CHARACTERIZATION OF THE SOLID PHASES OF PARACETAMOL AND FENAMATES AT EQUILIBRIUM IN SATURATED SOLUTIONS

Differential scanning calorimetry (DSC), supported by hot stage microscopy, IR spectroscopy and X-ray powder diffractometry, was used to investigate the characteristics of the solid phases of mefenamic, niflumic, and flufenamic acids and of paracetamol, before and after equilibration with saturated solutions in different solvents. Mixtures of Lewis base (dioxane and ethyl acetate) and am- phiprotic solvents (ethanol and water) were prepared for evaluating the influence of both nature and polarity of the solvents. Solid-state analysis performed on the original samples (commercial products) made it possible to establish that paracetamol, mefenamic acid and flufenamic acid were in their respective Form I. No polymorphic modifications are known for niflumic acid. Paracetamol, niflumic and mefenamic acid did not show any change after equilibration with the various solvents or solvent mixtures, re- gardless of their different chemical nature. In contrast, DSC, IR and X-ray analyses revealed the par- tial recrystallization of flufenamic into its polymorphic Form III in solid phases at equilibrium with ethanol, ethyl acetate and their blends, as well as in dioxane–water mixtures containing 30 to 100% dioxane and in ethanol–water mixtures with a water content less than 50%.