Periodic Reporting for period 1 - APPFlow (Active Pharmaceutical Production in Flow)
Período documentado: 2019-01-01 hasta 2020-12-31
APPFlow (Active Pharmaceutical Production in Flow) will develop three Early Stage Researchers (ESRs) in innovative research centred on flow chemistry, an area that is essential for the pharmaceutical and fine chemical industries in Europe. APPFlow is a European Industrial Doctorate (EID) scheme and the three ESRs will work towards obtaining a PhD (awarded by Queen’s University, Belfast) while collaborating closely with industrial collaborators (Arran Chemical Company and the Almac Group). The ESRs will carry out their research in both academic and industrial laboratories, giving them a broad and valuable range of experiences and training that will make them highly employable at the end of the programme.
The production of pharmaceuticals and many fine chemicals still relies on batch operations. Many modern efficient synthetic routes require hazardous reagents and conditions, which are dangerous to scale using batch reactions, for example, reactions that use highly reactive intermediates or flammable gases. Continuous operation allows much smaller reactors to be used, which makes the hazards associated with using dangerous conditions much easier to manage and therefore utilise on an industrial scale. APPFlow aims to develop safer and more efficient processes for the production of important chemicals. This is positive for society, as it means that these chemicals are produced in a more sustainable manner, producing less waste, and requiring less energy.
The programme will foster an environment that enables:
• industry relevant training that will give 3 ESRs skills and fundamental knowledge in cutting-edge sustainable chemistry and chemical engineering.
• the undertaking of innovative multidisciplinary research projects that will benefit the European chemical industry and consequently the European community as a whole
• the implementation of research expertise, transferable skills and career development skills through synergistic multidisciplinary interactions
• the development of flow processes, and dissemination of understanding that will enable industry to target a larger portfolio of chemistries.
The production of pharmaceuticals and many fine chemicals still relies on batch operations. Many modern efficient synthetic routes require hazardous reagents and conditions, which are dangerous to scale using batch reactions, for example, reactions that use highly reactive intermediates or flammable gases. Continuous operation allows much smaller reactors to be used, which makes the hazards associated with using dangerous conditions much easier to manage and therefore utilise on an industrial scale. APPFlow aims to develop safer and more efficient processes for the production of important chemicals. This is positive for society, as it means that these chemicals are produced in a more sustainable manner, producing less waste, and requiring less energy.
The programme will foster an environment that enables:
• industry relevant training that will give 3 ESRs skills and fundamental knowledge in cutting-edge sustainable chemistry and chemical engineering.
• the undertaking of innovative multidisciplinary research projects that will benefit the European chemical industry and consequently the European community as a whole
• the implementation of research expertise, transferable skills and career development skills through synergistic multidisciplinary interactions
• the development of flow processes, and dissemination of understanding that will enable industry to target a larger portfolio of chemistries.
The early stage researchers (ESRs) that have been recruited have embarked on three research projects aimed at developing know-how and understanding that will enable chemistry to move from batch to continuous processing.
ESR1 is examining chemistry which utilises organometallic reagents, which are highly reactive and dangerous to scale due to the flammability of such reactions. Studies comparing batch and flow processes, have shown the importance of issues such as mixing and effective heat management and demonstrated that conditions reported for batch chemistry cannot be scaled safely using the methods reported in academic studies.
ESR2 is studying oxidation chemistry and to-date has been examining catalytic reactions which employ peroxides as the active oxidants. These types of reactions can be extremely fast and heat management is important in order to ensure safety operation and avoid runaway reactions. In this project, catalyst screening has determined a method that enables the effective oxidation of alkenes (to epoxides) and alcohols (to carbonyls) with reaction rates that are suitable for continuous flow operation. Studies have shown that batch performance can be replicated in a flow system, offering a more scalable approach for such reactions.
ESR3 is examining catalytic reduction chemistry and is exploring transfer hydrogenation methods and those that utilise hydrogen gas. The utilisation of pyrophoric materials (e.g. metal hydrides) and flammable gases pose significant challenges for scaling these in batch mode. The use of flow reactors enables smaller reactors to be used and the hazards can be more easily managed. To-date, ESR3 has carried out studies of small-scale batch reactions in order to gain an understanding of kinetic profiles and determine product selectivities. Flow studies have now started and factors such as catalyst stability and long-term performance are being investigated.
The three ESRs have also availed of scientific and complimentary skills training at Queen’s University Belfast. This has ranged from technical training (e.g. analytical chemistry) to transferable areas such as writing and presentation skills. Furthermore, all of the ESRs have completed a course and obtained a recognised, accredited qualification from the Chartered Management Institute (CMI). This CMI course focused on leadership, project management and entrepreneurial practice.
ESR1 is examining chemistry which utilises organometallic reagents, which are highly reactive and dangerous to scale due to the flammability of such reactions. Studies comparing batch and flow processes, have shown the importance of issues such as mixing and effective heat management and demonstrated that conditions reported for batch chemistry cannot be scaled safely using the methods reported in academic studies.
ESR2 is studying oxidation chemistry and to-date has been examining catalytic reactions which employ peroxides as the active oxidants. These types of reactions can be extremely fast and heat management is important in order to ensure safety operation and avoid runaway reactions. In this project, catalyst screening has determined a method that enables the effective oxidation of alkenes (to epoxides) and alcohols (to carbonyls) with reaction rates that are suitable for continuous flow operation. Studies have shown that batch performance can be replicated in a flow system, offering a more scalable approach for such reactions.
ESR3 is examining catalytic reduction chemistry and is exploring transfer hydrogenation methods and those that utilise hydrogen gas. The utilisation of pyrophoric materials (e.g. metal hydrides) and flammable gases pose significant challenges for scaling these in batch mode. The use of flow reactors enables smaller reactors to be used and the hazards can be more easily managed. To-date, ESR3 has carried out studies of small-scale batch reactions in order to gain an understanding of kinetic profiles and determine product selectivities. Flow studies have now started and factors such as catalyst stability and long-term performance are being investigated.
The three ESRs have also availed of scientific and complimentary skills training at Queen’s University Belfast. This has ranged from technical training (e.g. analytical chemistry) to transferable areas such as writing and presentation skills. Furthermore, all of the ESRs have completed a course and obtained a recognised, accredited qualification from the Chartered Management Institute (CMI). This CMI course focused on leadership, project management and entrepreneurial practice.
We are currently at an early stage of the project. As the project progresses, the research will help lead to the development of new processes for the production of fine chemicals and pharmaceuticals. Such continuous flow processes will be safer, more efficient and more sustainable, which will ultimately benefit the wider society. The ESRs will receive research and transferable skills training that will make them well-equipped to become future leaders in areas such as the pharmaceutical industry.