Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches

In this article, we conduct a comprehensive
molecular relaxation
study of amorphous Quinidine above and below the glass-transition
temperature (Tg) through broadband dielectric
relaxation spectroscopy (BDS) experiments and theoretical density
functional theory (DFT) calculations, as one major issue with the
amorphous state of pharmaceuticals is life expectancy. These techniques
enabled us to determine what kind of molecular motions are responsible,
or not, for the devitrification of Quinidine. Parameters describing
the complex molecular dynamics of amorphous Quinidine, such as Tg, the width of the α relaxation (βKWW), the temperature dependence of α-relaxation times
(τα), the fragility index (m), and the apparent activation energy of secondary γ relaxation
(Ea‑γ), were characterized.
Above Tg (> 60 °C), a medium degree
of nonexponentiality (βKWW = 0.5) was evidenced.
An intermediate value of the fragility index (m =
86) enabled us to consider Quinidine as a glass former of medium fragility.
Below Tg (< 60 °C), one well-defined
secondary γ relaxation, with an apparent activation energy of Ea‑γ = 53.8 kJ/mol, was reported.
From theoretical DFT calculations, we identified the most reactive
part of Quinidine moieties through exploration of the potential energy
surface. We evidenced that the clearly visible γ process has
an intramolecular origin coming from the rotation of the CH­(OH)­C9H14N end group. An excess wing observed in amorphous
Quinidine was found to be an unresolved Johari–Goldstein relaxation.
These studies were supplemented by sub-Tg experimental evaluations of the life expectancy of amorphous Quinidine
by X-ray powder diffraction and differential scanning calorimetry.
We show that the difference between Tg and the onset temperature for crystallization, Tc, which is 30 K, is sufficiently large to avoid recrystallization
of amorphous Quinidine during 16 months of storage under ambient conditions.