Metrology for Pharmaceutical Manufacturing: Understanding activity from surface sub-microscale chemistry

Structure-property relationships are often poorly defined in advanced continuous pharmaceutical manufacturing processes and products and hence it is difficult to control final product performance to the degree required to deliver advanced functionality. The dynamics of particles within complex mixtures and the effect of processing and storage on their disposition and microstructure is also a measurement challenge. Hence, there is a clear need to have analytical techniques to measure physical parameters, such as composition, dynamics, and structure with increased spatial and temporal resolutions. The successful applicant will use ToF-SIMS and the 3D nanoSIMS instrument to obtain unprecedented 3D chemical imaging at the sub-micron scale and high performance mass spectral data from the Orbitrap detector that will enable spectroscopic identification of active ingredient, excipients and degradation products. Moreover, the project will deliver new measurements of surface composition and microstructure of pharmaceutical particles and formulated systems informing structure-property relationships. Drawing on optimised sample preparation methods, combining data from multiple techniques and image reconstruction, as well as, multivariate analytical techniques knowledge of the impact of process conditions on pharmaceutical products at the micron and submicron scale will be delivered. This will inform the development of innovative processes and product types to achieve particles and products with desired structures and performances. Whilst the immediate focus is on pharmaceutical systems, there is potential for application to other high value chemical sectors including agrochemicals, dyes and pigments. The Ph.D. is aligned with the EPSRC Centre in Continuous Manufacturing and Crystallisation (CMAC; www.cmac.ac.uk), with significant support from CMAC’s strategic partners (e.g. AstraZeneca, GlaxoSmithKline). Moreover, the project is in collaboration and co-supervised by the National Physical Laboratory (NPL), therefore the successful candidate will have to spend at least 30% of their time at NPL facilities in London.

Techniques to be used:
Atomic Force Microscopy (AFM), Micro Contact Angle Goniometry (CAG), Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), 3D nanoSIMS, nano-CT (Computed Tomography).