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

摘要

In this article, we conduct a comprehensive molecular relaxation study of amorphous Quinidine above and below the glass-transition temperature (T-g) 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 T-g, the width of the alpha relaxation (beta(KWW)), the temperature dependence of alpha-relaxation times (tau(alpha)), the fragility index (m), and the apparent activation energy of secondary gamma relaxation (Ea-gamma), were characterized. Above T-g (> 60 degrees C), a medium degree of nonexponentiality (beta(KWW) = 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 T-g (< 60 degrees C), one well-defined secondary gamma relaxation, with an apparent activation energy of Ea-gamma = 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 gamma 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-T-g experimental evaluations of the life expectancy of amorphous Quinidine by X-ray powder diffraction and differential scanning calorimetry. We show that the difference between T-g and the onset temperature for crystallization, T-c, which is 30 K, is sufficiently large to avoid recrystallization of amorphous Quinidine during 16 months of storage under ambient conditions.