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Acoustic-like dynamics of amorphous drugs in the THz regime.

Pogna EA, Rodríguez-Tinoco C, Krisch M, Rodríguez-Viejo J, Scopigno T - Sci Rep (2013)

Bottom Line: The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals.We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation.Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Fisica, Universitá di Roma La Sapienza, Rome, Italy.

ABSTRACT
The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals. We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation. Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively.

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Related in: MedlinePlus

Selection of room temperature inelastic x-ray scattering spectra of glassy Indomethacin at fixed exchanged momentum Q along with the best fits (red line) described in section Methods.The energy resolution (green line) normalized to the elastic peak (elastic component) is also reported, while the blue line corresponds to the inelastic, damped harmonic oscillator contribution. The experimental error is within the symbol.
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f2: Selection of room temperature inelastic x-ray scattering spectra of glassy Indomethacin at fixed exchanged momentum Q along with the best fits (red line) described in section Methods.The energy resolution (green line) normalized to the elastic peak (elastic component) is also reported, while the blue line corresponds to the inelastic, damped harmonic oscillator contribution. The experimental error is within the symbol.

Mentions: The x-ray diffraction measurements on Indomethacin (IMC) and Celecoxib (CXB), detected with a photodiode embedded in the inelastic analyzers bench, show a broad main peak centered at and , confirming the amorphous nature of the samples (see Fig. 1). A selection of inelastic x-ray scattering spectra of IMC in the glassy state are shown in Fig. 2 at five fixed values of exchanged momentum Q. They are dominated by an intense elastic feature due to the non-ergodicity of the glass, i.e. to density fluctuations frozen by the structural arrest. At both sides of the elastic component, well defined inelastic peaks are observed at finite energy transfer. The energy position ℏΩ of the inelastic peaks corresponds to the energy of the acoustic modes of momentum Q, while the peak width gives access to the life time of density fluctuations, i.e. to the sound attenuation Γ(Q). The IXS spectrum can be modeled by a delta function, describing the elastic component, combined with the power spectrum of a damped harmonic oscillator (DHO, corrected to account for the detailed balance condition) representing the inelastic scattering. Both contributions have been convoluted with the instrument response function (green line in Fig. 2, for further details see the Methods section) to correctly reproduce the experimental data. We note that the inelastic contributions to the total scattered intensity due to the Brillouin inelastic scattering from vibrational density fluctuations are well reproduced (blue line in Fig. 2). The energy position of the Brillouin component increases with exchanged momentum Q, testifying the propagating nature of the probed excitations. This general finding proves the existence of THz hypersonic waves in amorphous IMC and CXB. Since only one inelastic contribution is resolved at each Q value, the vibrational excitations can unambiguously be ascribed to a single longitudinal acoustic phonon branch. The inelastic component becomes less and less visible as the exchanged momentum increases, due to an increase of the acoustic attenuation (broadening of the inelastic features) and to the increase of the elastic component which follows the static structure factor S(Q) (see Fig. 1). The energy dispersion curves, ℏΩ(Q), of the longitudinal acoustic phonon are linear in the long wavelength-limit Q ≤ 3 nm−1; they then bend down reaching a maximum at Q around half of Qp, highly suggestive of the existence of a pseudo-Brillouin zone (see Fig. 3). The plateau in the phonon dispersion of Indomethacin indicates the end of the propagating behavior while in the Celecoxib the group velocity remains finite up to 0.8 Qp. The acoustic attenuation Γ shows for both samples a power law dependence on the acoustic frequency Ω(Q) compatible with the quadratic law found in different classes of glassy systems in a similar frequency regime (see Fig. 4).


Acoustic-like dynamics of amorphous drugs in the THz regime.

Pogna EA, Rodríguez-Tinoco C, Krisch M, Rodríguez-Viejo J, Scopigno T - Sci Rep (2013)

Selection of room temperature inelastic x-ray scattering spectra of glassy Indomethacin at fixed exchanged momentum Q along with the best fits (red line) described in section Methods.The energy resolution (green line) normalized to the elastic peak (elastic component) is also reported, while the blue line corresponds to the inelastic, damped harmonic oscillator contribution. The experimental error is within the symbol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3757359&req=5

f2: Selection of room temperature inelastic x-ray scattering spectra of glassy Indomethacin at fixed exchanged momentum Q along with the best fits (red line) described in section Methods.The energy resolution (green line) normalized to the elastic peak (elastic component) is also reported, while the blue line corresponds to the inelastic, damped harmonic oscillator contribution. The experimental error is within the symbol.
Mentions: The x-ray diffraction measurements on Indomethacin (IMC) and Celecoxib (CXB), detected with a photodiode embedded in the inelastic analyzers bench, show a broad main peak centered at and , confirming the amorphous nature of the samples (see Fig. 1). A selection of inelastic x-ray scattering spectra of IMC in the glassy state are shown in Fig. 2 at five fixed values of exchanged momentum Q. They are dominated by an intense elastic feature due to the non-ergodicity of the glass, i.e. to density fluctuations frozen by the structural arrest. At both sides of the elastic component, well defined inelastic peaks are observed at finite energy transfer. The energy position ℏΩ of the inelastic peaks corresponds to the energy of the acoustic modes of momentum Q, while the peak width gives access to the life time of density fluctuations, i.e. to the sound attenuation Γ(Q). The IXS spectrum can be modeled by a delta function, describing the elastic component, combined with the power spectrum of a damped harmonic oscillator (DHO, corrected to account for the detailed balance condition) representing the inelastic scattering. Both contributions have been convoluted with the instrument response function (green line in Fig. 2, for further details see the Methods section) to correctly reproduce the experimental data. We note that the inelastic contributions to the total scattered intensity due to the Brillouin inelastic scattering from vibrational density fluctuations are well reproduced (blue line in Fig. 2). The energy position of the Brillouin component increases with exchanged momentum Q, testifying the propagating nature of the probed excitations. This general finding proves the existence of THz hypersonic waves in amorphous IMC and CXB. Since only one inelastic contribution is resolved at each Q value, the vibrational excitations can unambiguously be ascribed to a single longitudinal acoustic phonon branch. The inelastic component becomes less and less visible as the exchanged momentum increases, due to an increase of the acoustic attenuation (broadening of the inelastic features) and to the increase of the elastic component which follows the static structure factor S(Q) (see Fig. 1). The energy dispersion curves, ℏΩ(Q), of the longitudinal acoustic phonon are linear in the long wavelength-limit Q ≤ 3 nm−1; they then bend down reaching a maximum at Q around half of Qp, highly suggestive of the existence of a pseudo-Brillouin zone (see Fig. 3). The plateau in the phonon dispersion of Indomethacin indicates the end of the propagating behavior while in the Celecoxib the group velocity remains finite up to 0.8 Qp. The acoustic attenuation Γ shows for both samples a power law dependence on the acoustic frequency Ω(Q) compatible with the quadratic law found in different classes of glassy systems in a similar frequency regime (see Fig. 4).

Bottom Line: The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals.We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation.Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively.

View Article: PubMed Central - PubMed

Affiliation: Dipartimento di Fisica, Universitá di Roma La Sapienza, Rome, Italy.

ABSTRACT
The high frequency dynamics of Indomethacin and Celecoxib glasses has been investigated by inelastic x-ray scattering, accessing a momentum-energy region still unexplored in amorphous pharmaceuticals. We find evidence of phonon-like acoustic dynamics, and determine the THz behavior of sound velocity and acoustic attenuation. Connections with ordinary sound propagation are discussed, along with the relation between fast and slow degrees of freedom as represented by non-ergodicity factor and kinetic fragility, respectively.

Show MeSH
Related in: MedlinePlus