Changes in Physical Stability of Supercooled Etoricoxib after Compression.

In the case of formulations with amorphous active pharmaceutical ingredients the risk of pressure-induced recrystallization should be carefully considered. We reported here that supercooled etoricoxib (ETB), which was found as a relatively stable system with low crystallization tendency at atmospheric pressure, crystallized quickly after compression. The observed strong pressure-dependence of the induction period suggests that during compression the first step of crystallization that is nucleation may be accelerated. To overcome the experimental challenge associated with studies at elevated temperatures and high pressures we applied broadband dielectric spectroscopy. Dielectric measurements gave us detailed insight into crystallization kinetics of ETB at varying ( T, p) conditions corresponding to the supercooled liquid state of a drug. We found that pressure-induced recrystallization of supercooled ETB, constituting a serious impediment from a technological point of view, can be efficiently inhibited when amorphous solid dispersion containing ETB and polymer polyvinylpyrrolidone PVP (10% w/w) was prepared. Besides, we performed the comprehensive analysis of molecular dynamics of both systems at elevated pressure to address some fundamental issues related to the pressure sensitivity of their supercooled dynamics.