16 research outputs found
Monitoring of Pentoxifylline Thermal Behavior by Novel Simultaneous Laboratory Small and Wide X-Ray Scattering (SWAXS) and Differential Scanning Calorimetry (DSC)
Comparative study of the AT1 receptor prodrug antagonist candesartan cilexetil with other sartans on the interactions with membrane bilayers
AbstractDrug–membrane interactions of the candesartan cilexetil (TCV-116) have been studied on molecular basis by applying various complementary biophysical techniques namely differential scanning calorimetry (DSC), Raman spectroscopy, small and wide angle X-ray scattering (SAXS and WAXS), solution 1H and 13C nuclear magnetic resonance (NMR) and solid state 13C and 31P (NMR) spectroscopies. In addition, 31P cross polarization (CP) NMR broadline fitting methodology in combination with ab initio computations has been applied. Finally molecular dynamics (MD) was applied to find the low energy conformation and position of candesartan cilexetil in the bilayers. Thus, the experimental results complemented with in silico MD results provided information on the localization, orientation, and dynamic properties of TCV-116 in the lipidic environment. The effects of this prodrug have been compared with other AT1 receptor antagonists hitherto studied. The prodrug TCV-116 as other sartans has been found to be accommodated in the polar/apolar interface of the bilayer. In particular, it anchors in the mesophase region of the lipid bilayers with the tetrazole group oriented toward the polar headgroup spanning from water interface toward the mesophase and upper segment of the hydrophobic region. In spite of their localization identity, their thermal and dynamic effects are distinct pointing out that each sartan has its own fingerprint of action in the membrane bilayer, which is determined by the parameters derived from the above mentioned biophysical techniques
Monitoring of Pentoxifylline Thermal Behavior by Novel Simultaneous Laboratory Small and Wide X-Ray Scattering (SWAXS) and Differential Scanning Calorimetry (DSC)
<div><p>The thermal and structural evolutions associated to active pharmaceutical ingredient (API) purity are monitored using a laboratory instrument (S3-MicroCaliX) allowing simultaneous time-resolved X-ray scattering at both wide and small angles (SWAXS) as a function of temperature. This is performed simultaneously with differential scanning calorimetric (DSC) that is carried out in the same apparatus at scanning rate of 2 K/min on the same sample in the range from 20° to 200°C. We have studied simultaneous thermal and structural properties of pentoxifylline, as an active pharmaceutical ingredient (API), for its purity quality control. We have found a satisfying API purity, due to obtained melting temperature and enthalpy values, which are in a well agreement with literature. We have also found that the combination of these techniques allows the thermal monitoring of scanning rates of 2 K/min, continuously without the need for static thermal equilibration, particularly for X-ray spectra. Hence, DSC and SWAXS allowing better identification of the structural thermal events recorded by following of the phase transitions simultaneously. This interpretation is much better possible when X-ray scattering at small and wide angles is coupled with DSC from the same sample. Hence, as a laboratory tool, the method presents a reproducible thermal and crystallographic API purity quality control of non-complex samples, as crucial information for pharmaceutical technology.</p></div
DSC spectra of pentoxifylline: Heating scan with a base line subtraction and slope correction displaying melting transition.
<p>Cooling scan with a base line subtraction displays a stabile amorphous state.</p
Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS
Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using a Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content of the mixture. It was established that crystallization temperatures were proportional to the volume content of the solvent in mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms b and g in all solvent mixtures. In a toluene/methanol 30:70 mixture, in addition to forms b and g, at least one of the forms A, D or a was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture
Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS
Crystallization of the drug entacapone from binary solvent mixtures was monitored in situ using Raman optical probe. The recorded Raman spectra and statistical analysis, which included the principal components method and indirect hard modeling made it possible to estimate the starting point of crystallization, to assess crystallization temperatures and to provide information on the polymorphic content in the mixture. It was established that the crystallization temperatures were proportional to the volume content of the solvent in the mixtures. The samples were also evaluated off-line via Raman spectroscopy and SWAXS. The collected data showed the presence of forms β and γ in all solvent mixtures. In toluene/methanol 30:70 mixture, in addition to forms β and γ at least one of the forms A, D or α was also indicated by SWAXS. The results have shown that the presence of a particular polymorph is strongly dependent on the nature and portion of the solvent in the binary solvent mixture
SWAXS cooling scans spectra of pentoxifylline in the temperature range of 140 to 80°C: a) SAXS cooling scan, b) WAXS cooling scan in the three dimensional plot.
<p>SWAXS cooling scans spectra of pentoxifylline in the temperature range of 140 to 80°C: a) SAXS cooling scan, b) WAXS cooling scan in the three dimensional plot.</p
a) WAXS heating scan in the three-dimensional plot, b) WAXS heating scans in a two dimensional contour plot.
<p>(SAXS exposure time one minute per frame, which corresponds to two°C per frame).</p
Fast real-time monitoring of entacapone crystallization and characterization of polymorphs via Raman spectroscopy, statistics and SWAXS
Surface Morphology of Textured Transparent Conductive Oxide Thin Film Seen by Various Probes: Visible Light, X-rays, Electron Scattering and Contact Probe
Fluorine-doped tin oxide thin films (SnO2:F) are widely used as transparent conductive oxide electrodes in thin-film solar cells because of their appropriate electrical and optical properties. The surface morphology of these films influences their optical properties and therefore plays an important role in the overall efficiencies of the solar cells in which they are implemented. At rough surfaces light is diffusely scattered, extending the optical path of light inside the active layer of the solar cell, which in term improves light absorption and solar cell conversion efficiency. In this work, we investigated the surface morphology of undoped and doped SnO2 thin films and their influence on the optical properties of the films. We have compared and analysed the results obtained by several complementary methods for thin-film surface morphology investigation: atomic force microscopy (AFM), transmission electron microscopy (TEM), and grazing-incidence small-angle X-ray scattering (GISAXS). Based on the AFM and TEM results we propose a theoretical model that reproduces well the GISAXS scattering patterns