The development of pharmaceutical freeze-drying production methods using novel process analytical technology. A self-funded PhD programme (for self-funded students only)

About the project

About the Project An overview of the project The project, supervised by Professors Geoff Smith ( ORCID ) and Muyiwa Oyinlola , is based in the School of Pharmacy within the Faculty of Health and Life Sciences at De Montfort University, located in the multicultural city of Leicester . You will be working with an emerging process analytical technology— Through-Vial Impedance Spectroscopy ( TVIS )—which is being developed into a commercial product by LyosenZ Ltd, a UK-based company also located in Leicester. This technology enables pharmaceutical development scientists to characterise and optimise the freeze-drying process, in which a drug product solution (contained within a vial) undergoes a sequence of stages: freezing (and optionally annealing), primary drying (sublimation of ice), and secondary drying (removal of water from the solids fraction via heat-driven desorption). The outcome is a porous “cake” with acceptable shelf life that can be easily reconstituted with water prior to patient administration. Our group also has access to Raman and Near-Infrared (NIR) spectroscopy, which may feature in your project depending on research direction and opportunities. For more information on the DMU LyoGroup see the link . You will have the chance to visit our partner organisations, which currently include Lonza and the UK Medicines and Healthcare Products Regulatory Agency (MHRA). Additional opportunities to gain experience installing and trialing the technology at other pharmaceutical companies are anticipated, in collaboration with LyosenZ Ltd. A limited travel budget will be available to support your participation in these visits and to provide training on the technology. TVIS offers the potential to reduce cycle times and production costs while lowering carbon emissions. By the end of the project, you will have developed a unique skill set and deep expertise in freeze-drying process development—positioning you strongly for a career in pharmaceutical manufacturing and technology innovation. The context for the project The biopharmaceutical industry is experiencing a steady increase in the number of injectable products introduced each year, with approximately 40% of these requiring batch freeze-drying to prolong shelf life. While advances in biotechnological methods have enabled the production of room-temperature-stable liquid formulations for some active drug molecules, the growing diversity and complexity of novel modalities—particularly antibody-drug conjugates, nanoparticles, and mRNA-based vaccines and therapeutics—continues to drive the need for freeze-drying as the preferred method for producing stable drug products and vaccines. There are also environmental benefits to freeze-drying, as it reduces reliance on refrigeration and cold-chain infrastructure during distribution. However, the rising number of freeze-dried products underscores a growing urgency to improve the sustainability of this time- and energy-intensive process, in which batch drying times typically range from 48 to 72 hours. Accelerating the drying phase can not only enhance batch throughput but also significantly reduce energy consumption, lowering production costs and mitigating associated emissions. The solution Novel, in-situ rapid analytical monitoring using a range of process analytical technologies (PAT) can provide real-time, automated data that can be linked to process models to enable continuous oversight and control of the complex freeze-drying procedure. This new level of insight has the potential to shorten development timelines, reduce the number of repetitive runs and product failures, lower environmental impact and bioburden, and ultimately enhance both product quality and uniformity. Furthermore, as the industry shifts toward personalized medicines, smaller batch runs, and "just-in-time" production schedules, it becomes increasingly important to adapt freeze-drying processes accordingly. Process analytical technology is seen as the cornerstone for delivering the real-time data needed for effective modelling and optimization. Your project You will be working with a relatively new method for monitoring the lyophilization cycle, in laboratory to pilot scale (developmental) dryers, called through-vial impedance spectroscopy (which is abbreviated to TVIS, and pronounced tee-vis). TVIS has a unique capability for the non-invasive characterisation of both the ice fraction and the solids fraction within the glass vial used to freeze-dry injectable drug products. This is achieved through the measurement of a range of dielectric and conductive processes, including the dielectric relaxation of ice and the conduction (i.e., percolation) of charge through the solids fraction. The diversity of phenomena measured by TVIS provides a unique opportunity to accurately determine the freezing temperature and freezing time, the stability of the solids fraction, individual vial ice interface temperatures, and sublimation rates. It also enables identification of the endpoints of each process stage—namely, the freezing stage, the sublimation of ice (primary drying), and the desorption of moisture (secondary drying)—with potential reductions in process time of 10–15%. Once determined you will then input data in the process models that we are developing for the optimization of each parameter. Industrial collaboration We are currently working with a number of pharmaceutical companies and the UK Medicines and Healthcare Products Regulatory Agency to support the implementation of TVIS technology in their freeze-drying process development. Through these collaborations, we aim to offer limited work experience opportunities, allowing you to visit their facilities and assist in the application of the technology. Additionally, through our partnership with LyosenZ Ltd—who are actively developing TVIS into a commercial platform—we hope to fund trips to engage with new collaborators, where you will play a key role in deploying the technology. Application Process To apply for the PhD project, you will need to first register on De Montfort University’s application portal. Click this link to create your account https://dmuhub.dmu.ac.uk/apply/index.html#/logon Your Research Proposal As part of the application process, you will be expected to complete a research proposal that outlines “The key challenges in the development of the freeze-drying process”. Advice on the Research Proposal will be given by Prof. Smith and therefore you are encouraged to discuss this with him prior to making your application. Some general advice is given on the university website ( link ). Upload your Research Proposal to the Application Portal when finalising your application.

Research areas