Above: Figure 3. Oxygen (O) EDS map of the
multi-vitamin in Fig. 2.
Right: Figure 4. Coating thickness of an ibuprofen tablet.
depending on the development process, equipment used,
location, and overall facility cleanliness. But, even the cleanest rooms can produce particulate matter shed by gowns,
gloves, skin, sample preparation equipment, and glassware.
Containers and closures, specifically rubber closures, contribute particulate matter due to leaching, chemical reactions, friction, and changes in physical properties.
Some of the most common materials identified in pharmaceutical environments are stainless steel, silica, aluminum,
salts, minerals, organic fluorinated compounds, and carbonaceous materials in varying sizes and shapes. 2 SEM Images
and EDS spectra of some of these particles are shown in
ACTIVE INGREDIENTS IN PHARMACEUTICAL
Pharmaceutical tablets are composed of a number of
different materials, each of which is designed to improve
performance. The Active Pharmaceutical Ingredient (API) is
intended to act on the particular disease or the symptoms
of the disease. The other components, referred to as excipients, act as fillers, bulking agents, tablet disintegrants,
and tablet coatings (to protect the core and to mask taste).
Consistent performance of the tablets depends directly
upon the amount of each excipient in the tablet.
During development, it is useful to have a means to investigate the distribution of excipients and API within the
tablet itself. The use of EDS maps and BSE (Back Scattered
Electron) images of tablet cross-sections are two related
means of directly examining excipient and API distribution
within a tablet. The example shown in Figure 2 highlights
the quantitative methods using a multi-vitamin tablet as a
test case using a backscatter image of the tablet cross-section along with the accompanying EDS map. 3
In addition to visually seeing all of the elements, the EDS
system can provide quantification by percent of the total
elements as shown in Table 1. Of note in the table is the incorporation of oxygen that was purposely excluded from the
EDS map of Figure 2.
Since oxygen bonds tightly with other elements to form oxides, it was left out of the comprehensive EDS map. Shown in
Figure 3 is the oxygen element EDS map in green. It is interesting to note the various elements that the oxygen binds to
by overlaying Figure 3 on top of Figure 2. As a note, the green
that is shown in Figure 2, is the combination of the mutliple
colors from the Iron (Fe), Zinc (Zn), and Calcium (Ca).
Besides monitoring for particulates in a production line,
and quantifying the API within the tablet, another quality
control check can be obtained by measuring thickness of the
tablet’s coating. Figure 4 shows the thickness value of a tablet coating from an Ibuprofen sample using a Back Scattered
Electron (BSE) Image.
Tablet coatings have numerous functions including
strengthening, controlled release,
ease of handling and packaging, pro-
tection of the tablet from moisture,
improved taste, facili-
tate swallowing, and to
provide tablet identity.
The adhesion of a
coating to the tablet
is influenced by the
strength of the interfacial bonds between film
and tablet. Poor adhesion results in peeling,
which reduces film functionality. The mechanical protection provided
by the coating can also
be compromised by loss of adhesion, leading to the accumulation of moisture at the film-tablet interface. This could affect
the stability of moisture sensitive drugs.
Implementing a SEM-EDS particle-characterization program
is a key step towards optimizing the design and therapeutic
effect of new pharmaceutical products, and controlling undesirable contamination. SEM imaging provides the resolution
required to evaluate both the size and shape of nanometer
scale particles. The large depth of focus of the SEM reveals
fine surface detail, even over large, irregularly-shaped particles. SEM and EDS image-based particle analysis provides
qualitative and quantitative capabilities for nanoscale particles far beyond the capability of optical microscopy.
1. Lich, B., Wilfen, U., 2009, When Size & Shape Matter, Drug
Discovery & Development. Vol. 12 Issue 2, p. 26
2. Vicens, M.C., 2012, A New Picture of Particles, Drug
Discovery & Development.
3. Carlton, R.A., 2010, Image Analysis of EDS and Backscatter
SEM Images of Pharmaceutical Tablets, Microscopy and
Microanalysis, v. 16 (Suppl2), p. 662-663. ■
Table 1. Quantitative Analysis of the Multi-vitamin Tablet
Elt. Intensity (c/s) Atomic Conc Units
C 84.95 37.169 25.796 wt.%
O 93.39 49.951 46.179 wt.%
Mg 46.42 3.310 4.648 wt.%
Si 6.49 0.295 0.479 wt.%
Ca 233.44 8.133 18.834 wt.%
Fe 7.89 0.456 1.472 wt.%
Zn 6.54 0.686 2.593 wt.%
100.000 100.000 wt.%