Dimitrios I. Gerogiorgis

The University of Edinburgh | UoE · School of Engineering, Institute for Materials and Processes (IMP)

Systematic nonlinear optimisation is a valuable tool toward evaluating the performance of Continuous Pharmaceutical Manufacturing (CPM) conceptual flowsheets. This study considers total cost minimisation for a multitude of plausible design choices and eight candidate antisolvents for the continuous recovery of artemisinin (a potent antimalarial Act...

Continuous Pharmaceutical Manufacturing (CPM) has been shown to provide significant process benefits, including cost savings and increased material efficiencies, over the currently implemented batch paradigm which suffers from poor heat transfer and mixing and high volumes of waste. The continuous flow synthesis of diphenhydramine, a first-generati...

Global demand for Low-Alcohol Beer (LAB) and Alcohol-Free Beer (AFB) has surged due to flavor attributes, health benefits, and lifestyle changes, prompting efforts for process intensification. This paper aims to offer a detailed modelling basis for LAB manufacturing study and optimisation. A first-principles dynamic model for conventional beer manu...

The variation of antigen binding sites on monoclonal antibodies (mAbs) enables manufacturing of the latter for targeted treatment of a variety of ailments, including cancer types and autoimmune diseases. Fed-batch operation of biochemical reactors used to manufacture mAbs grants the ability to manipulate cell dynamics via intermittent feeding of nu...

Integrated continuous bioprocessing (ICB) holds great promise towards achieving higher efficiency, a critical target for ensuring the advent of biopharmaceutical manufacturing. Culture productivity must be drastically improved to reduce production cost projections, especially in comparison to traditional fed-batch process platforms (Pollock et al.,...

This study analyses the impact of particle polydispersity using the Eulerian-Eulerian (EE) and Lagrangian-Eulerian (LE) modelling approaches in the context of wellbore cleaning operations in the drilling industry. Spherical particles of sizes 0.5 mm, 0.75 mm and 1 mm are considered, whereas a Power Law rheological model is used for the fluid phase...

This study presents a comparative computational examination of different cubic equations of state (EoS) on hydrate inhibition fluid systems involving real reservoir fluids. Two gas hydrate inhibitors (Monoethylene glycol – MEG and methanol) were considered alongside 4 cubic EoS namely; Cubic-Plus-Association (CPA) EoS coupled with Infochem mixing r...

Pharmaceutical manufacturing plants consist of a wide range of complex unit operations, from upstream processing aimed at synthesis of Active Pharmaceutical Ingredients (APIs) to intermediate purifications and downstream processing for final product formulation. To ensure high pharma plant performance at minimised total cost and solvent waste, oper...

Organic synthesis is a critical step in producing any Active Pharmaceutical Ingredient (API): it encompasses a series of organic (mostly catalytic) reactions and separations, whose purpose is to arrive at a solution of a target molecule, which must then undergo crystallisation for purification, followed by secondary (downstream) processing towards...

In this study, polydispersed spherical particulate systems are examined using the Eulerian-Eulerian (EE) and Lagrangian-Eulerian (LE) modelling approaches in the context of wellbore cleaning operations in the drilling industry. The particle sizes considered here are between 0.5 mm and 1mm, whereas a Power Law rheological model is used for the fluid...

Monoclonal antibodies (mAbs) are an example of therapeutic biomolecules which have been used for treatments of cancer, autoimmune diseases and other ailments. Numerous mAbs are currently being given market approval and the total mAb market value is predicted to increase for the foreseeable future. Traditionally, mAbs are manufactured via secretion...

Volatile Organic Compounds (VOCs) are a class of solvents extensively used for the production of Active Pharmaceutical Ingredients (APIs) in the pharmaceutical industry. To ensure adherence to environmental regulations, adsorption is widely implemented as an effective VOC emission abatement method. The present work relies on an adsorption model whi...

Continuous flow synthesis of Active Pharmaceutical Ingredients (APIs) can offer access to process conditions that are otherwise hazardous when operated in batch mode, resulting in improved mixing and heat transfer,...

The integrated management of oil and gas operations is a challenging task involving short to long-term decisions. Some of these decisions include valve configurations, choke openings and complex well-manifold routings [1, 2]. Hence, novel advancements in mathematics, algorithm development [3, 4] and related scientific fields have found tremendous a...

Large investments are required for the positioning and drilling of oil and gas wells, implying that decisions related to these activities may be significantly aided by sound and proven mathematical-oriented methods. The use of intuitive engineering judgement alone cannot guarantee sustainable profitability over long periods, especially under geolog...

Typical daily operations of oil and gas production systems are characterised by numerous decisions that must be carefully made if field profitability is to be sustained. These systems are usually nonlinear, nonconvex and involve binary decision variables; hence, the application of mathematical optimisation often results in an MINLP formulation. Pie...

Nosiheptide is a sulfur-containing peptide antibiotic, showing exceptional activity against critical pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE) with livestock applications that can be synthesized via fed-batch fermentation. A simplified mechanistic fed-batch fermentation model for...

Model-based oil production systems optimisation under pressure and facility routing constraints is a testing challenge, especially in presence of complex downhole wellbore phenomena (water coning, slugging, phase separation). Nonlinearities and nonconvexities from underlying physics and binary decisions exacerbate model complexity, yielding Mixed I...

Progress in continuous flow chemistry over the past two decades has facilitated significant developments in the flow synthesis of a wide variety of Active Pharmaceutical Ingredients (APIs), the foundation of Continuous Pharmaceutical Manufacturing (CPM), which has gained interest for its potential to reduce material usage, energy and costs and the...

The development of new and existing oil fields is very expensive and technically challenging; this provides an important economic incentive to improve oil recovery via efficient computational optimisation. Decisions related to these activities may be significantly aided by sound and proven mathematical-oriented methods. The use of intuitive enginee...

Active pharmaceutical ingredients (APIs) are highly valuable...

Ampicillin is a key β-lactam antibiotic listed as a World Health Organisation (WHO) Essential Medicine. Crystallisation is a unit operation of paramount importance in pharmaceutical manufacturing, whose design and operation are essential in controlling process yield and important product quality attributes, such as mean product crystal size (MCS) a...

The increased commercial presence and comparative health benefits of alcohol-free beer (AFB) provide a substantial impetus for research, particularly in the field of dynamic simulation whereby the development of accurate models can help reduce costs of experimentation. Cold Contact Fermentation (CCF) is an existing method of industrial-scale AFB pr...

Monoclonal antibodies (mAbs) are therapeutic proteins used for treating cancer, autoimmune diseases and many other critical ailments, thus constituting essential biopharmaceutical products in global healthcare. The mAb market turnover is predicted to significantly increase, with numerous new products and processes being developed each year. Current...

Industrial beer production faces many technical as well as economic challenges, with increased competition and trends towards craft beers and non-alcoholic beverages posing new challenges to brewers, who strive to minimise production costs and processing times whilst improving product quality. Milling, mashing and lautering are a major bottleneck i...

Continuous flow chemistry and synthesis have received significant attention over the past two decades for their potential for enhancing yields, selectivities, productivities, smaller operation and implementation of otherwise difficult/dangerous reactions. Recent demonstrations applied to a variety of different reaction types have highlighted the po...

Beer fermentation efficiency improvements have the strongest potential to boost profitability, as its long batch time renders this particular unit operation the throughput bottleneck of this complex, multistage biochemical process which mankind has employed for several millennia. Accurate fermentation models are critical for reliable dynamic simula...

Real-time decision making by production engineers in a petroleum field can be very challenging, especially when multiple wells with diverse operating conditions and production behaviours are present. Hence, semi-analytic or heuristic procedures are unlikely to yield an optimal operating strategy. This paper implements a Real-Time Production Optimis...

The ever‐increasing quest to identify, secure, access and operate oil and gas fields is continuously expanding to the far corners of the planet, facing extreme conditions towards exploring, securing and deriving maximum fluid benefits from established and unconventional fossil fuel sources alike: to this end, the unprecedented geological, climatic,...

In this study, the two-fluid Eulerian–Eulerian multiphase flow model in ANSYS Fluent (v17.1) is adopted for the simulation of cuttings transport in a deviated annular geometry using two different non-Newtonian drilling fluids (described using the power law and Herschel–Bulkley models). The Syamlal-O'Brien interphase momentum exchange coefficient is...

Ampicillin is a broad spectrum antibiotic and World Health Organization Essential Medicine whose crystallization is an essential unit operation in its production. A published model for the solubility of ampicillin as a function of pH as well as growth and nucleation kinetics allows for dynamic simulation and optimization of its batch crystallizatio...

Continuous pharmaceutical manufacturing (CPM) offers operational and economic benefits over the currently dominant methods implemented by industry. The demonstrated continuous flow synthesis of atropine facilitates modelling and optimization of its upstream continuous manufacturing. This work implements MINLP optimization of a continuous liquid‐liq...

Chinese Hamster Ovary (CHO) cells are widely used in fermentation towards biopharmaceutical manufacturing. The present paper presents dynamic mathematical models of two different CHO culture modes: one batch mode for the production of interferon (IFN)-γ, and one perfusion mode for the production of a monoclonal antibody (mAb). The dynamic models ha...

Amoxicillin belongs to the β-lactam family of antibiotics, a class of highly consumed pharmaceutical products used for the treatment of respiratory and urinary tract infections, and is listed as a World Health Organisation (WHO) “Essential Medicine”. The demonstrated batch enzymatic synthesis of amoxicillin is composed of a desired synthesis and tw...

Development of efficient and cost-effective manufacturing routes towards HIV Active Pharmaceutical Ingredients (APIs) is essential to ensure their global, affordable access. Continuous Pharmaceutical Manufacturing (CPM) is a new production paradigm for the pharmaceutical industry, whose potential for enhanced efficiency and economic viability over...

The Hall-Héroult process for the electrolytic reduction of alumina was developed at the end of the 19th century and is still currently the only industrial process for the production of primary aluminium. Today this process is ranked among the most energy and CO2 intensive industrial processes. The direct carbothermic reduction of alumina has been p...

A wide range of optimisation methodologies exist for solving optimal control trajectory problems. With most approaches it is necessary to solve iteratively, starting from an initialising solution (often referred to as an initial guess). In this paper we investigate the performance of two different dynamic optimisation strategies for batch beer ferm...

Epibacterium mobile BBCC367 is a marine bacterium that is common in coastal areas. It belongs to the Roseobacter clade, a widespread group in pelagic marine ecosystems. Species of the Roseobacter clade are regularly used as models to understand the evolution and physiological adaptability of generalist bacteria. E. mobile BBCC367 comprises two chro...

Continuous Pharmaceutical Manufacturing (CPM) can revolutionise industrial efficiency via potential operational and economic benefits over currently dominant batch methods. Process modelling and optimisation are valuable towards rapid design space evaluation and elucidation of optimal process design configurations, without expensive and time-consum...

Mixed Suspension-Mixed Product Removal (MSMPR) crystallizers are widely implemented as continuous crystallizers, allowing enhanced efficiency, flexibility and product quality compared to the currently dominant batch crystallizer designs. Establishing cost effective continuous crystallization process configurations for societally- and economically-i...

Accurate prediction of the flow behaviour of drill cuttings carried by a non-Newtonian fluid in an annular geometry is important for the successful and efficient design, operation, and optimisation of drilling operations. Although it is widely recognised that practical drilling operations hardly involve perfectly spherical cuttings, the relative ea...

Continuous Pharmaceutical Manufacturing (CPM) has the potential to revolutionise the pharmaceutical industry via operating and economic benefits over traditional batch techniques. Establishing efficient continuous separation processes following continuous flow syntheses of active pharmaceutical ingredients (APIs) is essential to obtain the desired...

Continuous Pharmaceutical Manufacturing (CPM) has a strong potential to catalyse pharmaceutical innovation. This paper analyses Continuous Oscillatory Baffled Crystalliser (COBC) optimal design and performance for paracetamol crystallisation, via systematic modelling and nonlinear optimization (NLP). Clear trends emerge, with rate of antisolvent us...

Continuous pharmaceutical manufacturing (CPM) has been recognized as a new production paradigm capable of achieving lower costs, higher yields and productivity, enhanced heat transfer and mixing, smaller equipment, and more economical energy and material usage. These potential benefits show significant advantages over the currently implemented batc...

Continuous pharmaceutical manufacturing (CPM) has the potential to attain several technical and operational economic benefits compared to the currently prevalent batch production paradigm. Despite the variety of demonstrated continuous flow syntheses of active pharmaceutical ingredients (APIs), the limited number of cost-effective continuous separa...

Keratin rich waste material is an abundant by-product from the agroindustry, particularly the meat and poultry industries: skin remains, bristle, animal hair, horns and hooves, feathers, etc. This waste may not be incinerated due to environmental concerns, so producers seek waste valorization by upcycling this non-biodegradable by-product by depoly...

Continuous Pharmaceutical Manufacturing (CPM) has received significant research interest as a way to achieve a step-change in the performance of pharmaceutical production, where innovations are incremental at best due to the current paradigm – batch production – being a relatively mature technology. In this work, a Continuous Oscillatory Baffled Cr...

In all drilling operations in the oil and gas industry, the generation and eventual distribution of formation rock cuttings along the wellbore constitutes a major concern to operational feasibility and profitability. The nature of the annular geometry/wellbore trajectory, rheological properties of the non-Newtonian carrier fluid and physical proper...

Continuous pharmaceutical manufacturing (CPM) has a documented potential to reduce production costs, offering opportunities to simultaneously streamline product development and improve economics for the pharmaceutical industry. Selecting technically feasible and economically viable candidate active pharmaceutical ingredients (APIs) for CPM is imper...

The treatment of diabetes as well as several other diseases which affect millions of patients worldwide strongly depend on deploying affordable technologies for frequent and accurate monitoring of blood glucose concentrations. Both theoretical and experimental investigations of novel blood glucose biosensor concepts pave the way for fast efficiency...

Continuous Pharmaceutical Manufacturing (CPM) is a promising new paradigm to produce active pharmaceutical ingredients (APIs), allowing reduced equipment dimensions, lower waste production and energy consumption, and safer operation in comparison to the industrially dominant batch methods. Rufinamide is an antiepileptic agent whose demonstrated con...

Continuous Pharmaceutical Manufacturing (CPM) has the potential to revolutionise the pharmaceutical industry, with many expected benefits in terms of cost, efficiency and quality. Process modeling and optimization are valuable methodologies for comparative technoeconomic evaluations: this paper pursues total upstream CPM cost minimisation via two n...

Understanding the intricacies of multiphase flows is paramount to any drilling operation, and this has been under continuing and intensive development for the past decades. A major complexity associated with this operation is the uncertainty in the transport phenomena of generated cuttings as drilling progresses under different attainable configura...

Fermentation is an essential step in beer brewing, often acting as the system bottleneck due to the time-consuming nature of the process stage (duration >120 h), where a trade-off exists between attainable ethanol concentration and required batch time. To explore this trade-off we employ a multi-objective plant propagation algorithm (the Strawberry...

Continuous crystallisation using Mixed Suspension-Mixed Product Removal (MSMPR) crystallisers has been demonstrated as a feasible method for implementing continuous separations in pharmaceutical manufacturing processes. This work conducts a steady-state process modelling and simulation study of the continuous cooling crystallisation of cyclosporine...

The increasing global energy demand has pushed the oil industry towards developing more innovative and advanced methods of enhancing oil recovery even under unfavourable technical and environmental conditions. The severity of many operational problems affecting the drilling and production of oil and gas wells is worsened by inaccessibility; hence,...

The declining alcohol industry in the UK and the concurrent surge in supply and variety of beer products has created extremely competitive environment for breweries, many of which are pursuing the benefits of process intensification and optimisation. To gain insight into the brewing process, an investigation into the influence of by-product thresho...

The pharmaceutical industry is currently dominated by the traditionally implemented, yet wasteful and inefficient, batch production paradigm. Continuous Pharmaceutical Manufacturing (CPM) shows potential to bring technological innovation, cost savings and environmental benefits to pharmaceutical production. This paper describes the process modellin...

The demand for more efficient and reliable oil and gas drilling fluid systems drives their development with unprecedented sophistication: the key challenge is to achieve predictable rheological properties, but also to enable their judicious customization, particularly for High Temperature High Pressure) (HTHP) applications and tough environments. T...

Temperature affects significantly the rheological behavior of neat water Wyoming Na-bentonite dispersions. The results of a very systematic study are presented regarding rheological measurements of 7% mass concentration at different temperatures, ranging between 25 and 80 °C at atmospheric pressure. Higher temperature increased the shear stresses a...

Continuous Pharmaceutical Manufacturing (CPM) has recently emerged as a promising alternative to current batch production methods which are plagued by issues of product quality, process reliability and cost. With advances in new continuous synthesis routes, demonstrations of full end-to-end continuous drug production and comparative analyses explic...

The pharmaceutical industry is currently dominated by the traditionally implemented, yet wasteful and inefficient, batch production paradigm. Continuous Pharmaceutical Manufacturing (CPM) shows potential to bring technological innovation, cost savings and environmental benefits to pharmaceutical production. This paper describes the process modellin...

The global pharmaceutical industry faces high R&D, regulatory and cost pressure which can be alleviated by the advent of Continuous Pharmaceutical Manufacturing (CPM). Embarking upon demonstrating and commissioning continuous processes is not trivial: judicious product selection and process design is quintessential for viable investments. Technolog...

Fermentation is an essential step in beer brewing: when yeast is added to hopped wort, sugars ferment into ethanol and higher alcohols. Progression is highly sensitive to the temperature manipulation invoked, influencing batch time and product quality. A novel computational implementation of a published kinetic model has been produced, rapidly gene...

Drilling fluids serve many applications in the oil-drilling process, including the removing of cuttings, drill bit cooling and the prevention of fluid transfer to and from the rock strata. With the addition of nanoparticles it is possible to facilitate in-situ control of the drilling fluid rheology, increasing the hydraulic efficiency of drilling c...

Continuous Pharmaceutical Manufacturing (CPM) is a strategy which can secure the economic competitiveness hampered by the innate drawbacks of batch production: this mature technology is the current norm for therapeutic molecules, but its key advantages are frequently outweighed by poor mixing and heat transfer, limited scalability and low Overall E...

Conventional crude oil is the currently dominant but a non-renewable energy resource. Despite the development and improvement of alternative energy technologies, there is still a large gap between the capability of renewable energy systems to capture and reliably supply power, and the ever-increasing global energy demand requirements. Therefore, un...

Continuous Pharmaceutical Manufacturing (CPM) is a strategy which can secure the economic competitiveness hampered by the innate drawbacks of batch production: this mature technology is the current norm for therapeutic molecules, but its key advantages are frequently outweighed by poor mixing and heat transfer, limited scalability and low Overall E...

Drilling fluids serve many applications in the oil-drilling process, including the removing of cuttings, drill bit cooling and the prevention of fluid transfer to and from the rock strata. With the addition of nanoparticles it is possible to facilitate in-situ control of the drilling fluid rheology, increasing the hydraulic efficiency of drilling c...

Fermentation is an essential step in beer brewing: when yeast is added to hopped wort, sugars ferment into ethanol and higher alcohols. Progression is highly sensitive to the temperature manipulation invoked, influencing batch time and product quality. A novel computational implementation of a published kinetic model has been produced, rapidly gene...

The global pharmaceutical industry faces high R&D, regulatory and cost pressure which can be alleviated by the advent of Continuous Pharmaceutical Manufacturing (CPM). Embarking upon demonstrating and commissioning continuous processes is not trivial: judicious product selection and process design is quintessential for viable investments. Technolog...

Fermentation is the central, most important unit operation in alcoholic beverage manufacturing and has already been studied by means of first-principles dynamic models, which explicitly consider the temperature effects and employ parameterisations obtained using industrial beer brewing campaign data. Nevertheless, the precise effect of initial cond...

Increasing Research and Development (R&D) costs, growing competition from generic manufacturers and dwindling rates of novel drug products reaching the market are giving impetus to the efforts of pharmaceutical firms to secure competitiveness by investigating Continuous Pharmaceutical Manufacturing (CPM). The present paper explores the CPM of two k...

Fermentation is an essential step in beer brewing: when yeast is added to hopped wort, sugars released from the grain during germination are fermented into ethanol and higher alcohols. To study, simulate and optimise the beer fermentation process, accurate models of the chemical system are required for dynamic simulation of key component concentrat...

Recent advances in pharmaceutical manufacturing techniques are showing the promise of continuous production: pharmaceutical firms currently rely on mature batch technology but increasingly evaluate the potential of Continuous Pharmaceutical Manufacturing (CPM). Continuous production techniques have efficiency, cost, reliability and quality advantag...

Continuous Pharmaceutical Manufacturing (CPM) emerges as a ground-breaking technology which can invigorate the global pharmaceutical industry by sustainably fostering its agility and the affordability of healthcare for large populations. Continuous production methods feature numerous significant technical advantages, which however need be ensured b...

Continuous Pharmaceutical Manufacturing (CPM) is a rapidly expanding research field with growing industrial importance: challenging the current batch production paradigm, it has a documented potential to deliver key cost, efficiency and environmental benefits. Ibuprofen, the potent painkiller, and artemisinin, a highly effective anti-malarial drug,...

Smart drilling fluids containing Fe3O4 nanoparticles have advantages toward increasing the hydraulic efficiency of drilling operations in a variety of reservoir environments. Exploring and optimizing the rheological behavior of such new drilling fluids is critical, implying direct and significant economic savings in developing new oil and gas field...

Beer production involves three essential, lengthy process stages: brewing, fermentation and conditioning. Process times have been established over many years' experience, and they vary due to different company philosophies. A commonly held belief by the purist brewer is that shortening fermenting or conditioning time compromises beer quality, as to...

Pharmaceutical corporations face rapidly rising process research and development (R&D) as well as production costs due to globalised competition. Batch production processes are dominant in the pharmaceutical industry and have multiple advantages, including equipment flexibility, high-fidelity quality control and the ability to recall specific batch...

Managed Pressure Drilling (MPD) addresses a multitude of technical problems encountered in carbonate reservoirs of numerous oil fields. The solid cuttings transport flowrate, stability and cost of cuttings transport from the carbonate rock formation towards the surface must be monitored accurately, because drilling safety and efficiency is of param...

Semiconductor photocatalysis in principle relies on the use of irradiation for catalyst activation and has received considerable attention over the past decades toward achieving efficient removal of organic toxic substances from wastewater effluents. Moreover, solar photocatalysis is considered as a cost-effective and sustainable water treatment te...

Pharmaceutical corporations face rapidly rising R&D as well as production costs. Batch production processes are dominant in the pharmaceutical industry and have multiple advantages, including equipment flexibility, efficient high-fidelity quality control and the ability to recall specific batches; however, they suffer known disadvantages such as li...

Recent advances in pharmaceutical manufacturing techniques are showing the promise of continuous production, and pharmaceutical firms, currently reliant on mature batch technology, are beginning to turn toward Continuous Pharmaceutical Manufacturing (CPM). Continuous production techniques have efficiency, cost, reliability and quality advantages: i...