Malte Kaspereit - Academia.edu (original) (raw)
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Papers by Malte Kaspereit
Industrial & Engineering Chemistry Research, 2009
Chemical Engineering Technology, 2009
Chemical Engineering Science, Sep 1, 2007
Chemical Engineering Research and Design, Jul 1, 2007
Chemie Ingenieur Technik, Jun 1, 2008
In dieser Studie werden im Rahmen des Kooperationsprojektes Intenant [1] verschiedene Konzepte zu... more In dieser Studie werden im Rahmen des Kooperationsprojektes Intenant [1] verschiedene Konzepte zur chiralen Trennung eines mit mehreren t/a racemisch hergestellten pharmazeutischen Wirkstoffs (API) verglichen. Der angewandte 2-Schritt-Prozess zur selektiven Kristallisation des Zielenantiomers nutzt gezielt eine Verschiebung der eutektischen Zusammensetzung aus [2] und ermöglicht die Gewinnung des API-Eutomers aus asymmetrischen Lösungen. Ausbeute und Reinheit des Produktkristallisats sind zunächst nicht vom Grad der Asymmetrie der Ausgangslösung abhängig. Hingegen fällt bei nahezu symmetrischer Ausgangslösung vermehrt racemisches Kristallisat im ersten Prozessschritt an, welches unerwünscht ist. Eine für die Kristallisation notwendige asymmetrische Ausgangslösung kann über eine Vortrennung mittels chiraler Chromatographie erhalten werden. Die Produktivität der Vortrennung ist gesteigert, da die Reinheitsanforderung aufgrund des nachgeschalteten Kristallisationsprozesses sinkt [3]. D...
EUROCON 2007 - The International Conference on "Computer as a Tool", 2007
In this contribution we present a dual thermal mass flow sensor arrangement based on the thermo-t... more In this contribution we present a dual thermal mass flow sensor arrangement based on the thermo-transfer principle (calorimeter) for in-line monitoring of liquid phase chemical reactions in residence time micro reactors. Focus is on micro plants used in chemical micro process engineering. Studies are based on commercially available sensors for low mass flow rates using constant power mode. We chose
Organic Process Research & Development, 2012
ABSTRACT Various promising concepts exist for improving the performance of productions of pure en... more ABSTRACT Various promising concepts exist for improving the performance of productions of pure enantiomers. An efficient approach is developed for the systematic conceptual design of such processes. The proposed three-step procedure aids a fast selection of the optimal process configuration out of many possible candidates and leads to an optimally designed process. The approach is applied in a case study for an industrially relevant compound, considering different process concepts based on simulated moving bed chromatography, enantioselective crystallization, and racemization. It is demonstrated that mixed-integer nonlinear programming is capable of predicting simultaneously the optimal process configuration and optimal design parameters.
Liquid Chromatography, 2013
Distributing Reactants to Improve Selectivity and Yield, 2010
2,6-Pipecoloxilidide (PPX) is an important intermediate for the synthesis of mepivacaine, ropivac... more 2,6-Pipecoloxilidide (PPX) is an important intermediate for the synthesis of mepivacaine, ropivacaine and bupivacaine, which are frequently used local anesthetics of the amide type for several purposes in medicine[1]. Based on its chiral nature, an enantioseparation of PPX is needed to exclude additional negative side effects from the counter-enantiomer. By combining three different techniques, chromatography, enantioselective crystallization and racemization, an improved process with a higher yield was achieved in comparison to the use of a single full-separation process. All 3 unit operations were executed within a jointly used solvent system with full recycling (counter-enantiomer of PPX and solvents) including a minimum requirement of solvent exchanges / removals. The target molecule was obtained with an enantiopurity of >99.5% in multi-gram scale. Within this contribution the design of the integrated process is presented with a focus on the final enantioselective crystalliza...
Journal of chromatography. A, Jan 21, 2005
Hybrid processes for enantioseparations have a considerable potential for reducing investment and... more Hybrid processes for enantioseparations have a considerable potential for reducing investment and operational costs. An example is the combination of simulated moving bed (SMB) chromatography and selective crystallisation. However, the design of integrated processes is a difficult task. A shortcut method is presented that can serve as a tool for design and estimation of the potential of such processes. The approach requires only limited experimental data and thus allows for systematic parameter studies. The method is based on the determination of the purity-performance characteristic of the SMB process and rigorous application of mass balances. The use of relative mass fluxes allows derivation of simple algebraic expressions for essential process parameters. The significant potential of combining SMB and crystallisation is demonstrated for the example of the separation of mandelic acid enantiomers.
ABSTRACT Besides SMB systems, several single-column techniques, such as closed-loop recycling and... more ABSTRACT Besides SMB systems, several single-column techniques, such as closed-loop recycling and peak shaving, have been suggested to enhance the yield of chromatographic separation by recycling the chromatogram partially or as a whole. Steady state recycling (SSR) chromatography is a further development of these concepts. In an SSR process, in addition to collecting the leading and trailing parts of the elution profile, a constant amount of fresh feed is added to each recycle fraction, which causes the process to attain a periodic steady state. Recently, we have presented a method for analysis and design of SSR chromatography with arbitrary purity or yield requirements at the limit of infinite column efficiency [1]. The approach applies to SSR processes in mixed-recycle operation and allows for the direct prediction of the steady state and the design parameters without performing dynamic simulations. Therefore, it simplifies optimal design of SSR processes and simultaneously enables evaluation of process performance. It was also shown theoretically, that the productivity of SSR chromatography is necessarily lower than that of an optimized batch process. On the other hand, the SSR process always outperforms batch chromatography in terms of eluent consumption and product concentrations. In the present work, separation of cycloketones on a hydrophobic polystyrene adsorbent XAD-16 is used as a model system. We present experimental data and numerical simulations that demonstrate the influence of limited column efficiency of the process performance (i.e., eluent consumption, specific productivity, product concentrations). A short-cut method for predicting the steady state of the SSR process from a single overloaded injection is presented and applied to the model system. In addition, we demonstrate how the short-cut method can be utilized to intensify the start-up phase of the SSR process. References [1] Sainio, T., Kaspereit, M., Analysis of steady state recycling chromatography using equilibrium theory, Sep. Purif. Technol., 66(2009), 918
Organic Process Research & Development, 2012
ABSTRACT A racemic mixture of bicalutamide, a drug substance used in the treatment of prostate ca... more ABSTRACT A racemic mixture of bicalutamide, a drug substance used in the treatment of prostate cancer, was separated by simulated moving bed chromatography, with the objective of maximizing throughput at reduced outlet purity. The enriched extract stream was purified further by a crystallization process exploiting a shift in the eutectic composition. The optimal purity in between both process steps was identified. The separation scheme developed was validated on a scale of 600 g, and the results were compared to those of state-of-the art and discussed. The investigated scheme revealed a wide range of promising coupling conditions while showing superior productivities and enhanced process robustness.
Organic Process Research & Development, 2012
Industrial & Engineering Chemistry Research, 2009
Chemical Engineering Technology, 2009
Chemical Engineering Science, Sep 1, 2007
Chemical Engineering Research and Design, Jul 1, 2007
Chemie Ingenieur Technik, Jun 1, 2008
In dieser Studie werden im Rahmen des Kooperationsprojektes Intenant [1] verschiedene Konzepte zu... more In dieser Studie werden im Rahmen des Kooperationsprojektes Intenant [1] verschiedene Konzepte zur chiralen Trennung eines mit mehreren t/a racemisch hergestellten pharmazeutischen Wirkstoffs (API) verglichen. Der angewandte 2-Schritt-Prozess zur selektiven Kristallisation des Zielenantiomers nutzt gezielt eine Verschiebung der eutektischen Zusammensetzung aus [2] und ermöglicht die Gewinnung des API-Eutomers aus asymmetrischen Lösungen. Ausbeute und Reinheit des Produktkristallisats sind zunächst nicht vom Grad der Asymmetrie der Ausgangslösung abhängig. Hingegen fällt bei nahezu symmetrischer Ausgangslösung vermehrt racemisches Kristallisat im ersten Prozessschritt an, welches unerwünscht ist. Eine für die Kristallisation notwendige asymmetrische Ausgangslösung kann über eine Vortrennung mittels chiraler Chromatographie erhalten werden. Die Produktivität der Vortrennung ist gesteigert, da die Reinheitsanforderung aufgrund des nachgeschalteten Kristallisationsprozesses sinkt [3]. D...
EUROCON 2007 - The International Conference on "Computer as a Tool", 2007
In this contribution we present a dual thermal mass flow sensor arrangement based on the thermo-t... more In this contribution we present a dual thermal mass flow sensor arrangement based on the thermo-transfer principle (calorimeter) for in-line monitoring of liquid phase chemical reactions in residence time micro reactors. Focus is on micro plants used in chemical micro process engineering. Studies are based on commercially available sensors for low mass flow rates using constant power mode. We chose
Organic Process Research & Development, 2012
ABSTRACT Various promising concepts exist for improving the performance of productions of pure en... more ABSTRACT Various promising concepts exist for improving the performance of productions of pure enantiomers. An efficient approach is developed for the systematic conceptual design of such processes. The proposed three-step procedure aids a fast selection of the optimal process configuration out of many possible candidates and leads to an optimally designed process. The approach is applied in a case study for an industrially relevant compound, considering different process concepts based on simulated moving bed chromatography, enantioselective crystallization, and racemization. It is demonstrated that mixed-integer nonlinear programming is capable of predicting simultaneously the optimal process configuration and optimal design parameters.
Liquid Chromatography, 2013
Distributing Reactants to Improve Selectivity and Yield, 2010
2,6-Pipecoloxilidide (PPX) is an important intermediate for the synthesis of mepivacaine, ropivac... more 2,6-Pipecoloxilidide (PPX) is an important intermediate for the synthesis of mepivacaine, ropivacaine and bupivacaine, which are frequently used local anesthetics of the amide type for several purposes in medicine[1]. Based on its chiral nature, an enantioseparation of PPX is needed to exclude additional negative side effects from the counter-enantiomer. By combining three different techniques, chromatography, enantioselective crystallization and racemization, an improved process with a higher yield was achieved in comparison to the use of a single full-separation process. All 3 unit operations were executed within a jointly used solvent system with full recycling (counter-enantiomer of PPX and solvents) including a minimum requirement of solvent exchanges / removals. The target molecule was obtained with an enantiopurity of >99.5% in multi-gram scale. Within this contribution the design of the integrated process is presented with a focus on the final enantioselective crystalliza...
Journal of chromatography. A, Jan 21, 2005
Hybrid processes for enantioseparations have a considerable potential for reducing investment and... more Hybrid processes for enantioseparations have a considerable potential for reducing investment and operational costs. An example is the combination of simulated moving bed (SMB) chromatography and selective crystallisation. However, the design of integrated processes is a difficult task. A shortcut method is presented that can serve as a tool for design and estimation of the potential of such processes. The approach requires only limited experimental data and thus allows for systematic parameter studies. The method is based on the determination of the purity-performance characteristic of the SMB process and rigorous application of mass balances. The use of relative mass fluxes allows derivation of simple algebraic expressions for essential process parameters. The significant potential of combining SMB and crystallisation is demonstrated for the example of the separation of mandelic acid enantiomers.
ABSTRACT Besides SMB systems, several single-column techniques, such as closed-loop recycling and... more ABSTRACT Besides SMB systems, several single-column techniques, such as closed-loop recycling and peak shaving, have been suggested to enhance the yield of chromatographic separation by recycling the chromatogram partially or as a whole. Steady state recycling (SSR) chromatography is a further development of these concepts. In an SSR process, in addition to collecting the leading and trailing parts of the elution profile, a constant amount of fresh feed is added to each recycle fraction, which causes the process to attain a periodic steady state. Recently, we have presented a method for analysis and design of SSR chromatography with arbitrary purity or yield requirements at the limit of infinite column efficiency [1]. The approach applies to SSR processes in mixed-recycle operation and allows for the direct prediction of the steady state and the design parameters without performing dynamic simulations. Therefore, it simplifies optimal design of SSR processes and simultaneously enables evaluation of process performance. It was also shown theoretically, that the productivity of SSR chromatography is necessarily lower than that of an optimized batch process. On the other hand, the SSR process always outperforms batch chromatography in terms of eluent consumption and product concentrations. In the present work, separation of cycloketones on a hydrophobic polystyrene adsorbent XAD-16 is used as a model system. We present experimental data and numerical simulations that demonstrate the influence of limited column efficiency of the process performance (i.e., eluent consumption, specific productivity, product concentrations). A short-cut method for predicting the steady state of the SSR process from a single overloaded injection is presented and applied to the model system. In addition, we demonstrate how the short-cut method can be utilized to intensify the start-up phase of the SSR process. References [1] Sainio, T., Kaspereit, M., Analysis of steady state recycling chromatography using equilibrium theory, Sep. Purif. Technol., 66(2009), 918
Organic Process Research & Development, 2012
ABSTRACT A racemic mixture of bicalutamide, a drug substance used in the treatment of prostate ca... more ABSTRACT A racemic mixture of bicalutamide, a drug substance used in the treatment of prostate cancer, was separated by simulated moving bed chromatography, with the objective of maximizing throughput at reduced outlet purity. The enriched extract stream was purified further by a crystallization process exploiting a shift in the eutectic composition. The optimal purity in between both process steps was identified. The separation scheme developed was validated on a scale of 600 g, and the results were compared to those of state-of-the art and discussed. The investigated scheme revealed a wide range of promising coupling conditions while showing superior productivities and enhanced process robustness.
Organic Process Research & Development, 2012