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Raman spectroscopy peers into pills

05 Mar 2008

A new laser analysis technique can characterize the bulk chemical content of pharmaceutical capsules without needing to open them.

Researchers at the Rutherford Appleton Laboratory in the UK have developed a technique to non-invasively quantify the presence of active ingredients in capsules on a pharmaceutical production line. The technique, known as spatially offset Raman spectroscopy (SORS), allowed them to measure the amounts present to a relative accuracy of 1%, and should readily allow the detection of fake or badly contaminated pharmaceuticals.

"This level of accuracy could not be achieved with alternative non-invasive methods," Pavel Matousek of the laboratory's Central Laser Facility (CLF) explained to optics.org. "Near-infrared absorption spectroscopy is widely used, but the Raman approach offers much higher chemical specificity."

Using a continuous-wave laser system supplying 250 mW of power at 827 nm, the SORS technique works by collecting Raman scattering from regions that are offset from the point of illumination. The laterally offset spectra contain contributions from layers located at different depths in the sample, rather than just the surface layer. Numerical methods are then used to separate out the spectra from the different depths.

"SORS is a new technique developed in our laboratory about two years ago," said Matousek. "The concept is being developed for a wide range of applications, including the diagnosis of cancer and bone disease, and detecting powder and liquid explosives through non-metallic containers. Our study, in co-operation with Pfizer, is the first feasibility study demonstrating the ability to quantify the content of active pharmaceutical ingredients and excipients [non-active ingredients] in capsules."

Conventional Raman analysis suffers from strong oversensitivity to surface layers and is of limited use for this kind of analysis, but SORS can look more deeply. "We previously demonstrated the ability of this method to suppress fluorescence and Raman signatures of the capsule shell or other overlaying signals," said Matousek. "These can often blind detectors with strong signals that preclude the observation of subsurface layers." A variation on SORS called the transmission Raman method collects signals from the opposite side of the capsule to the incident radiation, and provides bulk information on its composition to complement the SORS results.

The direct collaboration between CLF scientists and Pfizer that produced this breakthrough is a model for transferring research into commercial solutions, according to the Science and Technology Facilities Council that sponsors the Rutherford Appleton lab. "One of the key challenges is to gain deep insight into the requirements of the capsule manufacturing process, enabling us to optimize the technique that we are developing. This can only be achieved in close collaboration with the pharmaceutical industry, and we presently have several such partners," commented Matousek. "We have also spun out a new company called LiteThru that will bring this technology to market."

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