Characterization of crystallization processes with video imaging

Crystallization processes are extensively utilized for the purification and separation of a variety of final and intermediate products. Despite its widespread use, in the fine chemicals, pharmaceutical and food industries, crystallization still has many unknowns which can affect the purity, quality and quantity of the crystals produced. As a result, monitoring crystallization processes in order to better understand the underlying science is of utmost importance. To this end, various tools have been developed. They are, however, not without their flaws. The work in this PhD project aims to develop and demonstrate the viability of process video imaging as a reliable methodology for the monitoring, recording and analysis of crystallization processes which either minimizes or removes these flaws altogether. Experimental investigations to test the robustness of the process video imaging focused on three commonly found crystallization processes: melt crystallization in the form of clathrate hydrates, anti-solvent crystallization and cooling crystallization. The results from these investigations were compared to previously reported findings of similar systems in order to examine the degree of accuracy of the process video imaging tool. The significant findings from this work are that the process video imaging can be successfully implemented into melt, anti-solvent and cooling crystallization systems with relative ease. This allowed key crystallization parameters to be determined; including but not limited to: solubility, metastable zone width, crystallization rate and growth kinetics

Inducing Increased Bioplastic Production in \u3ci\u3eR. palustris\u3c/i\u3e CGA009

PHA’s (polyhydroxyalkanoates) are important bio polymers in different industries such as petroleum, medicine, and nano technology. In the microorganisms in which they are produced, they serve as an energy storage material by storing both carbon and usable electrons. This is useful in environments where the organisms are nutrient starved. PHA’s have a practical use especially in the medical field as bio-plastics because they are biodegradable and bio-compatible. Rhodopseudomonas. palustris, a common soil bacterium, is notable for its uncommon metabolic flexibility. Its diverse metabolism means that it can fix CO 2 and grow on many lignin based monomers in both aerobic and anaerobic environments. Currently, R. palustris already produces PHB (polyhydroxybutyrate), but there are other PHA’s and co polymers that have superior processing characteristics and applications. Our research will investigate the effect of the PHA production genes from Paraburkholderia sacchari DSM 17165 and Cupriavidus necator DSM 545 when introduced into R. palustris and potentially R. palustris strains with their native PHA production genes knocked out Both P. sacchari and C. necator produce higher titers of PHA’s as well as co polymers with improved processing characteristics and more applications than R. palustris ’ current PHB production. Our research will work to combine the metabolic flexibility of R. palustris with the higher PHA and co polymer production of P sacchari and C. necator by introducing genes for PhaA, PhaB, and PhaC production into R. palustris

Prediction of powder flow of pharmaceutical materials from physical particle properties using machine learning

Understanding powder flow and how it affects pharmaceutical manufacturing process performance remains a significant challenge for industry. This work aims to improve decision making for manufacturing route selection, achieving the key goal of digital design within Industry 4.0 of being able to better predict properties whilst minimizing the amount of material required and time to inform process selection during early-stage development. A Machine Learning model approach is proposed to predict the flow properties of new materials from their physical properties. The model’s implementation will enhance manufacturing quality by taking advantage of the data generated throughout the manufacturing process

Establishment of a continuous sonocrystallization process for lactose in an oscillatory baffled crystallizer

Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale

Development and characterisation of a cascade of moving baffle oscillatory crystallisers (CMBOC)

A novel four stage Cascade of Moving Baffle Oscillatory Crystallisers (CMBOC) is developed, characterised and implemented for continuous crystallisation of pharmaceuticals. The platform was fully automated with pressure controlled slurry transfer and process analytical tools (PAT) to support process monitoring and control. Model predictive control was used to achieve precise temperature control during operation of crystallisations. Mixing and flow characterisation for liquids and slurries was performed confirming near-ideal mixing performance for mean residence times in the range 20 – 90 min. Heat transfer characteristics were determined and shown to be well suited to the demands of cooling crystallisation processes. Heat transfer efficiency increased with increasing oscillatory Reynolds number (Reo). This cascade is shown to provide the advantages of more uniform mixing and efficient heat transfer performance compared to a traditional cascade of stirred tank crystallisers. Continuous crystallisations of both alpha lactose monohydrate (ALM) and paracetamol (PCM) were carried out in which the target size, form, agglomeration and encrustation were controlled. For ALM, the products showed a narrow particle size distribution (PSD) with dv50 = 65 ± 5 μm and a span of 1.4 ± 0.2, and achieved a yield of 70%. The continuous crystallisation of paracetamol in the CMBOC produced non-agglomerated product with dv50 = 398 ± 20μm with a span of 1.5 ± 0.2 and achieved an 85% yield. No fouling or encrustation in the vessels or transfer lines were observed during the processes. The flexible configuration and operation of the platform coupled with well characterised shear rate distribution, residence time distributions and heat transfer shows that this platform is well suited to a range of crystallisation modes including seeded, antisolvent, cooling or reactive processes, where careful control of crystal attributes is required

Characterization and modelling of antisolvent crystallization of salicylic acid in a continuous oscillatory baffled crystallizer

Using antisolvent crystallisation of salicylic acid as the model process, we report our experimental investigation into the temporal and spatial steady states of solution concentration and mean crystal size in a continuous oscillatory baffled crystallizer. The evolutions of the two parameters over time and distance along the crystallizer are measured for a variety of operating conditions. The results show that the attainment of long term temporal and spatial stabilities (>100 residence times) for the solute concentrations are easily achieved, whereas the temporal steady states of the mean crystal size are more difficult to accomplish, even though the spatial steady states have been obtained. A simplified population balance model is applied to the experimental data for the determination of nucleation and growth kinetic parameters. From which both the solution concentration and the mean size were predicted and matched to experimental values reasonably well. In addition, we have identified and executed the conditions of long term steady states for extended operation of 6.25. h to produce close to 1. kg of crystal product with minimal variation in crystal size (±3.01. μm)

Methodology for cokemaking technology selection for operating conditions and expansion of iron and steel works

Selection of cokemaking technology within an Iron & Steel Works (I&SW) setting is a complicated problem, involving analysis of coal quality, coke demand and supply, environmental regulations, and the plant energy balance. The methodology involves coal blend selection, preparation, charging, cokemaking and quenching technology selection to meet the blast furnaces’ coke quality requirements and the I&SW energy balance. Hatch’s mass and energy balance, OPEX, CAPEX, Energy/CO2 and Financial Models provide the client with NPV/IRR ranking and sensitivity analysis to assist in selecting the best strategy amongst by-product or heat recovery ovens, charging and quenching systems for replacement or expansion programs

Methodology for Cokemaking Technology Selection

The objective of this article is the selection of cokemaking technology within an Iron &amp; Steel Works (I&amp;SW), involving analysis of coal quality, coke demand and supply, environmental regulations, and the plant energy balance. The methodology involves coal blend selection, preparation, charging, cokemaking and quenching technology selection to meet the blast furnaces’ coke quality requirements and the I&amp;SW energy balance. Hatch’s mass and energy balance, OPEX, CAPEX, Energy/CO2 and Financial Models provide the client with NPV/IRR ranking and sensitivity analysis to assist in selecting the best strategy amongst by-product or heat recovery ovens, charging and quenching systems for replacement or expansion programs. The developedmethodology was successfully applied for development of coal and cokemaking strategy, estimation of required cokemaking capacity for the metallurgical giant, which incorporates four integrated iron and steel works, two stand alone coke plant and several coal and iron ore mines. Some of Hatch’s recommendationsare already implemented and tested by the client. The optimum selection of cokemaking technologies requires a careful analysis of the I&amp;SW and companyspecific requirements in order to develop a techno-economic analysis that will provide the optimum strategy to get the most from existing assets and to ensure competitive future coke production. Development by Hatch methodology could be successfully applied for selection and construction of green site cokemaking facilities as well as for brown field modernizations. Keywords: By-product cokemaking, heat recovery cokemaking, energy balance, financial analysi

Contribution of Fdh3 and Glr1 to Glutathione Redox State, Stress Adaptation and Virulence in Candida albicans

Acknowledgments: We thank Aaron Mitchell and Dominique Sanglard for providing the C. albicans protein kinase and transposon mutant libraries, and Louise Walker for the strain CAMY203.Peer reviewedPublisher PD