Influence of Nucleation on Relaxation, Molecular Cooperativity, and Physical Stability of Celecoxib Glass.

Abstract

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 Tg, which could be understood by diffusionless crystal growth.