Gerogiorgis, Dimitrios

Polydorides, Nicholas

Blair, Matthew William

Engineering and Physical Sciences Research Council (EPSRC)

EPSRC Industrial CASE Studentship

AstraZeneca

2026-01-29T12:55:12Z

2025-11-20

The development of cost-optimal yet sustainable manufacturing processes is a growing priority in the pharmaceutical industry, with many institutions hoping to become carbon neutral in the near future. However, the majority of research and development (R&D) activities within the sector still rely heavily on the use of experimental trials, making the design of new processes labour intensive and materially expensive. Consequently, process development costs have been rising amid increasingly stringent environmental regulations which demand the deployment of greener manufacturing platforms. It has therefore been postulated that mathematical modelling should be used as a means of accelerating R&D activities by using predictive science to reduce the number of experimental trials required. However, there is currently a lack of organised frameworks available to support this type of work – especially when it comes to process optimisation. Considering this, this PhD presents numerical modelling frameworks which can be used to quickly simulate, visualise and optimise pharmaceutical manufacturing processes. Further to this, it demonstrates how these processes may be modelled using data which is already routinely collected by pharmaceutical companies during early-stage drug development (i.e., kinetic reaction and solubility data). To achieve this goal, high-fidelity process models have been developed for common unit operations seen in pharmaceutical manufacturing (i.e., reactors, crystallisers and liquid-liquid extraction units). With the identification, development and parameterisation of fit-for-purpose kinetic reaction and solubility models forming an important part of this work. Meanwhile, established process economics models have been used alongside green metrics (e.g., E-factor, Scope 1 and 2 emissions) to assess the cost, emissions and material efficiency of these processes. To display the capabilities of these tools, manufacturing processes involved in the production an experimental anti-cancer drug, adavosertib (AZD1775), and a non-steroidal anti-inflammatory drug (NSAID), flurbiprofen, have been studied – though the principles used to conduct this work could be easily applied to a wide range of other pharmaceuticals. Consequently, the design space associated with each process has been visualised to explore the impact of solvent choice, system, temperature, process volume, and reagent concentrations on process viability – ultimately, allowing their manufacturing costs, campaign times and carbon emissions to be minimised.

https://era.ed.ac.uk/handle/1842/44350

https://doi.org/10.7488/era/6870

en

The University of Edinburgh

Blair, M.; Molaei Chalchooghi, M.; Cox, R.; Gerogiorgis, D. I. Reaction Kinetics for the Synthesis of an Anti-Cancer Drug (Adavosertib) Precursor. React. Chem. Eng., 2025. DOI: 10.1039/D5RE00082C.

Blair, M.; Molaei Chalchooghi, M.; Cox, R.; Gerogiorgis, D. I. Solubility Modelling for Key Organic Compounds Used in Adavosertib (Anti-cancer API) Manufacturing. ACS Omega, 2025, 10, 27964−27975. DOI: 10.1021/acsomega.5c01526

Blair, M.; Molaei Chalchooghi, M.; Cox, R.; Gerogiorgis, D. I. Design Space Visualization and Technoeconomic Evaluation of a Batch Manufacturing Process for the Green Production of an Anti-cancer Drug (Adavosertib) Precursor. Org. Proc. Res. Dev., 2025. DOI: 10.1021/acs.oprd.5c00056.

Blair, M.; Gerogiorgis, D. I. Solvent selection, sustainability analysis, technoeconomic evaluation and optimisation of batch cooling crystallisation for flurbiprofen production. Comput. Chem. Eng., 2025, 199, 109116. DOI: 10.1016/j.compchemeng.2025.109116

Blair, M.; Gerogiorgis, D.I., Cost-optimal Solvent Selection for Batch Cooling Crystallisation of Flurbiprofen. In 35th European Symposium on Computer Aided Process Engineering (ESCAPE35), J.F.M. Van Impe, G. Léonard, S.S. Bhonsale, M.E. Polańska, F. Logist, Eds.; Systems & Control Transactions; Elsevier: 2025; pp 2510- 2515. DOI: 10.69997/sct.170946

2031-01-29

computational modelling

pharmaceutical industry

common unit operations

optimisation

environmentally friendly manufacturing platforms

adavosertib

non-steroidal anti-inflammatory drug

flurbiprofen

drug development

Technoeconomically and environmentally optimal design of reactors and separators in pharmaceutical manufacturing of adavosertib and flurbiprofen

Thesis or Dissertation

Doctoral

PhD Doctor of Philosophy

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