Svoboda Roman
Department of Physical Chemistry, Faculty of Chemical Technology, University of Pardubice, nam. Cs Legii 565, 532 10 Pardubice, Czech Republic.
Molecules. 2025 Jan 4;30(1):175. doi: 10.3390/molecules30010175.
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 for the temperature shift, but with a significantly higher value of ~500 kJ·mol 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 α and β polymorphs, enantiotropic β → β' transformation, and β/β' → α 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 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.
采用非等温差示扫描量热法（DSC）和拉曼显微镜研究了非晶态硝苯地平中与粒径相关的结构弛豫和晶体生长过程。用Tool-Narayanaswamy-Moynihan模型描述了焓弛豫，弛豫运动在温度变化时表现出279 kJ·mol的活化能，但从玻璃态快速转变为过冷液态时获得的值明显更高，约为500 kJ·mol（后者与粘性流动的活化能一致）。这可能表明在缓慢加热和快速加热过程中表现出不同类型的弛豫动力学，只有一部分弛豫运动发生，其取决于给定温度范围和时间框架的参数。发现DSC记录的结晶过程很复杂，由四个子过程组成：α和β多晶型的初级晶体生长、双向β→β'转变以及β/β'→α再结晶。总体而言，发现硝苯地平易于在玻璃化转变温度以下发生快速的玻璃-晶体生长；非晶相的低温降解趋势随着粒径减小而显著增加（主要原因是表面和体相微裂纹以及机械诱导缺陷的数量增加）。DSC监测的结晶过程的活化能在100 - 125 kJ·mol范围内变化，这与显微镜测量的晶体生长活化能一致。考虑到在过渡区理论中解释的结构弛豫和晶体生长过程之间的潜在相关性，可能存在协作区域的复杂性和大小的某个阈值（由结构弛豫确定），如果超过该阈值可能导致晶体生长减慢。
