(BACKGROUND: PHOTOS.COM, IMAGING PHOTOS: CHEMIMAGE)
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Like most of the world, the scientific community is now more than ever reliant on images to gain valuable information. When
pixels replace pens, and the image of a new drug candidate can make or break a project, it becomes clear that a picture can
be worth much more than 1000 words.
Uniting single-point spectroscopy and digital imaging, chemical imaging is slowly being adapted for the analysis of tablets
and capsules. Advanced from traditional optical microscopy, which uses a material's refractive index among other material
properties as the basis for generating image contrast, chemical imaging instead uses the underlying spectroscopy associated
with the materials being analyzed at each spatial location as a means to produce image contrast. Multivariate analysis and
chemometric software then translate this chemical image information into useful quantitative data.
The motivation for adapting chemical imaging lies primarily in the changing nature of today's dosage forms. "Definitely the
business is moving in the direction of more complicated formulations, and the standard tools don't provide the information
needed to characterize these products," says Linda Kidder, product manager, Chemical Imaging Systems, at Malvern Instruments, Inc. (Columbia, MD). "The single-point spectroscopies just can't do it, and HPLC [high-performance liquid chromatography]
just can't do it. This is where the need is growing, and most of the companies working on advanced formulation, really understand
this need."
Applications
The advantage of chemical imaging in solid-dosage form analysis is the ability determine the distribution and size of the
active pharmaceutical ingredients (APIs) and excipients. The information is then correlated to optimize process operations
and understand how ingredients interact within the tablet. "This information aids in quality control, trying to help understand
how things dissolve, and their lifetimes with respect to shelf lives," says Richard Bormett, PhD, business manager at Renishaw (Hoffman Estates, IL). "Tableting processing can change the crystal form of the API, and being able to map where the API
is and discriminate between its polymorphic forms is an important tool."
Previous methods of viewing the distribution didn't offer the quality that analysts needed. The time required to collect the
data was long, making it not feasible, and high spatial-resolution mapping could take days. As Bormett observes, "If you looked
at a whole tablet at a time, the spatial resolution of the probe became poorer and poorer so you had to look at larger and
larger sections. If an API reached 5 to 1 microns, it wasn't always easy to see or determine its distribution."
Variations.
The primary distinction between chemical imaging systems is the type of spectroscopic technique. Within the pharmaceutical
industry, numerous spectroscopies have advanced, including Raman, mid-infrared (mid-IR), near-infrared (NIR) absorption–reflectance,
UV–vis absorption–reflectance and luminescence. Each have been demonstrated useful for many applications.
Figure 1: Data processing software allows analysts to obtain quantitative information about a whole tablet or portions of
a tablet.
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Vibrational techniques such as Raman spectroscopy can pick up the unique chemical signatures for polymorphs of an API, which
help analysts determine the cause of poor efficacy. Imaging with Raman spectroscopy is also useful in contamination identification.
"In the world of tablet or capsule analysis, we often have the luxury of knowing what is present in the tablet based on a
list of ingredients," says Matthew Nelson, PhD, director of application science at ChemImage (Pittsburgh, PA). "Often, this information allows us to develop a spectral library of the compounds that are present and
to understand the chemical signatures for those components. We can collect data on small parts of a tablet, the whole tablet,
or multiple tablets using chemical imaging. With data processing software, we can provide qualitative and quantitative information"
(see Figure 1).
