The properties of drugs can be improved by using high pressure to make different crystalline forms, claim UK scientists.

Unusually short hydrogen bonds form between paracetamol and piperazine in the cocrystal

Iain Oswald and Colin Pulham at the University of Edinburgh studied the cocrystallisation of paracetamol and piperazine under high pressure. They observed unexpected structural properties, such as unusually short hydrogen bonds, which disappeared when they reduced the pressure.

Cocrystallisation involves combining two or more molecules to form new crystals. It is a useful tool in the pharmaceutical industry because the new crystals can show improved properties over the individual crystals, such as solubility and stability. Until now, however, cocrystallisation of pharmaceuticals at high pressure has not been studied.

Oswald explains that interactions between molecules at high pressure are poorly understood, making it difficult to predict a crystal's properties. He says he hopes that analysing the structures of cocrystals at high pressure will provide some insight. 'The method will not only increase our understanding of the organic solid state at pressure but it will also provide the cocrystal community with an extra dimension in materials discovery,' says Oswald.

Andrew Bond, an expert in solid state structure interactions at the University of Southern Denmark, Odense, finds the work exciting. 'It allows the forces between molecules in condensed phases to be perturbed and new crystallisation outcomes observed,' he commented.

Oswald and Pulham plan to investigate other cocrystals under pressure to find structures that are also stable at atmospheric pressure. They will also use larger pressure chambers to produce bulk quantities of material. 'This will allow the industrial viability of crystals to be assessed under ambient conditions,' says Oswald.

Harriet Brewerton