Application of Incoherent Inelastic Neutron Scattering in Pharmaceutical Analysis: Relaxation Dynamics in Phenacetin | Sciact - CRIS-system of Boreskov Institute of Catalysis

Application of Incoherent Inelastic Neutron Scattering in Pharmaceutical Analysis: Relaxation Dynamics in Phenacetin Full article

Journal

Molecular Pharmaceutics
ISSN: 1543-8384 , E-ISSN: 1543-8392

Output data

Year: 2012, Volume: 9, Number: 9, Pages: 2434-2441 Pages count : 8 DOI: 10.1021/mp2006032

Tags

activation energy; density functional theory-based methods; methyl dynamics; neutron scattering

Authors

Bordallo Heloisa N. ¹ , Zakharov Boris A. ^2,3 , Boldyreva Elena V. ^2,3 , Johnson Mark R. ⁴ , Koza Michael Marek ⁴ , Seydel Tilo ⁴ , Fischer Jennifer ⁵

Affiliations

1	Niels Bohr Institute University of Copenhagen, Universitetsparken 5, 2100, Copenhagen, Denmark
2	REC-008 Novosibirsk State University, ul. Pirogova 2, Novosibirsk 630090, Russia
3	Institute of Solid State Chemistry and Mechanochemistry, ul. Kutateladze 18, Novosibirsk 630128, Russia
4	Institut Laue-Langevin, BP 156, 38042 Grenoble Cedex 9, France
5	Forschungszentrum Jülich, Institut of Complex Systems, Marie Göcking, ICS-3 52425 Jülich, Germany

This study centers on the use of inelastic neutron scattering as an alternative tool for physical characterization of solid pharmaceutical drugs. On the basis of such approach, relaxation processes in the pharmaceutical compound phenacetin (p-ethoxyacetanilide, C10H13NO2) were evidenced on heating between 2 and 300 K. By evaluating the mean-square displacement obtained from the elastic fixed window approach, using the neutron backscattering technique, a crossover of the molecular fluctuations between harmonic and nonharmonic dynamical regimes around 75 K was observed. From the temperature dependence of the quasi-elastic line-width, summed over the total Q range explored by the time-of-flight technique, it was possible to attribute the onset of this anharmonicity to methyl grouprotations. Finally, using density functional theory-based methods, we were able to calculate the lattice vibrations in the harmonic approximation. The overall spectral profile of the calculated partial contributions to the generalized density of states compares satisfactorily to the experimental spectra in the region of the lattice modes where the intermolecular interactions are expected to play an important role. This study contributes to understanding the relationships between intermolecular hydrogen bonds, intramolecular dynamics, and conformational flexibility in pharmaceuticals on a molecular level, which can help in evaluating phase stability with respect to temperature variations on processing or on storage, and is related to control of polymorphism and pseudopolymorphism. © 2012 American Chemical Society.

Bordallo H.N. , Zakharov B.A. , Boldyreva E.V. , Johnson M.R. , Koza M.M. , Seydel T. , Fischer J.
Application of Incoherent Inelastic Neutron Scattering in Pharmaceutical Analysis: Relaxation Dynamics in Phenacetin
Molecular Pharmaceutics. 2012. V.9. N9. P.2434-2441. DOI: 10.1021/mp2006032 WOS Scopus ANCAN OpenAlex

Submitted:	Nov 25, 2011
Accepted:	Jul 23, 2012
Published online:	Aug 9, 2012
Published print:	Sep 4, 2012

Web of science:	WOS:000308263700006
Scopus:	2-s2.0-84865966101
Chemical Abstracts:	2012:1069852
Chemical Abstracts (print):	157:365818
OpenAlex:	W2324438843

DB	Citing
Web of science	16
Scopus	15
OpenAlex	16