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.

Spontaneous Crystalline-to-Amorphous Phase Transformation of Organic or Medicinal Compounds in the Presence of Porous Media, Part 1: Thermodynamics of Spontaneous Amorphization

“…It is also noted that although vapor pressure alone does not dictate the amorphization time, it may still be an important parameter in vapor phase‐mediated phase transformation. Vapor pressures of pharmaceutical solids have been compiled in Table 3 20,21,33–39. Vapor pressure increases as temperature increases; whereas at the same time, the chemical stability may decrease.…”

“…Vapor pressures of pharmaceutical solids have been compiled in Table 3. 20,21,[33][34][35][36][37][38][39] Vapor pressure increases as temperature increases; whereas at the same time, the chemical stability may decrease. An optimal processing temperature and pressure would have to be determined for each compound.…”

Fenamate Cocrystals with 4,4′-Bipyridine: Structural and Thermodynamic Aspects

“…32 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 large clusters of molecules of initial API, the enthalpies of formation are -5.6 ± 1.4 kJ mol -1 and -3.9 ± 0.6 kJ mol -1 , respectively. In this case, the packing energy gain for the co-crystals is mainly caused by weak van der Waals API-BP and BP-BP interactions as the energy of API-API intermolecular interactions inside the clusters should be comparable to that of the pure APIs.…”

Nonamorphism in Flufenamic Acid and a New Record for a Polymorphic Compound with Solved Structures

“…During that time numerous investigations concerning the spectroscopic, conformational, and thermodynamic relationships among the proposed FFA poly-morphs have emerged. 8 Elucidation of the first crystal structure (form III) occurred in 1973, 9 and nearly ten years later the structure of a second form (form I) was reported. 10 The existence of polymorphism in this compound has offered a challenge for methodologies developed for polymorph discovery and control from the use of soluble additives 11 to epitaxy 12 and now polymer-induced heteronucleation (PIHn).…”