Helping to push the industry into adopting chemical imaging into its analytical labs are developments in both hardware and
New types of electronic packages have been developed for spectrometers' data acquisition software. "Historically Raman spectrometers
were put together with piece components that were just bought off the shelf," explain Bormett. "You would buy a spectrometer,
gratings, and a detector. Once you decided exactly how these pieces fit and function together, you could customize the electronic
packages in each of these components to allow high-speed data acquisition." Renishaw customized its electronic packages that
go into the CCD to control stage and sample movement, then synchronized it with spectrometer data acquisition. "The individual
pieces have been always there, but they have never been able to be packaged together until the last couple of years," says
Data transfer also has evolved. "In our initial products, the camera spoke to a frame grabber which then dumped the data,"
says Kidder. "Now our cameras connect through gigabyte Ethernet cables, enabling data to transfer more quickly." Kidder also
explains that the speed and duty cycle of the cameras have increased. Whereas earlier systems would collect 80,000 spectra
in 4 minutes, for example, data can now be collected in about a minute with the same signal-to-noise properties. "You may
wonder if [data collection speed] matters," says Kidder. "One of the interesting cases is when you are doing QbD [quality
by design] and your DOE [design of experiments] includes 100 different tablets, for example. If it takes you 40 minutes to
collect the data, you have to multiply that by100, compared with 10 minutes or even 1 minute for data collection. It really
starts to make a difference if the technique is used as a routine tool."
Treado attributes the innovations in spectrometers, specifically the liquid crystal imaging spectrometer. He also credits
the use of imaging cameras or focal-point arrays. In IR, it's typically indium gallium arsenide, indium antimonide, or mercury
cadmium telluride cameras. For Raman- and fluorescent-based systems, it's CCD or CMOS detectors. "If you couple those with
multivariate software, you have powerful combination," he says.
As the tools to analyze data advance, so too should the tools to increase the understanding of the information that is generated.
"Early on, people would pull out a single wavelength image without having properly preprocessed their data with a baseline
correction or normalization, for example," says Kidder. "These steps were standard for single-point spectroscopy, but somehow
analysts lost track of the fact that imaging was really just parallel spectroscopy, and the basics still had to be applied.
There have also been strides in the quantitative , versus qualitative, assessments that can be made. People used to look at
a picture and compare it with another picture and say 'this looks more homogeneous.' Obviously that doesn't work, and it doesn't
Data analysis tools are now much more sophisticated, and researchers are developing metrics to see an image from a statistical
point of view. "The 'standard deviation' of a image can actually give you a quantitative measure of the heterogeneity of a
tablet, and you can then start putting the image to good quantitative use," says Kidder. "In our early days, most of our reports
were filled with pictures. Now, they're mostly filled with tables of numbers comparing the statistics of our results.The ability
to generate quantitative, objective, and reproducible results allows imaging to become an analytical workhorse, rather than
just a fun tool."
The big picture
Chemical imaging companies see real promise in applying their technologies to the tableting market and are eyeing validation.
"The industry is struggling with the best way to validate these techniques, but we have started working with customers in
QA/QC departments to get them accepted," says Kidder. "Large pharmaceutical companies want to roll chemical imaging out to
replace or complement wet chemistry techniques." Although single-point spectroscopies methods have been validated for some
time, the respective imaging technique will still take considerable revalidation work.
But the promises that imaging may bring can make that the revalidation work worthwhile. One future application, for example,
includes correlating an image with a dissolution curve. "If they can prove this correlation—which has been done for a variety
of products already—and because it is a fast technique, we could look at a lot of tablets in a batch to make sure they have
the correct 'image parameter,'" says Kidder. The parameter could indicate whether the tablets were good dissolution candidates
and wet chemistry would only be used to sample a small subsection of that. Regular dissolution testing would still be done
on a subset of samples, but more if not all samples could be tested using vibrational imaging. "It's definitely cutting edge
... that is the big picture people are looking at."