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NMR researchers unlock hydrogen's secrets to spot polymorphism in pharmaceuticals
Date:10/17/2007

Researchers at the University of Warwick and Astra Zeneca have found a new way to use solid-state NMR equipment to crack the secrets of hydrogen atoms and thus spot unwanted polymorphs in pharmaceuticals.

Pharmaceuticals companies are constantly battling the problem of polymorphism in which an active drug can actually exist in more than one form or crystal structure which can cause the drug to act in very different ways. Now researchers at the University of Warwick and Astra Zeneca have devised a new method of using solid-state NMR (nuclear magnetic resonance) equipment to spot unwanted polymorphs that should be adopted as a routine tool by pharmaceutical companies.

NMR equipment is already used to detect polymorphism in pharmaceuticals. However the standard technique looks at the carbon 13C nuclei in the drugs by a method called cross-polarisation magic-angle spinning (CP MAS). This is a very insensitive technique as only 1 in 100 carbon nuclei are the 13C isotope. This means that 99 out of 100 carbon nuclei are a NMR-invisible form of carbon. Only one-dimensional spectra are routinely possible from such an experiment.

Researchers have long wished to be able to couple this carbon based solidstate NMR technique with one that looks at hydrogen nuclei. It has been possible to look at hydrogen when the sample is a solution (solution-state NMR) but this is not as easy in solid-state NMR as the extensive network of coupled together 1H nuclei leads to broad lines in the spectrum that are hard to tell apart. This makes it almost useless when you are examining a tablet. Tablets are also particularly difficult to examine as the active drug within the tablet is combined with a mixture of other filler compounds (excipients).

This breakthrough by the Warwick team opens up hydrogen nuclei to useful study by solid-state NMR which will bring immense benefits to the study of polymorphism in drugs and organic molecules in general. This is because
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Contact: Peter Dunn
p.j.dunn@warwick.ac.uk
0247-652-3708
University of Warwick
Source:Eurekalert

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