eBook: Raman Imaging in Pharmaceutical Research - 8

Combined Raman-SEM Imaging
for Pharmaceutical Studies
Eleni Kallis and Ute Schmidt
WITec GmbH, Ulm, Germany; www.WITec.de, info@WITec.de
This article presents correlative Raman Imaging and
Scanning Electron (RISE) microscopy as a useful tool
for investigating the fine structure and chemical
composition of pharmaceutical samples.
Confocal Raman imaging is a well-established spectroscopic
method for investigating a sample's chemical
composition. It is based on the Raman effect,
which results from the inelastic scattering of incident
light by molecules. Characteristic energy shifts
in the scattered photons are visible in unique Raman
spectra, which can be used to identify chemical compounds.
In Raman imaging microscopy, a complete
Raman spectrum is acquired from each image pixel
and the resulting Raman image visualizes the spatial
distribution of the sample components. The beam
path geometry of confocal Raman microscopes creates
a sharply defined plane for data acquisition that
can be scanned through the z-axis of transparent
samples, enabling 3D image generation.
Advantages of Raman Imaging for
Pharmaceutical Applications
During production and quality control, the composition
of pharmaceutical formulations needs to be
monitored and contaminations need to be detected
in order to assure the purity, safety and efficacy of
drugs. As many active pharmaceutical ingredients
(APIs) produce a strong Raman signal due to their
pi-bonds, Raman spectroscopy can easily identify
them.1
Polymorphs of a substance can be distinguished
by their Raman spectra, which is relevant
because they often differ in their bioavailability.1-3
The distribution of the sample components can be
analyzed by Raman imaging, revealing, for example,
the sample's level of homogeneity. The technique is
applicable to liquid or solid pharmaceuticals without
causing damage to the sample and doesn't
require specialized sample preparation, large sample
volumes or high material concentrations. For
high-throughput industrial applications, the Raman
measurement process, including alignment, can be
standardized and automated to guarantee optimal
system performance as well as consistency and repeatability
of results. A high degree of automation
also enables remote-controlled operation in enclosed
environments. Additionally, Raman imaging
can be combined with complementary techniques
for structural investigation, such as scanning electron
microscopy (SEM), as detailed and illustrated in
the following.
RISE: Raman Imaging and Scanning
Electron Microscopy
Many pharmaceutical studies profit from the correlation
of chemical and high-resolution structural
information.2
Scanning electron microscopy (SEM) is
8
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