Equilibrium Solubility and Density Functional Theory Study of Tolfenamic Acid in Several Neat Solvents from 283.15 to 323.15 K
Qiong Wu, J. G. Wang
Abstract
The saturation shake-flask technique was employed herein to determine the equilibrium solubility of tolfenamic acid in 12 monosolvents, including ethylene glycol, 1-pentanol, 1-hexanol, 1-heptanol, ethyl formate, ethyl acetate, 1,4-dioxane, acetonitrile, cyclohexane, dimethyl sulfoxide, N, N -dimethylformamide, and pentyl acetate. The effects of the solvent properties on the solubility were studied using the linear solvation energy relationship. Correlation of the magnitudes of equilibrium solubility was conducted by means of several semiempirical equations and activity coefficient models such as Wilson, Apelblat, λ h, and NRTL. The mixing solution properties and activity coefficient together with partial molar excess enthalpy at infinite dilution were also estimated using the Wilson equation. Additionally, the electrostatic characteristics of the basicity and acidity of the tolfenamic acid molecule were explained using a quantitative study of the molecular surface. To further explore tolfenamic acid’s miscibility in the chosen solvents, Gaussian 09 was used. The strong interaction between tolfenamic acid and solvents resulted in higher solubility.