eBook: Raman Imaging in Pharmaceutical Research - 6

and this will indicate the relative amount of the respective
chemical. Further, grain size distributions
can be obtained for individual components by applying
particle analysis algorithms to the Raman image,
as demonstrated in the following.
A high-resolution Raman image of a 1x1 mm² area
of a painkiller tablet's surface was recorded (Figure
2A). It shows the distribution of the tablet's main
chemical compounds color coded according to their
Raman spectra (Figure 2B). The main analgesic ingredients
were acetaminophen and aspirin. Caffeine
is often added to these analgesics as an adjuvant for
improved pain relief. The tablet also contained magnesium
stearate as a lubricant and lactose and starch
as fillers and binders. From the Raman images of the
individual components (Figure 2C), the respective
area fractions were quantified (Figure 2D). Together,
the APIs aspirin and acetaminophen accounted for
about two thirds of the tablet's surface, while the adjuvant
caffeine contributed about 4%.
The grain size of an ingredient can influence a tablet's
properties and is therefore of interest for analysis.
Both caffeine and lactose were mostly present in
A
B
small defined spots, but caffeine seemed to be found
in slightly larger grains (Figure 2C). Quantitative distributions
of grain sizes can be obtained by analyzing
Raman images with particle analysis algorithms,
such as those featured by the WITec ParticleScout
software tool. For the caffeine and lactose identified
on the tablet surface, ParticleScout located hundreds
of individual grains and sorted them according
to size. The area size distributions for both components
reveal that lactose indeed formed smaller
grains on average than caffeine (Figure 2E). More
than 90% of the lactose grains, but only 24% of the
caffeine grains were smaller than 50 µm².
Low-Dosage API Detection
Very potent drugs usually represent only a very
small fraction of the tablet's mass. Using highly
sensitive confocal Raman microscopes, they
can still be detected, as demonstrated in the following
using a tablet for type 2 diabetes (sample
courtesy of by Mr. Aravindhanathan Venkatesan
and Prof. Gowthamarajan Kuppuswamy, JSS college
of Pharmacy, Rocklands, Ooty, State of Tamil
C
Figure 3. Analysis of a tablet for type 2 diabetes. The components' distribution is shown in the Raman images of all components combined (A) and of the
low-dosage API glimepiride alone (B). The images are color coded according to the compounds' Raman spectra (C): lactose monohydrate (green), glimepiride
(red), metformin (yellow), PVP K30 (blue) and magnesium stearate (purple). Sample courtesy of Mr. Aravindhanathan Venkatesan and Prof. Gowthamarajan
Kuppuswamy (JSS college of Pharmacy, Rocklands, Ooty, State of Tamil Nadu, India)
6

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