Research Center for Macromolecules and Biomaterials, National Institute for Materials Science, 1-1 Namiki, Tsukuba, Ibaraki 305-0044, Japan.
Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8577, Japan.
Mol Pharm. 2024 Apr 1;21(4):1794-1803. doi: 10.1021/acs.molpharmaceut.3c01116. Epub 2024 Feb 24.
Although nucleation is considered the first step in the crystallization of glass materials, the structure and properties of the nuclei are not understood well. Influence of nucleation on the structure and dynamics of celecoxib glass was evaluated in this study. The nuclei for Form III were induced by annealing the glass at freezing temperature, and their impact on the relaxation behavior was investigated using thermal analysis and broadband dielectric spectroscopy to find accelerated α relaxation and suppressed β relaxation. In addition, observed after nucleation was a decrease in cooperativity of the molecular motion, presumably because of the appearance of void spaces in the glass structure. During long-term isothermal crystallization studies, crystal growth to Form III was accelerated in the presence of the nuclei, whereas this effect was less remarkable when a different crystal form dominated the crystallization behavior. These observations should provide more detailed insights into the nucleation mechanism and impact of nucleation on molecular dynamics including physical stability of pharmaceutical glasses. In addition, discussed is the remarkable acceleration of the crystallization rate of the celecoxib glass just below its , which could be understood by diffusionless crystal growth.
尽管成核被认为是玻璃材料结晶的第一步，但核的结构和性质还没有得到很好的理解。本研究评估了成核对塞来昔布玻璃结构和动力学的影响。通过在冷冻温度下退火玻璃来诱导 III 型晶核，并使用热分析和宽频介电谱研究它们对弛豫行为的影响，以发现加速的α弛豫和抑制的β弛豫。此外，成核后观察到分子运动协同性降低，可能是由于玻璃结构中出现了空隙。在长期等温结晶研究中，晶核的存在加速了 III 型晶体的生长，而当另一种晶体形式主导结晶行为时，这种影响就不那么显著。这些观察结果应该为成核机制以及成核对包括药物玻璃物理稳定性在内的分子动力学的影响提供更详细的见解。此外，还讨论了塞来昔布玻璃在其玻璃化转变温度以下的结晶速率的显著加速，这可以通过无扩散晶体生长来理解。
