Raman's New Reach

March 14, 2012
Allied with other imaging techniques, Raman spectroscopy is being used for more QC, process control, and QbD efforts.

Experts often repeat the fact that no single analytical technology should dominate any pharmaceutical quality control toolkit. Each method, from the ubiquitous near-infrared (NIR) spectroscopy on, has its strengths. However, what was clear from a tour of technology exhibits at the 26th IFPAC meeting in late January, and Pittcon 2012 in March, is the fact that Raman is developing more of a presence in pharma QC applications.

Raman has become a more popular screening technology, especially as portable miniaturized systems have entered the marketplace, since it allows for remote in-situ measurements, and can take readings of material within containers. It can also help users discern polymorphs, and crystalline vs. hydrated forms of the same material.

As applications grow in anticounterfeiting and raw material quality verification, Raman is also seeing increased use in process monitoring and control applications. Pharmaceutical manufacturers, including companies
such as BMS and Vertex, are also using Raman in drug development, in efforts to define the Design Space and optimize critical quality attributes and process parameters.

For traditional Raman spectroscopy, the National Institute of Standards and Technology (NIST) is working on calibration and validation standards that would make it easier to compare spectra from different vendors’ instruments. FDA has also been involved in work designed to make Raman spectral libraries more useful and openly accessible.

Today, three-dimensional visualization techniques are incorporating Raman spectroscopy, allowing users to image surface areas in greater detail. In confocal Raman imaging, for instance, a Raman device is combined with microscopy to allow analysis at the micron level, for example, for trace levels of API. Filters optimize the level of light reaching the detector, allowing image contrast to be closely adjusted. Thousands of individual spectra are then combined to form one highly detailed image.

Spatially Offset Raman, meanwhile, offers analysis at depths that conventional Raman spectrometers, using backscattering light collectors, cannot reach. Based on technology developed at Rutherford Appleton Laboratory, and commercialized by Cobalt Light Systems, the technology allows materials to be analyzed, even in opaque containers.

Raman is also being combined with other methods, including light-induced fluorescence (LIF) and machine vision. Raman’s combination with machine vision was the topic of a recent presentation by Mustard Tree Instruments. In May, the Royal Society of Chemistry will hold a symposium on the topic of pharmaceutical applications of novel Raman platforms. (For more information, click here.)

Here is a brief summary of some of the Raman platforms that are now available for pharmaceutical development, quality control and other applications.

Bruker Optics offers a number of hybrid systems combining confocal Raman and FTIR, as well as Raman with atomic force microscopy, photoluminescense and atomic force microscopy. The company also offers Tip-Enhanced Raman Scattering (TERS), allowing Raman to be used in nanoscale applications.

B&W Tek recently added BWIQ, a chemometric software package, to its i-Raman platform, which features CleanLaze technology for improved laser stabilization and line width. The device now offers an 830-nm excitation wavelength option in addition to the 785nm and 532nm configurations. BWIQ combines traditional chemometric methods such as Partial Least Squares Regression (PLSR) and Principal Component Analysis (PCA) with new methods, such as B&W Tek’s adaptive iteratively reweighted Penalized Least Squares airPLS) algorithm. The company also introduced the NanoRam handheld instrument designed for in-plant applications, enabling qualitative and quantitative analysis, and the ability to analyze both organic and inorganic compounds over a wide spectral range.

Cobalt Light Systems’ TRS100 rapid analysis system is designed to analyze capsules, tablets, powders and other dosage forms, in tact in opaque containers. Included is chemometric package, ContentQC, which helps with trending analysis.

Horiba Scientific offers confocal Raman including ARAMIS and XploRA for polymorphic analyses and applications involving coatings, among others. Its product line includes transmission Raman for content uniformity, Raman probes for blend uniformity, Raman microscopy for composition analysis.

Kaiser Optical Systems offers the Raman Workstation, which combines transmission Raman spectroscopy and Raman microscopy. The company’s RamanRXN systems offer solutions designed to span the lab to the pilot plant to manufacturing.

Mustard Tree Instruments offers Lab2Line solutions set designed to work from lab-to-line. Its VTT 1000, for example, incorporates Raman, machine vision and RGB detection. The company recently introduced a YouTube channel devoted to Raman spectroscopy and other relevant imaging solutions (www.YouTube.com/

Real-Time Analyzers offers a range of Raman analyzers for process and laboratory use. Its industrial Raman Analyzers can be used for applications ranging from raw material identification to polymorph analysis and tablet uniformity studies.

Rigaku Raman Technologies, founded in Japan, specializes in x-ray diffractometers and Raman spectrometers, including its First Guard and Xantus portable Raman spectrometers.

Thermo Scientific’s portable TruScan and TruScan RM are proven technologies for pharmaceutical QC and screening applications.

Witec offers confocal Raman technologies. Its CRM 200, for instance, can identify different polymorphs of a crystalline solid, normally undetectable via traditional imaging techniques. This technology allows users to map samples, noninvasively, at deeper levels than possible with traditional Raman.

About the Author

Agnes Shanley | Editor in Chief