Polymorphism and phase transformations of a cocrystal of nicotinamide and pimelic acid

Abstract

With the overwhelming interest in pharmaceutical cocrystals, studies concerning polymorphism in multi-component crystals are becoming increasingly valuable. We present herein our polymorphism studies of a 1 : 1 cocrystal involving nicotinamide and pimelic acid. The polymorphs were unequivocally characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and hot-stage microscopy. Crystal structure analysis revealed different conformations of nicotinamide and pimelic acid. Thermal analysis and solid-state grinding experiments suggested an enantiotropic relationship between the polymorphs. Slurry experiments on powder samples of polymorphs revealed that the thermodynamic transition temperature lies between 85 and 90 °C, with Form 1 being the stable form at room temperature.