Polymorphs and solvates of felodipine: analysis of crystal structures and thermodynamic aspects of sublimation and solubility processes

Abstract

Single crystals of the crystallosolvates [felodipine + N-methylformamide] and [Fel + DMF] with 1 : 1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. The crystal structures were analyzed together with the already published felodipine forms I and II, and crystallosolvate [Fel + formamide]. The temperature dependence of saturated vapor pressure for polymorphic form I was obtained and thermodynamic characteristics of sublimation process with crystal lattice energy estimation were calculated. The fusion processes of solvatomorphs were investigated and their thermophysical parameters were determined. The differences in crystal lattice energy of the three crystallosolvates and those of the unsolvated forms were obtained by solution calorimetry technique. The impact of the “guest”/solvent molecules on the crystal lattice energy of the crystallosolvates was analyzed. The dissolution kinetics of felodipine form I, [Fel + FA], [Fel + N-Me-FA] and [Fel + DMF] in water was investigated. The solution calorimetric and solubility experiments were used to obtain the thermodynamic characteristics of phase transitions (crystallosolvate → unsolvated phase).