jouyban-Acree-van’t Hoff model and the obtained mean percentage deviations are 80.1%, 6.7% and 6.6%, respectively. From the variation of solubility with temperature, the apparent thermodynamic analysis of dissolution and mixing processes was performed in all the mixtures and neat solvents. From inverse Kirkwood-Buff integrals (IKBI) calculations is observed that SMR exhibits low negative preferential solvation parameters by EG in water-rich mixtures. Otherwise, SMR is preferentially solvated by EG in the interval (0.24 < x1 < 1.00).

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

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.