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,^1,2 amino acids,³ energetic materials⁴ as well as other types such as metal-organic framework materials.⁵

This PhD 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.

We have shown that under compaction, materials can change polymorphic form but our understanding of what drives these transitions is lacking.⁶ This project will build a database of observations that can be used in conjunction with information from the Cambridge Structural Database to begin understanding how the structure (both molecular and crystal) are impacted by tabletting pressures.

This quality of observations will enable the use of multi-dimensional techniques such as Principal Component Analysis to provide a framework to assess whether materials are likely to transform under these conditions.

This work is aligned to the recently awarded EPSRC MediForge Hub (CMAC) & CEDAR CDT programs 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

References

(1) Boldyreva, E. V. Non-Ambient Conditions in the Investigation and Manufacturing of Drug Forms. Curr. Pharm. Des. 2016, No. 32, 4981–5000.

(2) Jones, E. C. L.; Bebiano, S. S.; Ward, M. R.; Bimbo, L. M.; Oswald, I. D. H. Pressure-Induced Superelastic Behaviour of Isonicotinamide. Chem. Commun. 2021, 57 (89), 11827–11830. 

(3) Novelli, G.; Maynard-Casely, H. E.; McIntyre, G. J.; Warren, M. R.; Parsons, S. Effect of High Pressure on the Crystal Structures of Polymorphs of L-Histidine. Cryst. Growth Des. 2020, 20 (12), 7788–7804. 

(4) Millar, D. I. A.; Oswald, I. D. H.; Francis, D. J.; Marshall, W. G.; Pulham, C. R.; Cumming, A. S. The Crystal Structure of Beta-RDX-an Elusive Form of an Explosive Revealed. Chem. Commun. Camb. Engl. 2009, No. 5, 562–564.

(5) McMonagle, C. J.; Turner, G. F.; Jones, I.; Allan, D. R.; Warren, M. R.; Kamenev, K. V.; Parsons, S.; Wright, P. A.; Moggach, S. A. Pressure and Guest-Mediated Pore Shape Modification in a Small Pore MOF to 1200 Bar. Chem. Commun. 2022, 58 (82), 11507–11510.

(6) Gasol-Cardona, J.; Ward, M. R.; Gutowski, O.; Drnec, J.; Jandl, C.; Stam, D.; Maloney, A. G. P.; Markl, D.; Price, S. W. T.; Oswald, I. D. H. Spatial and Temporal Visualization of Polymorphic Transformations in Pharmaceutical Tablets. Angew. Chem. Int. Ed. 2025, 64 (2), e202412976.