(330a) Kinetic Study for Comprehensive Understanding of Solid State Phase Transitions of Nicotinamide/Pimelic Acid Co-Crystals

For many material, understanding of solid-state phase transformation (SSPT) is beneficial not only for the fundamental reasons but in the case of pharmaceuticals, for the avoidance of product issues due to the change in physicochemical properties. Despite the fact that this topic has been regarded as an interesting research subject, the mechanism of SSPT is still not fully understood. It is especially surprising that most co-crystal studies have been biased to identify novel polymorphs of co-crystals and to reveal their crystal structures with very little effort on understanding the kinetics. Herein we presented the comprehensive kinetic study of the polymorphic system of 1:1 Nicotinamide (NA)-pimelic acid (PA) co-crystals with the combination of different experimental techniques. The bulk kinetic modeling with powder x-ray diffraction (PXRD) indicated that polymorphic transition in the solid state of NA/PA co-crystals occurs by nucleation and growth mechanism, and no phase separation of components in the co-crystals was observed during the transitions. In-situ atomic force microscopy (AFM) observation was performed to monitor the surface morphology change during transitions at the nanoscale to supplement the bulk kinetic analysis.

Differential scanning calorimetry (DSC) thermal analysis was also conducted to obtain insight into the dependence of the crystal sizes and the defects on the kinetics of transitions. The deviation in the activation energies of SSPT for both powder and polycrystalline form were achieved respectively. In addition, the change in the tendency of transition point with increase in the number of transition recycling was observed (initially decrease then after increases), which might be attributed to the change in crystal sizes and defect inclusions during the transition process.