Hydrogen gives up imposter drug's secret

Scientists have found a new way to tackle a problem in the pharmaceutical industry - one that can render drugs completely useless.

Active drugs can exist in more than one form causing them to act in very different ways

Pharmaceuticals companies are constantly battling the problem of polymorphism in which an active drug can 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.

The research team led by Dr Steven Brown from the University of Warwick’s Department of Physics have exploited recent developments in NMR hardware and pulse sequence design allowing them to gain high-resolution solid-state NMR spectra by a method called CRAMPS (combined rotation and multiple-pulse spectroscopy).

Dr Steven Brown said: “This Hydrogen 1H solid-state NMR method gives powerful new insight that complements established Carbon 13C based techniques - this new approach should be adopted as a routine tool in pharmaceutical characterisation”

NMR equipment is already used to detect polymorphism in pharmaceuticals. However the standard technique looks at the carbon 13C nuclei in the drugs. This is a very insensitive technique as only 1 in 100 carbon nuclei are the 13C isotope, meaning that 99 out of 100 carbon nuclei are a NMR-invisible form of carbon.

Researchers have long wished to be able to couple this carbon based solid–state NMR technique with one that looks at hydrogen nuclei. This is because hydrogen bonding is often the driving force in determining how organic molecules differ in their methods of 3D packing - forming polymorphs.

The new NMR technique can identify which polymorph of an active pharmaceutical is present in a complete tablet.