Physical stability is one of the main challenges when developing robust amorphous pharmaceutical formulations. This article reports fast crystal growth behaviors of the γ and α forms of indomethacin (IMC) initiated by bubbles in the interior of a supercooled liquid. Bubble-induced crystal growth of γ-IMC exhibits approximately the same kinetics as its surface crystal growth, supporting the view that bubble-induced crystal growth is a surface-facilitated process. In contrast, the rates of bubble-induced crystal growth of α-IMC are much faster than those of its surface crystal growth. These results indicate that the bubble-induced crystal growth not only depends on the interface created by the bubble but also strongly correlates with the true cavitation of the bubble. Moreover, bubble-induced fast crystal growth of γ- and α-IMC can be terminated at different temperatures by cooling. These outcomes are meaningful for the in-depth understanding of physical stability and pre-formulation study of amorphous pharmaceutical solids showing surface-facilitated crystal growth.

中文翻译：

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过冷液体中吲哚美辛多晶型物的气泡诱导快速晶体生长

在开发稳健的无定形药物制剂时，物理稳定性是主要挑战之一。本文报告了由过冷液体内部的气泡引发的 γ 和 α 形式的吲哚美辛 (IMC) 的快速晶体生长行为。γ-IMC 的气泡诱导晶体生长表现出与其表面晶体生长大致相同的动力学，支持气泡诱导晶体生长是表面促进过程的观点。相比之下，α-IMC 的气泡诱导晶体生长速度比其表面晶体生长速度快得多。这些结果表明气泡诱导的晶体生长不仅取决于气泡产生的界面，而且还与气泡的真实空化密切相关。而且，γ-和α-IMC 的气泡诱导快速晶体生长可以通过冷却在不同温度下终止。这些结果对于深入了解物理稳定性和显示表面促进晶体生长的无定形药物固体的预制剂研究具有重要意义。