Rigid Nuclei and Flexible Nuclei: Appearance and Disappearance of Nuclei in Indomethacin Glass Revealed by a Long-Term Annealing Study

In this study, nucleation/crystallization behaviors of indomethacin glass are discussed with emphasis on the fate of nuclei, which is explained using a notion of "rigid" and "flexible" nuclei. The observation was made mainly by thermal analysis of indomethacin glass after long-term annealing at various temperatures. Formation of nuclei was evaluated by observing cold crystallization behaviors of the annealed glasses, as they should be dominated by the "nuclei form" produced in the glass. Nuclei of forms α and γ, which have opposite stability trends, were found to appear over a wide temperature range. The nuclei of form α were stable even in the presence of other crystal forms, whereas those of form γ were likely to be easily integrated into other crystals during their growth, which was explained by a notion of rigid and flexible nuclei. Moreover, unconventionally fast crystallization in the glass-transition region and the finding of a new crystal form are also reported.