Thermodynamic solubility of celecoxib in organic solvents

The present work investigates the solubility of the stable polymorph of celecoxib (CEL) drug in a range of pure organic solvents, including methanol, isopropanol, butanol, ethyl acetate, acetonitrile and toluene, within the temperature range 278-303 K. The solid form used has been characterized by SEM, PXRD, DSC, TGA, FTIR and Raman spectroscopy. The solid form studied exhibited a melting temperature of 437.45 K, with an associated melting enthalpy of 35.93 kJ mol(-1). The experimental solubility data obtained was fitted to empirical and semi-empirical models, so that the parameters obtained enable the interpolation of further solubility data within the range explored. In the studied solvents, the solubility decreases in the order: ethyl acetate > acetonitrile > methanol > isopropanol > butanol > toluene. In all the solvents used, except for in toluene, the experimental solubility values are higher than the ideal ones, indicating negative deviation with respect to Raoult's law and favourable solute-solvent interactions. The solubility order of CEL in alcohols correlated well with the solvent polarity and this finding is complemented with the CEL-solvent interactions determined by molecular dynamics simulations. The high solubility of CEL in ethyl acetate is attributed to the similar Hildebrand solubility parameter of both species.