Kinetic Study for Comprehensive Understanding of Solid-State Polymorphic Transitions of Nicotinamide/Pimelic Acid Cocrystals

Abstract

Solid-state polymorphic transition (SSPT) has been regarded as an interesting research subject for a long time, but kinetics and the mechanism of these phase transitions are still not fully understood. Particularly, kinetic studies on the SSPT process of cocrystals are not widely reported even though extensive novel cocrystal polymorphs have been discovered over the recent decades. Herein we presented a comprehensive kinetic study of the enantiotropic polymorphic system of 1:1 nicotinamide (NA)–pimelic acid (PA) cocrystals with the combination of various analytical methods. Bulk kinetic studies conducted with powder X-ray diffraction and differential scanning calorimetry indicated that both directions of SSPT (form 1 ↔ form 2) occur by a nucleation and growth mechanism. In addition, large activation energy barriers of form 1 → form 2 with a wide range (337.1–514.2 kJ mol–1) and variations in the onset transition temperature were observed, depending on the crystal conditions. In situ atomic force microscopy analysis was also carried out to monitor the surface morphology change at the nanoscale to supplement the bulk kinetics.

In situ investigation of controlled polymorphism in mechanochemistry at elevated temperature

“…This slow conversion of Form II → Form I at room temperature has been previously noted. 42 In full agreement with stability test experiments, slurrying 1 : 1 mixtures of Form I and Form II in a range of solvents also led to formation of pure Form I , ESI S1.3,† lending support to the thermodynamic stability of Form I over Form II at room temperature. Moreover, we note previous high temperature slurry experiments, which indicated that the reverse transformation of Form I → Form II occurs when slurried > 85 °C.…”

“…Form I of NA:PA is reported to be thermodynamically stable under ambient conditions, with Form II becoming the stable form at elevated temperatures. 40,42 Both forms can be prepared by ball milling: Form I is reportedly obtained by neat grinding at ambient temperature 40 and, as we have found in this work (ESI S2 †), Form II is obtained by ball milling at elevated temperatures. Consistent with the literature, 40 our differential scanning calorimetry (DSC) measurements of Form I, Fig.…”

Applications of Kinetic Methods in Thermal Analysis: A Review

“…The kinetic parameters of the solid-state phase transformation reactions such as mineral, alloy glass and pharmaceutical ingredient phase transformations are always obtained via using non-isothermal technique. [54][55][56][57][58][59][60] Except the Kissinger and Ozawa methods, a special method that only suitable for investigating heterogeneous solid-state reactions was developed based on Avrami law (Equation 40), which could be used to describe most solid phase transformation reactions.…”

Solid-State Phase Transition of Agomelatine–Phosphoric Acid Molecular Complexes along the Salt–Cocrystal Continuum: Ab Initio Powder X-ray Diffraction Structure Determination and DFT-D2 Analysis

“…Therefore, a more pertinent description would be the RTform is more stable below transition temperature (42 °C), and HT is more stable above transition temperature and the activation energy of RT-form ↔ HT-form kinetics is on the order of 30−40 kJ/mol. 38 The magnitude of activation energy for the AGL-P system is significantly less as compared to a (1:1) nicotine−pimelic acid cocrystal, 83 which was reported to exhibit a solid-state phase transition via nucleation and growth mechanism, unlike the current system. In summary, all this information refers to the point that the interplay of thermodynamic stability and kinetic activation barrier is very delicate for the AGL-P system.…”