PhD programmes

Our MPhil/PhD projects are at the forefront of research into the next generation process analytical technologies(PAT) used for the development of pharmaceutical freeze-drying processes. Freeze-drying is increasingly being used in the pharma industry for the stabilization of drugs for injection, and especially for novel biologic drug products (which are often referred to as “new modalities”) which is a significant factor underpinning the growth in freeze-drying equipment sales (Report Ocean, 2022). These new modalities (from antibody-drug conjugates to nanoparticulate solids, and liposomal mRNA vaccines) are significantly more complex than the traditional small molecule injectable drug products. This complexity places additional demands of how best to create products with optimal shelf-life stability while allowing for ease of administration to the patient; The requirement for ultra-low temperature storage of the Pfizer BioNTech vaccines being a case in point.

Our freeze-drying research programmes are part of a wider university research focus on Lifelong wellbeing. Lifelong wellbeing is an over-arching research theme promoting interdisciplinary research across all faculties and researchers at DMU. The World Health Organization (WHO) defines health as “a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity.” Against the backdrop of mapping the human genome, leading to an ever increasing diversity of drug therapies and vaccines, the opportunities provided by pharmaceutical interventions has never been greater.

Here at the Leicester School of Pharmacy we are well placed to make a real contribution to the development of these novel therapeutic products, through our work on the optimization of the freeze-drying process. We have a unique approach of “multiplexing” a number of individual PAT systems for real-time monitoring of critical aspects of the product as it undergoes the freeze-drying process. We work with instrumentation companies specialising in Raman, near-infrared and terahertz spectroscopy (respectively IS Instruments Ltd, Ocean Optics and Teraview Ltd) to combine these technologies with our novel impedance technology (known as through-vial impedance spectroscopy, TVIS) alongside more traditional approaches such as the batch endpoint (to primary drying) using comparative pressure measurements, and single vial thermocouple temperature sensors. Each technology can be used in a stand-off mode and therefore adaptable for use in continuous freeze-drying, especially those production methods whereby single vials (i.e. the final product container) are suspended and passed through a series of chambers in order to first freeze, then dry the product under vacuum.

Such combinations of technologies are key to evaluating each aspect of the process. For example, Raman and terahertz spectroscopies are capable of discriminating between different crystalline states (polymorphic forms) within the solids fraction of the frozen and/or dried product; Infrared is capable of detecting and quantifying the moisture content of the solids fraction (which is an important attribute in terms of the stability of the drug substance during shelf life); whereas impedance spectroscopy measures the (i) dielectric relaxation of ice, and (ii) the percolation of charge through the solids fraction, and is therefore sensitive to the properties of both the ice fraction (inc. ice temperature and ice mass) and the solids fraction (inc. the glass transition and devitrification). Applications for through-vial impedance spectroscopy therefore span the freezing stage (to determine the ice nucleation temperature and ice solidification time), through the annealing stage (to assess devitrification and recrystallization phenomenon), and to the primary drying stage (to determine ice temperatures, sublimation rates and sublimation end points).

We are working in partnership with the pharma industry (e.g. AstraZeneca’s formulation development of next generation therapeutics), freeze-drying specialists (e.g. Biopharma Group), process engineering companies (GEA LyoPhil, Germany), and the UK Medicines Regulator (the MHRA) who prepare stable formulations and standards for biologicals, through its National Institute for Biological Standards and Control. Many of these organizations currently have our TVIS technology in their research laboratories and are actively working with us on developing real world applications for this unique process analytical technology.

If you would like to study for a post graduate degree (MPhil to PhD) then we are always interested in considering applications from self-funded international and home students, with suitable qualifications.