Extended Hildebrand Approach: An Empirical Model for Solubility Prediction of Etodolac in 1,4-Dioxane and Water Mixtures

Models for predicting the solubility of drugs in solvent mixtures have an important practical application in drug formulation. Etodolac is a non-steroidal anti-inflammatory agent whose physicochemical properties in solution have not been adequately studied. The extended Hildebrand solubility approach (EHSA) is effectively applied to assess the equilibrium solubility of etodolac in binary solvent mixtures at 298.15 K. 1,4-dioxane and water were selected as solvents because they exhibit extremes of polarity. Experimental equilibrium solubility and some properties, enthalpy of fusion of this drug, were characterized. A satisfactory correlation-performance of the EHSA was found using a standard polynomial model in order five of the 'W' interaction energy against the solubility parameter of the mixtures (the overall mean percentage deviation is 0.535 %). In addition, the mean deviation obtained in the estimated solubility with respect to experimental equilibrium solubility is less significant compared with an empirical regression of order five of the logarithm of the experimental solubility as a function of the binary solvent mixtures' solubility parameters (5.03 %). Therefore, this empirical model has potential use in preformulation and formulation studies during which solubility prediction is important for drug design processes.