Measurement and modelling of econazole nitrate in twelve pure organic solvents at temperatures from 278.15 K to 318.15 K

• Solubility of econazole nitrate in twelve pure organic solvents were determined.
• Solubility data were correlated and calculated by modified Apelblat equation and λh equation.
• The apparent dissolution enthalpy for the dissolution processes were calculated.

The solubility of econazole nitrate (racemic mixture) in organic solvents is of clear importance for the design of separation processes and further theoretical studies. In this work, the solubilities of econazole nitrate in methanol, ethanol, n-butanol, isopropanol, ethyl acetate, 2-butanone, 3-methyl-1-butanol, acetonitrile, 1,4-dioxane, N,N-dimethylformamide (DMF), 1-methyl-2-pyrrolidinone (NMP) and acetone were determined at the temperatures from 278.15 K to 318.15 K under atmosphere pressure (p = 101.2 kPa) by high-performance liquid chromatography (HPLC). It was found that the econazole nitrate solubilities in mole fraction in selected solvents increased with the increase in temperature. At a given temperature, they obeyed the following order from high to low in different solvents: NMP > DMF > methanol > 2-butanone > acetone > (3-methyl-1-butanol, ethanol) > acetonitrile > n-butanol > isopropanol > 1,4-dioxane > ethyl acetate. The experimental solubility data were correlated with the modified Apelblat equation and the Buchowski–Książczak λh equation. The calculated solubilities using the modified Apelblat solubility model were in better agreement with the experimental values. The largest percentage of average relative deviation was 1.53% for solubility of econazole nitrate in isopropanol calculated with the λh equation, and the maximum value of root-mean-square deviation was 2.11 × 10−4. Based on the modified Apelblat equation, the apparent dissolution enthalpies of econazole nitrate in twelve pure solvent were derived. The results indicate that the dissolution of econazole nitrate in all studied cases is endothermic process.

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