Nucleation and crystallization of celecoxib glass: Impact of experience of low temperature on physical stability

Abstract

Although the amorphous state has been successfully employed for developing many poorly soluble drugs, a sufficient understanding of the crystallization behavior of pharmaceutical glass has not yet been achieved. This paper describes the importance of a comprehension of the nucleation process for controlling the crystallization of pharmaceutical glasses using celecoxib (CEL) as a model compound. The optimum temperature for nucleation of CEL glass was found to be ca. −50 °C by exploratory isothermal annealing at various temperatures. After annealing, cold crystallization was observed in a reproducible manner only when the nuclei were created at sufficiently low temperatures. This observation indicates the importance of a knowledge of the optimum nucleation temperature, which may be very low temperature, when amorphous solid dispersions are stored.