Computational models for the simulation of turbulent poly-dispersed flows: Large Eddy Simulation and Quadrature-Based Moment Method

This work focuses on the development of efficient computational tools for the simulation of turbulent multiphase polydispersed flows. In terms of methodologies we focus here on the use of Large Eddy Simulation (LES) and Quadrature-Based Methods of Moments (QBMM). In terms of applications the work is finalised, in order to be applied in the future, to particle production processes (precipitation and crystallisation in particular). An important part of the work concerns the study of the flow field in a Confined Impinging Jets Reactor (CIJR), frequently used in particle production processes. The first part is limited to the comparison and analysis of micro Particle Image Velocimetry (μPIV) experiments, carried out in a previous work, and Direct Numerical Simulation (DNS), carried out in this thesis. In particular the effects of boundary and operating conditions are studied and the numerical simulations are used to understand the experimental predictions and demonstrate the importance of unavoidable fluctuations in the experimental inlets. This represents a preparatory work for the LES modelling of the CIJR. Before investigating the accuracy of LES predictions for this particular application, the model and the implementation are studied in a more general context, represented by a well-known test case such as the periodic turbulent channel flow: the LES model implementation in TransAT, the code used in this work, is compared with DNS data and with predictions of other codes. LES simulations for the CIJR, provided with the proper boundary conditions obtained by the previous DNS/μPIV study, are then performed and compared with experiments, validating the model in a more realistic test case. Since particle precipitation and crystallization often result in complex interactions between particles and the continuous phase, in the second part of the work particular attention has been paid in the modelling of the momentum transfer and the resulting velocity of the particles (relative to the fluid). In particular the possibility of describing poly-disperse fluid-solid systems with QBMM together with LES and Equilibrium Eulerian Model (EEM) is assessed. The study is performed by comparing our predictions with DNS Lagrangian data in the turbulent channel flow previously described, seeded with particles corresponding to a realistic Particle Size Distribution (PSD). The last part of the work deals with particle collisions, extending QBMM to the investigation of non-equilibrium flows governed by the Boltzmann Equation with a hard-sphere collision kernel. The evolution of the particle velocity distribution is predicted and compared with other methods for kinetic equations such as Lattice Boltzmann Method (LBM), Discrete Velocity Method (DVM) and Grad’s Moment Method (GM). The overall results of this thesis can be extended to a broad range of other applications of single-phase, dispersed multiphase and non-equilibrium flows

Multiphase flow dynamics and mass transfer in different multiphase reactor for shear controllable synthesis process

In short, this thesis gives insight in detailed particle synthesis process modelling in two main multiphase reactors (IJR and SVFR) and experiments of synthesis of FePO4 and SiO2 aggregated particles are performed to analysis effect of hydrodynamics on particle properties. The attempt of combination of fast-mixer and external ultrasound field in micro/nano-particle synthesis has successfully intensified turbulence and such combination has positive effects on aspects of chemical reaction, mixing performance and mass transfer. Except for experimental work, the simulation work has been carried out to analyse flow patterns, turbulent intensity, chemical reaction as well as particle fluid interaction in particle synthesis process in multiphase reactors. Such investigation makes it possible to build correlations on hydrodynamic parameters and particle characteristics and helps to predict the behaviour and properties of particles. This is meaningful for design, upgrade and scale-up of multiphase reactor in synthesis process

MULTISCALE SIMULATION OF POLYMER NANOPARTICLES PRECIPITATION FOR PHARMACEUTICAL APPLICATIONS

This work focuses on the development and use of a multiscale computational tool for the simulation of the process of precipitation of polymeric nanoparticles in micro-mixers. This process, as will be shown through the rest of the thesis, is not very easy to model with single scale model (i.e., Computational Fluid Dy- namics, Population Balances, Molecular Dynamics). The main reason stands in the complex behaviour of the system investigated (the polymer); the behaviour at atomistic scale influences the macro-scale. With micro-scale (which is equivalent in our notation to the atomistic scale) we refer to all the phenomena occurring at length-scales of nanometres (1 nm = 10−9 m) and time-scales of picoseconds (1 ps = 10−12 s), whereas with macroscale we intend all the phenomena occur- ring at length-scale of meters and at time-scale of seconds. There are different models used to describes these (apparently) uncorrelated phenomena. Computa- tional Fluid Dynamics (CFD) which describes at the macroscale the motion of a fluid in a given domain often coupled with Population Balance Model (PBM) to describe the presence of a dispersed colloidal phase, and Molecular Dynamics (MD) which describes the motion of a collection of atoms in an interval of time. The coupling of these methods in a unique description of the problem is called multiscale modelling, a research area which has raised much interests in the last few years. In this work, precipitation of nanoparticles occurs in a micromixer, is investigated trough CFD-PBM, whilst the precipitation process is described by extracting some information from MD simulations, hence, coupling these differ- ent models in one description. The thesis is structured as follows: 1. The First Chapter is an introduction to the investigated problem. A brief description of the use of polymer nanoparticles in the pharmaceutical in- dustry is given, with the current state of the art. A brief overview of the different production processes and devices used will be also given 2. The Second Chapter in intended to give all the theoretical background re- quired for the understanding of the subsequent chapters. Starting from the very beginning, the governing equations for the generic N-body prob- lem are derived together with the description of the theoretical tools for the molecular dynamics. By using the Boltzmann Equation we show how to move from a description of the problem a the micro-scale (here repre- sented by the MD) to a description of the problem at the macro-scale (rep- resented by the CFD). The introduction of the Boltzmann equation (and the mesoscale) is also useful since the PBM is a kinetic equation very similar to the Boltzmann equation 3. The Third Chapter involves the description of the CFD model of the micro- mixer used in this study. The polymeric nanoparticles precipitation model is presented along with its intrinsic limitations highlighting the need of a more fundamental approach 4. In the Fourth Chapter we discuss the improvement of the CFD model by developing a nucleation theory adequate to the description of the polymer particle formation. The parameters appearing in this theory are estimated by using the standard full atoms MD simulations. Eventually the nucle- ation theory is integrated into the CFD-PBM and used to simulate the entire process 5. The Fifth Chapter is devoted to the extension of the MD framework. In fact, in order to further investigate the polymer particle formation process, larger systems, involving many polymeric chains have to be described. This requires some form of partial coarse-graining, resulting in hybrid atomistic/coarse-grained model. The framework to do this is in this chapter described, showing how the model allows to speed up the simulation by ne- glecting some Degrees of Freedom of the original problem but maintaining the necessary details where needed 6. In the last Chapter some conclusions from the simulations presented are draw

Multiphase flow dynamics and mass transfer in different multiphase reactor for shear controllable synthesis process

In short, this thesis gives insight in detailed particle synthesis process modelling in two main multiphase reactors (IJR and SVFR) and experiments of synthesis of FePO4 and SiO2 aggregated particles are performed to analysis effect of hydrodynamics on particle properties. The attempt of combination of fast-mixer and external ultrasound field in micro/nano-particle synthesis has successfully intensified turbulence and such combination has positive effects on aspects of chemical reaction, mixing performance and mass transfer. Except for experimental work, the simulation work has been carried out to analyse flow patterns, turbulent intensity, chemical reaction as well as particle fluid interaction in particle synthesis process in multiphase reactors. Such investigation makes it possible to build correlations on hydrodynamic parameters and particle characteristics and helps to predict the behaviour and properties of particles. This is meaningful for design, upgrade and scale-up of multiphase reactor in synthesis process

Optimization and design of reactive crystallization process

Crystallization is an important process used in a wide range of industries, which has made it the main process in the primary manufacturing stage, and thereby the quality of crystals produced has a major impact on downstream processes such as filtration, milling and drying, as well as transport and storage processes. Organic reactive crystallization, which is widely used in the production of active pharmaceutical ingredients (APIs), has many unique features that make it different from cooling or anti-solvent crystallization, even leading to some concepts and methods not directly applicable to this process. A survey of the literature reveals that previous research on reactive crystallization has mainly been conducted for inorganic materials which are known to be simpler than crystallization of organic materials. For example, it is known that compared with inorganic materials, organic materials tend more to aggregation and form amorphous. In addition, the published literature in this research area is often concerned with laboratory scale crystallization, rather than industrial scale processes. The focus of this research project is to carry out research on the process design, optimization, simulation and scale-up of organic reactive pharmaceutical crystallization. The objective is to research the process and crystallizer design which takes advantage of the features of the reactive crystallization process and on simulation, optimization and scale-up techniques with the aim of manufacturing high quality products measured by the products’ crystallinity, stability, purity, and processability. Process analytical technology (PAT) is used as a supporting tool to achieve the above stated objectives. An off-patent drug, sodium cefuroxime which is considered as a second generation antibiotic, is used as the case study drug. Firstly, on-line Attenuated Total Reflection-Fourier Transform InfraRed spectroscopy (ATR-FTIR) was used to monitor the change in the supersaturation in order to optimize the flow rate of the anti-solvent during the anti-solvent re-crystallization process of sodium cefuroxime. The solubility of sodium cefuroxime under various temperatures T, pH values and solvents was measured and correlated in models. The effect of the anti-solvent (95% ethanol) flow rate on crystallinity was examined and the results showed that appropriate anti-solvent flow rate could improve the stability of sodium cefuroxime. The optimized anti-solvent re-crystallization process provided a new method to obtain high-quality seeds of sodium cefuroxime. Secondly, Process Analytical Technology (PAT) based on Focused Beam Reflectance Measurement (FBRM) was used to optimize the parameters of the reactive synthesis process of sodium cefuroxime, such as the feed order, the reaction temperature, the stirring speed, the feed rate/speed and the amount of seeds. An impinging jet mixer, which could provide rapid mixing effectiveness of reactants, was applied and optimized. After that, the optimized process was scaled-up from 1L to 10L with a volumetric scaling-up factor of 10. The product had superior crystallinity, uniform size distribution, higher stability and purity, which indicated that this optimization methodology and impinging jet mixer design could be applied in other similar reactive crystallization processes. Finally, Process Analytical Technology (PAT) including Ultraviolet–Visible Spectrometry (UV) and FBRM was used to study the reaction kinetics and the mechanism of crystal growth in the reactive synthesis process of sodium cefuroxime. A process and crystallizer was designed based on the data obtained above. This process provided two reactors in series for conducting a rapid reactive crystallization process of pharmaceutical compounds in continuous mode. It involved a tank reactor with the use of an impinging jet mixer and stirrer to create intensive mixing of the reactants before nucleation and a tubular reactor with suitable length to avoid back mixing of the products. The results showed that by using this process, the product had uniform size distribution, higher stability and superior crystallinity, in both laboratory scale and 50L scaled-up processes

Proceedings of the 10th Australasian Heat and Mass Transfer Conference (AHMT2016)

Proceedings of The 10th Australasian Heat and Mass Transfer Conference (AHMT2016). The proceedings contain the selected full-length papers from the 10th Australasian Conference of Heat and Mass Transfer held in Brisbane, Australia on 14-15 July 2016. The conference was organised by Queensland University of Technology under the auspices of the Australasian Fluid and Thermal Engineering Society (AFTES) of Engineers Australia. Scientifically, these collected articles reflect recent progress made in heat and mass transfer in the Australasian community, including both fundamental and applied topics in the broad areas of convection, conduction, radiation, turbulence, multi-phase flow, combustion, drying, heat exchangers, phase change, computational methods, experimental methods, and other significant thermal processes in environmental, industrial, and process engineering. All the papers published in this volume were reviewed under a rigorous review process, where at least two reviews were received for each paper, according to the HERDC standard. The Organizing Committee is grateful to all of the contributors who made this volume possible. We would like to express our sincere appreciation to all authors and reviewers for their excellent contributions as well as the AHMT2016 scientific committee and financial support provided by Queensland University of Technology and Engineers Australi

Process Simulation of Technical Precipitation Processes - The Influence of Mixing

This work develops and shows up methods to tackle multi-scale challenges in particle formation during precipitation crystallization. Firstly, molecular, micro- and meso-scale interactions in confined impinging jet mixers are investigated and simulatively predicted. Secondly, to build up on developed methods, macroscale as present for instance in stirred tank reactors is added to the considerations

Heat Transfer

Over the past few decades there has been a prolific increase in research and development in area of heat transfer, heat exchangers and their associated technologies. This book is a collection of current research in the above mentioned areas and describes modelling, numerical methods, simulation and information technology with modern ideas and methods to analyse and enhance heat transfer for single and multiphase systems. The topics considered include various basic concepts of heat transfer, the fundamental modes of heat transfer (namely conduction, convection and radiation), thermophysical properties, computational methodologies, control, stabilization and optimization problems, condensation, boiling and freezing, with many real-world problems and important modern applications. The book is divided in four sections : "Inverse, Stabilization and Optimization Problems", "Numerical Methods and Calculations", "Heat Transfer in Mini/Micro Systems", "Energy Transfer and Solid Materials", and each section discusses various issues, methods and applications in accordance with the subjects. The combination of fundamental approach with many important practical applications of current interest will make this book of interest to researchers, scientists, engineers and graduate students in many disciplines, who make use of mathematical modelling, inverse problems, implementation of recently developed numerical methods in this multidisciplinary field as well as to experimental and theoretical researchers in the field of heat and mass transfer