The equilibrium solubility of benzocaine (BZC) in several {methanol (1) + water (2)} mixtures at 298.15K was determined. Solubility values are expressed in mole fraction and molarity and were calculated with the Jouyban-Acree model. Preferential solvation parameters of BZC by methanol (x(1,3)) were derived from their thermodynamic solution properties using the inverse Kirkwood-Buff integrals method. x(1,3) values are negative in water-rich mixtures (0.00<x(1)<0.32) but positive in the other mixtures (0.32 < x(1)<1.00). To explain the preferential solvation by water in the former case, it is conjecturable that the hydrophobic hydration around non-polar groups of BZC plays a relevant role in the solvation. Moreover, the higher solvation by methanol in mixtures of similar cosolvent compositions and methanol-rich mixtures could be explained in terms of the higher basic behaviour of methanol regarding water.

The equilibrium solubility of meloxicam in methanol + water binary mixtures at 298.15 K was determined and the preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals method. From solvent effect studies, it is found that this drug is sensitive to specific solvation effects. The preferential solvation parameter by methanol δx1,3, is negative in water-rich mixtures but positive in compositions from 0.30 in mole fraction of methanol to pure methanol. It is conjecturable that in the former case the hydrophobic hydration around aromatic rings and/or methyl groups plays a relevant role in the solvation. The more solvation by methanol in mixtures of similar co-solvent compositions and in methanol-rich mixtures could be explained in terms of the bigger basic behavior of the co-solvent interacting with hydrogen-donor groups of the drug.

Utilizando algunas propiedades termodinámicas clásicas de disolución se calcularon los parámetros de solvatación preferencial dx1,3) de L-arabinosa y ácido DL-málico en mezclas etanol + agua mediante el método de las integrales inversas de Kirkwood-Buff (IKBI, por sus siglas en inglés); estos parámetros dx1,3 corresponden a las diferencias entre las fracciones molares locales alrededor del soluto y en el grueso de la solución. Se observó que estos compuestos son sensibles a efectos específicos de solvatación según la composición de la mezcla cosolvente. Así, los valores de dx1,3 para la L-arabinosa son positivos en mezclas ricas en agua pero negativos en composiciones desde 0.25 en fracción molar de etanol hasta el etanol puro. Sin embargo, en el caso del ácido DL-málico los valores de dx1,3 son negativos en todas las composiciones cosolventes analizadas. En mezclas ricas en agua la mayor solvatación de la L-arabinosa por parte de las moléculas de etanol podría deberse principalmente a efectos de polaridad. De otro lado, la preferencia que manifiestan ambos compuestos por el agua en mezclas ricas en etanol, podría explicarse en términos de la mayor acidez del agua, la cual estaría interactuando con los grupos aceptores de hidrógeno presentes en los dos solutos.

Solubility is a very important property of drugs involved in purification processes and the different pharmaceutical dosage form design stages. Otherwise, caffeine and theophylline are alkaloid drugs widely used in several solid and liquid pharmaceutical formulations. The equilibrium solubility of caffeine and theophylline were determined in {methanol + water} binary mixtures at 298.15 K by means of the shaken flask method and both mass balance and UV spectrophotometric composition analyses. Solubility is expressed in both molarity and mole fraction. Maximum solubility of both drugs is observed in a mixture of similar proportions of methanol and water instead of the neat cosolvent. All these solubility values were correlated with the Jouyban–Acree model. Preferential solvation parameters by methanol (δx 1,3) of these xanthines were derived from their thermodynamic solution properties by using the inverse Kirkwood–Buff integrals method. For both compounds the δx 1,3 values are negative in water-rich and methanol-rich mixtures but positive in mixtures with almost the same proportion of methanol and water. It is conjectured that in the former case the hydrophobic hydration around non-polar groups of these drugs plays a relevant role in the solvation. Besides, the preferential solvation of these solutes by methanol in mixtures of similar cosolvent compositions could be explained in terms of the higher basicity of methanol compared to water. Finally, the preferential solvation by water in methanol-rich mixtures could be a consequence of the higher acidity of water compared to methanol.

Utilizando algunas propiedades termodinamicas clasicas de disolucion se calcularon los parametros de solvatacion preferencial dx 1,3 ) de L-arabinosa y acido DL-malico en mezclas etanol + agua mediante el metodo de las integrales inversas de Kirkwood-Buff (IKBI, por sus siglas en ingles); estos parametros dx 1,3 corresponden a las diferencias entre las fracciones molares locales alrededor del soluto y en el grueso de la solucion. Se observo que estos compuestos son sensibles a efectos especificos de solvatacion segun la composicion de la mezcla cosolvente. Asi, los valores de dx 1,3 para la L-arabinosa son positivos en mezclas ricas en agua pero negativos en composiciones desde 0.25 en fraccion molar de etanol hasta el etanol puro. Sin embargo, en el caso del acido DL-malico los valores de dx 1,3 son negativos en todas las composiciones cosolventes analizadas. En mezclas ricas en agua la mayor solvatacion de la L-arabinosa por parte de las moleculas de etanol podria deberse principalmente a efectos de polaridad. De otro lado, la preferencia que manifiestan ambos compuestos por el agua en mezclas ricas en etanol, podria explicarse en terminos de la mayor acidez del agua, la cual estaria interactuando con los grupos aceptores de hidrogeno presentes en los dos solutos.

ABSTRACT The equilibrium solubilities of naproxen (NAP), ketoprofen (KTP), and ibuprofen (IBP) in methanol + water binary mixtures at 298.15 K were determined and the preferential solvation parameters were derived by means of the inverse Kirkwood–Buff integrals (IKBI) method. These drugs are very sensitive to specific solvation effects. The preferential solvation parameters by methanol δx1,3 are negative in water-rich mixtures but positive in compositions from 0.32 in mole fraction of methanol to pure methanol. It is conjecturable that in the former case the hydrophobic hydration around aromatic rings and/or methyl groups plays a relevant role in the solvation. The higher solvation by methanol in mixtures of similar co-solvent compositions and in methanol-rich mixtures could be explained in terms of the higher basic behaviour of this co-solvent interacting with the hydroxyl group of the drugs. Moreover, drug solubilities were correlated by using the modified nearly ideal binary solvent/Redlich–Kister model obtaining average percentage deviations (APDs) lower than 9.0%.

Benzocaine (BZC) is a local anaesthetic commonly used in therapeutics. Based on published thermodynamic quantities of dissolution, partitioning, and sublimation of BZC, the thermodynamic quantities of solvation for this drug in some mutually saturated solvents were calculated. Organic solvents under consideration were cyclohexane (CH), isopropyl myristate (IPM), and 1-octanol (ROH). In all cases, these thermodynamic quantities (i.e. Delta G(subl)(o), Delta H-subl(o), and Delta S-subl(o)) were negative, indicating that dissolution is the more favourable state for BZC. Thermodynamic quantities of drug dilution in the organic solvents were also calculated. Accordingly, Gibbs energies of dilution were not favourable in all the three organic solvents (i.e. Delta G(dil-o)(o) > 0). From the obtained values for the different transfer processes, an interpretation based on solute-solute and solute-solvent interactions was developed.

The equilibrium solubility of three pharmaceutical salts, namely, sodium naproxen (Na.NAP), procaine hydrochloride (PC.HCl), and lysine clonixinate (Lys.Clon), was determined in propylene glycol (PG) + water mixtures at 298.15 K. If the mole fraction concentration scale is considered, the mixtures' composition-dependence on solubility was different for these drugs. Thus, the solubility of Na.NAP increased nonlinearly from pure water to pure PG. By contrast, the solubility of PC.HCl decreased nonlinearly from pure water to pure PG. In a different way, the solubility of Lys. Clon increased from pure water to the mixture with mass fraction of PG, w(1) = 0.80, and later, it decreased to reach a lower value in pure PG. A good correlation of the solubility data was obtained by using the modified NIBS/R-K model. Otherwise, the apparent specific volumes at saturation of these drugs were also calculated in all the mixtures under study.

The equilibrium solubilities of sulfanilamide, sulfamethizole and sulfapyridine in methanol + water mixtures at 298.15 K were determined and the preferential solvation parameters were derived from their thermodynamic solution properties by means of the inverse Kirkwood–Buff integrals. In all cases the drug solubility was the lowest in neat water and highest in neat methanol. The preferential solvation parameters for methanol (δx 1,3) are negative in water-rich mixtures but positive in compositions from 0.32 in mole fraction of methanol to pure methanol. Based on these results it is conjecturable that in the former case hydrophobic hydration around the aromatic rings plays the main role in the drug’s solvation. The higher solvation by methanol in mixtures of similar cosolvent compositions and in methanol-rich mixtures can be explained in terms of the higher basic behavior of this co-solvent interacting with the Lewis acidic groups of the drugs. Besides, the drugs’ solubilities were mathematically represented by using the Jouyban–Acree model obtaining average percentage deviations lower than 2.6 % for correlative studies.

The solubility of sulfadiazine (SD) in some 1,4-dioxane + water co-solvent mixtures was measured at five temperatures from 293.15 to 313.15 K in all the polarity range. By using the van't Hoff and Gibbs equations the thermodynamic functions Gibbs energy, enthalpy, and entropy of solution were obtained from these data. The maximal solubility of this drug expressed in mole fraction was found in the mixture with 0.85 in mass fraction of 1,4-dioxane (w(1) = 0.85, delta(1+2) = 24.7 MPa1/2) and the minimum solubility in pure water (delta = 47.8 MPa1/2) at almost all the temperatures studied. By using the ideal solubility values reported in literature, the thermodynamic quantities of mixing were also calculated. Non-linear enthalpy-entropy relationship was observed for SD in the plot of enthalpy vs. Gibbs energy of solution with variable positive slopes in the regions with 0.00 <= w(1) <= 0.90 and 0.95 <= w(1) <= 1.00. Hence, the driving mechanism for SD solution process is the enthalpy in nearly all the compositions. In addition, the preferential salvation of this drug by both solvents was analyzed by means of the inverse Kirkwood-Buff integrals observing that it is preferentially solvated by water in water-rich and 1,4-dioxane-rich mixtures but preferentially solvated by 1,4-dioxane in those mixtures with intermediate compositions. (C) 2015 Elsevier B.V. All rights reserved.

The equilibrium solubility of meloxicam (MEL) in polyethylene glycol (PEG) 400+water binary mixtures at temperatures from 298.15K to 318.15K was determined and the respective thermodynamic quantities of solution and mixing were calculated. MEL solubility increases with the increasing of the PEG 400 proportion in the mixtures at all temperatures. MEL equilibrium solubility in mole fraction increased from x3=4.24×10−7 in pure water to x3=9.32×10−3 in pure PEG 400 at 298.15K. Activity coefficients of MEL decreased from 7260 in pure water to 0.33 in pure PEG 400 at the same temperature. Both Gibbs energy and enthalpy of dissolution were positive in all the mixtures under analysis. Otherwise, dissolution entropy is positive in mixtures with mass fractions of PEG 400 equal or lower than 0.40 but negative in all the other mixtures. Non-linear enthalpy–entropy compensation was found for this drug in these mixtures with variant positive slope in the plot of ΔsolnH° vs. ΔsolnG°. Thus, enthalpy-driving was found for transfer processes in all the mixtures evaluated.

Extended Hildebrand solubility approach (EHSA) was applied to evaluate the solubility of sulphanilamide, sulphapyridine and sulphamethizole in some propylene glycol + water mixtures at 298.15 K. Reported experimental solubility and some properties of fusion of this drug were used for the calculations. In particular, a good predictive character of EHSA has been found by using a regular polynomial in order five of the interaction parameter W as a function of the solubility parameter of solvent mixtures free of drug. Nevertheless, the predictive character of EHSA is the same as the one obtained by direct correlation between drug solubilities and the same descriptor of polarity of the co-solvent mixtures.

The thermodynamic quantities of partitioning of methyl paraben (MP) and propyl paraben (PP) were studied at five temperatures in several organic solvent/buffer systems, namely, 1-octanol (ROH/W), isopropyl myristate (IPM/W), chloroform (CLF/W) and cyclohexane (CH/W). In all cases, the values of the mole fraction partition coefficient (K-o/w(x)) were greater than unity; therefore, the standard Gibbs free energies of transfer are negative indicating a high affinity of MP and PP for all the organic media evaluated. The K-o/x(w) values were approximately 470-fold and 1700-fold higher in the ROH/W system with respect to the CH/W for MP and PP, thus indicating a high degree of hydrogen bonding contribution to partitioning. Otherwise, in the case of the IPM/W system, the K-o/x(w) values were in the orders of 0.48 or 0.30 of those observed in ROH/W, whereas, in the case of CLF/W system, the K-o/x(w) values were in the orders of 0.03 to 0.04 of those observed in ROH/W. On the other hand, enthalpies and entropies of transfer of PP from water to organic solvents were all positive but in the case of MP the quantities were variable, negative or positive as well. These results could indicate some degree of participation of the hydrophobic hydration on the MP and PP partitioning processes. (C) 2015 Elsevier Ltd. All rights reserved.

The equilibrium solubility of propranolol hydrochloride in aqueous binary mixtures of 1,4-dioxane (D), acetonitrile (ACN), polyethylene glycol 400 (PEG), propylene glycol (PG), or methanol (MeOH), at T = 298.15 K was determined. In all cases the maximum solubility values expressed in molarity (mol.dm(-3)) in a mixture instead of neat water were obtained, while the lowest drug solubility values in the neat cosolvents were obtained. Otherwise, if the maximum mole fraction solubility obtained in every cosolvent system is considered, the following order is obtained: ACN + W > D + W > MeOH + W > PEG + W > PG + W; whereas, if the molarity scale is considered the maximum solubility decreases in the order: ACN + W > MeOH + W > D + W > PG +W > PEG + W. In a quantitative way the drug solubility expressed in mole fraction varies from 1.77 x 10(-4) in neat 1,4-dioxane to 2.95 x 10(-2) in the mixture with 0.50 in mass fraction of acetonitrile. A correlation of the solubility data obtained was made by means of the modified NIBS/R-K model; thus, regressions in second and third order were obtained according the cosolvent system. Otherwise, apparent specific volumes at saturation (phi(sp)(V)) in all the mixtures were also calculated; in particular, a phi(sp)(V) mean value of 0.837 cm(3).g(-1) was obtained.

The preferential solvation parameters by ethanol (EtOH) or propylene glycol (PG) of daidzein were derived from their solution thermodynamic properties by means of the inverse Kirkwood-Buff integrals and the quasi-lattice-quasi-chemical (QLQC) methods. According to IKBI method, the preferential solvation parameter by the co-solvent, δx1,3, is negative in water-rich mixtures but positive in co-solvent-rich mixtures in both kinds of systems. This could demonstrate the relevant role of hydrophobic hydration around the aromatic rings in the drug solvation in water-rich mixtures. Furthermore, the more solvation by co-solvent in co-solvent-rich mixtures could be due mainly to polarity effects and acidic behavior of the hydroxyl groups of the compound in front to the more basic solvents present in the mixtures, i.e. EtOH or PG. Otherwise, according to QLQC method, this drug is preferentially solvated by the co-solvents in all the mixtures in both kind of systems.

The preferential solvation parameters of ketoprofen (KTP) in ethanol (EtOH) + water and propylene glycol (PG) + water binary solvent mixtures were obtained from their thermodynamic properties by means of the inverse Kirkwood–Buff integrals (IKBI) and quasi-lattice quasi-chemical methods. According to the IKBI method, it is found that KTP is very sensitive to specific solvation effects, so the preferential solvation parameter by co-solvents, δx 1,3 , is negative in the water-rich mixtures of both binary systems but positive in the other compositions at temperatures of 293.15, 303.15 and 313.15 K. From this it can be assumed that, in water-rich mixtures, hydrophobic hydration around the aromatic rings and the methyl group, present in the drug, plays a relevant role in the solvation. The bigger amount of drug solvation by the co-solvent in mixtures of similar solvent proportions and in co-solvent-rich mixtures could be due mainly to polarity effects. Moreover, in these mixtures the solute will be acting as a Lewis acid with the co-solvent molecules, because they are more basic than water.

The equilibrium solubility of meloxicam in 1,4-dioxane and water binary mixtures at temperatures from 293.15 to 313.15 K was determined, and the respective thermodynamic quantities of solution were calculated. Additionally, the preferential solvation parameters of the drug were derived from their thermodynamic solution properties by means of the inverse KirkwoodBuff integrals method. From solvent effect studies, it is found that this drug is sensitive to specific solvation effects. The preferential solvation parameter by 1,4-dioxane, dx(1,3), is negative in water-rich mixtures but positive in compositions in which 0.18 < x(1) < 1.00. It could be possible that in water-rich mixtures the hydrophobic hydration around aromatic rings and/or methyl groups plays a relevant role in the drug solvation. The greater solvation by 1,4-dioxane in mixtures of similar cosolvent compositions and 1,4-dioxane-rich mixtures could be explained in terms of the greater basic behavior of the cosolvent interacting with the hydrogen-donor groups of the drug.

The preferential solvation parameters of methocarbamol in dioxane+water, ethanol+water, methanol+water and propylene glycol+water mixtures are derived from their thermodynamic properties by using the inverse Kirkwood-Buff integrals (IKBI) method. This drug is sensitive to solvation effects, being the preferential solvation parameter x(1,3), negative in water-rich and co-solvent-rich mixtures, but positive in mixtures with similar proportions of solvents, except in methanol+water mixtures, where positive values are found in all the methanol-rich mixtures. It is conjecturable that the hydrophobic hydration around the non-polar groups in water-rich mixtures plays a relevant role. Otherwise, in mixtures of similar solvent compositions, the drug is mainly solvated by co-solvent, probably due to the basic behaviour of the co-solvents; whereas, in co-solvent-rich mixtures, the preferential solvation by water could be due to the acidic behaviour of water. Nevertheless, the specific solute-solvent interactions present in the different binary systems remain unclear.

Equilibrium solubility of methocarbamol was determined in binary mixtures of dioxane, polyethylene glycol 400, ethanol, methanol or propylene glycol, and water at 298.15K. From maximum values in drug solubility and theoretical calculations involving the method proposed by Fedors a discussion was made about the Hildebrand solubility parameter for this drug. On the other hand, solubility values were correlated and/or predicted with the Jouyban–Acree model. The overall mean percentage deviations for the correlated and predicted solubilities were 2.7% and 89.0%, respectively. Finally, density of saturated and drug free solution binary solvent mixtures was also calculated using the Jouyban–Acree model.