eBook: Raman Imaging in Pharmaceutical Research - 10

sample areas revealed the particles' porous surface
structures at high resolution (Figures 1E and 1F).
They were recorded under low vacuum conditions
(30 Pa) using 15 kV accelerating voltage and a BSE detector.
The combined Raman-SEM images correlate
the chemical and structural information, thus giving
insight into the distribution of the chemical components
on the particle surface (Figures 1G and 1H). Of
course, using particle analysis algorithms, structural
information such as the particle size distribution can
also be established by such measurements.
Combining Chemical and Structural
Information of Polymorphs
Titanium dioxide (TiO2
) is used extensively as a white
pigment, for example in tooth paste, sun screen,
wall paint, food, cosmetics and pharmaceuticals.
However, its use has been under debate since the
International Agency for Research on Cancer (IARC)
classified it as being possibly carcinogenic to humans
when inhaled.6
TiO2 exists in several modifications, two of which
- anatase and rutile - were examined here by RISE
A
B
microscopy. The SEM image was recorded under
high vacuum conditions using 5 kV accelerating voltage
and a BSE detector. An excitation wavelength of
532 nm was used for the Raman measurement. The
two polymorphs can be clearly distinguished by
their Raman spectra at relative wavenumbers between
300 and 800 cm-1
(Figure 2A). The SEM image
of a mixture of anatase and rutile powder visualizes
the fine structure of the TiO2
particles, but cannot
distinguish between the two forms (Figure 2B). A
Raman image was thus overlaid onto the high-resolution
SEM image, revealing the chemical identity of
the particles (Figure 2C). Both particle types formed
agglomerates in which the rutile particles were larger
than the anatase particles.
Conclusion
Raman imaging is a powerful tool for chemically
identifying the molecules in pharmaceutical formulations
and revealing their spatial distribution.
Its ability to distinguish polymorphs is a notable
advantage over other techniques because the
drugs' crystallinity influences their bioavailability.
C
Figure 2. Correlative Raman-SEM (RISE) analysis of TiO2 polymorphs.
A: Raman spectra of anatase (blue) and rutile (red). B: SEM image of a mixture of anatase and rutile particles. C: RISE image correlating chemical and structural
information. Anatase particles (blue) were smaller than rutile particles (red).
10

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