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Zoltan K Nagy - One of the best experts on this subject based on the ideXlab platform.
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mathematical modeling design and optimization of a multisegment multiaddition Plug Flow crystallizer for antisolvent crystallizations
2015Co-Authors: Brahim Benyahia, Zoltan K Nagy, Chris RiellyAbstract:In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations. This paper takes a process systems engineering (PSE) approach to the optimal design of a continuous antisolvent addition crystallizer to deliver the most promising product qualities, such as the crystal size distribution. A multisegment multiaddition Plug-Flow crystallizer (MSMA-PFC) is considered as an example of a continuous antisolvent crystallization process, in which the total number, location, and distribution of antisolvent additions are to be optimized. First-principles dynamic and steady-state mathematical models for the MSMA-PFC are presented, based on example kinetic models for nucleation and growth of paracetamol crystallizing in acetone, with water as the antisolvent. The performances of different cry...
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dynamic modeling of encrust formation and mitigation strategy in a continuous Plug Flow crystallizer
2015Co-Authors: Aniruddha Majumder, Zoltan K NagyAbstract:Encrustation, also known as fouling or scale formation, on the wall of Plug Flow crystallizers (PFC) can cause major operational and economic problems in pharmaceutical industries. These include increased energy requirements due to increment of thermal resistance and pressure drop, and clogging of the crystals due to reduction of Flow area. In this work, a mathematical model for predicting the dynamic behavior of a PFC undergoing encrustation is presented. This model describes the formation of encrust layer by considering various mechanisms such as rate of solute transport from bulk to the wall, integration and removal due to shear stress induced by fluid turbulence. A population balance model for describing the crystallization process in the PFC is also coupled with the encrustation model in order to obtain the appropriate concentration profile in the PFC as well as product crystal size distribution (CSD). Based on this model, a mitigation strategy is proposed that relies on injection of pure solvent to ...
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fines removal in a continuous Plug Flow crystallizer by optimal spatial temperature profiles with controlled dissolution
2013Co-Authors: Aniruddha Majumder, Zoltan K NagyAbstract:This work presents a systematic study for obtaining the optimal temperature profile in a continuous Plug Flow crystallizer (PFC). The proposed PFC consists of multiple segments where the temperature of each segment can be controlled individually. An optimization problem is formulated for a target crystal size distribution (without fines) with the temperature of the segments as decision variables. The results indicate that for the crystallization kinetics considered, dissolution steps are necessary for the reduction of fines due to nucleation. A systematic study on the form of growth and dissolution kinetics suggested that the key factor that determines whether the dissolution steps will be successful in reducing fines, without compromising the final size of the crystals from seed, is the size dependence of the growth and dissolution kinetics. Best fines removal is achieved when the larger crystals grow faster than the smaller ones and the smaller crystals dissolve faster than the larger ones. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4582–4594, 2013
Aniruddha Majumder - One of the best experts on this subject based on the ideXlab platform.
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dynamic modeling of encrust formation and mitigation strategy in a continuous Plug Flow crystallizer
2015Co-Authors: Aniruddha Majumder, Zoltan K NagyAbstract:Encrustation, also known as fouling or scale formation, on the wall of Plug Flow crystallizers (PFC) can cause major operational and economic problems in pharmaceutical industries. These include increased energy requirements due to increment of thermal resistance and pressure drop, and clogging of the crystals due to reduction of Flow area. In this work, a mathematical model for predicting the dynamic behavior of a PFC undergoing encrustation is presented. This model describes the formation of encrust layer by considering various mechanisms such as rate of solute transport from bulk to the wall, integration and removal due to shear stress induced by fluid turbulence. A population balance model for describing the crystallization process in the PFC is also coupled with the encrustation model in order to obtain the appropriate concentration profile in the PFC as well as product crystal size distribution (CSD). Based on this model, a mitigation strategy is proposed that relies on injection of pure solvent to ...
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Population Balance Model-Based Multiobjective Optimization of a Multisegment Multiaddition (MSMA) Continuous Plug-Flow Antisolvent Crystallizer
2014Co-Authors: Bradley J. Ridder, Aniruddha MajumderAbstract:Crystallization is a major separation process in the pharmaceutical industry. Most crystallizations are performed batchwise, but there is great incentive for converting them to continuous operations. This paper investigates the modeling, simulation, and optimization of a special antisolvent Plug-Flow crystallizer: the multisegmented, multiaddition Plug-Flow crystallizer (MSMA-PFC). The MSMA-PFC accepts multiple antisolvent Flows along its length, permitting finer control of supersaturation. A steady-state population balance equation was applied for tracking the crystal size distribution, and a mass balance equation was used to track the depletion of dissolved solute (flufenamic acid). A multiobjective optimization framework was applied to determine the antisolvent Flow rates into each segment that simultaneously maximize the average crystal size, and minimize the coefficient of variation. The set of coupled differential equations was solved, depending on circumstance, with either the method-of-moments (MO...
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fines removal in a continuous Plug Flow crystallizer by optimal spatial temperature profiles with controlled dissolution
2013Co-Authors: Aniruddha Majumder, Zoltan K NagyAbstract:This work presents a systematic study for obtaining the optimal temperature profile in a continuous Plug Flow crystallizer (PFC). The proposed PFC consists of multiple segments where the temperature of each segment can be controlled individually. An optimization problem is formulated for a target crystal size distribution (without fines) with the temperature of the segments as decision variables. The results indicate that for the crystallization kinetics considered, dissolution steps are necessary for the reduction of fines due to nucleation. A systematic study on the form of growth and dissolution kinetics suggested that the key factor that determines whether the dissolution steps will be successful in reducing fines, without compromising the final size of the crystals from seed, is the size dependence of the growth and dissolution kinetics. Best fines removal is achieved when the larger crystals grow faster than the smaller ones and the smaller crystals dissolve faster than the larger ones. © 2013 American Institute of Chemical Engineers AIChE J, 59: 4582–4594, 2013
Panagiota Angeli - One of the best experts on this subject based on the ideXlab platform.
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experimental and numerical hydrodynamic studies of ionic liquid aqueous Plug Flow in small channels
2017Co-Authors: Panagiota AngeliAbstract:The hydrodynamic characteristics of liquid-liquid Plug Flow were studied in microchannels with 0.2 and 0.5 mm ID both experimentally and numerically. For the experiments high speed imaging and bright field micro-Particle Image Velocimetry were used, while the numerical simulations were based on the volume-of-fluid (VOF) method. The two immiscible liquids were a 1 M HNO3 aqueous solution which formed the dispersed Plugs and a mixture of 0.2 M n-octyl(phenyl)-N,N-diisobutylcarbamoylmethyphosphine oxide (CMPO) and 1.2 M Tributylphosphate (TBP) in the ionic liquid 1-butyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]amide ([C4min][NTf2]). The thickness of the film surrounding the Plugs, and the Plug velocity and length were measured and compared against literature correlations. For the cases studied (0.0224 < Ca < 0.299) it was observed that the liquid film was largely affected by the changes in the shape of the front cap of the Plug. The Plug length was affected by both the Capillary number and the ratio of the aqueous to ionic liquid phase Flow rates while the Plug volume depended on the channel diameter and the mixture velocity. The numerical simulations showed that, in agreement with the measurements, a parabolic velocity profile develops in the middle of the Plugs while the circulation patterns in the Plug are affected by the channel size. The pressure profile along the channel with a series of Plugs and slugs was predicted numerically while the pressure drop agreed well with a correlation which included the dimensionless slug length and the ratio Ca/Re.
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effect of channel size on liquid liquid Plug Flow in small channels
2016Co-Authors: Dimitrios Tsaoulidis, Panagiota AngeliAbstract:The hydrodynamic properties of Plug Flow were investigated in small channels with 0.5-, 1-, and 2-mm internal diameter, for an ionic liquid/aqueous two-phase system with the aqueous phase forming the dispersed Plugs. Bright field Particle Image Velocimetry combined with high-speed imaging were used to obtain Plug length, velocity, and film thickness, and to acquire velocity profiles within the Plugs. Plug length decreased with mixture velocity, while for constant mixture velocity it increased with channel size. Plug velocity increased with increasing mixture velocity and channel size. The film thickness was predicted reasonably well for Ca > 0.08 by Taylor's (Taylor, J Fluid Mech. 1961;10(2):161–165) model. A fully developed laminar profile was established in the central region of the Plugs. Circulation times in the Plugs decreased with increasing channel size. Pressure drop was predicted reasonably well by a modified literature model, using a new correlation for the film thickness derived from experimental values.
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effect of channel size on mass transfer during liquid liquid Plug Flow in small scale extractors
2015Co-Authors: Dimitrios Tsaoulidis, Panagiota AngeliAbstract:In this paper the effect of channel size on the mass transfer characteristics of liquid-liquid Plug Flow was investigated for capillaries with internal diameter ranging from 0.5 to 2 mm. The extraction of {UO2}2+ ions from nitric acid solutions into TBP/IL mixtures, relevant to spent nuclear fuel reprocessing, was studied for different residence times, dispersed phase fractions, and mixture velocities. It was found that extraction efficiencies increased as the channel size decreased. For a given channel length and for all channel sizes, an increase in mixture velocity decreased the extraction efficiency. The overall mass transfer coefficients (kLα) for all channels varied between 0.049 and 0.29 s-1 and decreased as the channel size increased. The evolution of the kLα along the extraction channel showed a decreasing trend for all the channel sizes. The experimentally obtained mass transfer coefficients were compared with existing models for liquid-liquid and gas-liquid segmented Flows from the literature. The results showed good agreement with the empirical correlation proposed for a liquid-liquid system. A finite element model was developed that solved the velocity and concentration fields in the channel for both phases considering a unit cell (one Plug and one slug) with periodic boundary conditions at the inlet and the outlet. The model used experimental data for the geometric characteristics of the Plug Flow and predicted reasonably well the experimentally measured extraction efficiencies (with mean relative error of 11 %).
Chris Rielly - One of the best experts on this subject based on the ideXlab platform.
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mathematical modeling design and optimization of a multisegment multiaddition Plug Flow crystallizer for antisolvent crystallizations
2015Co-Authors: Brahim Benyahia, Zoltan K Nagy, Chris RiellyAbstract:In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations. This paper takes a process systems engineering (PSE) approach to the optimal design of a continuous antisolvent addition crystallizer to deliver the most promising product qualities, such as the crystal size distribution. A multisegment multiaddition Plug-Flow crystallizer (MSMA-PFC) is considered as an example of a continuous antisolvent crystallization process, in which the total number, location, and distribution of antisolvent additions are to be optimized. First-principles dynamic and steady-state mathematical models for the MSMA-PFC are presented, based on example kinetic models for nucleation and growth of paracetamol crystallizing in acetone, with water as the antisolvent. The performances of different cry...
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Mathematical modeling, design, and optimization of a multisegment multiaddition Plug-Flow crystallizer for antisolvent crystallizations
2015Co-Authors: Brahim Benyahia, Zoltan Nagy, Chris RiellyAbstract:In the pharmaceutical industries, the requirements of rapid process development and scalable design have made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes, capable of replacing conventional capital- and labor-intensive batch operations. This paper takes a process systems engineering (PSE) approach to the optimal design of a continuous antisolvent addition crystallizer to deliver the most promising product qualities, such as the crystal size distribution. A multisegment multiaddition Plug-Flow crystallizer (MSMA-PFC) is considered as an example of a continuous antisolvent crystallization process, in which the total number, location, and distribution of antisolvent additions are to be optimized. First-principles dynamic and steady-state mathematical models for the MSMA-PFC are presented, based on example kinetic models for nucleation and growth of paracetamol crystallizing in acetone, with water as the antisolvent. The performances of different crystallizer configurations operated under optimal design conditions are then compared. The configuration in which antisolvent could be added at a variety of different locations along the tube length and at optimal Flow rates was able to outperform previous designs in the literature which considered equally spaced antisolvent additions. The use of dynamic models to detect problems during startup of an MSMA-PFC was also highlighted
Steven Ferguson - One of the best experts on this subject based on the ideXlab platform.
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automated self seeding of batch crystallizations via Plug Flow seed generation
2014Co-Authors: Steven Ferguson, Gary Morris, Mark Barrett, Hongxun Hao, Brian GlennonAbstract:Abstract In this study, seed slurry from a single addition anti-solvent Plug Flow crystallization of benzoic acid was used to seed the equivalent batch cooling crystallization. The experimental conditions were carried out to simulate automated self-seeding. This involves withdrawal of solution from a batch crystallizer, which is then mixed with anti-solvent within a Plug Flow crystallizer, in order to generate a seed slurry which is fed directly back to the batch crystallizer. This seeding strategy allowed the final CSD of the batch crystallization to be controlled by variation of the crystal size from the Plug Flow seeding device at a constant seed loading. The ability to use unequal feed/anti-solvent inlet Flowrates (in the Roughton vortex mixer) proved effective in controlling the batch CSD at 2% seed loading and constant feed composition. The morphology of batch product from Plug Flow seeding was found to have a much lower aspect ratio than the more needle like dry seed and primary nucleated product. Unlike dry seed, which was found to have rough irregular growth on the crystal surface, the Plug Flow product had flat regular growth as per primary nucleated batch crystallization.
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characterization of the anti solvent batch Plug Flow and msmpr crystallization of benzoic acid
2013Co-Authors: Steven Ferguson, Gary Morris, Mark Barrett, Brian GlennonAbstract:Abstract Continuous operation allows process conditions that are not attainable within batch crystallizers to be utilized. This in turn allows for product crystal attributes that are not possible in the equivalent batch crystallizations to be produced. In this study, the product crystal size distributions attainable from the anti-solvent crystallization of benzoic acid in Plug Flow, MSMPR and the equivalent fed batch and batch reverse addition crystallizations, were characterized. It was found that the continuous Plug Flow and MSMPR crystallizers were able to access crystal size distributions that are both smaller and larger than could be produced via the equivalent batch crystallizations, in addition to providing huge increases in productivity. In-situ process analytical techniques (FBRM, ATR-FTIR) were employed to characterize each of these processes, including a calibration-free ATR-FTIR technique. Furthermore, a novel intermittent pneumatic MSMPR withdrawal method, which negated clogging/fouling of transfer lines, is demonstrated. It is hoped that the use of such techniques may facilitate the uptake of continuous processes in pharmaceutical crystallization where limitations on development time and concerns about slurry transport are perceived to be barriers to the implementation of this technology.
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in situ monitoring and characterization of Plug Flow crystallizers
2012Co-Authors: Steven Ferguson, Gary Morris, Mark Barrett, Brian GlennonAbstract:Abstract This work presents a study of a Roughton-type vortex mixer combined with a tubular reactor for the drowning out crystallization of benzoic acid from aqueous ethanol solutions using water as the anti-solvent. Mixing times in vortex mixers have been shown to be as low as 1 ms and have also been found to be largely independent of the relative Flow rates of inlet streams. This enables operation with larger anti-solvent ratios, without sacrificing mixing efficiency. Permitting the generation of higher supersaturations, and smaller particles, while also increasing flexibility of the system by broadening the range of compounds that can be used. Process analytical technologies (FBRM, PVM, ATR FT-IR) were applied in-situ in order to characterize crystallization via the use of a novel Flow cell. A calibration-free method for concentration monitoring was successfully utilized to monitor the progress of the process. It was seen that the achievable particle size could be significantly reduced in size compared to batch operation, with a reduction in the square-weighted chord length from 152 to 52 μm. For a given feed concentration, significant control over the product size within the Plug Flow crystallizer could be achieved, with an average square weighted chord length range of 52–87 μm observed for the conditions investigated in this work.
