Kinetics of Phase Transitions in Amorphous Carbamazepine: From Sub-Tg Structural Relaxation to High-Temperature Decomposition

Abstract

Thermokinetic characterization of amorphous carbamazepine was performed utilizing non-isothermal differential scanning calorimetry (DSC) and thermogravimetry (TGA). Structural relaxation of the amorphous matrix was described in terms of the Tool-Narayanaswamy-Moynihan model with the following parameters: Delta h* approximate to 200-300 kJ center dot mol(-1), beta = 0.57, x = 0.44. The crystallization of the amorphous phase was modeled using complex Sestak-Berggren kinetics, which incorporates temperature-dependent activation energy and degree of autocatalysis. The activation energy of the crystal growth was determined to be >320 kJ center dot mol(-1) at the glass transition temperature (T-g). Owing to such a high value, the amorphous carbamazepine is stable at T-g, allowing for extensive processing of the amorphous phase (e.g., self-healing of the quench-induced mechanical defects or internal stress). A discussion was conducted regarding the converse relation between the activation energies of relaxation and crystal growth, which is possibly responsible for the absence of sub-T-g crystal growth modes. The high-temperature thermal decomposition of carbamazepine proceeds via multistep kinetics, identically in both an inert and an oxidizing atmosphere. A complex reaction mechanism, consisting of a series of consecutive and competing reactions, was proposed to explain the second decomposition step, which exhibited a temporary mass increase. Whereas a negligible degree of carbamazepine degradation was predicted for the temperature characteristic of the pharmaceutical hot-melt extrusion (similar to 150 degrees C), the degradation risk during the pharmaceutical 3D printing was calculated to be considerably higher (1-2% mass loss at temperatures 190-200 degrees C).