Less common applications of simulated moving bed chromatography in the pharmaceutical industry (original) (raw)
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Simulated Moving Bed Chromatography – The Next Step in HPLC
CHIMIA, 2006
Simulated Moving Bed (SMB) technology, a continuous chromatographic separation process, is of increasing interest in the field of pharmaceuticals, fine chemicals, and biotechnology. The complexity of SMB asks for a deeper understanding of the mathematical design and physical adsorption processes, along with the practical training in chromatography and process engineering. This makes SMB a technology which is also suitable for educational purposes. The principle of SMB separation is described with a short introduction of its mathematical design for a simulation. A method of measuring the adsorption isotherms, which are crucial for a process simulation, is also discussed. As an example, the application of SMB to the separation of two groups of biologically important vitamin E compounds, i.e. tocopherols and tocotrienols from natural-source material is presented.
Enantiomers separation by simulated moving bed chromatography
Journal of Chromatography A, 1999
The simulated moving bed (SMB) technology, first conceived for large bulk-scale separations in the petrochemical industry, has found increasingly new applications in the pharmaceutical industry. Among these, the separation of fine chemicals has been the subject of considerable study and research. This work presents the modeling, simulation and design of the operation of a SMB plant in order to separate a binary chiral mixture. The usual assumption of instantaneous equilibrium at the solid-fluid interface is questioned and a first-order kinetics of adsorption is taken into account. The cases of linear, Langmuir and modified Langmuir equilibria are studied. The equivalent true moving bed (TMB) model was used assuming axial dispersion for the fluid flow and plug flow for the solid-phase flow. Intraparticle diffusion was described by a linear driving force (LDF) approximation. Simulation results indicate that, under certain conditions, equilibrium is not actually reached at the adsorbent surface. This leads to different unit performances, in terms of product purities and recoveries, as compared to those predicted assuming instantaneous equilibrium. Moreover, SMB units may be improperly designed by the usual methods (flow-rate ratio separation regions) if non-equilibrium effects are overlooked.
Advanced Operating Strategies to Extend the Applications of Simulated Moving Bed Chromatography
Chemical Engineering & Technology, 2017
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the final Version of Record (VOR). This work is currently citable by using the Digital Object Identifier (DOI) given below. The final VoR will be published online in Early View as soon as possible and may be different to this Accepted Article as a result of editing. Readers should obtain the final VoR from the journal website shown below when it is published to ensure accuracy of information. The authors are responsible for the content of this Accepted Article.
Journal of Chromatography A, 2012
This study deals with the separation of ternary mixtures based on Simulated Moving Bed chromatography to isolate target components with intermediate adsorption strength. To overcome the limitations of conventional SMB systems, which are designed for binary separations and unable to perform centercut separations, several modifications have been proposed. The purpose of this study was to provide a theoretical comparison of several of advanced SMB configurations capable to separate ternary mixtures. Emphasis is given to those techniques, which have already been used in practice, and to those having potential for future industrial application. SMB cascades connected in series via the extract or raffinate ports of the first unit are analyzed and compared are as well as an integrated 8-zone SMB unit with internal recycle. Additionally, the commercialized pseudo SMB process (JO process) was evaluated. The performance of these modified SMB systems was investigated based on the assumption of linear adsorption isotherms for all three components considering three separation problems characterized by different separation difficulty. Besides the influence of separation factors, the concentrations of the impurities in the feed mixture and the purity requirements for the target product were studied systematically.
Two-step solvent gradients in simulated moving bed chromatography
Journal of Chromatography A, 2002
The application of gradients in simulated moving bed (SMB) chromatography has recently attracted interest as a method for further improving the performance of this continuous separation process. One possible implementation of gradients consists in setting the solvent strength in the desorbent stream higher than that in the feed stream. As a result, the components to be separated are more retained in the zones upstream of the feed position and more easily eluted in the zones downstream of the feed position. If a liquid mobile phase is used, gradients can be created by dosing different solvents into the feed and desorbent ports. In a closed-loop gradient SMB arrangement the solvent strength within the unit will depend on the two feed compositions and on the characteristic flow-rates of the process. In this work an equilibrium stage model describing a true moving bed process is used to analyze numerically the main features of a two-step gradient SMB process. The adsorption isotherms are assumed to be always linear under isocratic conditions. The relevant Henry constants depend in a nonlinear manner on the composition of the solvent. Based on numerical simulations the impact of the two inlet solvent compositions is demonstrated in terms of the size and shape of regions of applicable flow-rates. Different strategies of designing the process are discussed and compared with respect to maximizing productivities and minimizing desorbent requirements.
Experimental analysis of a chiral separation through simulated moving bed chromatography
Chemical Engineering Science, 1999
An eight column HPLC-Simulated Moving Bed (SMB) laboratory unit for the separation of enantiomers has been built and operated. The separation of the enantiomers of the TroK ger's base compound on triacetylcellulose has been considered as model separation. First the thermodynamics of adsorption has been characterised on a single analytical chromatographic column, then the separation has been scaled-up to the SMB laboratory unit. SMB experiments with di!erent operating parameters, i.e., switch time and #ow rates, have been run in order to analyse the separation performance of the laboratory unit. The experimental results are discussed in the light of the triangle theory for SMB operation.
Step gradients in 3-zone simulated moving bed chromatography
Journal of Chromatography A, 2007
The simulated moving bed (SMB) technology is a proven tool for efficient separation of binary mixtures. However, relying on isocratic conditions limits the applicability of the classical SMB approach when considering the field of bioseparations. Here, the use of gradients opens up new possibilities. A gradient in a SMB process can be established by using different solvent strengths in the incoming feed and desorbent streams, resulting in two internal plateaus of elution strength. Thus, compared to the conventional process, the overall amount of solvent needed can be reduced, productivity can be increased and more concentrated product streams can be obtained. In this contribution, two case studies will be presented. At first, the separation of bovine IgG from lysozyme will be analyzed as a model system. Antibodies are a common target substance in bio-chromatography, as therapeutic monoclonal antibodies are among the most promising biopharmaceuticals. Using adsorption data obtained from single-column experiments, an appropriate SMB process was designed and implemented. The second target component is the active dimeric form of the bone morphogenetic protein-2 (BMP-2). This protein was isolated from a renaturation solution, which also contained its inactive monomeric form as well as other undefined proteins from the bacterial production strain. A 3-zone open-loop gradient-SMB approach was used successfully for both separations.