Postgraduate research opportunities Effect of hydrostatic and non-hydrostatic compression on pharmaceutical materials

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,^1–3 amino acids,^4,5 energetic materials^6,7 as well as other types such as metal-organic framework materials⁸. This project is aligned to the EPSRC funded ‘Pressure-Induced Nucleation for the Continuous Manufacture of supramolecular assemblies’ where pressure is used to isolate new multi-component materials for use as seeds in ambient pressure crystallisations^9–11. The pressures that have been used are generally in excess of 5000 atmospheres which is far beyond the pressure regime of a tabletting press. This PhD program will investigate changes that occur in pharmaceutically relevant materials under conditions similar to those in the tabletting press. We will investigate the hydrostatic and non-hydrostatic regime using diffraction and spectroscopy to elucidate the changes that occur in a range of materials from active pharmaceutical ingredients to fillers and glidants. It is anticipated that even under these pressures there will be different behaviours found for these materials. The database of knowledge that will be built will be coupled with information from the Cambridge Structural Database to begin understand how the structure (both molecular and crystal) are impacted by tabletting pressures.

This work is aligned to the EPSRC Future Manufacturing Hub Centre for Manufacture and Advanced Crystallisation located at the University of Strathclyde. PhD candidates will have access to state-of-the-art equipment for analysis during their PhD studies as well as access to programs for their own personal development

Techniques used

• High-pressure
• X-ray and neutron diffraction (Single crystal and powder)
• IR & Raman spectroscopy
• thermal analysis

Further information

1. M. A. Neumann, J. Van De Streek, F. P. A. Fabbiani, P. Hidber and O. Grassmann, Nat. Commun., 2015, 6, 7793.
2. I. D. H. Oswald, A. R. Lennie, C. R. Pulham and K. Shankland, CrystEngComm, 2010, 12, 2533.
3. B. A. Zakharov, Y. V Seryotkin, N. A. Tumanov, D. D. Paliwoda, M. Hanfland, A. V Kurnosov and E. V Boldyreva, RSC Adv., 2016, 6, 92629–92637.
4. S. A. Moggach, W. G. Marshall and S. Parsons, Acta Crystallogr. Sect. B Struct. Sci., 2006, 62, 815–825.
5. C. L. Bull, G. Flowitt-Hill, S. de Gironcoli, E. Küçükbenli, S. Parsons, C. H. Pham, H. Y. Playford and M. G. Tucker, IUCrJ, 2017, 4, 569–574.
6. A. J. Davidson, I. D. H. Oswald, D. J. Francis, A. R. Lennie, W. G. Marshall, D. I. A. Millar, C. R. Pulham, J. E. Warren and A. S. Cumming, CrystEngComm, 2008, 10, 162–165.
7. L. E. Connor, C. A. Morrison, I. D. H. Oswald, C. R. Pulham and M. R. Warren, Chem. Sci., 2017, 8, 4872–4878.
8. G. A. Craig, A. Sarkar, C. H. Woodall, M. A. Hay, K. E. R. R. Marriott, K. V Kamenev, S. A. Moggach, E. K. Brechin, S. Parsons, G. Rajaraman and M. Murrie, Chem. Sci., 2018, 9, 1551–1559.
9. A. J. Cruz-Cabeza, R. J. Davey, I. D. H. Oswald, M. R. Ward and I. J. Sugden, CrystEngComm, 2019, 21, 2034–2042.
10. M. R. Ward, S. Younis, A. J. Cruz-Cabeza, C. L. Bull, N. P. Funnell and I. D. H. Oswald, CrystEngComm, 2019, 21, 2058–2066.
11. M. R. Ward and I. D. H. Oswald, CrystEngComm, 2019, 21, 4437–4443.