Title :

Investigation by Dielectric Relaxation Spectroscpy and Molecular Dynamics simulations of the influence on amorphous Terfenadine dynamics of strongly Hydrogen-bonded water molecules

Author(s) :

Bama, Jeanne-Annick [Auteur]
Dudognon, Emeline [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207
Affouard, Frédéric [Auteur]
Unité Matériaux et Transformations (UMET) - UMR 8207

Conference title :

GDR 2035 SolvATE : Journées SolvATE 2021

City :

Villeneuve d'Ascq

Country :

France

Start date of the conference :

2021-12-09

HAL domain(s) :

Physique [physics]/Matière Condensée [cond-mat]/Science des matériaux [cond-mat.mtrl-sci]
Physique [physics]/Matière Condensée [cond-mat]/Matière Molle [cond-mat.soft]
Physique [physics]/Matière Condensée [cond-mat]/Systèmes désordonnés et réseaux de neurones [cond-mat.dis-nn]

English abstract : [en]

Terfenadine (TFD), C32H41NO2, is an active pharmaceutical ingredient that is poorly soluble in water in the crystalline state but, remarkably, it can absorb a few amount of water (~2%) in the amorphous state. By means of ...
Show more >Terfenadine (TFD), C32H41NO2, is an active pharmaceutical ingredient that is poorly soluble in water in the crystalline state but, remarkably, it can absorb a few amount of water (~2%) in the amorphous state. By means of complementary Dynamic Relaxation Spectroscopy (DRS) and Molecular Dynamics simulations (MD), we investigate [1] the impact of such low water concentration on the dynamics of amorphous TFD, in particular on localised intramolecular mobilities the microscopic origin of which often remains unclear while they may have impacts on sub-Tg re-crystallisation. By DRS, we evidence that these residual water molecules give rise to a new secondary relaxation mode in the glassy state. It originates through the motion of water molecules Hydrogen-bonded to TFD molecules and this dynamic is coupled to the intramolecular motions of the flexible central part of TFD molecules. MD computations and analyses of the hydrogen bonding interaction (HB) allows to understand and rationalise these results. They establish that these water molecules can be divided in two categories: - a majority of weakly or moderately HB water molecules to TFD which are easily removed from the system by usual drying process, - a minority of much more highly HB water molecules strongly interacting with the OH hydroxyl group and the nitrogen atom located in the central part of the TFD molecules, creating some kind of bridges between TFD molecules. These strongly HB water molecules localise themselves in small pockets in empty space existing between the TFD molecules due to the poor packing of the glassy state and are much more difficult to remove without a specific treatment. This project has received funding from the Interreg 2 Seas program 2014-2020 co-funded by the European Regional Development Fund (FEDER) under subsidy contract 2S01-059_IMODE. REFERENCES [1] Bama, J-A., Dudognon, E., Affouard, F. “Impact on low Concentration of Strongly Hydrogen-Bonded Water Molecules on the Dynamics of Amorphous Terfenadine: Insights from Molecular Dynamics Simulations and Dielectric Relaxation Spectroscopy”, J. Phys. Chem. B 125, 11292-11307 (2021)Show less >

Language :

Anglais

Peer reviewed article :

Non

Audience :

Nationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
CNRS
INRA
ENSCL

Collections :

• Unité Matériaux et Transformations (UMET) - UMR 8207

Research team(s) :

Matériaux Moléculaires et Thérapeutiques

Submission date :

2022-01-28T16:03:11Z
2022-01-31T10:33:17Z