Fleming Martínez

Thermodynamic Study of the Solubility of Some Sulfonamides in Octanol, Water, and the Mutually Saturated Solvents

The free energy, enthalpy and entropy of solution, were evaluated from solubility data for a group of sulfonamides from 25 to 40°C in octanol, water, and the mutually saturated solvents. In aqueous media, the solubility was determined at the isoelectric point and ionic strength 0.15 mol-L−1. The excess free energy and the activity coefficients of the solutes also were determined. The results are discussed in terms of solute–solvent interactions.

TEMPERATURE-DEPENDENCE OF THE SOLUBILITY OF SOME ACETANILIDE DERIVATIVES IN SEVERAL ORGANIC AND AQUEOUS SOLVENTS

The thermodynamic functions free energy, enthalpy, and entropy of solution, were evaluated from the solubility data of acetanilide, acetaminophen, and phenacetin, determined at several temperatures in water, octanol, isopropyl myristate, and chloroform. These three organic solvents mutually saturated with water, and finally, in cyclohexane. In the aqueous media, the solubility was determined at pH 7.4 and ionic strength 0.15 mol L−1. The excess free energy and the activity coefficients of the solutes were also determined. The solubility for acetanilide and phenacetin was higher in organic media such as octanol and chloroform than is those obtained in the aqueous media and cyclohexane, while for acetaminophen the solubility was higher in octanol than those obtained in the other solvents.

Preferential solvation of methocarbamol in aqueous binary co-solvent mixtures at 298.15 K

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 δx1,3, 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.

Thermodynamic quantities relative to solution processes of Naproxen in aqueous media at pH 1.2 and 7.4

Based on van’t Hoff and Gibbs equations, the thermodynamic functions Gibbs free energy, enthalpy, and entropy of solution, mixing and solvation of naproxen (NAP) in water at pH 1.2 and 7.4, were evaluated from solubility values determined at several temperatures. The solubility at pH 7.4 and 25.0°C was almost 150 times higher with respect to pH 1.2. The enthalpies of solution were positive and greater for pH 1.2, while the entropies of solution were both negative, thereby implying a greater molecular organization at pH 7.4. The results were discussed in terms of solute–solvent interactions.

Thermodynamic study of the solubility of some sulfonamides in cyclohexane

The thermodynamic functions Gibbs energy, enthalpy and entropy of solution in cyclohexane, were evaluated from solubility data for a group of sulfonamides over the temperature range from 20.0 to 40.0 °C. The excess Gibbs energy and the activity coefficients of the solutes were also determined. The results are discussed in terms of solute-solvent interactions.

Estimation of the solubility of sulfonamides in aqueous media from partition coefficients and entropies of fusion

Semi empirical equation developed by Yalkowsky and Valvani, and another equation extended by Jain and Yalkowsky were used to estimate the aqueous solubility S w , of some sulfonamides using experimental octanol-water partition coefficients P , entropies of fusion j S f , and melting points t m , determined by DSC measurements. The calculated solubilities were compared with those experimentally determined. When experimental j S f and t m were used, the S w calculated values were in good agreement in most cases.

Thermodynamic Study of the Solubility of Benzocaine in some Organic and Aqueous Solvents

The thermodynamic functions free energy, enthalpy, and entropy of solution, were evaluated from solubility data of benzocaine determined at several temperatures in octanol, water, and the mutually saturated solvents, in isopropyl myristate, water, and the mutually saturated solvents, and in cyclohexane. In aqueous media the solubility was determined at pH 7.4 and ionic strength 0.15 mol-L−1. The excess free energy and the activity coefficients of the solutes also were determined. The solubility was higher in organic media, such as octanol and isopropyl myristate, than in aqueous media and cyclohexane.

Preferential solvation of some structurally related sulfonamides in 1-propanol + water co-solvent mixtures

The preferential solvation parameters by 1-propanol of sulfadiazine, sulfamerazine and sulfamethazine in 1-propanol + water mixtures were derived from their solution thermodynamic properties by means of the inverse Kirkwood–Buff integrals method. These sulfonamides are sensitive to solvation effects, so the preferential solvation parameter δx1,3 is negative in water-rich and 1-propanol-rich mixtures but positive in intermediate compositions. It is possible that the hydrophobic hydration around aromatic rings and/or other non-polar groups plays a relevant role in the solvation in water-rich mixtures. The more solvation by 1-propanol in mixtures of similar composition could be due mainly to polarity effects and acidic behaviour of the sulfonamides in front to the more basic solvent 1-propanol. Otherwise, the more solvation by water in 1-propanol-rich mixtures could be due to basic behaviour of the sulfonamides in front to water, which is the more acidic solvent.

Solubility of phenobarbital in aqueous cosolvent mixtures revisited: IKBI preferential solvation analysis

ABSTRACT The preferential solvation parameters of phenobarbital in aqueous binary mixtures of 1,4-dioxane, t-butanol, n-propanol, ethanol, propylene glycol and glycerol were derived from solution thermodynamic properties by using the IKBI method. This drug is sensitive to preferential solvation effects in all these mixtures. The preferential solvation parameter by the cosolvent (δx1,3) is negative in almost all the water-rich mixtures but positive in mixtures with similar proportions of solvents and cosolvent-rich mixtures, except in 1-propanol + water mixtures, where negative values are also found in mixtures with x1 ≥ 0.70. Hydrophobic hydration around the non-polar ethyl and phenyl groups of this drug in water-rich mixtures could play a relevant role in drug solvation. Otherwise, in mixtures of similar solvent compositions and in cosolvent-rich mixtures the preferential solvation by cosolvent could be due to the acidic behaviour of the drug.

Thermodynamics of partitioning and solvation of ketoprofen in some organic solvent/buffer and liposome systems

The ketoprofen (KTP) partitioning thermodynamics was studied in different solvent/buffer systems such as cyclohexane (CH/W), octanol (ROH/W), isopropyl myristate (IPM/W), chloroform (CLF/W); as well as in dimyristoyl phosphatidylcholine (DMPC) and dipalmitoyl phosphatidylcholine (DPPC) liposome systems. In all cases, the rational partition coefficients (KXO/w) were greater than unit; therefore standard transfer free energies were negative in sign indicating a high affinity of KTP for organic media. KXO/w values were approximately eightyfive-fold higher in the ROH/W system regarding the CH/W system, thus indicating a high degree of hydrogen bonding contribution to partitioning. While in the case of IPM/W and CLF/W systems, KXO/w values were approximately only three or four-fold lower than those observed in ROH/W. On the other hand, KXO/w values were approximately seventy-five or one hundred fifty-fold higher in the liposomes compared to ROH/W system indicating a high degree of bilayers immobilization and/or an electrostatic contribution to partitioning. In all cases, standard transfer enthalpies and entropies of KTP from water to organic media were positive in sign indicating some degree of participation of the hydrophobic hydration on the partitioning processes. Finally, by using the reported data for solvation of KTP in water, the associated thermodynamic functions for KTP solvation in all tested organic phases were also calculated.