Inside information

Researchers have perfected a new laser-based technique which they claim can 'see' the bulk chemical content of drug capsules — without opening them.

The technology is the result of a joint collaboration between the

(STFC) at Rutherford Appleton Laboratory in Oxfordshire and teams from global pharmaceutical giant

.

They claim the method can determine the quantity of active pharmaceutical ingredient in capsules to a relative error of one per cent. Other established non-invasive methods tried by the teams were unable to reach the same level of accuracy with the same sample.

The development — which holds great potential for a range of process control applications in the pharmaceutical industry — stems from research into a novel Raman spectroscopy method, Spatially Offset Raman Spectroscopy.

This is under development at STFC for a wide range of applications, including the detection of explosives in non-metallic containers, 'spotting' counterfeit drugs through opaque packaging and the non-invasive diagnosis of bone disease and cancer.

The concepts, which are relatively simple to implement, were developed through experiments involving STFC's large-scale facilities which provided crucial insight into photon transport processes.

Project leader, Prof Pavel Matousek, said the most popular spectroscopy detection method currently used in pharmaceutical applications is near-infrared absorption spectroscopy, but it cannot be used to penetrate capsules on the production line.

'It is overwhelmed by signals from the capsule shell,' said Matousek. 'This is similar to not seeing stars during the day. They are there, but you are blinded by the sunlight.'

Raman spectroscopy has been around for many years, but it was mainly a technique for surface detection. The STFC was able to increase its penetration depth by using a concept called 'diffused component of light'.

The researchers shone a laser on to a sample capsule, and instead of collecting the signal from the same surface on which they shone the laser, they collected a signal from the other side of the capsule.

'That enabled us to suppress this blinding signal and separate the surface from sub-surface signal to such a degree that we could see very clearly what is inside,' said Matousek. 'It extended penetration depth with tablets to several millimetres and when we experimented with human tissue it increased penetration up to 20mm.'

So, with such a simple solution, why had it not been done before?

'Simply, no-one had thought of it,' said Matousek. 'Raman spectroscopy is a technique which is inherently very weak. People didn't think photons could be found so far away from the deposition point. Our experiments made us realise that the lifetime of a photon was much longer than people thought.'

When the photons come back from the sample they are dispersed with a spectrograph — which is like dispersing sunlight into different colours using a prism. With a charge-coupled device (CCD) camera a pattern of colours can be examined. 'Each molecule will have its own pattern that is distinct, like a fingerprint, and the compound can easily be identified,' said Matousek.

The system could be packaged into something the size of a shoe box, which could be easily integrated on to a production line.

In experiments it took between one to five seconds to shine the laser and retrieve information about the contents of the tablet. But Matousek said with some slight modifications they could reduce that to a fraction of a second.

The technique — which could be up and running on the production lines of some of the world's biggest pharmaceutical manufacturers in a year — is planned for commercialisation through STFC's spin-out company LiteThru. The team has already received interest from AstraZeneca and GlaxoSmithKline.

Beyond the production line, Matousek sees the technology used to identify counterfeit drugs. 'This is of great importance because in developing countries a large percentage of drugs purchased are fake,' he said. 'As a result many people die, so this is another very important area we hope the technology can address.'