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Engineering Solutions for the Process Industry

Periodic Reporting for period 1 - PROCESS (Engineering Solutions for the Process Industry)

Reporting period: 2018-08-13 to 2020-08-12

PROCESS is running from August 2018-2023 and is understood as ‘Engineering Solutions for the PROCESS Industry’. The programme proposes two-year Career Development Fellowships based at the University of Limerick. PROCESS ran two calls during the first year: which is currently in its infancy with three Fellows finished year one. Each Fellow completes a mandatory secondment of between three to six months with a non-academic partner. The goal of PROCESS is to deliver world-class training and research opportunities to post-doctoral Fellows in order to increase Europe’s critical mass in the field of advanced manufacturing. The aims are to:

FOR FELLOWS: Provide a cutting-edge research environment to develop PROCESS researchers as the scientific leaders of tomorrow; deliver high quality, tailor-made scientific training to equip Fellows with skills and experience to meet their career goals and address contemporary skill gaps; provide excellent training in transferable skills; provide industry-specific training and placements in dairy and pharmaceutical sectors; and provide an attractive and supportive working environment.
FOR ACADEMIC and INDUSTRIAL HOSTS: Strengthen and raise the excellence and impact of European particulate processing and advanced manufacturing research; build partnerships between academia and industry; opportunity for industry to shape training component to ensure Fellows graduate with industry-relevant skills to fill the growing needs of the food and pharmaceutical sectors; and innovation based on a deeper understanding of key technologies with interdisciplinary knowledge sharing and transfer.

The overall objectives of PROCESS is advanced manufacturing of high volume products and engineering solutions with a particular emphasis on particulate product processing for new products in the dairy and pharmaceutical sectors. Core research focus areas are incorporating process modelling and integrated process control with Process Analytical Technology, heat, mass momentum transfer, hybrid processing and smart data management. From an Industry 4.0 framework perspective: agility, processing and flexibility are promoted. Sharing knowledge and findings between academia and industry is a primary focus and adds value through encouragement of innovation based on a deep understanding of their key technologies. The importance for society is Open Science and Innovation to meet the growing global demand for innovative solutions in the processing sector and employment opportunities. Skilled engineers, scientists and researchers will lead and drive transformational changes in the dairy and pharmaceutical sectors with their expertise in continuous processing, flexibility and process understanding. Optimising the potential in continuous particulate processing and advanced manufacturing will ensure the Irish and EU manufacturing sector remains globally competitive.
The first research project is about multi-steps paliperidone synthesis over four steps in flow chemistry mode. The project title is ‘Reactor Design for Continuous Paliperidone’. The four steps span milestones and deliverables set and achieved to date. The first milestone is the synthesis of high purity paliperidone using multi-step batch experiment while the second milestone is reactor design for flow synthesis paliperidone. Similarly, the first deliverable is to provide a detailed understanding of the underlying parameters affecting the synthesis of paliperidone while the second deliverable is to determine the best continuous reactor configuration for flow of omeprazole. A summary of the research work done highlights: (i) a literature review about batch and continuous paliperidone synthesis; (ii) preparation of chemicals and equipment; (iii) conducting batch experiments for synthesis of first step; (iv) preparation of flow chemistry system using coil reactor; (v) fabrication of chip reactor using 3D printing technique; and (vi) preliminary modeling and simulation of API synthesis in continuous mode.The second research project is about is about (i) experimental work on co-crystal formation: generating experimental data for a “API+conformer” system; (ii) DFT Analysis: generating trajectories and molecular descriptors; and (iii) PBM analysis: particle level model for TSG process. The project title is ‘Generating and Evaluating Trajectories required to Train and Build our ML algorithm in order to use Ramen Spectra as a quality indicator and Control Decision Factor in TSG’. With multiple milestones and deliverables set and achieved to date, a summary of the research work so far points out that on-the-fly-learning can be implemented onto TSG and therefore a ML-based controller can be realized as a commercial output at this stage.The third research project is about (i) preparation of multi-component pharmaceutical materials (MPM’s); (ii) solid-state and (bio)pharmaceutical profiling of MPM’s and (iii) oral formulation prototypes and pharmaceutical scale up.The project title is ‘Chalcogen and Halogen Bonding for the Synthesis of Multi-component Pharmaceutical Materials: from Crystal Engineering to Formulation’. With multiple milestones and deliverables set and achieved to date, a summary of the research work so far maintains that most new chemical entities being studied for use as the active pharmaceutical ingredient (API) of a medicine are classified as ‘low solubility’, an indicator that low bioavailability could limit their clinical utility, especially when delivered as an oral medicine. This research is focused on using multi-component crystalline materials (cocrystals or salts) to solving the problems of low solubility and low bioavailability of APIs used for treatment of major diseases including diabetes, mental disorders and prevention of blood clots and strokes. Prior to experimental work, the Cambridge Structural Database (CSD) was surveyed to enable a detailed analysis of the solid state supramolecular chemistry of several target APIs in the context of identifying pharmaceutically acceptable coformers. A library of pharmaceutically acceptable coformers were chosen with a range of solubility, hydrogen and halogen bonding capabilities. In each case, the selected coformers were required to be inexpensive, commercially available and exhibit LD50 values of >0.1g/kg. Several families of novel solid forms (salts and cocrystals) were prepared for antipsychotic and anticoagulant APIs and characterised using various solid-state and solution analytical techniques. Aqueous solubility, powder dissolution and stability studies are currently in progess to identify the most suitable solid forms for further development.
The socio-economic impact and the expected metrics of the project will be realized towards the end of the timeframe. The current maturity is at 12 months where the first cohort of Fellows started work October 2019. COVID-19 global health pandemic presented challenging times during lockdown for the Fellows during 2020 restricting their access under government guidelines to the laboratories which impacted by delaying their experiments. Outcomes will accelerate throughout the lifetime of the project and strive for progress beyond state of the art raising the excellence and impact of European particulate processing and advanced manufacturing research.