Thermodynamics Research Center / ThermoML | Journal of Chemical and Engineering Data

ABSTRACT

Polymorphism occurs in non-steroidal anti-inflammatory drug flufenamic acid (FFA) and brings about differences in physical and chemical properties among various polymorphs. Form I and form III of FFA were characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and scanning electron microscope (SEM). The mole fraction solubility of FFA form I and form III was measured in (water + acetonitrile) and (water + 2-propanol) binary mixed solvents with different solvent compositions by using a static method. It was observed that the solubility trends varied in the two mixed solvent systems with the increase of the fraction of the organic solvent. The experimental solubility data was correlated with the solvent composition or/and temperature by using the modified Apelblat equation, Jouyban-Acree model and CNIBS/R-K model. It came out that the calculated solubility was consistent with the experimental data thus the established model was suitable for both mixed solvent systems and the predicted solubility of FFA in the binary mixed solvent with various compositions was attainable. Computational studies on solubility behaviour were performed by using both density functional theory (DFT) calculations and NMR determination. The results concluded that the water molecules may not directly interact with the solute molecules but interact with the solute-organic solvent complexes in the binary solvents, thus the formation of solute-organic solvent complexes could play an important role in the solubility of FFA in the two binary solvent systems.