Oscillatory flow reactors (OFRs) for continuous manufacturing and crystallization

Continuous crystallization is an attractive approach for the delivery of consistent particles with specified critical quality attributes (CQAs), which are attracting increased interest for the manufacture of high value materials, including fine chemicals and pharmaceuticals. Oscillatory flow reactors (OFRs) offer a suitable platform to deliver consistent operating conditions under plug-flow operation while maintaining a controlled steady state. This review provides a brief overview of OFR technology before outlining the operating principles and summarizing applications, emphasizing the use for controlled continuous crystallization. While significant progress has been made to date, areas for further development are highlighted that will enhance the range of applications and ease of implementation of OFR technology. These depend on specific applications but include scale down, materials of construction suitable for chemical compatibility, encrustation mitigation, the enhancement of robust operation via auto...

[1]  M. Mackley,et al.  The functionalization of carbon nanotubes using a batch oscillatory flow reactor , 2012 .

[2]  Adam Harvey,et al.  Mixing Through Oscillations and Pulsations—A Guide to Achieving Process Enhancements in the Chemical and Process Industries , 2003 .

[3]  X. Ni,et al.  Scale-up correlation for mass transfer coefficients in pulsed baffled reactors , 1996 .

[4]  Andrew G. Livingston,et al.  Use of Continuous MSMPR Crystallization with Integrated Nanofiltration Membrane Recycle for Enhanced Yield and Purity in API Crystallization , 2014 .

[5]  K. Plumb,et al.  Continuous Processing in the Pharmaceutical Industry: Changing the Mind Set , 2005 .

[6]  Malcolm H. I. Baird,et al.  Handbook of Solvent Extraction , 1991 .

[7]  Ping Gao,et al.  Photooxidation of a model pollutant in an oscillatory flow reactor with baffles , 2003 .

[8]  Malcolm R. Mackley,et al.  A pulsatile flow bioreactor , 1992 .

[9]  Adam Harvey,et al.  Process intensification of biodiesel production using a continuous oscillatory flow reactor , 2003 .

[10]  Hongbing Jian,et al.  On modelling turbulent flow in an oscillatory baffled column – RANS model or large‐eddy simulation? , 2002 .

[11]  Dimitri Mignard,et al.  On the evaluation of droplet breakage and coalescence rates in an oscillatory baffled reactor , 2002 .

[12]  Jun-ichi Yoshida,et al.  Green and sustainable chemical synthesis using flow microreactors. , 2011, ChemSusChem.

[13]  Xiongwei Ni,et al.  A Systematic Study of the Effect of Geometrical Parameters on Mixing Time in Oscillatory Baffled Columns , 1998 .

[14]  Gerry Steele,et al.  Continuous Crystallization of Pharmaceuticals Using a Continuous Oscillatory Baffled Crystallizer , 2009 .

[15]  Dimitri Mignard,et al.  Determination of breakage rates of oil droplets in a continuous oscillatory baffled tube , 2006 .

[16]  J. Fortuin,et al.  Axial dispersion in single-phase flow in a pulsed packed column containing structured packing , 1991 .

[17]  Clive A. Greated,et al.  Experimental Study of Flocculation of Bentonite and Alcaligenes Eutrophus in a Batch Oscillatory Baffled Flocculator , 2001 .

[18]  R. Field,et al.  Enhancement of liquid phase adsorption column performance by means of oscillatory flow: an experimental study , 2004 .

[19]  Kevin J. Roberts,et al.  On the Crystal Polymorphic Forms of l-Glutamic Acid Following Temperature Programmed Crystallization in a Batch Oscillatory Baffled Crystallizer , 2004 .

[20]  P. Stonestreet,et al.  The Effects of Oscillatory Flow and Bulk Flow Components on Residence Time Distribution in Baffled Tube Reactors , 1999 .

[21]  M. Baird,et al.  Characteristics of a countercurrent reciprocating plate bubble column. II. Axial mixing and mass transfer , 1988 .

[22]  Allan S. Myerson,et al.  Development of Continuous Anti-Solvent/Cooling Crystallization Process using Cascaded Mixed Suspension, Mixed Product Removal Crystallizers , 2012 .

[23]  Xiongwei Ni,et al.  A study of oil-water dispersion in a pulsed baffled reactor , 1996 .

[24]  Brian Glennon,et al.  Characterization of the anti-solvent batch, plug flow and MSMPR crystallization of benzoic acid , 2013 .

[25]  Eva Roblegg,et al.  Continuous Sonocrystallization of Acetylsalicylic Acid (ASA): Control of Crystal Size , 2012 .

[26]  Xiongwei Ni,et al.  Droplet size distribution in a continuous oscillatory baffled reactor , 2001 .

[27]  Christopher L. Burcham,et al.  Regions of attainable particle sizes in continuous and batch crystallization processes , 2014 .

[28]  On the investigation of the effect of apparatus configurations on the nucleation mechanisms in a cooling crystallization of sodium chlorate , 2014 .

[29]  Xiongwei Ni,et al.  Effects of mixing, seeding, material of baffles and final temperature on solution crystallization of l-glutamic acid in an oscillatory baffled crystallizer , 2010 .

[30]  António A. Vicente,et al.  Residence times and mixing of a novel continuous oscillatory flow screening reactor , 2004 .

[31]  Malcolm R. Mackley,et al.  Experimental observations on flow patterns and energy losses for oscillatory flow in ducts containing sharp edges , 1989 .

[32]  Xiongwei Ni,et al.  Correlation of polymer particle size with droplet size in suspension polymerisation of methylmethacrylate in a batch oscillatory-baffled reactor , 1999 .

[33]  Anh N. Phan,et al.  Development and evaluation of novel designs of continuous mesoscale oscillatory baffled reactors , 2010 .

[34]  P. T. Anastas,et al.  Chapter 2 The twelve principles of green engineering as a foundation for sustainability , 2006 .

[35]  Cameron J. Brown,et al.  Evaluation of growth kinetics of antisolvent crystallization of paracetamol in an oscillatory baffled crystallizer utilizing video imaging , 2011 .

[36]  A. W. Nienow,et al.  Impeller Power Numbers in Closed Vessels , 1971 .

[37]  Tony Howes,et al.  Experimental axial dispersion for oscillatory flow through a baffled tube , 1990 .

[38]  Xiongwei Ni,et al.  On the determination of axial dispersion coefficient in a batch oscillatory baffled column using laser induced fluorescence , 2003 .

[39]  Aniruddha B. Pandit,et al.  Enhancement of gas-liquid mass transfer using oscillatory flow in a baffled tube , 1993 .

[40]  Alan Jones,et al.  Experimental investigation into dynamics and stability of continuous MSMPR agglomerative precipitation of CaCO3 crystals , 1997 .

[41]  P. Stonestreet,et al.  Evaluation of a novel self‐aerating, oscillating baffle column , 1998 .

[42]  E. Kougoulos,et al.  Continuous crystallization of adipic acid with ultrasound , 2011 .

[43]  G. Whitesides.  The origins and the future of microfluidics , 2006, Nature.

[44]  Allan S. Myerson,et al.  Continuous Plug Flow Crystallization of Pharmaceutical Compounds , 2010 .

[45]  R. I. Ristic,et al.  Oscillatory Mixing for Crystallization of High Crystal Perfection Pharmaceuticals , 2007 .

[46]  K. Piotrowski,et al.  Crystallization of vitamin C in a continuous DT MSMPR crystallizer – Size independent growth kinetic model approach , 2008 .

[47]  X. Ni,et al.  Characterization of a gas‐liquid OBC: Bubble size and gas holdup , 2004 .

[48]  Cameron J. Brown,et al.  Online evaluation of paracetamol antisolvent crystallization growth rate with video imaging in an oscillatory baffled crystallizer , 2011 .

[49]  J. Teixeira,et al.  Aqueous two-phase micellar systems in an oscillatory flow micro-reactor: study of perspectives and experimental performance , 2011 .

[50]  Michael J. Hounslow,et al.  Population balance modelling of droplet coalescence and break-up in an oscillatory baffled reactor , 2004 .

[51]  M. Baird,et al.  Power consumption and gas hold-up in a pulsed column , 1967 .

[52]  K. Piotrowski,et al.  Continuous reaction crystallization of struvite from diluted aqueous solution of phosphate(V) ions in the presence of magnesium ions excess , 2014 .

[53]  Ryan L. Hartman,et al.  Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. , 2011, Angewandte Chemie.

[54]  Daniel Hsieh,et al.  Development and Scale-Up of Three Consecutive Continuous Reactions for Production of 6-Hydroxybuspirone , 2008 .

[55]  Malcolm R. Mackley.  Process innovation using oscillatory flow within baffled tubes , 1991 .

[56]  R. A. Bajura,et al.  A Numerical Analysis of Pulsating Laminar Flow Through a Pipe Orifice , 1991 .

[57]  Timothy F. Jamison,et al.  Continuous flow multi-step organic synthesis , 2010 .

[58]  Jeremy L. Steinbacher,et al.  Greener approaches to organic synthesis using microreactor technology. , 2007, Chemical reviews.

[59]  Nuno M. Reis,et al.  Novel oscillatory flow reactors for biotechnological applications , 2006 .

[60]  A. Phan,et al.  Rapid Production of Biodiesel in Mesoscale Oscillatory Baffled Reactors , 2012 .

[61]  Malcolm R. Mackley,et al.  The simulation of stretch rates for the quantitative prediction and mapping of mixing within a channel flow , 1995 .

[62]  J. Teixeira,et al.  Proof‐of‐concept of a novel micro‐bioreactor for fast development of industrial bioprocesses , 2006, Biotechnology and bioengineering.

[63]  The development of asymmetry and period doubling for oscillatory flow in baffled channels , 1996 .

[64]  Cameron J. Brown,et al.  Determination of metastable zone width, mean particle size and detectable number density using video imaging in an oscillatory baffled crystallizer , 2012 .

[65]  O. Levenspiel.  Chemical Reaction Engineering , 1972 .

[66]  X. Ni.  A study of fluid dispersion in oscillatory flow through a baffled tube , 1995 .

[67]  Malcolm R. Mackley,et al.  The mixing and separation of particle suspensions using oscillatory flow in baffled tubes , 1993 .

[68]  Reinaldo Giudici,et al.  Analysis of axial dispersion in an oscillatory-flow continuous reactor , 2003 .

[69]  Paul Bowen,et al.  Development of a Continuous Segmented Flow Tubular Reactor and the “Scale-out” Concept – In Search of Perfect Powders , 2003 .

[70]  G. Vilar,et al.  On line analysis of structure of dispersions in an oscillatory baffled reactor using electrical impedance tomography , 2008 .

[71]  Adam Harvey,et al.  Operation and Optimization of an Oscillatory Flow Continuous Reactor , 2001 .

[72]  David C. Sherrington,et al.  Butylation of phenylacetonitrile in an oscillatory baffled reactor , 2005 .

[73]  P. Stonestreet,et al.  Energy dissipation in oscillatory flow within a baffled tube , 1995 .

[74]  D. Pritchard,et al.  A study of mass transfer in yeast in a pulsed baffled bioreactor , 1995, Biotechnology and bioengineering.

[75]  M. Baird,et al.  Gas absorption in a pulsed bubble column , 1972 .

[76]  Ricardo Nuno Correia Pereira,et al.  Enhanced Gas−Liquid Mass Transfer of an Oscillatory Constricted-Tubular Reactor , 2008 .

[77]  Adam Harvey,et al.  Fluid Mechanics and Design Aspects of a Novel Oscillatory Flow Screening Mesoreactor , 2005 .

[78]  S. Y. Wong,et al.  Modeling the Crystallization Kinetic Rates of Lactose via Artificial Neural Network , 2010 .

[79]  António A. Vicente,et al.  The intensification of gas–liquid flows with a periodic, constricted oscillatory-meso tube , 2007 .

[80]  Richard D Braatz,et al.  Control Systems Engineering in Continuous Pharmaceutical Manufacturing May 20-21, 2014 Continuous Manufacturing Symposium. , 2015, Journal of pharmaceutical sciences.

[81]  R. I. Ristic,et al.  Crystallization by Oscillatory and Conventional Mixing at Constant Power Density (R&D Note) , 2005 .

[82]  H. Muhr,et al.  Effect of calcium based additives on the sodium bicarbonate crystallization in a MSMPR reactor , 2014 .

[83]  Xiongwei Ni,et al.  Computational fluid dynamic modelling of flow patterns in an oscillatory baffled column , 2002 .

[84]  Ian Sobey.  The occurrence of separation in oscillatory flow , 1983 .

[85]  Cameron J. Brown,et al.  Evaluation of rate of cyclopentane hydrate formation in an oscillatory baffled column using laser induced fluorescence and energy balance , 2010 .

[86]  M. Ralph.  Oscillatory flows in wavy-walled tubes , 1986, Journal of Fluid Mechanics.

[87]  Ricardo J. Bogaert-Alvarez,et al.  Continuous Processing to Control a Potentially Hazardous Process: Conversion of Aryl 1,1-Dimethylpropargyl Ethers to 2,2-Dimethylchromenes (2,2-Dimethyl-2H-1-Benzopyrans) , 2001 .

[88]  Jaroslav Nývlt,et al.  Kinetics of nucleation in solutions , 1968 .

[89]  Iain D. H. Oswald,et al.  From discovery to scale-up: alpha-lipoic acid : nicotinamide co-crystals in a continuous oscillatory baffled crystalliser , 2014 .

[90]  X. Ni,et al.  Probing into nucleation mechanisms of cooling crystallization of sodium chlorate in a stirred tank crystallizer and an oscillatory baffled crystallizer , 2012 .

[91]  Ian R. Baxendale,et al.  The integration of flow reactors into synthetic organic chemistry , 2013 .

[92]  Hector Gomez,et al.  Experimental and computational modeling of oscillatory flow within a baffled tube containing periodic-tri-orifice baffle geometries , 2013, Comput. Chem. Eng..

[93]  Adam Harvey,et al.  Rapid process development using oscillatory baffled mesoreactors - A state-of-the-art review , 2015 .

[94]  Anh N. Phan,et al.  Characterisation of fluid mixing in novel designs of mesoscale oscillatory baffled reactors operating at low flow rates (0.3–0.6 ml/min) , 2011 .

[95]  Malcolm R. Mackley,et al.  Experimental fluid dispersion measurements in periodic baffled tube arrays , 1993 .

[96]  D. Skala,et al.  Mass transfer characteristics in a gas‐liquid reciprocating plate column. I. Liquid phase volumetric mass transfer coefficient , 1988 .

[97]  T. Nishimura,et al.  Mass transfer characteristics in a channel with symmetric wavy wall for steady flow. , 1985 .

[98]  Anh N. Phan,et al.  Characterisation of mesoscale oscillatory helical baffled reactor—Experimental approach , 2012 .

[99]  Tony Howes,et al.  Polymer product engineering utilising oscillatory baffled reactors , 1999 .

[100]  M. J. Slater,et al.  Liquid-liquid extraction equipment , 1994 .

[101]  Clive A. Greated,et al.  On the measurement of strain rate in an oscillatory baffled column using particle image velocimetry , 2000 .

[102]  M. Mackay,et al.  Oscillations flow within tubes containing wall or central baffles , 1991 .

[103]  S. Y. Wong,et al.  Development of Continuous Crystallization Processes Using a Single-Stage Mixed-Suspension, Mixed-Product Removal Crystallizer with Recycle , 2012 .

[104]  Malcolm R. Mackley,et al.  AN EXPERIMENTAL INVESTIGATION INTO THE SCALE-UP OF OSCILLATORY FLOW MIXING IN BAFFLED TUBES , 2006 .

[105]  Xiongwei Ni.  Residence time distribution measurements in a pulsed baffled tube bundle , 1994 .

[106]  Cameron J. Brown,et al.  Characterization and modelling of antisolvent crystallization of salicylic acid in a continuous oscillatory baffled crystallizer , 2015 .

[107]  R. Skelton,et al.  Photocatalytic mineralisation of methylene blue using buoyant TiO2-coated polystyrene beads , 2000 .

[108]  Xiongwei Ni,et al.  Gas hold-up and bubble diameters in a gassed oscillatory baffled column , 2001 .

[109]  I. Sobey.  On flow through furrowed channels. Part 1. Calculated flow patterns , 1980, Journal of Fluid Mechanics.

[110]  Hongbing Jian,et al.  An investigation of the effect of viscosity on mixing in an oscillatory baffled column using digital particle image velocimetry and computational fluid dynamics simulation , 2005 .

[111]  Stefan Radl,et al.  Continuously Seeded, Continuously Operated Tubular Crystallizer for the Production of Active Pharmaceutical Ingredients , 2010 .

[112]  Zoltan K. Nagy,et al.  Evaluation of crystallization kinetics of adipic acid in an oscillatory baffled crystallizer , 2014 .

[113]  A. A. Vicente,et al.  Application of a Novel Oscillatory Flow Micro-bioreactor to the Production of γ-decalactone in a Two Immiscible Liquid Phase Medium , 2006, Biotechnology Letters.

[114]  X. Ni,et al.  Effect of hydrodynamics on mass transfer in a gas–liquid oscillatory baffled column , 2004 .

[115]  Zoltan K. Nagy,et al.  Fines removal in a continuous plug flow crystallizer by optimal spatial temperature profiles with controlled dissolution , 2013 .

[116]  Paul Sharratt,et al.  Achieving Continuous Manufacturing: Technologies and Approaches for Synthesis, Workup, and Isolation of Drug Substance May 20-21, 2014 Continuous Manufacturing Symposium. , 2015, Journal of pharmaceutical sciences.

[117]  Narayan S. Tavare,et al.  Mixing in continuous crystallizers , 1986 .

[118]  B. Glennon,et al.  Characterizing the metastable zone width and solubility curve using lasentec FBRM and PVM , 2002 .

[119]  Deducing primary nucleation parameters from metastable zone width and induction time data determined with simulation , 2013 .

[120]  Volker Hessel,et al.  Novel process windows for enabling, accelerating, and uplifting flow chemistry. , 2013, ChemSusChem.

[121]  James J. De Yoreo,et al.  Crystallization of Paracetamol under Oscillatory Flow Mixing Conditions , 2004 .

[122]  Adam Harvey,et al.  A Mixing-Based Design Methodology for Continuous Oscillatory Flow Reactors , 2002 .

[123]  Zoltan K. Nagy,et al.  Population Balance Model-Based Multiobjective Optimization of a Multisegment Multiaddition (MSMA) Continuous Plug-Flow Antisolvent Crystallizer , 2014 .

[124]  Ramiro Saraiva,et al.  The quantitative description of fluid mixing using Lagrangian- and concentration-based numerical approaches , 1999 .

[125]  H. Müller-Steinhagen,et al.  Reduction of heat transfer fouling by the addition of wood pulp fibers , 1998 .

[126]  Malcolm R. Mackley,et al.  Process and product innovation , 2003 .

[127]  Malcolm R. Mackley,et al.  Residence time distribution enhancement in reactors using oscillatory flow , 1996 .

[128]  Allan S. Myerson,et al.  Continuous Crystallization of Aliskiren Hemifumarate , 2012 .

[129]  Xiongwei Ni,et al.  On the discussion of the dimensionless groups governing oscillatory flow in a baffled tube , 1997 .

[130]  Zoltan K. Nagy,et al.  Pharmaceutical crystallisation processes from batch to continuous operation using MSMPR stages: Modelling, design, and control , 2015 .

[131]  M. Takriff,et al.  Interstage Backmixing in Oscillatory Flow in a Baffled Column , 2002 .

[132]  Malcolm R. Mackley,et al.  Heat transfer performance for batch oscillatory flow mixing , 2002 .

[133]  Effects of Cooling Rate and Solution Concentration on Solution Crystallization of l-Glutamic Acid in an Oscillatory Baffled Crystallizer , 2008 .

[134]  X. Ni,et al.  On the Effect of Surfactant on Mass Transfer to Water–Glycerol Solutions in a Pulsed Baffled Reactor , 1997 .

[135]  Jagjit Singh Srai,et al.  A supply network configuration perspective on international supply chain development , 2008 .

[136]  Yang Yang,et al.  Combined Cooling and Antisolvent Crystallization in Continuous Mixed Suspension, Mixed Product Removal Cascade Crystallizers: Steady-State and Startup Optimization , 2015 .

[137]  R. Skelton,et al.  The application of oscillatory flow mixing to photocatalytic wet oxidation , 1999 .

[138]  J. Mydlarz,et al.  Continuous crystallization and subsequent solid-liquid separation of potassium sulphate. I: MSMPR kinetics , 1989 .

[139]  Anh N. Phan,et al.  Continuous screening of base-catalysed biodiesel production using New designs of mesoscale oscillato , 2011 .

[140]  Clive A. Greated,et al.  Experimental Investigation of Bentonite Flocculation in a Batch Oscillatory Baffled Column , 1998 .

[141]  C. A. Greated,et al.  Measurements of velocities of single particles for steady and oscillatory flows in plain and baffled tubes , 1995 .

[142]  A. C. Jealous,et al.  POWER REQUIREMENTS FOR PULSE GENERATION IN PULSE COLUMNS , 1955 .

[143]  Richard D. Braatz,et al.  Application of Continuous Crystallization in an Integrated Continuous Pharmaceutical Pilot Plant , 2014 .

[144]  Adam Harvey,et al.  Rapid Determination of the Residence Time Distribution (RTD) Function in an Oscillatory Baffled Reactor (OBR) Using a Design of Experiments (DoE) Approach , 2014 .

[145]  Brahim Benyahia,et al.  Development of a Multi-Step Synthesis and Workup Sequence for an Integrated, Continuous Manufacturing Process of a Pharmaceutical , 2014 .

[146]  Tony Howes,et al.  On the effect of tracer density on axial dispersion in a batch oscillatory baffled column , 2002 .

[147]  Kirsi Immonen,et al.  Evaluation of axial dispersion and mixing performance in oscillatory baffled reactors using CFD , 2013 .

[148]  Malcolm R. Mackley,et al.  Experimental residence time distribution measurements for unsteady flow in baffled tubes , 1989 .

[149]  Hongbing Jian,et al.  A Numerical Study on the Scale-Up Behaviour in Oscillatory Baffled Columns , 2005 .

[150]  H. Müller-Steinhagen,et al.  Influence of Surface Properties and Characteristics on Fouling in Plate Heat Exchangers , 2005 .

[151]  Malcolm R. Mackley,et al.  Heat transfer and associated energy dissipation for oscillatory flow in baffled tubes , 1995 .

[152]  Ali N. Saleemi,et al.  Automated direct nucleation control for in situ dynamic fines removal in batch cooling crystallization , 2012 .

[153]  Adam Harvey,et al.  Reduced power consumption compared to a traditional stirred tank reactor (STR) for enzymatic saccharification of alpha-cellulose using oscillatory baffled reactor (OBR) technology , 2014 .

[154]  M. Alves,et al.  CO2 dissolution and design aspects of a multiorifice oscillatory baffled column , 2014 .

[155]  M. Zheng,et al.  Biodiesel Reaction Screening Using Oscillatory Flow Meso Reactors , 2007 .

[156]  Brian Glennon,et al.  Development and Characterization of a Single Stage Mixed-Suspension, Mixed-Product-Removal Crystallization Process with a Novel Transfer Unit , 2014 .

[157]  X. Ni,et al.  Experimental flow visualisation in a modified pulsed baffled reactor. , 1997 .

[158]  Andreas Kirschning,et al.  Ten key issues in modern flow chemistry. , 2011, Chemical communications.

[159]  Allan S. Myerson,et al.  Crystallization of Cyclosporine in a Multistage Continuous MSMPR Crystallizer , 2011 .

[160]  A. Phan,et al.  Rapid determination of reaction order and rate constants of an imine synthesis reaction using a mesoscale oscillatory baffled reactor , 2013 .

[161]  Anton P. J. Middelberg,et al.  The influence of mixing on lysozyme renaturation during refolding in an oscillatory flow and a stirred-tank reactor , 2002 .

[162]  António A. Vicente,et al.  Continuous-Flow Precipitation of Hydroxyapatite at 37 °C in a Meso Oscillatory Flow Reactor , 2013 .

[163]  Z. Nagy,et al.  Dynamic Modeling of Encrust Formation and Mitigation Strategy in a Continuous Plug Flow Crystallizer , 2015 .

[164]  Malcolm R. Mackley,et al.  On eddy motions near plates and ducts, induced by water waves and periodic flows , 1980, Philosophical Transactions of the Royal Society of London. Series A, Mathematical and Physical Sciences.

[165]  James M. B. Evans,et al.  End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation. , 2013, Angewandte Chemie.

[166]  Malcolm R. Mackley,et al.  Experimental heat transfer measurements for pulsatile flow in baffled tubes , 1990 .

[167]  M. J. Joyce,et al.  A STUDY OF VELOCITY VECTOR PROFILE AND STRAIN RATE DISTRIBUTION FOR LAMINAR AND OSCILLATORY FLOWS IN A BAFFLED TUBE USING PARTICLE IMAGE VELOCIMETRY , 1995 .

[168]  J. Teixeira,et al.  Precipitation of hydroxyapatite at 37 °C in a meso oscillatory flow reactor operated in batch at constant power density , 2013 .

[169]  Xiongwei Ni,et al.  An investigation of droplet size and size distribution in methylmethacrylate suspensions in a batch oscillatory-baffled reactor , 1998 .

[170]  X. Ni,et al.  On the characterisation of wax deposition in an oscillatory baffled device , 2006 .

[171]  A. Harvey,et al.  Intensification of Biobutanol Production in Batch Oscillatory Baffled Bioreactor , 2012 .

[172]  M. Baird,et al.  Power dissipation and flow patterns in reciprocating baffle‐plate columns , 1995 .

[173]  Xiongwei Ni,et al.  A comparative study of mass transfer in yeast for a batch pulsed baffled bioreactor and a stirred tank fermenter , 1995 .

[174]  Anh N. Phan,et al.  Effect of geometrical parameters on fluid mixing in novel mesoscale oscillatory helical baffled designs , 2011 .

[175]  C. Xuereb,et al.  Liquid-liquid dispersion in a continuous oscillatory baffled reactor - Application to suspension polymerization , 2015 .

[176]  Allan S. Myerson,et al.  Continuous Crystallization and Polymorph Dynamics in the l-Glutamic Acid System , 2014 .

[177]  X. Ni,et al.  An investigation into the effect of mixing on the secondary nucleation of sodium chlorate in a stirred tank and an oscillatory baffled crystallizer , 2014 .

[178]  I. Sobey.  Observation of waves during oscillatory channel flow , 1985, Journal of Fluid Mechanics.

[179]  J. Teixeira,et al.  O2 mass transfer in an oscillatory flow reactor provided with smooth periodic constrictions. Individual characterization of kL and a , 2015 .

[180]  Anh N. Phan,et al.  Numerical study of the flow pattern and heat transfer enhancement in oscillatory baffled reactors with helical coil inserts , 2012 .

[181]  X. Ni,et al.  Flow patterns and oil—water dispersion in a 0.38 m diameter oscillatory baffled column , 2000 .

[182]  Siti Kartom Kamarudin,et al.  Effect of oscillation amplitude on velocity distributions in an oscillatory baffled column (OBC) , 2012 .

[183]  Xiongwei Ni,et al.  Suspension polymerization of acrylamide in an oscillatory baffled reactor: From drops to particles , 2001 .

[184]  F. Rocha,et al.  Metastable zone width for secondary nucleation and secondary nucleation inside the metastable zone , 2011 .

[185]  António A. Vicente,et al.  Liquid backmixing in oscillatory flow through a periodically constricted meso-tube , 2010 .

[186]  Ed Jones,et al.  Scaling Up Biocatalysis Reactions in Flow Reactors , 2012 .

[187]  Malcolm R. Mackley,et al.  Mixing and dispersion in a baffled tube for steady laminar and pulsatile flow , 1991 .

[188]  R. Ristic,et al.  Characterisation of impeller driven and oscillatory mixing by spatial and temporal shear rate distributions , 2004 .

[189]  Heinrich Hofmann,et al.  Calcium carbonate precipitation using new segmented flow tubular reactor , 2000 .

[190]  Hongbing Jian,et al.  Evaluation of Turbulent Integral Length Scale in an Oscillatory Baffled Column Using Large Eddy Simulation and Digital Particle Image Velocimetry , 2003 .

[191]  Dimitrios I. Gerogiorgis,et al.  Economic Analysis of Integrated Continuous and Batch Pharmaceutical Manufacturing: A Case Study , 2011 .

[192]  Tony Howes,et al.  THE SIMULATION OF CHAOTIC MIXING AND DISPERSION FOR PERIODIC FLOWS IN BAFFLED CHANNELS , 1991 .

[193]  Richard D. Braatz,et al.  Assessment of Recent Process Analytical Technology (PAT) Trends: A Multiauthor Review , 2015 .

[194]  M. Mackley,et al.  The axial dispersion performance of an oscillatory flow meso-reactor with relevance to continuous flow operation , 2008 .

[195]  Narayan Variankaval,et al.  From Form to Function: Crystallization of Active Pharmaceutical Ingredients , 2008 .

[196]  Jianjun Tao,et al.  The development of asymmetry for oscillatory flow within a tube containing sharp edge periodic baffles , 2007 .

[197]  Xiongwei Ni,et al.  Parameters affecting fluid dispersion in a continuous oscillatory baffled tube , 2000 .

[198]  Johannes G. Khinast,et al.  Continuous Crystallization of Proteins in a Tubular Plug-Flow Crystallizer , 2015, Crystal growth & design.

[199]  E. Roberts.  A numerical and experimental study of transition processes in an obstructed channel flow , 1994, Journal of Fluid Mechanics.

[200]  H Leuenberger,et al.  New trends in the production of pharmaceutical granules: batch versus continuous processing. , 2001, European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V.

[201]  Neal G. Anderson,et al.  Using Continuous Processes to Increase Production , 2012 .

[202]  B. Cichy,et al.  Obtaining Monodisperse Melamine Phosphate Grains by a Continuous Reaction Crystallization Process , 2014 .

[203]  Zhiqun Yu,et al.  A Continuous Kilogram-Scale Process for the Manufacture of o-Difluorobenzene , 2012 .