eBook: Raman Imaging in Pharmaceutical Research - 9

often combined with energy-dispersive X-ray spectroscopy
(EDX), which can identify the elements in
a sample. Raman microscopy is the perfect addition
because it can identify molecules and even distinguish
polymorphs. Raman Imaging and Scanning
Electron (RISE) microscopy was developed with
these types of correlative studies in mind.4,5
RISE microscopes
make it possible to acquire Raman and
high-resolution SEM images at precisely the same
sample position as the sample is automatically transferred
between the Raman and SEM measuring positions
within the vacuum chamber. The presented
measurements were performed with a WITec/Tescan
RISE microscope.
Analyzing Pharmaceutical Particles
Microparticles are common carrier systems for drugs
and their morphology and composition can affect
A
B
the bioavailability of the delivered API.1,2
Here, the
particles in an anti-asthma inhaler were investigated
after applying the spray to a silicon substrate. Largearea
white-light images revealed differently sized
particles (Figure 1A). A Raman image (using a 532
nm excitation laser) was acquired from two areas,
each containing one selected particle of only a few
microns in length and width. Four chemical components
were detected in both images and identified
by their Raman spectra (Figure 1B), which determined
the color-coding of the Raman images of
the particles (Figures 1C and 1D). The particles consisted
mainly of lactose in two different hydration
states (blue, green). The API was the glucocorticoid
fluticasone propionate (red), which is commonly
prescribed for asthma treatment. A fourth component
represented milk constituents (pink), which
are sometimes present in formulations containing
lactose from cow's milk. SEM images of the same
C
D
E
F
G
H
Figure 1. Correlative Raman-SEM (RISE) analysis of particles from an anti-asthma inhaler.
A: Example white-light image of the particles. B: Raman spectra of the four chemical components identified in the particles: the API fluticasone propionate (red),
lactose in two different hydration states (blue, green) and milk components (pink). C, D: Raman images of two particles, both color-coded according to the spectra
in B. E, F: SEM images of the same particles shown in C and D, respectively. G, H: RISE images: overlays of the corresponding Raman and SEM images.
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eBook: Raman Imaging in Pharmaceutical Research

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