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Herman J. M. Kramer - One of the best experts on this subject based on the ideXlab platform.

  • crystallization kinetics in an airlift and a stirred draft tube crystallizer secondary nucleation models revisited
    Chemical Engineering Research & Design, 2018
    Co-Authors: Fatemeh Anisi, Herman J. M. Kramer
    Abstract:

    Abstract In this research, a process model has been developed for an airlift and compared with that of a draft tube stirred crystallizer to clarify the crystallization kinetics in this novel type of crystallizer. Recently it has been shown that although secondary nucleation is strongly suppressed in this crystallizer, it is not completely absent and further development and scale up requires a more quantitative prediction of the kinetics in this type of crystallizer. A number of growth and nucleation models were examined in a parameter estimation study in which a dataset of a number of seeded batch experiments has been used to estimate the kinetics in both an airlift and a draft tube stirred crystallizer. It is shown that a kinetic model, consisting of a two-step growth model and two additive nucleation mechanisms, i.e. an attrition based and a surface nucleation mechanism, gives an excellent and statistically acceptable description of all studied experiments with one parameter set each for both type of Crystallizers. The main difference in the two types of Crystallizers being that the attrition terms by crystal-impeller and crystal–crystal collisions in the airlift crystallizer can be completely neglected.

  • an air lift crystallizer can suppress secondary nucleation at a higher supersaturation compared to a stirred crystallizer
    Crystal Growth & Design, 2014
    Co-Authors: Richard Lakerveld, Jeroen Van Krochten, Herman J. M. Kramer
    Abstract:

    Secondary nucleation is suppressed in an air-lift crystallizer at levels of supersaturation where in a stirred crystallizer a clear contribution of secondary nucleation is visible. A comparison of batch crystallization of l-ascorbic acid in an air-lift crystallizer and in a stirred crystallizer is presented. The results demonstrate that at low supersaturation, secondary nucleation can be suppressed in both the air-lift crystallizer and the stirred crystallizer. At higher supersaturation, nucleation starts to dominate in the air-lift crystallizer. At an intermediate level of supersaturation, a clear contribution of secondary nucleation in the final product obtained from the stirred crystallizer is visible. However, experiments with similar conditions in the air-lift crystallizer show a significantly smaller contribution of secondary nucleation. The observed enlargement of the operating window in terms of supersaturation where secondary nucleation is suppressed in an air-lift crystallizer may have important...

  • 2-D Flow and Temperature Measurements in a Multiphase Airlift Crystallizer
    Industrial & Engineering Chemistry Research, 2013
    Co-Authors: Anamaria Soare, Sergio A. Pérez Escobar, Marcos Rodriguez Pascual, Andrzej Stankiewicz, Herman J. M. Kramer
    Abstract:

    A combined particle image velocimetry (PIV) and particle image thermometry (PIT) method was applied to visualize and measure simultaneously the 2-D velocity and temperature fields in a crystallizer. The 2-D supersaturation field can be also determined before nucleation or seeding takes place. The hydrodynamic behavior in an internal loop airlift crystallizer was studied for different air flow rates, sparger types, and crystal holdups to get insight in the optimal process conditions for this crystallizer, i.e. uniform temperatures and particle concentration. The 2-D velocity and temperature gradients showed that in a 2 L crystallizer the mixing is sufficient to ensure uniform supersaturation profiles at an overall superficial air velocity higher than 2.3 mm/s. Suspension tests showed that a superficial air velocity of 7 mm/s was sufficient to avoid settling of the crystals. This air flow rate assured the lifting of the solids from the bottom of the crystallizer for crystals with a mean size of 1.5 mm and h...

  • Rapid crystallization process development strategy from lab to industrial scale with PAT tools in skid configuration
    Organic Process Research and Development, 2012
    Co-Authors: Somnath S Kadam, Jochem A.w. Vissers, Marco Forgione, Andrzej I. Stankiewicz, Peter J. Daudey, Rob M. Geertman, Herman J. M. Kramer
    Abstract:

    Batch cooling crystallization is a commonly used separation and purification step in the pharmaceutical industry. Various properties of the crystalline product from a batch crystallizer can have a strong impact on the efficiency of downstream processes such as filtration and drying, on the formulation process and on the dissolution behaviour of the drug. Development of the crystallization processes presents a major challenge in the process development of an active pharmaceutical ingredient (API). Therefore, it is beneficial to develop a rapid crystallization process development strategy to industrial scale. In this paper we present a strategy for rapid process development and apply this strategy for androsta-1,4-diene-3,17-dione, cyclic 17-(2,2-dimethyltrimethylene acetal), a pharmaceutical intermediate produced by Merck Sharp and Dohme. The major advantages of the strategy are that there is no requirement of the crystallizer design modification, the calibration of the process analytical technology (PAT) tools can be performed at industrial scale, and the determination of the operating window can be done directly at the industrial scale. This strategy allows for process optimization directly at the industrial scale, thus eliminating the need for time-intensive scale-dependent study. The implementation of this strategy at industrial scale was performed with the help of PAT tools arranged in a unique skid-based configuration. The skid which contains both the concentration sensors and the crystal size distribution (CSD) sensors can be connected to the existing Crystallizers, thereby avoiding the time and cost-intensive modifications in the crystallizer design. The modular nature of the skid offers opportunities to choose the PAT tools which complement the solute-solvent model system. The skid makes it possible to gather the relevant information concerning the thermodynamics and kinetics of the model system in situ during the crystallization runs at the industrial scale. A strategy for process development based on a sensor skid is beneficial for the industry as it is intrinsically rapid and can be combined with the development of control strategies which lead to consistent product quality. © 2012 American Chemical Society.

  • Nonlinear Model-Based Control of a Semi-Industrial Batch Crystallizer Using a Population Balance Modeling Framework
    IEEE Transactions on Control Systems Technology, 2012
    Co-Authors: A Mesbah, Zoltan K Nagy, Adrie E. M. Huesman, Herman J. M. Kramer
    Abstract:

    This paper presents an output feedback nonlinear model-based control approach for optimal operation of industrial batch Crystallizers. A full population balance model is utilized as the cornerstone of the control approach. The modeling framework allows us to describe the dynamics of a wide range of industrial batch Crystallizers. In addition, it facilitates the use of performance objectives expressed in terms of crystal size distribution. The core component of the control approach is an optimal control problem, which is solved by the direct multiple shooting strategy. To ensure the effectiveness of the optimal operating policies in the presence of model imperfections and process uncertainties, the model predictions are adapted on the basis of online measurements using a moving horizon state estimator. The nonlinear model-based control approach is applied to a semi-industrial crystallizer. The simulation results suggest that the feasibility of real-time control of the crystallizer is largely dependent on the discretization coarseness of the population balance model. The control performance can be greatly deteriorated due to inadequate discretization of the population balance equation. This results from structural model imperfection, which is effectively compensated for by using the online measurements to confer an integrating action to the dynamic optimizer. The real-time feasibility of the output feedback control approach is experimentally corroborated for fed-batch evaporative crystallization of ammonium sulphate. It is observed that the use of the control approach leads to a substantial increase, i.e., up to 15%, in the batch crystal content as the product quality is sustained.

Zoltan K Nagy - One of the best experts on this subject based on the ideXlab platform.

  • chord length distribution based modeling and adaptive model predictive control of batch crystallization processes using high fidelity full population balance models
    Industrial & Engineering Chemistry Research, 2018
    Co-Authors: Botond Szilagyi, Paul şerban Agachi, Zoltan K Nagy
    Abstract:

    The control of batch Crystallizers is an intensively investigated topic as suitable crystallizer operation can reduce considerably the downstream operation costs and produce crystals of desired properties (size, shape, purity, etc.). Nevertheless, the control of Crystallizers is still challenging. In this work the development of a fixed batch time full population balance model based adaptive predictive control system for cooling batch Crystallizers is presented. The model equations are solved by the high resolution finite volume algorithm involving fine discretization, which provides a high fidelity, accurate solution. A physically relevant crystal size distribution (CSD) to chord length distribution (CLD) transformation is also developed making possible the direct, real-time application of the focused beam reflectance measurement (FBRM) probe in the control system. The measured CLD and concentration values are processed by the growing horizon estimator (GHE), whose roles are to estimate the unmeasurable ...

  • a comparative study of coupled preferential Crystallizers for the efficient resolution of conglomerate forming enantiomers
    Pharmaceutics, 2017
    Co-Authors: Aniruddha Majumder, Zoltan K Nagy
    Abstract:

    The separation of enantiomers is of great importance due to their possible differences in therapeutic properties. Preferential crystallization in various configurations of coupled batch Crystallizers is used as an attractive means to separate the conglomerate-forming enantiomers from racemic mixtures. However, the productivity of such batch processes can be limited by the nucleation of the counter enantiomer and consumption of the supersaturation. In this work, a recently proposed process configuration, which uses coupled mixed suspension mixed product removal (MSMPR) with liquid phase exchange, is investigated by simulation studies. A detailed study on the effect of process parameters (e.g., feed flow rate, seed mass, and liquid phase exchange) on the productivity and yield of the coupled MSMPR has been presented. Moreover, a comparison of various coupled crystallizer configurations is carried out. It is shown through simulation studies that the productivity of the enantiomeric separation can be significantly improved compared to the previously proposed batch modes when the continuous configuration is used. The effect of nucleation kinetic parameters on the performances of various crystallizer configurations is studied as well. A set of coupled population balance equations (PBEs) was used to describe the evolution of the crystal phase of the both enantiomers in each vessel. These equations were solved numerically using the quadrature method of moments. The insights obtained in this study will be useful in the process design of coupled crystallizer systems.

  • mathematical modelling and experimental validation of a novel periodic flow crystallization using msmpr Crystallizers
    Aiche Journal, 2017
    Co-Authors: Qinglin Su, Chris D Rielly, Keddon A Powell, Zoltan K Nagy
    Abstract:

    The challenges of insufficient residence time for crystal growing and transfer line blockage in conventional continuous MSMPR operations are still not well addressed. Periodic flow crystallization is a novel method whereby controlled periodic disruptions are applied to the inlet and outlet flows of an MSMPR crystallizer in order to increase its residence time. A dynamic model of residence time distribution in an MSMPR crystallizer was first developed to demonstrate the periodic flow operation. Besides, process models of periodic flow crystallizations were developed with an aim to provide a better understanding and improve the performance of the periodic flow operation, wherein the crystallization mechanisms and kinetics of the glycine-water system were estimated from batch cooling crystallization experiments. Experiments of periodic flow crystallizations were also conducted in single-/three-stage MSMPR Crystallizers to validate the process models and demonstrate the advantages of using periodic flow operation in MSMPR stages. This article is protected by copyright. All rights reserved.

  • Application of nonlinear model predictive control in continuous crystallization systems
    2015 American Control Conference (ACC), 2015
    Co-Authors: Yang Yang, Zoltan K Nagy
    Abstract:

    Continuous Crystallizers have great advantages on crystal quality consistency and process efficiency. In this study, a continuous two stage mixed suspension mixed product removal (MSMPR) cascade crystallizer is modeled using population balance model (PBM), with both cooling and antisolvent addition applied to generate supersaturation. The application of nonlinear model predictive control (NMPC) is discussed considering both yield and crystal size as objectives.

  • Simultaneous design and control framework for multi-segment multi-addition plug-flow crystallizer for anti-solvent crystallizations
    2015 American Control Conference (ACC), 2015
    Co-Authors: Qinglin Su, Chris D Rielly, Zoltan K Nagy
    Abstract:

    Tubular reactors, which are often assumed to behave as plug-flow reactors, have many applications in chemical reaction engineering, because of their narrow residence time distribution and ease of scaling-up. In the pharmaceutical industries, the requirements of fast development and scalable design have also made the tubular crystallizer a promising platform for continuous manufacturing and crystallization processes which are widely recognized as an emerging technology for pharmaceutical manufacturing which aims to replace conventional capital- and labor-intensive batch operations. However, the interaction of effects, such as supersaturation, seed loading, nucleation and crystal growth, tube configuration and mean residence time have not yet been fully understood and optimized, from a process systems engineering (PSE) perspective, to achieve the most promising product qualities, such as the crystal size distribution. In this study, standardized modules representing plug-flow crystallizer (PFC) segments are assembled into a multi-segment multi-addition plug-flow crystallizer (MSMA-PFC) to facilitate the versatile design and control of anti-solvent crystallization processes, in which the total number, locations, and distribution of anti-solvent addition are to be optimized. An anti-solvent crystallization system of paracetamol-acetone-water was used as an example to compare the performances of different crystallizer configurations operated under optimal design. It was noticed that the proposed design outperforms the previous designs in literature which considered equally-spaced anti-solvent additions. Furthermore, the possibility of replacing existing batch Crystallizers by MSMA-PFC is also discussed.

A Mesbah - One of the best experts on this subject based on the ideXlab platform.

  • Nonlinear Model-Based Control of a Semi-Industrial Batch Crystallizer Using a Population Balance Modeling Framework
    IEEE Transactions on Control Systems Technology, 2012
    Co-Authors: A Mesbah, Zoltan K Nagy, Adrie E. M. Huesman, Herman J. M. Kramer
    Abstract:

    This paper presents an output feedback nonlinear model-based control approach for optimal operation of industrial batch Crystallizers. A full population balance model is utilized as the cornerstone of the control approach. The modeling framework allows us to describe the dynamics of a wide range of industrial batch Crystallizers. In addition, it facilitates the use of performance objectives expressed in terms of crystal size distribution. The core component of the control approach is an optimal control problem, which is solved by the direct multiple shooting strategy. To ensure the effectiveness of the optimal operating policies in the presence of model imperfections and process uncertainties, the model predictions are adapted on the basis of online measurements using a moving horizon state estimator. The nonlinear model-based control approach is applied to a semi-industrial crystallizer. The simulation results suggest that the feasibility of real-time control of the crystallizer is largely dependent on the discretization coarseness of the population balance model. The control performance can be greatly deteriorated due to inadequate discretization of the population balance equation. This results from structural model imperfection, which is effectively compensated for by using the online measurements to confer an integrating action to the dynamic optimizer. The real-time feasibility of the output feedback control approach is experimentally corroborated for fed-batch evaporative crystallization of ammonium sulphate. It is observed that the use of the control approach leads to a substantial increase, i.e., up to 15%, in the batch crystal content as the product quality is sustained.

  • optimal operation of industrial batch Crystallizers a nonlinear model based control approach
    2010
    Co-Authors: A Mesbah
    Abstract:

    Batch crystallization is extensively employed in the chemical, pharmaceutical, and food industries to separate and purify high value-added chemical substances. Despite their widespread application, optimal operation of batch Crystallizers is particularly challenging. The difficulties primarily result from the complexity of process models, uncertainties in crystallization kinetics, sensor limitations for reliable measurement of process variables, and the inherent process uncertainties that may impair the effectiveness of advanced control strategies. In addition, the optimal operation of batch Crystallizers is often hampered by lack of process actuators. Nonetheless, advanced control of batch Crystallizers offers ample opportunities to effectively respond to the dynamic market demands of crystalline products. This is to realize the stringent product specifications of the consumer-driven market as enhancing the process productivity. In this thesis, a nonlinear model-based control approach is developed to address the inherent challenges of real-time control of existing industrial batch Crystallizers. The primary requirement on the control approach is its applicability to a wide range of industrial batch Crystallizers. This calls for a generic modeling framework, which allows us to describe the dynamics of diverse crystallization kinetics of any complexity and to incorporate the effect of different actuating mechanisms. The generic framework of the process model necessitates the use of computationally efficient model solution techniques and optimization strategies to ensure the real-time feasibility of the control approach. In addition, model imperfections, along with process disturbances, make the online adaptation of model predictions a prerequisite for successful application of the control approach. In pursuit of the research objective, the contributions of this thesis are structured in three major directions: 1. Population balance modeling: A full population balance modeling framework is developed as the cornerstone of the control approach. The inference of model parameters from experimental data is discussed. In addition, various population balance solution methods are investigated in terms of the performance requirements essential for online control applications. 2. Nonlinear state estimation: The effectiveness of several nonlinear state estimation techniques for output feedback control of industrial batch Crystallizers is evaluated. The ability of the state estimators in coping with model imperfections and process uncertainties is examined. 3. Real-time dynamic optimization: The feasibility of real-time dynamic optimization of population balance models is explored using different direct optimization strategies. The research program leads to the design of an output feedback nonlinear model-based control approach. The distinct contribution of this thesis lies in using a full population balance modeling framework, which is essential for the applicability of the control approach to a wide range of industrial batch Crystallizers. It is shown that the numerical difficulties of solving the population balance equation can be alleviated by using high order finite volume methods combined with a flux limiting function. These numerical techniques facilitate efficient model solution, which is a prerequisite for real-time control. In addition, it is shown that the multiple shooting strategy is well-suited for online dynamic optimization of population balance models. Successful application of the control approach is demonstrated by several simulation case studies, viz a single-input single-output semi-industrial crystallizer and a multi-input multi-output industrial crystallizer. It is illustrated that model imperfections and process uncertainties are largely detrimental to the performance of the nonlinear model-based controller. The performance inadequacy can be effectively compensated for by using an extended Kalman filter or an unscented Kalman filter with time-varying process noise covariance matrix. The real-time performance of the control approach is demonstrated experimentally by several implementations on a semi-industrial crystallizer. It is shown that lack of actuation may obstruct the optimal operation of industrial Crystallizers throughout the entire batch run.

James B. Rawlings - One of the best experts on this subject based on the ideXlab platform.

  • Crystallization of para‐xylene in scraped‐surface Crystallizers
    Aiche Journal, 2020
    Co-Authors: Daniel B Patience, James B. Rawlings, Hazim A Mohameed
    Abstract:

    Crystallization kinetics of para-xylene in batch pilot-scale scraped-surface Crystallizers were determined for commercial crystallization of a xylene mixture currently produced in Amoco plants. Dynamic mass and energy balances, coupled with the dynamic population balance, were used to model the scraped-surface crystallizer. The model assumes that crystal nucleation occurs at the walls of the crystallizer and crystal growth occurs in the bulk. The parameters in the kinetic models were estimated from online measurements of bulk temperature and slurry transmittance. Concentration measurements show that the xylene mature is always saturated (supersaturation is essentially zero) during all crystallization runs. Therefore, a reduced, two-parameter, high growth rate model was developed to describe these Crystallizers. The kinetic parameters were correlated highly for the reduced model. A new batch experiment with an alternative temperature profile was determined that removes the correlation and allows both parameters to lie determined uniquely.

  • crystallization of para xylene in scraped surface Crystallizers
    Aiche Journal, 2001
    Co-Authors: Daniel B Patience, James B. Rawlings, Hazim A Mohameed
    Abstract:

    Crystallization kinetics of para-xylene in batch pilot-scale scraped-surface Crystallizers were determined for commercial crystallization of a xylene mixture currently produced in Amoco plants. Dynamic mass and energy balances, coupled with the dynamic population balance, were used to model the scraped-surface crystallizer. The model assumes that crystal nucleation occurs at the walls of the crystallizer and crystal growth occurs in the bulk. The parameters in the kinetic models were estimated from online measurements of bulk temperature and slurry transmittance. Concentration measurements show that the xylene mature is always saturated (supersaturation is essentially zero) during all crystallization runs. Therefore, a reduced, two-parameter, high growth rate model was developed to describe these Crystallizers. The kinetic parameters were correlated highly for the reduced model. A new batch experiment with an alternative temperature profile was determined that removes the correlation and allows both parameters to lie determined uniquely.

  • modelling and control of Crystallizers
    Powder Technology, 1992
    Co-Authors: James B. Rawlings, W. R. Witkowski, John W Eaton
    Abstract:

    Abstract This paper provides an overview of modelling, measurement, identification and control issues arising in Crystallizers. The crystal size distribution is modelled with a population balance. The remaining reactor states, such as concentrations temperature, are modelled with integro-differential equations. The models are solved numerically with global orthogonal collocation for continuous reactors and orthogonal collocation on finite elements for batch reactors. The ill-conditioned problem of estimating crystal size distribution from laser light scattering data is examined. The estimation of crystallization kinetic constants from supersaturation data and light scattering data is also discussed. Finally control problems are discussed and an optimal batch crystallization temperature profile is computed.

Blagajana Herzog Velikonja - One of the best experts on this subject based on the ideXlab platform.

  • haloarchaeal communities in the Crystallizers of two adriatic solar salterns
    Canadian Journal of Microbiology, 2007
    Co-Authors: Poklar Ulrih, Miklavž Grabnar, Blagajana Herzog Velikonja
    Abstract:

    Solar salterns operate only for short dry periods of the year in the north shore of the Adriatic Sea because of its relatively humid and cold Mediterranean climate. In a previous paper, we showed that the NaCl precipitation ponds (Crystallizers) of Northern Adriatic Seovlje salterns have different haloarchaeal populations from those typically found in dry and hot climates such as Southern Spain. To check whether there is a common pattern of haloarchaeal diversity in these less extreme conditions, diversity in Crystallizers of other Adriatic solar salterns in Ston, Croatia was ascertained by molecular and culture methods. In addition, the cultivation approach was used to further describe haloarchaeal diversity in both salterns. Over the period of two solar salt collection seasons, isolates related to species of the genera Haloferax, Haloarcula, and Haloterrigena were recovered from both salterns. Within the same sampling effort, relatives of the genus Halorubrum and a Natrinema-like isolate were cultivated from Slovenian Seovlje salterns while Halobacterium related isolates were obtained from the Croatian Ston salterns. Concurrent with our previous findings, a library of Croatian saltern crystallizer PCR-amplified 16S rRNA genes was dominated by sequences related to the genus Halorubrum. The microbial community structure was similar in both salterns but diversity indices showed greater values in Slovenian salterns when compared with Croatian salterns.

  • diversity of halophilic archaea in the Crystallizers of an adriatic solar saltern
    FEMS Microbiology Ecology, 2005
    Co-Authors: Lejla Pasic, Sergio G Bartual, Natasa Poklar Ulrih, Miklavž Grabnar, Blagajana Herzog Velikonja
    Abstract:

    Haloarchaeal diversity in the Crystallizers of Adriatic Secovlje salterns was investigated using gene fragments encoding 16S rRNA and bacteriorhodopsin as molecular markers. Screening of 180 clones from five gene libraries constructed for each gene targeted revealed 15 different 16S rRNA and 10 different bacteriorhodopsin phylotypes, indicating higher haloarchaeal diversity than previously reported in such hypersaline environments. Furthermore, results of rarefaction analysis indicated that analysis of an increasing number of clones would have revealed additional diversity. Finally, most sequences from the Crystallizers grouped within the Halorubrum branch, whereas square-shaped ‘Haloquadratum’ relatives, repeatedly reported to dominate crystallizer communities, were rare. Presence of such special and diverse haloarchaeal community could be attributed to the Secovlje salterns rare continuous short-cycling salt production mechanism.