Understanding how liquid dynamics govern crystallization is critical for maintaining the physical stability of amorphous pharmaceutical formulations. In the present study, griseofulvin (GSF), a classic antifungal drug, was used as the model system to investigate the correlations between crystal growth kinetics and liquid dynamics. The temperature dependence of the kinetic part of the bulk crystal growth in a supercooled liquid of GSF was weaker than that of the structural relaxation time τ_α and scaled as τ_α^−0.69. In the glassy state, GSF exhibited the glass‐to‐crystal (GC) growth behavior, whose growth rate was too fast to be under the control of the α‐relaxation process. Moreover, from the perspective of τ_α, the GC growth of GSF also satisfied the general condition for GC growth to exist: D/u < 7 pm, where D is the diffusion coefficient and u the speed of crystal growth. Also compared were the fast surface crystal growth rates u_s and surface relaxation times τ_surface predicted by the random first‐order transition theory. Here, the surface crystal growth rate u_s of GSF exhibited a power‐law dependence upon the surface structural relaxation time: u_s ∝ τ_surface^−0.71, which was similar to that of the bulk growth rate and τ_α. These findings are important for understanding and predicting the crystallization of amorphous pharmaceutical solids both in the bulk and at the surface.

中文翻译：

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扩散控制和“无扩散”晶体生长：灰黄霉素的液体动力学与生长动力学之间的关系

了解液体动力学如何控制结晶对于维持无定形药物制剂的物理稳定性至关重要。在本研究中，灰黄霉素（GSF），一种经典的抗真菌药物，被用作模型系统来研究晶体生长动力学和液体动力学之间的相关性。在过冷液体GSF的块状晶体生长的动力学部分的温度依赖性比的结构弛豫时间τ的较弱的_α和缩放为τ _α ^-0.69。在玻璃态下，GSF表现出玻璃到晶体（GC）的生长行为，其生长速度太快，无法在α松弛过程的控制下。而且，从τ的角度_α，GSF的GC生长也满足存在GC生长的一般条件：D / u <7 pm，其中D是扩散系数，u是晶体生长的速度。也比较有快速表面晶体生长速率ù _š和表面弛豫时间τ_表面由随机第一级转变理论所预测的。在此，表面晶体生长速率Ù _š GSF表现出在表面结构弛豫时间幂律依赖：ü_小号ατ_表面^-0.71，这是类似于散装增长率和τ _α。这些发现对于理解和预测无定形药物固体在本体和表面的结晶都是重要的。