1 research outputs found
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
(<i>T</i>, <i>p</i>) 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