Zaira J. Cárdenas

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.

Solubility and preferential solvation of phenacetin in methanol + water mixtures at 298.15 K

ABSTRACT The mole fraction solubility of phenacetin (PNC) in methanol + water binary solvent mixtures at 298.15 K was determined along with density of the saturated solutions. All these solubility values were correlated with the Jouyban–Acree model. Preferential solvation parameters of PNC by methanol (δx1,3) were derived from their thermodynamic solution properties using the inverse Kirkwood–Buff integrals (IKBI) method. δx1,3 values are negative in water-rich mixtures but positive in methanol mole fraction of >0.32. It is conjecturable that in the former case the hydrophobic hydration around non-polar groups of PNC plays a relevant role in the solvation. 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.

Solubility of celecoxib in N-methyl-2-pyrrolidone+water mixtures at various temperatures: Experimental data and thermodynamic analysis

Solubility is one of the most significant physicochemical properties of drugs, and improving the solubility of drugs is still a challenging subject in pharmaceutical sciences due to requirements of enhancing their bioavailability. Celecoxib, according to the biopharmaceutics classification system (BCS), is a class 2 drug, possessing low water solubility (<5 μg·mL−1) and high permeability. Increasing the solubility of this group can lead to improved bioavailability, dose reduction and subsequently, increased efficiency and reduced side effects. In this study, celecoxib solubility was determined in binary mixtures of N-methyl-2-pyrrolidone (NMP)+water at 293.2, 298.2, 303.2, 308.2 and 313.2 K. The solubility of celecoxib is increased with the addition of NMP to the aqueous solutions and reaches a maximum value in neat NMP. In addition, increased temperature leads to enhanced solubility of celecoxib in a given solvent composition. The solubility data of celecoxib in NMP+water at different temperatures were correlated using different mathematical models including, the Jouyban-Acree model and a combination of the Jouyban-Acree and van’t Hoff models. Thermodynamic parameters, Gibbs energy, enthalpy and entropy of dissolution processes were performed based on Gibbs and van’t Hoff equations. Thermodynamic analysis allowed observing two main entropy or enthalpy-driven dissolution mechanisms, varying according to the composition of aqueous mixtures. Moreover, preferential solvation of celecoxib by water is observed in water-rich mixtures but preferential solvation by NMP was seen in mixtures with similar composition and also in NMP-rich mixtures.

Solubility and preferential solvation of some non-steroidal anti-inflammatory drugs in methanol + water mixtures at 298.15 K

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%.

Solubility and preferential solvation of benzocaine in {methanol (1) + water (2)} mixtures at 298.15 K

ABSTRACT The equilibrium solubility of benzocaine (BZC) in several {methanol (1) + water (2)} mixtures at 298.15 K 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 (δx1,3) were derived from their thermodynamic solution properties using the inverse Kirkwood–Buff integrals method. δx1,3 values are negative in water-rich mixtures (0.00 < x1 < 0.32) but positive in the other mixtures (0.32 < x1 < 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.

Solubility and Apparent Specific Volume of Some Pharmaceutical Salts in Propylene Glycol + Water Mixtures at 298.15 K

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, w1 = 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.

Extended Hildebrand solubility approach applied to some sulphonamides in propylene glycol + water mixtures

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.

Solvation and dilution thermodynamics of benzocaine in some aqueous and organic solvents

ABSTRACT 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. , , and ) 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. > 0). From the obtained values for the different transfer processes, an interpretation based on solute–solute and solute–solvent interactions was developed.