Crystal Growth of Celecoxib from Amorphous State: Polymorphism, Growth Mechanism, and Kinetics

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The crystal growth kinetics of amorphous celecoxib (CEL), an anti-inflammatory BCS class II drug, was systematically investigated for developing effective stabilization strategies to enhance solubility of CEL. In comparison to the bulk, the surface crystal growth was much faster, e.g., ?80-fold higher at (Tg +3) °C. Both surface and bulk growths near and below Tg were accelerated over those predicted from a diffusion-limited process, which are attributed to solid-state crystal growth and glass-to-crystal growth mechanisms, respectively. These two growth modes were disrupted by fluidity differently upon heating, with a much wider transition zone on the surface in comparison to the bulk. In fact, the surface transition zone of CEL is the widest among all systems studied so far. The phenomenon of cross-nucleation was also observed between CEL polymorphs, forms I and III, which exhibited different crystal growth rates in the diffusion-controlled region both on the surface and in the bulk.

Original languageEnglish (US)
Pages (from-to)3592-3600
Number of pages9
JournalCrystal Growth and Design
Issue number6
StatePublished - Jun 5 2019

Bibliographical note

Funding Information:
K.W. thanks the Undergraduate Research Opportunities Program (UROP) of the University of Minnesota and the Edward G. Rippie Fellowship and David Grant Fellowship of the University of Minnesota Department of Pharmaceutics for partial financial support. The authors also thank Jiangnan Dun for help in taking SEM photographs. Parts of this work were carried out in the Characterization Facility, University of Minnesota, which receives partial support from the NSF through the MRSEC program.

Publisher Copyright:
© 2019 American Chemical Society.


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