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  Linking molecular structure to mechanical properties of pharmaceutical materials


   Strathclyde Institute of Pharmacy & Biomedical Sciences

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  Dr I Oswald, Dr D Markl  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This 4-year EPSRC ICASE PhD studentship in collaboration with GlaxoSmithKline aims to probe the mechanical properties of pharmaceutical materials. You will be using high-pressure and nanoindentation techniques to develop an understanding of the impact of molecular structure on the mechanical properties. 

Background and Motivation

Pressure is a valuable tool in the assessment of the solid-state forms of organic materials. It has been repeatedly demonstrated that pressure can enable the isolation of new solid-state forms of pharmaceuticals, amino acids, energetic materials. Plus other types of materials such as metal-organic frameworks. This project builds on previous work in the group that investigates the role that pressure plays on the molecular structure. The pressures that have been used to date are generally in excess of 5000 atmospheres. But even at pressures between 0-1500 bar, the structure of materials may change in ways that have the potential to affect their macroscopic properties during tabletting, for example. We have evidence that mefenamic acid converts between polymorphs with pressure of manual grinding. Glycolide, a pre-cursor to the pharmaceutical polymer poly(glycolic acid), undergoes a phase transition at 1500 bar to a recoverable metastable phase.

This Project

This PhD program will investigate changes that occur in pharmaceutically relevant materials using high pressure and nanoindentation techniques. We will investigate the impact of pressure on the crystal structure of pharmaceutically relevant materials. And we will couple these observations to nanoindentation measurements performed on individual crystals. The role of hydrostatic and non-compression regimes will be explored using X-ray and neutron diffraction as well as Raman. And IR spectroscopies to elucidate the structural changes that occur. The different compression regimes will allow a more complete understanding of the response of these materials under lower, more industrially relevant pressures. As part of the project there will be opportunities to travel and conduct experiments at Central Facilities such as Diamond Light Source and ISIS Neutron and Muon Source. You will also interact with world-leading instrument scientists to maximise the impact of the work. 

Environment

This is an exciting opportunity for the successful candidate to work at University of Strathclyde and alongside scientists at GlaxoSmithKline. The candidate will have access to a dedicated national network of world-class, state-of-the-art facilities. This will include the £34M UK-RPIF funded CMAC National Facility at the University of Strathclyde (Glasgow, UK). The candidate will have opportunities to interact with fellow students in Strathclyde Institute of Pharmacy and Biomedical Sciences from those studying drug discovery to those investigating the manufacture and delivery of drug products. And in particular, students associated with the world-leading EPSRC Future Continuous Manufacturing and Advanced Crystallisation Centre (CMAC, www.cmac.ac.uk ). There will also be the opportunity for a secondment to the GlazoSmithKline. GlaxoSmithKline is an enthusiastic company that greatly values the contribution of PhD candidates. They have a large number of students working together to encourage cross-collaboration and ideas sharing and there will be regular opportunities to present work and network with students, post-docs and GSK colleagues. The student will benefit from working in this highly interdisciplinary research environment.


Chemistry (6)

Funding Notes

Funding available to UK students. EU and International are eligible to apply but costs in fees need to be covered.

References

1. Jones Eleanor C.L., Bebiano Suse S., Ward Martin R., Bimbo Luis M., Oswald Iain D.H. Chemical Communications, 2021, Vol 57, pp. 11827-11830
2. Bebiano Suse S., ter Horst Joop H., Oswald Iain D.H., Crystal Growth and Design, 2020, Vol 20, pp. 6731-6744.
3. Connor, Lauren E.; Vassileiou, Antony D.; Halbert, Gavin W.; Johnston, Blair F.; Oswald, Iain D.H. CrystEngComm, 2019, Vol. 21, No. 30, 4465.
4. Hutchison, Ian; Bull, Craig L.; Marshall, William G.; Urquhart, Andrew J.; Oswald, Iain D.H. Molecules, 2019, Vol. 24, No. 11, 2174.
5. Bhardwaj, Rajni M.; McMahon, Jennifer A.; Nyman, Jonas; Price, Louise S.; Konar, Sumit; Oswald, Iain D. H.; Pulham, Colin R.; Price, Sarah L.; Reutzel-Edens, Susan M. Journal of the American Chemical Society, 2019, Vol. 141, No. 35, 13887.

Where will I study?

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