Thermodynamic and Structural Aspects of Some Fenamate Molecular Crystals

Abstract

Crystal lattice characteristics from the literature for different polymorphic forms of some nonsteroidal anti-inflammatory drugs (diclofenac, niflumic, flufenamic, tolfenamic, mefenamic acid) and structural relative compounds (N-phenylanthranilic acid and diphenylamine) were summarized and compared. Molecular conformational states in the crystal lattices and hydrogen bond networks were described and analyzed. Temperature dependencies of vapor pressure of the molecular crystals were measured and sublimation thermodynamic parameters calculated. Thermodynamic characteristics of fusion and vaporization processes were derived. Relationships between the sublimation thermodynamic functions and the torsion angles between the benzene motives of the compounds and the polymorphic forms were revealed. Dependence between the sublimation enthalpies and the melting points was observed. Correlation of the fusion entropies with the free volume per molecule in the crystal lattices was found. The absolute values of the crystal lattices energies of the polymorphic forms I and II of mefenamic acid and forms I and III of flufenamic acid were evaluated on basis of the sublimation and solution calorimetric experiments.