Tablet manufacturers seeking vibrational spectroscopy-based chemical imaging use three factor when choosing between Raman,
mid-IR, NIR—and in some cases fluorescence—methods: specificity, sensitivity, and spatial resolution.
Patrick Treado, PhD, chief technology officer at ChemImage explains that in general, fluorescence is the most sensitive approach
but the least specific, and spatial resolving power can be on the order of a couple hundred nanometers. NIR is reasonably
sensitive but also relatively nonspecific, and resolution is on the order of tens of microns. NIR is the most inexpensive,
however, and provides fast data collection. Raman is not as inexpensive, though cost effective, but it's very specific although
a little less sensitive. Moreover, explains Bormett,"IR is limited in its lateral spatial resolution. It's hard to perform
IR imaging with lateral spatial resolutions better than about 30 microns."
"NIR spectroscopy has been seen to be a workhorse in industrial technology, whereas the Raman and the mid IR are seen more
as specialist techniques," says Kidder. In some ways this parallels on the imaging side as well. "NIR can probably solve 85%
of the problems we see for the pharmaceutical industry. Some of our customers who have multiple technologies tend to go to
NIR first and determine whether they can solve it with NIR because of its fast data collection time time (just over a minute
for a standard tablet), no sample preparation required, and ability to accommodate different types of samples. For samples
that require higher spatial resolution or higher spectral selectivity though, other techniques may be needed." As with the
single-point technique, chemical imaging with NIR and mid-IR spectroscopies do not work well with inorganic compounds.
Raman spectroscopy, however, can accommodate inorganic compounds and recent advances are extending its application. ChemImage,
for example, has innovated a dynamic chemical imaging capability. "Historically if you are going to use Raman to evaluate
an entire tablet or a process that is occurring in real time, it took a long time to gather the information," says Treado.
"Our approach has been to capture images dynamically in real time or near real time, in the time scale it is relevant to the
process you are trying to monitor. Another way of thinking of this is Raman imaging 'movies' —it is drilling down and extracting
information content from the monitoring of these dynamic processes." Capabilities include monitoring processes that can't
be slowed down (through temperature control for example) and the kinetics of the process is not on the time scale of seconds
or a few minutes. "Crystallization, dissolution, and recrystallization are specific application where dynamic chemical imaging
is proving itself," says Treado.
Dynamic chemical imaging with Raman spectroscopy uses wide-field imaging. "Typically this means the use of wide-field illumination
in combination with liquid crystal imaging spectrometers, electron multiplying CCD detectors, and a high degree of automation
in the software to allow the instrument to monitor a process in real time or near real time in an unbiased fashion," says
Raman mapping techniques also have advanced. Renishaw, for example, has developed a Raman spectrometer that is designed for
high-speed imaging of small parts or a whole tablet. For Raman-based instruments measure individual spectra in a "raster mode"
on the tablet. Rows of data are collected to create a two-dimensional map. "Ten to 15 years ago when the pharmaceutical industry
started doing this kind of mapping on a tablet, it might take from 8 to 12 hours to obtain," says Bormett. "Providing a tool
that can create images for these same tablets in tens of minutes, at an hour at the longest, is a phenomenal tool for the