This study ce
nters o
n the use of i
nelastic
neutro
n scatteri
ng as a
n alter
native tool for physical characterizatio
n of solid pharmaceutical drugs. O
n the basis of such approach, relaxatio
n processes i
n the pharmaceutical compou
nd phe
naceti
n (
p-ethoxyaceta
nilide, C
10H
13NO
2) were evide
nced o
n heati
ng betwee
n 2 a
nd 300 K. By evaluati
ng the mea
n-square displaceme
nt obtai
ned from the elastic fixed wi
ndow approach, usi
ng the
neutro
n backscatteri
ng tech
nique, a crossover of the molecular fluctuatio
ns betwee
n harmo
nic a
nd
no
nharmo
nic dy
namical regimes arou
nd 75 K was observed. From the temperature depe
nde
nce of the quasi-elastic li
ne-width, summed over the total Q ra
nge explored by the time-of-flight tech
nique, it was possible to attribute the o
nset of this a
nharmo
nicity to methyl group聽rotatio
ns. Fi
nally, usi
ng de
nsity fu
nctio
nal theory-based methods, we were able to calculate the lattice vibratio
ns i
n the harmo
nic approximatio
n. The overall spectral profile of the calculated partial co
ntributio
ns to the ge
neralized de
nsity of states compares satisfactorily to the experime
ntal spectra i
n the regio
n of the lattice modes where the i
ntermolecular i
nteractio
ns are expected to play a
n importa
nt role. This study co
ntributes to u
ndersta
ndi
ng the relatio
nships betwee
n i
ntermolecular hydroge
n bo
nds, i
ntramolecular dy
namics, a
nd co
nformatio
nal flexibility i
n pharmaceuticals o
n a molecular level, which ca
n help i
n evaluati
ng phase stability with respect to temperature variatio
ns o
n processi
ng or o
n storage, a
nd is related to co
ntrol of polymorphism a
nd pseudopolymorphism.
Keywords:
n/doSearch?action=search&searchText=methyl+dynamics&qsSearchArea=searchText">methyl dynamics; n/doSearch?action=search&searchText=activation+energy&qsSearchArea=searchText">activation energy; n/doSearch?action=search&searchText=density+functional+theory%5C-based+methods&qsSearchArea=searchText">density functional theory-based methods; n/doSearch?action=search&searchText=neutron+scattering&qsSearchArea=searchText">neutron scattering