Thermally Induced Phenomena in Amorphous Nifedipine: The Correlation Between the Structural Relaxation and Crystal Growth Kinetics

Abstract

The particle size-dependent processes of structural relaxation and crystal growth in amorphous nifedipine were studied by means of non-isothermal differential scanning calorimetry (DSC) and Raman microscopy. The enthalpy relaxation was described in terms of the Tool-Narayanaswamy-Moynihan model, with the relaxation motions exhibiting the activation energy of 279 kJ.mol(-1) for the temperature shift, but with a significantly higher value of similar to 500 kJ.mol(-1) being obtained for the rapid transition from the glassy to the undercooled liquid state (the latter is in agreement with the activation energy of the viscous flow). This may suggest different types of relaxation kinetics manifesting during slow and rapid heating, with only a certain portion of the relaxation motions occurring that are dependent on the parameters of a given temperature range and time frame. The DSC-recorded crystallization was found to be complex, consisting of four sub-processes: primary crystal growth of alpha(p) and beta(p) polymorphs, enantiotropic beta(p) -> beta(p)' transformation, and beta(p)/beta(p)' -> alpha(p) recrystallization. Overall, nifedipine was found to be prone to the rapid glass-crystal growth that occurs below the glass transition temperature; a tendency of low-temperature degradation of the amorphous phase markedly increased with decreasing particle size (the main reason being the increased number of surface and bulk micro-cracks and mechanically induced defects). The activation energies of the DSC-monitored crystallization processes varied in the 100-125 kJ.mol(-1) range, which is in agreement with the microscopically measured activation energies of crystal growth. Considering the potential correlations between the structural relaxation and crystal growth processes interpreted within the Transition Zone Theory, a certain threshold in the complexity and magnitude of the cooperating regions (as determined from the structural relaxation) may exist, which can lead to a slow-down of the crystal growth if exceeded.