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PARTICLE SHAPE
PARTICLE SIZE
CHEMICAL IDENTIFICATION
TECHNICAL NOTE
information permits creation of chemical classifications from which component- specific
particle size distributions are determined. This can provide extra compositional
information about samples that can be invaluable in research and development or
investigative situations.
TECHNICAL NOTE
TECHNICAL NOTE
Figure 4: Overlay of the Raman spectra from two reference library components.
Figure 5: Particle spectrum (blue header) compared to reference library spectrum (green header)
showing the correlation score.
Figure 5 (top) shows the Raman spectrum from a particle measured in the nasal
spray sample with the reference library spectrum (bottom). The correlation score of
0.995 indicates the particle spectrum shows a good correlation to the reference. The
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TECHNICAL NOTE
correlation scores can be used to create chemical classifications for the sample data in
order to separate components.
Correlation scores can be calculated over the entire spectral range, or the range can
be limited to include only regions of interest. For the example application, the primary
interest is to identify active particles in order to generate the 'active only' particle
size distribution. In this case limiting the spectral range to 1500 cm-1 to 1800 cm-1
optimizes the correlation calculation to achieve the aim of the application.
Additionally the spectral data can be pre-processed using a number of different
derivative settings, which may help enhance the signal-to-noise ratio and minimize
baseline artifacts in the acquired spectra.
Figure 6: Example spectra from four particles (blue header) with the reference library spectra below
(green headers).
Once the Raman data has been acquired, the particles can be sorted according to their
chemical correlation to the library components. Figure 6 shows particle images from
the nasal spray sorted by their correlation to the active component. The four particles
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TECHNICAL NOTE
with the highest correlation scores are selected to show their spectra in the stacked
view along with the library spectra.
The scattergram function, used to relate standard morphological parameters obtained
in a Morphologi G3 measurement, can also be used to relate different Raman
correlation scores. This can aid visualization of the different chemical populations and
help with the subsequent chemical classification of the particles. The scattergram
in Figure 7 shows the relationship of particle correlation to the active and excipient
references for the example data. Figure 7 also indicates how the particles were
chemically classed.
The contribution of each class within a sample, relative to each other, can be
compared using the classification chart function. Figure 8 shows a classification chart
(in percentage count) for the chemical classes in the nasal spray example with some
particle images from each class. The classification chart can be viewed by particle
count, showing the actual number of particles found in each class; percentage count;
TECHNICAL NOTE
or percentage volume, which can be useful when comparing different samples with
varying numbers of particles analyzed.1
(For quantitative results, detailed method development from sampling through
to chemical acquisition is required; otherwise results should be viewed as semiquantitative.)
Component-specific distributions
For some applications, the interest may be in obtaining the morphological information
for a specific component within the sample dispersion. A new record can be created
for each chemical class, which enables the user to perform component-specific particle
analysis. Figure 9 shows the overlay of the particle size distributions (PSDs) for the
individual active and excipient components as well as for the overall nasal spray
formulation in terms of number (where every particle has equal weighing).
Figure 10: Overlay of component-specific elongation distributions for the active and excipient
components.
As with all Morphologi G3 results, distributions for all the morphological parameters
calculated for the particle images are reported. Figure 10 shows an overlay of the
elongation distributions for the two nasal spray components which indicates differences
between them. In this case, particles with an elongation value of greater than 0.4 are
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TECHNICAL NOTE
not likely to be the active component; the component of interest. In the morphological
analysis a filter can be applied to exclude particles with elongation values greater than
0.4 improving the targeting for the Raman acquisition towards the active component
only. Optimising the particle targeting towards the component of interest in this way
reduces the overall measurement time.
Alternatively, the reference materials could be analyzed independently and their
particle morphology evaluated to optimize the targeting of the Raman acquisition.
Unknown chemical ID
There may be applications where particles with unknown identities are present in the
sample. For example: as a result of sample contamination or due to the presence of
unknown polymorphs of a substance. In these situations, where no "pure" materials
are available to use as the references, the usual procedure is to compare any unknown
spectrum or spectra of interest to a spectral database.
Commercial databases contain a wide selection of reference spectra which may allow
identification of the unknown, or give a better understanding of what it might be.
To enable the use of third party spectral databases, the particle spectra can be
exported from the Morphologi software in industry standard file formats such as .spc
or .csv.
TECHNICAL NOTE
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the right to deviate from information, descriptions, andspecifications in this publication without notice. Malvern
Instruments shall not be liable forerrors contained herein or for incidental or consequential damages in connection with
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