Solubility and Solution Thermodynamics of Flufenamic Acid Polymorphs in Two Binary Solvents

Abstract

Polymorphism occurs in nonsteroidal 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, differential scanning calorimetry, and scanning electron microscopy. 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 using a static method. It was observed that the solubility trends varied in the two mixed solvent systems with an increase in the fraction of the organic solvent. The experimental solubility data were correlated with the solvent composition or/and temperature using the modified Apelblat equation, the Jouyban–Acree model, and the CNIBS/R–K model. It was found that the calculated solubility was consistent with the experimental data; thus, the established model was suitable for both mixed solvent systems and the predicted s...