Simulated Moving Bed Unit Research Articles

Enantiomers separation by simulated moving bed chromatography: Non-instantaneous equilibrium at the solid–fluid interface

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.

Development of an high-performance liquid chromatographic simulated moving bed separation from an industrial perspective

A binary test mixture consisting of cyclopentanone and cycloheptanone is used for the performance evaluation of a pilot-scale simulated moving bed unit. The involved adsorption equilibria and the kinetic behavior are discussed in detail. The results of the test runs are evaluated using the recently introduced “triangle theory” which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to select optimal operating conditions. Under optimized conditions the separation of 735 g test mixture/kg stationary phase per day with purities >99.9% for extract and raffinate stream has been achieved.

Design of Simulated Moving Bed Units under Nonideal Conditions

The influence of dispersive effects (axial mixing and mass-transport resistance) on the performance of simulated moving bed (SMB) units is studied through detailed modeling. The results are represe...

Standing wave design of nonlinear SMB systems for fructose purification

AbstractDesign equations were derived from standing wave analysis for continuous moving bed (CMB) and simulated moving bed (SMB) systems with nonlinear isotherms. Simple wave solutions and hodograph plots from batch elution experiments can be used to derive the optimal operation conditions for SMB systems without mass‐transfer effects. The design equations are tested with results from computer simulations and experimental data from two pilot‐scale SMB units for the separation of fructose from glucose. Batch equilibrium tests of single component and binary solutions are used to estimate adsorption isotherm parameters. Overall mass‐transfer and axial dispersion coefficients are estimated from eight sets of pulse, frontal and elution data at different concentrations and flow rates. The isotherm and mass‐transfer parameters are used in the standing wave analysis to determine the zone flow rates and switching times for the two SMB units. Experimental column profiles, product purities, and product concentrations agree closely with simulation results. This method gives robust operation conditions for SMB systems with nonlinear isotherms, and optimal cycle time and zone flow rates for nonlinear systems without mass‐transfer effects can be determined from the standing wave analysis.

Continuous chromatographic separation through simulated moving beds under linear and nonlinear conditions

Simulated Moving Bed (SMB) technology is receiving more and more attention as a convenient technique for the production scale continuous chromatographic separation of fine chemicals. Thanks to the efficient simulated countercurrent contact between the stationary and the fluid phase, SMB units can operate under high productivity overload conditions. These lead to nonlinear competitive adsorption behavior, which has to be accounted for when designing and optimising new SMB separations. The so called `Triangle Theory', which is briefly revised here, provides explicit criteria for the choice of the operating conditions of SMB units to achieve the prescribed separation of a mixture characterized by Langmuir, modified Langmuir and bi-Langmuir isotherms. In all these cases, the effect of increasing nonlinearity of the separation, due to increased feed concentration can be predicted. In this paper, the use of this approach for the design of linear and nonlinear SMBs is considered, with reference to examples reported previously. Alternative strategies have been proposed in the literature, which are based on the use of safety factors for linear systems and on an adaptation of this for nonlinear ones. In the cases considered, which involve experimental data for a linear system and numerical experiments for a nonlinear Langmuir system, it is shown that `Triangle Theory' allows attainment of a better understanding of and a deeper insight into the behavior of SMB units.

Continuous enantiomer separation of the volatile inhalation anesthetic enflurane with a gas chromatographic simulated moving bed unit

The separation of the enantiomers of the racemic inhalation anesthetic enflurane was achieved by continuous gas phase simulated moving bed chromatography (GC–SMB). The productivity of the unit and the enantiomeric excess of the obtained streams were somehow low mainly because of the high operating temperature, i.e., T=50°C. As chiral stationary phase, an unpurified cyclodextrin derivative, consisting of various isomers and homologues and dissolved in an apolar polysiloxane matrix, was used. The competitive adsorption isotherms of ( R)-(−)-enflurane and ( S)-(+)-enflurane were determined by gas chromatographic measurements at increasing values of the pulse concentration in the range from linear to overload conditions. It has been shown that the adsorption behavior of the two enantiomers can be explained by considering enantioselective and non-enantioselective sites on the stationary phase. These results demonstrate the feasibility of the chiral resolution of enflurane by GC–SMB.

Optimization strategy for simulated moving bed systems

Simulated moving bed (SMB) systems are of rising interest in the purification of pharmaceuticals or specialty chemicals (racemic mixtures, proteins, organic acids, etc.). This is particularly due to their advantage in solvent reduction, obtained productivity and purities as well as investment costs in comparison to eluent chromatography. This paper evolved from the need for a readily available algorithm in order to find optimal operating conditions for SMB chromatography systems with nonlinear or coupled adsorption isotherms. The herein developed algorithm is based on a semi-deterministic two-step approach. First, optimal operating conditions with regard to an objective function are found by knowing adsorption measurements only. In a second step actual SMB results are used to adapt the initial isotherm measurements and match the simulation with the experiment. The algorithm is verified on a bench-scale SMB unit applied for the separation of a racemic epoxide with Chiralcel-OD as stationary phase. The developed algorithm improved the productivity of the investigated experimental design by 24%.

Simulated moving bed chromatographic resolution of a chiral antitussive

The behavior of a laboratory simulated moving bed (SMB) unit for continuous chromatographic separation of enantiomers has been considered. This was applied to the resolution of a chiral antitussive agent, guaifenesin, on Chiralcel OD, during an experimental campaign involving nineteen runs. The application of recently developed criteria for the design and optimization of SMB units allows us to understand and rationalize the experimental results, as well as to indicate how to optimize the separation performances. A three-step procedure to determine the adsorption isotherms needed to apply these criteria is proposed; it is reliable and may be applied also where pure components are not available.

Effect of the flow rates in linear, ideal, simulated moving‐bed chromatography

AbstractThe algebraic solution for linear, ideal simulated moving‐bed (SMB) chromatography derived previously revealed important new properties of the SMB process. This solution was validated by comparing with experimental data and with the results of numerical solutions of the equilibrium–dispersive and the lumped kinetic model. This earlier solution, however, was limited to the simple case in which the safety factor was assumed to be the same for the flow rates in all four sections. An extension of this solution to the case in which the safety factors differ and allow an independent selection of the four different flow rates (within limits) is derived. This solution accounts well for most practical situations. It permits the discussion of the influence of different flow rates on the performance of an SMB unit, an issue of critical importance for the optimization of the design and operation of these separators.

Optimal operation of simulated moving bed units for nonlinear chromatographic separations

The simulated moving bed (SMB) technology is receiving more and more attention as a convenient technique for the production scale continuous chromatographic separation of fine chemicals. Characteristic features of SMBs are improved performances with respect to preparative chromatography and nonlinear competitive adsorption behavior. The selection of the operating conditions to achieve high separation performances under nonlinear conditions is acknowledged to be the major problem in running a SMB unit for a new application. This problem is solved in this paper, where a general theory is developed which provides explicit criteria for the choice of the operating conditions of SMB units to achieve the prescribed separation of a mixture characterized by both constant selectivity Langmuir isotherms and variable selectivity modified Langmuir isotherms. The space of the operating parameters, i.e. the fluid to solid flow-rate ratios, is divided in regions with different separation regimes. The effect of increasing nonlinearity of the system on the operating conditions and the separation performances, namely desorbent requirement, enrichment, productivity and robustness of the separation, is thoroughly analyzed. The obtained results are shown to provide a very convenient tool to find both optimal and robust operating conditions of SMB units. Finally, a comparison between model predictions and experimental data dealing with the resolution of different racemic mixtures assesses the reliability and accuracy of the obtained theoretical findings.

Continuous Isotope Separation in Systems with Solid Phase. II. Separation of Nitrogen Isotopes with Use of Ion-Exchange Resin

Abstract This work deals with the separation of nitrogen isotopes by chemical exchange between ammonia in an aqueous solution and a cation-exchange resin in the NH± 4 form. Using this system, a continuous process in a simulated moving bed (SMB) is developed. Two operations, the column under total reflux and a continuous feed operation, have been studied. In the latter, the product enriched in heavy nitrogen 15N was removed from the unit. The operating conditions (2.1–30.5 cm/s superficial liquid velocity, 0.7 mm average resin granules size, and 0.98 N solution of a displacement agent) were close to those used in industrial applications. By studying the separation of nitrogen isotopes, it was shown that displacement ion-exchange chromatography in a practically standard liquid-phase SMB unit provides the opportunity for the flexible production of a number of isotopes of light elements. We found that flow converting is robust, and the operation and control are simple. It appears that the process design propo...

Design of Optimal Operating Conditions of Simulated Moving Bed Adsorptive Separation Units

The design of the optimal operating conditions for simulated moving bed (SMB) adsorptive separation units is considered. A procedure for the a priori selection of the operating conditions to achieve an assigned separation requirement is developed in the frame of equilibrium theory for the equivalent four section countercurrent unit, using a model where the adsorption equilibria are described through the constant selectivity stoichiometric model, while both mass transfer resistance and axial dispersion are neglected. The space of the operating parameters, i.e. the mass flow rate ratios m[sub j], is divided in regions with different separation regimes. Curves at constant outlets purity and recovery are drawn in the (m[sub 2],m[sub 3]) plane. The introduction of three performance parameters, desorbent requirement, adsorbent requirement, and productivity, allows the development of a procedure for the design of optimal operating conditions. This procedure is completed, accounting for the effect of the switching time on the separation performances, with a detailed model of the SMB unit, considering both axial dispersion and mass transfer resistance. This result constitutes a useful tool for determining the range of operating conditions to achieve an assigned separation requirement and then for selecting the optimal operating condition within this range.