title: Molecular Relaxations in Supercooled Liquid and Glassy States of Amorphous Quinidine: Dielectric Spectroscopy and Density Functional Theory Approaches.
abstract: 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.
authors.affiliation: Normandie Univ, Laboratoire SMS - EA3233, Univ Rouen , F-76821 Mont Saint Aignan, France.|AMME-LECAP EA 4528 International Lab, Avenue de l'Université, BP12, Normandie Univ, Université de Rouen Normandie , 76801 St Etienne du Rouvray, France.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Schammé
authors.affiliation: Normandie Univ, Laboratoire SMS - EA3233, Univ Rouen , F-76821 Mont Saint Aignan, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Mignot
authors.affiliation: Normandie Univ, Laboratoire SMS - EA3233, Univ Rouen , F-76821 Mont Saint Aignan, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Couvrat
authors.affiliation: COBRA UMR 6014 and FR 3038, Normandie Univ, Université de Rouen, INSA Rouen, CNRS , F-76821 Mont Saint Aignan, Cedex, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Tognetti
authors.affiliation: COBRA UMR 6014 and FR 3038, Normandie Univ, Université de Rouen, INSA Rouen, CNRS , F-76821 Mont Saint Aignan, Cedex, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Joubert
authors.affiliation: Normandie Univ, Laboratoire SMS - EA3233, Univ Rouen , F-76821 Mont Saint Aignan, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dupray
authors.affiliation: AMME-LECAP EA 4528 International Lab, Avenue de l'Université, BP12, Normandie Univ, Université de Rouen Normandie , 76801 St Etienne du Rouvray, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Delbreilh
authors.affiliation: AMME-LECAP EA 4528 International Lab, Avenue de l'Université, BP12, Normandie Univ, Université de Rouen Normandie , 76801 St Etienne du Rouvray, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Dargent
authors.affiliation: Normandie Univ, Laboratoire SMS - EA3233, Univ Rouen , F-76821 Mont Saint Aignan, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Coquerel