Simulated Moving Bed Separation Research Articles

Simulated moving bed chromatography with supercritical fluids for the resolution of bi-naphthol enantiomers and phytol isomers

The combination of the simulated moving bed (SMB) technique with supercritical fluid chromatography (SFC) leads to a process with unique features. Besides the known advantages of the SMB process, the use of supercritical carbon dioxide as the mobile phase offers the advantages of reduction in organic solvents and an easy eluent/solute separation. Because of the low viscosity and high diffusion coefficients of supercritical fluids, a high efficiency is possible. The steps of process development for SMB SFC are presented using the separations of the bi-naphthol enantiomers and phytol isomers as examples. The development of a packed column SFC method at an analytical scale is shown for the separation of the bi-naphthol enantiomers on a chiral stationary phase and CO 2 with a modifier as the mobile phase. The influence of the modifier, modifier content, and column configuration on productivity of the SMB SFC process was investigated by simulation. The first set of experiments was performed in the SMB separation of phytol isomers at low concentration to test the feasibility of the SMB SFC high purity separation of the binary mixtures. In the second set of experiments, the productivity of the process was increased by increasing the feed concentration up to 54 grams feed per liter stationary phase (SP) and hour (g feed/l SP h).

Impact of a modification in the production process of an amylose derived stationary phase on the SMB separation of a pharmaceutical intermediate

The propensity of helical homochiral polymers derived from amylose to resolve optical isomers is being exploited intensively for the production of active pharmaceutical ingredients (APIs), using either high performance lipid chromatography (HPLC) or the simulated moving bed (SMB) principle. Several lots of an amylose derived stationary phase, Chiralpak® AS™, and its successor, Chiralpak® AS-V™, were compared by pulse injections with increasing amounts of various racemates in order to determine the loading capacity and the competitive adsorption isotherms. Software simulations allowed to assess the possible effects due to the observed variations between the chiral stationary phases (CSPs) on the performance of a pilot SMB unit. The obtained results were verified by two multi-kilogram separations performed under current Good Manufacturing Practice (cGMP) guidelines employing the two CSPs. The results of the two production runs are discussed in the light of the recently introduced “triangle theory,” which allows to account for the overload conditions prevailing under preparative chromatographic conditions and to predict optimal operating conditions. Under optimized conditions the enantiomer separation of 1.4 kg racemate/kg stationary phase per day with purities >99.6% for the target enantiomer has been achieved.

Scale‐up of analytical chromatography to the simulated moving bed separation of the enantiomers of the flavour norterpenoids α‐ionone and α‐damascone

AbstractThe scale‐up of the HPLC separation of the enantiomers of the flavour norterpenoid ketones α‐ionone and α‐damascone from analytical to preparative scale was achieved using the chromatographic simulated moving bed (SMB) technique. Commercial HPLC columns, with heptakis‐(2,3,6‐per‐O‐methyl)‐β‐cyclodextrin bound to silica gel as chiral stationary phase, were employed for the separation. High‐purity enantiomers of both chiral compounds have been obtained with a rather satisfactory productivity. Copyright © 2002 John Wiley & Sons, Ltd.

Simulated moving bed chromatography (SMB) for application in bioseparation.

Simulated Moving Bed (SMB) technology is of rising interest in the field of bioseparation. This is particularly due to its advantages such as reduction of solvent consumption, high productivity and final purities as well as low investment costs in comparison to eluent chromatography. SMB units can operate under high productivity overloaded conditions. This leads to non-linear competitive adsorption behavior, which has to be accounted for when designing and optimizing new SMB separations. The so called "Triangle Theory", which is briefly reviewed in this chapter, 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. The application of the SMB-technique to the downstream processing of biotechnological products requires some specific changes to meet the special demands of bioproduct isolation. Some exemplary applications are given including separations of sugars, proteins, monoclonal antibodies, ionic molecules and optical isomers and for desalting.

Shortcut experimental method for designing chiral SMB separations

AbstractThe simulated moving‐bed (SMB) chromatographic separation of the Tröger's base enantiomers with ethanol as eluent on microcrystalline triacetate cellulose was studied. An experimental technique to design nonlinear SMB separations with few column experiments is presented. This shortcut technique allows the rigorous solution of the Equilibrium Theory model to be approximated without knowing the adsorption equilibria, and therefore can be useful in developing new separations. The predictions of the shortcut method are compared with the experimental results of the SMB separation. The effect of the feed concentration and of the nonideal contributions, such as mass‐transfer resistance and extracolumn band broadening, are elucidated.

Application of gradients in the simulated moving bed process

In the last decade the simulated moving bed (SMB) process was implemented successfully in the pharmaceutical industry to perform difficult separations of valued added products. Mainly liquid solvent mixtures with adjusted but constant composition were applied as the mobile phases (isocratic operation). Only recently the potential of modulating the solvent strength during the process was realised (gradient operation). The purpose of this paper is to present the results of studying a two-step gradient SMB process using a weaker solvent to introduce the feed and a stronger solvent for efficient adsorbent regeneration. A mathematical model for the simulation of this process was proposed and solved numerically. Systematic calculations were performed in order to identify suitable operating conditions as a function of averaged desorbent concentrations taking into account the locally changing nonlinear adsorption equilibria. Based on the predictions and on preliminary experimental investigations devoted to determine the required model parameters the separation of a mixture of two cycloketons using normal-phase silica was designed. A two-step gradient SMB process was applied using pure n-hexane as the weak solvent in the feed stream and pure ethyl acetate as the strong solvent in the desorbent stream. The achieved purities and concentrations in the raffinate and extract streams confirmed the potential of the gradient technique applied. In agreement with the theoretical results a significant improvement in the process performance compared to the common isocratic SMB separation was found.

SMB chromatography applied to the separation/purification of fructose from cashew apple juice

The simulated moving-bed (SMB) technology has been successfully used in separations in petrochemical, food and fine chemical industries. This work is intended to show a potencial economic alternative for the industrial processing of the cashew apple juice. The cashew tree is a native tropical plant abundant in Northeastern Brazil, whose commercial value relies mainly on the processing of its nut. The penduncle of the fruit is called the cashew apple. Despite its high nutrition value, around 90% of the crop spoils on the soil. Simulation and experimental results are presented for SMB separation of fructose from glucose, both present (<FONT FACE="Symbol">~</FONT>40 kg/m³) in the aqueous phase of comercial cashew apple juice. Kinetic and equilibrium data for fructose and glucose on packed columns using cation-exchange resins are reported. Experimental results for SMB operation indicate close to 90% purity in each product (fructose-rich extract and glucose-rich raffinate). Simulated unit performance and internal profiles agree well with experimental values. To increase the added-value and versatility of the products, either a step of isomerization of the raffinate or diverse SMB fluid-solid flowrate ratios may be applied. By this way, a wide range of products may be obtained, from nearly pure fructose to 42%, 55% and 90% solutions, which are the standard high fructose syrup concentrations. If solids content is conveniently raised to the usual HFCS (high fructose corn syrup) comercial standards, these products may be used as food additives, thus confirming a potentially attractive use of cashew apple juice.

Obtainment of High-Fructose Solutions from Cashew (Anacardium occidentale) Apple Juice by Simulated Moving-Bed Chromatography

The simulated moving-bed (SMB) technology has been successfully used in separations in the petrochemical, food, and fine chemicals industries. This work is intended to demonstrate the possibility of using this technology to obtain high-fructose solutions from the cashew apple juice, which may represent an attractive economic alternative for its industrial exploitation. The cashew tree is a native tropical plant abundant in Northeastern Brazil, the commercial value of which relies mainly on the processing of its nut. Despite the high nutritional value of the penduncle of the fruit, the cashew apple, approximately 90% of the crop spoils on the soil. Simulation and experimental results are presented for SMB separation of fructose from glucose, both present (˜40 kg/m3) in the aqueous phase of concentrated cashew apple juice. Kinetic and equilibrium data for fructose and glucose on packed columns using cation-exchange resins are reported. Experimental results for SMB operation at 30°C indicate purities close to 90% in each product (fructose-rich extract and glucose-rich raffinate). Simulated predictions of the unit performance and internal profiles agree well with experimental data. To increase the added value and versatility of the products, either an isomerization step for the raffinate or diverse SMB fluid–solid flow rate ratios may be applied. In this way, a wide range of products may be obtained, from nearly pure fructose to 42, 55, and 90% solutions, which are the standard high-fructose syrup concentrations. If solids content is conveniently raised to the standards of commercial high-fructose syrups, these products may be used as food additives, thus confirming a potentially attractive use of the cashew apple juice.

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.

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.

Separation of a racemic pharmaceutical intermediate using closed-loop steady state recycling

Closed-loop steady state recycling (formerly called closed-loop recycling with periodic intra-profile injection or CLRPIPI) is similar to simulated moving bed (SMB) chromatography. Both steady state recycling (SSR) and SMB are steady state, binary chromatographic techniques in which fresh sample is injected into the interior of the circulating chromatographic profile and two fractions or product streams are collected from either end of the profile. However, SMB is a continuous process, whereas SSR is a repetitive, though discontinuous, process. Underlying mechanisms of closed-loop SSR were studied using the separation of a racemic pharmaceutical intermediate. We have found that creation of a stable steady state chromatographic profile is crucial to obtaining high purity fractions. The structure of the steady state profile, also called the steady state inventory, is controlled by the size of the fractions collected and by the location of the injection points. These SSR parameters have corresponding SMB parameters. For example, increasing the size of Fraction 1 in SSR is equivalent to increasing the raffinate flow-rate in SMB; increasing the distance from the injection point to fraction 1 in SSR is equivalent to increasing the size of zone III in SMB; etc. Finally, the SSR results were compared to those of an SMB separation of the same racemic pharmaceutical intermediate. Using the same chiral stationary phase (CSP) and mobile phase, the production rates (SSR, 255 g racemate/kg CSP/day; SMB, 240 g racemate/kg CSP/day), purities (SSR, 98% e.e. for both enantiomers; SMB, 98% e.e. for both enantiomers), and recoveries (SSR, 99% for both enantiomers; SMB, 99% for both enantiomers) for the two techniques were similar, but SSR used more mobile phase per gram of racemate than SMB. SSR, however, used less mobile phase than batch HPLC.

Parabolic intraparticle concentration profile assumption in modeling and simulation of nonlinear simulated moving-bed separation processes

This communication will focus on the application of the LDF (Linear Driving Force) mass transfer model in the mathematical simulation moving-bed separation processes with nonlinear adsorption isotherms to compare with the linear pore diffusion model, in order to determine its validity as well as to establish the equivalence between the two models.

Complete separation conditions for a local equilibrium TCC adsorption unit

AbstractA new technique presented can offer analytical solutions for the local equilibrium true countercurrent model to study the simulated moving‐bed (SMB) separation process. This equilibrium theory could be vey useful for predicting both optimal and robust operation conditions for the SMB separation process, if the results can be easily calculated. However, analytical solution was available only in the limiting case of binary separation. With this analytical solution for multicomponent systems, the application of equilibrium theory will be more practical. While developing these solutions, a new way of applying the well‐known ω‐transformation to nonlinear adsorption system was conceived. This approach may have broader applications than are presented here.

5470464 Small scale simulated moving bed separation apparatus and process : Priegnitz James W Elgin, IL, United States assigned to UOP

5470464 Small scale simulated moving bed separation apparatus and process : Priegnitz James W Elgin, IL, United States assigned to UOP