Right first time: pioneering new methods of drug manufacture

Ensuring drug crystals are formed correctly is crucial to their efficacy and the efficiency of pharmaceutical manufacturers' operations. Using self-assembled monolayers, the team has been able to show that crystals form into their desired product form with the correct shape and particle structure, without the usual problems of polymorphism which results in huge losses to the pharmaceutical sector each year.

"If you imagine the way that oil sits on top of water, that's similar to how the monolayer works," says Professor Kevin Roberts of University's Faculty of Engineering. "We've shown that we can produce a well-defined crystal structure using a self-assembled monolayer bound onto a metal substrate within a regular reactor. This is exciting stuff, because it's a relatively simple system, but could make a huge difference in the efficiency of drug manufacture."

One of the first stages of the crystallisation process is called nucleation. During nucleation, particles are introduced into a reactor to encourage the formation of crystals. However, the way in which this is currently carried out is difficult to control and can often lead to the wrong shape, size or structure of drug crystal, something which affects the usefulness and efficacy of the compound.

The new system proven to work by the Leeds team, working alongside Ana Kwokal from Croatian pharmaceutical company PLIVA, has shown that introducing a self-assembled monolayer - a layer of self-organising molecules that is attractive to the substance being crystallised - into a reactor enables consistent crystal formation.

Professor Roberts says: "Because this is a really simple solution to ensuring consistent crystallisation, it has huge potential commercially. Our next steps are to make sure it's just as efficient on an industrial scale."
This work draws on previous research and experimental systems developed through the Chemicals Behaving Badly II initiative, an Engineering and Physical Sciences Research Council (EPSRC) programme which includes universities and industrial partners.


Further information from:
Clare Elsley, Campuspr: tel 0113 258 9880, mob: 07767 685168, email:
clare@campuspr.co.uk

Guy Dixon, University of Leeds Press Office: tel 0113 343 8299, email g.dixon@leeds.ac.uk


Notes to editors:
1.    This research is published in a paper entitled Polymorph-Directing Seeding of Entacapone Crystallization in Aqueous/Acetone Solution Using a Self-Assembled Molecular Layer on Au (100) in a special edition of Crystal Growth & Design, published by ACS Publications.

A copy of the paper is available to journalists on request.
2.    Chemicals Behaving Badly II is primarily concerned with optimal design of batch reactors using in-process measurement and advanced modelling techniques. It works in measurement and modelling across the length scales relevant to pharmaceutical and inorganic fine chemical production.

3.    The Faculty of Engineering at the University of Leeds comprises five Schools:
Civil Engineering; Computing; Electronic and Electrical Engineering; Mechanical Engineering and Process, Materials and Environmental Engineering. All schools in the Faculty have the highest 5 or 5* Research Assessment Exercise ratings, top teaching assessments and strong industrial connections. There are approximately 3,000 students in the Faculty, 80% undergraduates and 20% postgraduates.  Two-thirds of our students are from the UK with the remainder representing over 90 different nationalities.

4.    The 2008 Research Assessment Exercise showed the University of Leeds to be the UK's eighth biggest research powerhouse. The University is one of the largest higher education institutions in the UK and a member of the Russell Group of research-intensive universities. The University's vision is to secure a place among the world's top 50 by 2015. www.leeds.ac.uk

5.    The Engineering and Physical Sciences Research Council (EPSRC) is the UK's main agency for funding research in engineering and the physical sciences. The EPSRC invests more than £800 million a year in research and postgraduate training to tackle the challenges of the 21st Century.  www.epsrc.ac.uk