Energetic Aspects of Diclofenac Acid in Crystal Modifications and in Solutions—Mechanism of Solvation, Partitioning and Distribution

ABSTRACTTemperature dependency of saturated vapor pressure and heat capacity for the diclofenac acid (Form II) were measured and thermodynamic functions of sublimation calculated (ΔGsub298 = 49.3 kJ · mol−1; ΔHsub298 = 115.6 ± 1.3 kJ · mol−1; ΔSsub298 = 222 ± 4 J · mol−1 · K−1). Crystal polymorphic Forms I (P21/c) and II (C2/c) of diclofenac acid have been prepared and characterized by X-ray diffraction experiments. The difference between crystal lattice energies of the two forms were obtained by solution calorimetry: ΔΔHsol(I → II) = 1.6 ± 0.4 kJ · mol−1. Temperature dependencies of the solubility in buffers with pH 2.0 and 7.4, n-octanol and n-hexane were measured. The thermodynamic functions of solubility, solvation, and transfer processes were deduced. Specific and non-specific solvation terms were distinguished using the transfer from the “inert” n-hexane to the other solvents. The transfer of diclofenac acid molecules from the buffers to n-octanol (partitioning and distribution) is an entropy driven process.