Solubility and preferential solvation of econazole nitrate in binary solvent mixtures of methanol, ethanol and 1,4-dioxane in water

- Solubility of econazole nitrate in methanol/ethanol/1,4-dioxane + water were determined.
- Preferential solvation parameters were derived by IKBI method.
- Econazole nitrate was preferentially solvated by alcohol in intermediate composition and alcohol-rich mixtures.
- Econazole nitrate is preferentially solvated by cosolvent in intermediate composition for 1,4-dioxane mixtures.

The solubility of econazole nitrate in binary mixed solvents of (methanol + water, ethanol + water and 1,4-dioxane + water) were measured experimentally via the isothermal dissolution equilibrium method in the temperature range of (278.15-318.15) K under 101.2 kPa. For the (1,4-dioxane + water) system, at a certain composition of 1,4-dioxane, the solubility of econazole nitrate increased with an increase in temperature; nevertheless at the same temperature, they increased at first and then decreased with an increase in mass fraction of 1,4-dioxane. At the same temperature and mass fraction of methanol, ethanol or 1,4-dioxane, the solubility of econazole nitrate was greater in (methanol + water) than in the other two mixed solvents. The solubility values were correlated by using Jouyban-Acree model, and the dissolution enthalpies of the dissolution process were computed. Preferential solvation parameters of econazole nitrate were also derived by means of the inverse Kirkwood-Buff integrals method. The preferential solvation parameter by water δx1,3 is negative in water-rich mixtures but positive in compositions from 0.31 to 1.0 in mole fraction of methanol and from 0.24 to 1.0 in mole fraction of ethanol. It is conjecturable that in intermediate composition of alcohol and alcohol-rich mixtures the interaction by acidic hydrogen-bonding by methanol/ethanol on the basic sites of econazole nitrate played a relevant role in the drug solvation. However in 1,4-dioxane (1) + water (2) mixtures with 0.18 < x1 < 0.50 positive δx1,3 values were observed, but with 0.50 < x1 < 1.0 negative δx1,3 values were observed again. The solubility data presented in this work expand the physicochemical information about drugs in binary aqueous-co-solvent mixtures.

221