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Bubble-induced fast crystal growth of indomethacin polymorphs in a supercooled liquid
Journal of Applied Crystallography  (IF3.304),  Pub Date : 2021-08-18, DOI: 10.1107/s1600576721007068
Qin Shi, Fang Li, Jia Xu, Lingling Wu, Junbo Xin, Hao Chen, Bai Ling

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.