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 |
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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 | ||||||||||
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Abstract:
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.
Cite:
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
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
Dates:
Submitted: | Nov 25, 2011 |
Accepted: | Jul 23, 2012 |
Published online: | Aug 9, 2012 |
Published print: | Sep 4, 2012 |
Identifiers:
Web of science | WOS:000308263700006 |
Scopus | 2-s2.0-84865966101 |
Chemical Abstracts | 2012:1069852 |
Chemical Abstracts (print) | 157:365818 |
OpenAlex | W2324438843 |