Nabumetone Solubility Prediction in Dioxane-Water Mixtures Using Extended Hildebrand Solubility Approach

The extended Hildebrand solubility parameter approach is used to estimate the solubility of nabumetone in binary solvent systems. The solubility of nabumetone in various dioxane-water mixtures was analyzed in terms of solute-solvent interactions using a modified version of Hildebrand-Scatchard treatment for regular solutions. The solubility of nabumetone in the binary solvent, dioxane-water shows a bell-shaped profile with a solubility maximum well below the ideal solubility of the drug. This is attributed to solvation of the drug with the dioxane-water mixture, and indicates that the solute-solvent interaction energy is larger than the geometric mean (δ1δ2) of regular solution theory. The new approach provides an accurate prediction of solubility once the interaction energy (W) is obtained. In this case, the energy term is regressed against a polynomial in δ1 of the binary mixture. Quadratic, cubic, and quartic expressions of ‘W’ in terms of solvent solubility parameter were utilized for predicting the solubility of nabumetone in various dioxane-water mixtures. But from these three polynomial expressions, a quartic expression of ‘W’ in terms of solvent solubility parameter was found suitable for predicting the solubility and yields an error in mole fraction solubility of ~7.346%, a value approximating that of the experimentally determined solubility. Thus the method has potential usefulness in preformulation and formulation studies during which solubility prediction is important for drug design.