Understanding the α relaxation of amorphous celecoxib: From macro to nano structures

Recently, celecoxib has emerged as an outstanding candidate for therapeutic repurposing in oncology, psychiatry, and infectiology. Nevertheless, there are huge spatiotemporal gaps among experimental, computational, and theoretical studies on the molecular dynamics of celecoxib in the amorphous phase. Inspired by the elastically collective nonlinear Langevin equation, we develop a zero-adjustable-parameter approach to decipher the structural relaxation of amorphous celecoxib at various time and size scales. Hard-sphere fluids are utilized to evaluate how local interactions, collective distortions, and density fluctuations affect activated hopping events in macroscopic and nanoscopic systems. These ideal spheres are connected with real molecules via a simple chemical mapping. The transition between super-Arrhenius and Arrhenius-like behaviors is also considered through the jump of thermal expansivity at the vitrification point. On that basis, we can simultaneously explain experimental data for melt-quenched, spin-coated, and vapor-deposited samples at the quantitative level. Some open predictions of recrystallization kinetics in different disordered structures are also provided to facilitate the search for stabilization strategies. Our theoretical results would actively contribute to the development of celecoxib-based formulations in supercooled, vitrified, and confined states.