eBook: Raman Imaging in Pharmaceutical Research - 4

Analyzing Pharmaceutical
Tablets with Confocal
Raman Imaging
Miriam Böhmler, Satheesh Kumar, Damon Strom, and Eleni Kallis
WITec GmbH, Lise-Meitner-Str. 6, 89081 Ulm, Germany; www.WITec.de, info@WITec.de
This study presents Raman imaging as a tool for
pharmaceutical tablet analysis. It describes its use
for visualizing the distribution of chemical ingredients,
quantifying their relative amounts and even reliably
detecting low-dosage drugs. The comparison
of grain sizes of selected compounds by dedicated
particle analysis algorithms is also shown.
Raman Imaging of
Pharmaceutical Tablets
In order to ensure the efficacy and safety of pharmaceutical
formulations, their chemical composition
needs to be monitored during the entire development
and production process. Confocal Raman imaging
is well-suited for this task.1-3
This spectroscopic
method is based on the Raman effect, which results
from the inelastic scattering of incident light by molecules.
The scattered photons show characteristic
energy shifts that are visible in a compound's unique
Raman spectrum. A Raman image of a sample is generated
by recording a complete Raman spectrum at
each image pixel and color-coding the resulting map
according to the spectra. Raman images of pharmaceutical
tablets visualize the spatial distribution of
their active pharmaceutical ingredients (API) and
excipients and reveal contaminations as well as the
sample's homogeneity.1-3
Polymorphs of the same
substance can be distinguished, which is important
for chemicals that have different properties in different
polymorphic forms.2
Raman microscopy is nondestructive
and label-free and it can be combined
with complementary imaging techniques such as
atomic force microscopy (AFM) or scanning electron
microscopy (SEM) for high-resolution chemical and
structural characterization.
When investigating large areas of tablets with rough
or curved surfaces it is important to ensure that the
sample stays in focus. Thus, the Raman measurements
presented in the following were performed
on a WITec alpha300 Raman microscope equipped
with the TrueSurface module for active focus stabilization.
This technology uses a profilometer to trace
the sample surface and compensate for height differences
during the simultaneous Raman measurement.
The surface therefore stays in focus while the
sample topography is revealed along with the chemical
information. The topographic Raman image of a
pharmaceutical tablet depicts the distribution of its
4
http://www.WITec.de
eBook: Raman Imaging in Pharmaceutical Research

Table of Contents for the Digital Edition of eBook: Raman Imaging in Pharmaceutical Research
