University of Cambridge

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Non clinical PhD Studentship (Fixed Term) in Magnetic resonance imaging studies of freeze drying and reconstitution of pharmaceuticals

Applications are invited for 3.5-year PhD studentship based in the Department of Chemical Engineering & Biotechnology, University of Cambridge and the new AstraZeneca Discovery Centre at Cambridge. The student will be working on a collaborative project jointly supervised by Prof Mick Mantle in The Department of Chemical Engineering & Biotechnology and Dr Richard Storey and Dr Les Hughes at AstraZeneca and will have the opportunity to work across the two sites. The project is in the field pharmaceutical/biopharmaceutical development that has generated much excitement in both academia and industry.

Freeze drying has the ability to improve stability of both large and small molecules permitting more temperate storage conditions and hence energy saving across the lifetime of the product. The technique is widely used for small molecules, "next generation therapeutics" and larger biopharmaceuticals. Examples include hormones and monoclonal antibodies (mAbs). Of these, mAbs accounted for 50% of the top ten best-selling drugs in 2020, with sales of $59 billion, and more than 800 are currently being studied in clinical trials. Reconstitution times of lyophilized (freeze dried) formulations can often be variable and result in heterogeneous suspensions, especially when high solids content is present, as is often the case to minimise drying times, dosage volumes and transportation costs. This variability, and the links between freeze-drier conditions (e.g., cooling rates, annealing and drying times) and product performance, are not always well understood and tend to rely on empirical development. In order to build a digital twin for lyophilization this link needs to be better understood and key product parameters are needed to build and verify the model, e.g., lyophile (solid cake) porosity and tortuosity. Recent work by Cambridge and Medimmune (now AZ) demonstrated the potential of magnetic resonance imaging and relaxometry to quantify reconstitution times of mAb based formulations in-situ. This proposal aims to build upon our previous research(1), (2) with new avenues of research: (i) we will build an MRI compatible freeze drying/lyophilization rig that fits within a MRI magnet in Cambridge, allowing us to monitor, in real time, freeze drying; (ii) 3D characterization of the freeze dried solid cake porosity and tortuosity using gas and liquid phase MRI; (iii) Establish the link between freeze-drier operating conditions and product reconstitution performance.

The magnetic resonance research centre at the Department of Chemical Engineering & Biotechnology in Cambridge is a world class facility housing a vibrant and diverse research group. The are 8 superconducting NMR/MRI instruments along with a number of lower field permanent magnet systems which cover a large range of magnetic fields. The successful applicant will have the opportunity to spend extended periods of time working in AstraZeneca's research facilities based in Macclesfield, UK. Applicants for this PhD position should have a first-class or high upper second-class undergraduate degree. Note the fully funded studentship is only available to UK residents or those with UK residential status. Non-UK residents may apply on the understanding that they are responsible for the additional fees and costs associated with overseas student status.

1.) "Application of Magnetic Resonance to Assess Lyophilized Drug Product Reconstitution". Thomas A. Partridge, Mahammad Ahmed, Sureshkumar B. Choudhary, Christopher F. van der Walle, Sajal M. Patel, Steven M. Bishop & Mick D. Mantle , Pharmaceutical Research 36, 71, 2019.

2.) "NMR and Thermal Studies for the Characterization of Mass Transport and Phase Separation in Paracetamol/Copovidone Hot-Melt Extrusion Formulations". Pisa, E. Hughes, LP. Wren, SAC. Booth, J. McCabe, JF. Whittaker, DTE. Mantle, MD. Molecular Pharmaceutics, 17, Issue 6, 2021-2033.

We are looking for a highly motivated and enthusiastic individual capable of thinking and working independently. Applicants should have or shortly expect to obtain a first or high second-class degree from a UK university, or an equivalent standard ( from an overseas university, in a relevant subject such as Chemistry, Biology, Engineering or a related discipline. This position is open to UK citizens or overseas students who meet the UK residency requirements ( or are able to augment the funds to cover the extra costs associated with overseas student fees. (Note for Overseas Fee Rate applicants: If you wish to additionally be considered for the University's funding competition, you must submit the formal application (details below) for admission by 1 Dec 2022.)

Full details of the University's entrance requirements are specified on the following link:

Full funding covering Maintenance and the University Composition Fee and is provided for the studentship, with effect from 1 October 2023.

Application Process Information on our PhD programme, along with further information on entry requirements and a link to the on-line application, is available via the University's Course Directory:*iv0l7c*gaMTI0NTUyNzYwNS4xNjY3Mzg1MzA0gaP8Q1QT5W4K*MTY2NzM4NTMwNC4xLjEuMTY2NzM4NTU0NS4wLjAuMA..

To be considered for this studentship, applicants must submit a formal application for admission along with all required supporting documents (please see above link). Applicants must note Prof Mick Mantle as the prospective supervisor and that you wish to be considered for Non clinical PhD Studentship (Fixed Term) in Magnetic resonance imaging studies of freeze drying and reconstitution of pharmaceuticals (NQ34152) in the application. Late or incomplete applications will not be considered.

The closing date for applications is 31st January 2023. We anticipate that interviews will take place in early March.

Please quote reference NQ34152 on your application and in any correspondence about this vacancy.

The University actively supports equality, diversity and inclusion and encourages applications from all sections of society.

The University has a responsibility to ensure that all employees are eligible to live and work in the UK.