Solubility and Solution Thermodynamics of Meloxicam in 1,4-Dioxane and Water Mixtures

Abstract

The equilibrium solubility of meloxicam in 1,4-dioxane and water binary mixtures at temperatures from 293.15 to 313.15 K was determined, and the respective thermodynamic quantities of solution were calculated. Additionally, the preferential solvation parameters of the drug were derived from their thermodynamic solution properties by means of the inverse KirkwoodBuff integrals method. From solvent effect studies, it is found that this drug is sensitive to specific solvation effects. The preferential solvation parameter by 1,4-dioxane, dx(1,3), is negative in water-rich mixtures but positive in compositions in which 0.18 < x(1) < 1.00. It could be possible that in water-rich mixtures the hydrophobic hydration around aromatic rings and/or methyl groups plays a relevant role in the drug solvation. The greater solvation by 1,4-dioxane in mixtures of similar cosolvent compositions and 1,4-dioxane-rich mixtures could be explained in terms of the greater basic behavior of the cosolvent interacting with the hydrogen-donor groups of the drug.