Equilibrium solubility determination and thermodynamic aspects of aprepitant (form I) in four binary aqueous mixtures of methanol, ethanol, acetone and 1,4-dioxane

Abstract

This contribution reported the equilibrium solubility of aprepitant (form I) in four binary aqueous mixtures of methanol, ethanol, acetone and 1,4-dioxane acquired through a shake-flask method from 283.15 K to 323.15 K under local atmospheric pressure of 101.2 kPa. At the same mass fraction compositions of methanol/ethanol/acetone/1,4-dioxane and temperature, the mole fraction solubility of aprepitant was greater in (1,4-dioxane + water) mixture than in ethanol/acetone/methanol (1) + water (2) mixtures. The relative importance of solute-solvent and solvent-solvent interactions upon the solubility variation was studied by using the linear solvation energy relationships of solvent effect. The Hildebrand solubility parameter and dipolarity-polarizability of the solvents had the main contributions to the solubility variation in methanol/ethanol/1,4-dioxane + water mixtures; while merely dipolarity-polarizability, in (acetone + water) mixture. The preferential solvation was studied by using the method of inverse Kirkwood-Buff integrals in terms of thermodynamic solution properties. The preferential solvation parameters for methanol, ethanol, acetone and 1,4-dioxane presented positive values in methanol/ethanol/acetone/1,4-dioxane-rich and intermediate compositions in the four mixtures, indicating that aprepitant (I) was solvated preferentially by the methanol/ethanol/acetone/1,4-dioxane. It is conjecturable that in these regions aprepitant (I) acts as a Lewis acid with methanol/ethanol/acetone/1,4-dioxane molecules. Moreover, the drug’s solubility was mathematically represented via the Jouyban-Acree model obtaining the average relative deviations less than 6.21%. Finally, the standard dissolution enthalpies (ΔHsolo) for aprepitant (I) dissolved in solvent mixtures were obtained from the van’t Hoff analysis.