Simulated Moving Bed Separation Research Articles

Discrete Dynamic System Modeling for Simulated Moving Bed Processes

Although the simulated moving bed (SMB) process boasts advantages such as high productivity and low consumption, the cost of obtaining optimized parameters through practical experiments to control the separation process can be enormous due to its complex nonlinear characteristics. Consequently, the successful transformation of the SMB separation process into a mathematical dynamic model for computer simulation would greatly reduce the research costs associated with experimental studies. In this study, the Crank–Nicolson method was employed to discretize and dynamize the SMB process, enabling the simulation of processes under both linear and Langmuir isotherms. The results of the simulation experiments demonstrated the feasibility and high efficiency of this approach, thereby establishing a solid foundation for further advancements in online control strategies.

Separation of p-xylene and m-xylene by simulated moving bed chromatography with MIL-53(Fe) as stationary phase

The separation of p-xylene (PX) and m-xylene (MX) isomers with near boiling points is a worldwide problem. The metal-organic framework material is an ideal stationary phase for chromatographic separation because of its high porosity, homogeneous pore diameter and good chemical stability. In this paper, a simulated moving bed (SMB) chromatography system with MIL-53(Fe) as the stationary phase and petroleum ether-dichloromethane as the mobile phase was designed to separate PX and MX at ambient temperature. Firstly, according to the elution curves of a single column, nonlinear competitive Langmuir adsorption isotherm equation was confirmed by equilibrium dispersive chromatography model. Then, the SMB separation zone was determined based on triangle theory, and the SMB operating conditions were optimized. Finally, the purity, recovery and productivity of PX reached 100.0%, 99.1% and 93.1 g/L/h, respectively; the purity, recovery and productivity of MX reached 96.4%, 100.0% and 23.5 g/L/h, respectively; the solvent consumption was 0.42 L/g.

Techno-economic assessment of subcritical water hydrolysis process for sugars production from brewer’s spent grains

Breweries generate a high amount of brewer’s spent grains (BSG), which is a valuable feedstock for industrial applications. In the current study, a techno-economic assessment of the flow-through subcritical water hydrolysis reactor to produce sugars from BSG was performed. Simulations were done for a sequential hydrolysis process in three-extractor vessels of 10 L (pilot-plant) and 500 L (industrial-plant), coupled or not to a separation system. The sugar separation system was composed of a five-zone simulated moving bed (SMB) process. A study on the cost of manufacturing (COM), profitability indicators, and sensitivity analysis was conducted to verify the project feasibility. Moreover, the mass and energy balance of the industrial process was accomplished to evidence the main operational parameters. Simulation results indicated that the scale-up process from pilot to industrial scale reduced the COM by approximately 80 %. In the process coupled with the SMB separation system, arabinose and galactose represented 83.68 % of the costs for sugars separation. Arabinose COM decreased from 64.10 USD kg–1 in pilot-plant to 7.22 USD kg–1 in industrial-plant. The implementation of a separation system recovering six sugars with high added-value can be an advantage in the industrial-plant process when comparing to the process without SMB process, which produces a single hydrolysate fraction with low commercial value. Finally, the integrated subcritical water hydrolysis of BSG coupled with a separation system can be a promising alternative to produce different concentrated sugars in a biorefinery concept.

The first attempt at simulated-moving-bed separation of medically utilizable ingredients from neoagarooligosaccharides generated through the β-agarase hydrolysis of agarose in red algae

Recently, it has been discovered that neoagarohexaose (NA6) contained in neoagarooligosaccharides (NAO), which originate from the β-agarase hydrolysis of agarose in red algae, has various medical effects. This has led to growing interest in establishing an industrial-utilizable process for high-purity separation of NA6 from NAO, which has, however, yet to be realized. To address this issue, we attempt to develop an efficient simulated-moving-bed (SMB) process for continuous-mode separation of NA6 from NAO with high purity and high yield, which was named “NA6-SMB” in this article. It was found first that the most suitable adsorbent for the targeted SMB separation was the ion-exclusion resin of sodium form with 4% crosslinkage, and its proper operating temperature was 60 °C. For the selected absorbent with the aforementioned properties, the intrinsic parameters of all NAO components were determined. Using the resultant parameter values, the configuration and operation parameters of the NA6-SMB were designed such that the high-purity separation of NA6 could be realized and kept stable throughout a long period of SMB operation while maximizing throughput. The separation efficiency of such designed NA6-SMB was first validated by model simulations, and then verified by experiments, which confirmed that the NA6 product of 98.7% purity could be obtained continuously throughout the long-term NA6-SMB processing while keeping its loss below 1%. Finally, an additional SMB was developed to treat the non-product stream of the NA6-SMB for the purpose of producing high-purity NA4 (>99%), which has been considered worthy of testing its medical efficacy and physiological activation in large quantity.

Optimal design of a simulated-moving-bed chromatographic process for high-purity separation of acetoin from 2,3-butanediol in a continuous mode

For the high-purity production of acetoin or 2,3-butanediol (BD) from related fermentation processes, it is essential to accomplish a detailed separation between acetoin and BD in an economical mode. To address this issue, we aimed to develop a highly-efficient simulated-moving-bed (SMB) process for the continuous-mode separation of acetoin from BD with high purity and small loss. As a first step for this task, the adsorption and mass-transfer parameters of acetoin and BD on a proven adsorbent were estimated while assuming that BD isomers (meso-BD and DL-BD) would be identical in adsorption and mass-transfer behaviors. The resultant parameters from such estimation were applied to the optimal design of the acetoin-BD separation SMB. The designed SMB was then experimentally investigated, which revealed that some sign of BD isomerism occurred in the SMB column-profile data and thus had an adverse effect on the SMB separation performance. To resolve this problem, the individual parameters of BD isomers were determined on the basis of the SMB column-profile data and an inverse-method principle. The resulting parameters of BD isomers were used in the re-design of the target SMB, which was then experimentally checked for its separation performance. It was confirmed that such SMB re-designed in consideration of BD isomerism was quite effective in the continuous-mode separation of acetoin from BD with high purity (> 99.2%) and small loss (< 1.52%).

C&amp;EN profiles Laurus Labs, upping the chemistry ante in India

In 2014, India’s Laurus Laboratories acquired simulated moving bed (SMB) technology, a $5 million investment in its generic pharmaceutical chemicals business. Although not a huge sum to pay for the chiral separations equipment, which is commonly used in the U.S. and Europe, it was a risky move in India, a region known for low-cost, basic chemistry services. But it paid off. Today, Laurus may be the only company of its kind in India doing SMB separations. The SMB investment was one of many for a firm that has grown over the past 10 years from a small R&D contractor to one of India’s most successful pharmaceutical contract development and manufacturing organizations. It is also indicative of the firm’s commitment to high-end pharmaceutical chemistry. Last year, Laurus struck a deal to manufacture sofosbuvir, the key active pharmaceutical ingredient (API) in Gilead Sciences’ hepatitis C drugs, for marketing in developing countries. Laurus

Separation of Nadolol Stereoisomers Using Chiralpak IA Chiral Stationary Phase.

Chiralpak IA adsorbent is used for both analytical and preparative chromatographic separation of nadolol stereoisomers. The results include a complete screening of the mobile phase composition for both the baseline resolution of all four nadolol stereoisomers (analytical separation) and the simulated moving bed (SMB) pseudo-binary separation of the most retained stereoisomer. The experimental results show that analytical baseline resolution of nadolol stereoisomers can be achieved using alcohol/hydrocarbon and alcohol/acetonitrile solvent mixtures. The 10%ethanol/90%acetonitrile mixture is presented as the one that presents baseline resolution with lower retention. For the preparative pseudo-binary separation, pure ethanol, pure methanol, alcohol/acetonitrile, and alcohol/tetrahydrofuran mixtures proved to allow good separation results. The 100%methanol/0.1%diethylamine solvent composition was selected to perform the experimental SMB separation. Using a 10g/L total feed concentration, the more retained stereoisomer was recovered at the extract outlet stream with 99.5% purity, obtaining a system productivity of 1.98 gL(-1) h(-1) and requiring a solvent consumption of 3.13L/g of product. Comparing these results with the ones recently presented by Ribeiro et al. (2013), this work shows that the Chiralpak IA chiral adsorbent is an interesting alternative to Chiralpak AD for the separation of nadolol stereoisomers at both analytical and preparative scales. Chirality 28:399-408, 2016. © 2016 Wiley Periodicals, Inc.

Simulated moving bed chromatography for the separation of ethyl esters of eicosapentaenoic acid and docosahexaenoic acid under nonlinear conditions

In this study, ethyl esters of eicosapentaenoic acid and docosahexaenoic acid were separated with simulated moving bed (SMB) chromatography, where the stationary phase was C18 silica gel with particle size of 10μm packed in eight columns, and the mobile phase was pure methanol. The Henry constants, transport parameters and total porosity were measured from pulse response chromatographic experiments using a single column. The Henry constants were obtained from the first moment analysis. The transport parameters including axial dispersion coefficients and effective mass transfer coefficients were obtained from the second moment analysis. Nonlinear adsorption equilibrium isotherms for the pure components and their mixture were determined from adsorption-desorption method. The Langmuir model was used to fit the experimental data, and the corresponding parameters were further used to predict the competitive adsorption equilibria of the mixture. The validity of mathematical model parameters was checked by a frontal chromatography experiment. The simulated results of the SMB process using these parameters agreed well with the experimental results. At the feed concentration of 100g/L, the SMB separation was able to produce both solutes with relative purity above 99%, productivity of 13.11g/L adsorbent/h, and solvent consumption of 0.46L/g.

Simulated moving bed separation of agarose-hydrolyzate components for biofuel production from marine biomass

The economically-efficient separation of galactose, levulinic acid (LA), and 5-hydroxymethylfurfural (5-HMF) in acid hydrolyzate of agarose has been a key issue in the area of biofuel production from marine biomass. To address this issue, an optimal simulated moving bed (SMB) process for continuous separation of the three agarose-hydrolyzate components with high purities, high yields, and high throughput was developed in this study. As a first step for this task, the adsorption isotherm and mass-transfer parameters of each component on the qualified adsorbent were determined through a series of multiple frontal experiments. The determined parameters were then used in optimizing the SMB process for the considered separation. Finally, the optimized SMB process was tested experimentally using a self-assembled SMB unit with four zones. The SMB experimental results and the relevant computer simulations verified that the developed process in this study was quite successful in the economically-efficient separation of galactose, LA, and 5-HMF in a continuous mode with high purities and high yields. It is thus expected that the developed SMB process in this study will be able to serve as one of the trustworthy ways of improving the economic feasibility of biofuel production from marine biomass.

Effects of a malfunctional column on conventional and FeedCol-simulated moving bed chromatography performance

The effects of a malfunctional column on the performance of a simulated moving bed (SMB) process were studied experimentally and theoretically. The experimental results of conventional four-zone SMB (2-2-2-2 configuration) and FeedCol operation (2-2-2-2 configuration with one feed column) with one malfunctional column were compared with simulation results of the corresponding SMB processes with a normal column configuration. The malfunctional column in SMB processes significantly deteriorated raffinate purity. However, the extract purity was equivalent or slightly improved compared with the corresponding normal SMB operation because the complete separation zone of the malfunctional column moved to a lower flow rate range in zones II and III. With the malfunctional column configuration, FeedCol operation gave better experimental performance (up to 7%) than conventional SMB operation because controlling product purity with FeedCol operation was more flexible through the use of two additional operating variables, injection time and injection length. Thus, compared with conventional SMB separation, extract with equivalent or slightly better purity could be produced from FeedCol operation even with a malfunctional column, while minimizing the decrease in raffinate purity (less than 2%).

Stepwise Model Evaluation in Simulated Moving‐Bed Separation of Ketamine

AbstractA stepwise model with lumped mass transfer kinetics (SW‐LM) is applied for chromatographic column modeling in simulated moving bed (SMB) separation of a racemic mixture of the anesthetic ketamine. The SW‐LM model can easily represent the SMB separation process of ketamine considering the retention factors equal to the equilibrium constants of the R‐ and S‐enantiomers. The equilibrium data was utilized only in the previous column characterization for the determination of mass transfer kinetic parameters used later in the SMB design. The SW‐LM model achieves similar transient results of enantiomer concentrations in the extract and raffinate compared to a robust equilibrium dispersive model.

Supercritical Fluid Extraction of &lt;i&gt;Polygonum cuspidatum&lt;/i&gt; and Subsequent Isolation by Simulated Moving Bed Chromatography

In this work, supercritical carbon dioxide with ethanol as cosolvent was employed to extract bioactive compounds fromPolygonum Cuspidatum. Effect of temperature for 40 and 50 C on the extraction at 35 MPa was examined. It was found that extraction at 50 C resulted in high yield. A two-stage extraction at 50 C and 35 MPa was then designed to investigate effect of cosolvent on the recovery of resveratrol and emodin. The first stage extraction by solely using carbon dioxide can rarely extract resveratrol, but adding ethanol as cosolvent in the second stage significantly increases the extraction of resverarol and emodin. The crude extract obtained in the second stage was very stable against agglomeration and precipitation, because the first stage extraction helped to remove impurities from thePolygonum Cuspidatum. The stable crude extract was subsequently used as the feed for the SMB (simulated moving bed) separation. In this work, experimental validation was completed by solely using single SMB to isolate resveratrol, emodin, and physcion from the crude extract. As conducting the SMB experiments, the Triangle theory was used to help to determine the separable operating conditions. From the discussion of the experimental results, the criterion to obtain the pure resveratrol and physcion, and the concentrated emodin were depicted. Since both the extraction and the purification are conducted at low temperature, the bioactivity of the produced natural products will totally be preserved. The two-stage extraction and subsequent purification in this paper will provide greener and effective alternative for the development of botanical drugs.

Separation of epigallocatechin gallate from tea polyphenol by simulated moving bed chromatography

(−)-Epigallocatechin gallate (EGCG) was purified from tea polyphenol by a two-step simulated moving bed (SMB) chromatographic process with C18-bonded silica gel as stationary phase and a mixture of methanol and water as mobile phase, removing the more retained components firstly and the less retained components secondly. An open-loop 3-zone SMB approach was used, a gradient of solvent strength in zones I and II was formed by different methanol dosage in purge and desorbent solutions and pre-equilibration was reached by the elution at the end of zone III. Under the approximation including linear adsorption and ideal chromatographic model, the operating parameters of the simulated moving bed were selected according to the “triangle theory”. In the first SMB separation, a solution of tea polyphenol with 55.5% purity of EGCG was used for feeding and a raffinate solution with 92.2% purity and 99.7% recovery of EGCG was obtained. The raffinate solution was concentrated for feeding in the second SMB separation and an extract solution with 97.8% purity and 99.8% recovery of EGCG was obtained.

Comparison of various ternary simulated moving bed separation schemes by multi-objective optimization

Over the past decade, many modifications have been proposed in simulated moving bed (SMB) chromatography in order to effectively separate a binary mixture. However, the separation of multi-component mixtures using SMB is still one of the major challenges. In addition, the performance of SMB system highly depends on its operating conditions. Our study address this issue by formulating a multi-objective optimization problem that maximizes the productivity and purity of intermediate eluting component at the same time. A number of optimized isocractic ternary SMB operating schemes are compared both in terms of productivity and amount of desorbent to feed ratio. Furthermore, we propose a generalized full cycle (GFC) formulation based on superstructure formulation encompassing numerous operating schemes proposed in the literature. We also demonstrate that this approach has a potential to find the best ternary separation strategy among various alternatives.

Optimal design and experimental validation of a three-zone simulated moving bed process based on the Amberchrom-CG161C adsorbent for continuous removal of acetic acid from biomass hydrolyzate

In the production process of bio-ethanol from biomass, acetic acid is recognized as the key impurity to be removed from the sugar components that are generated by hydrolyzing biomass. In regard to this issue, it has recently been confirmed that the Amberchrom-CG161C resin was highly qualified as the adsorbent of a simulated moving bed (SMB) process for continuous separation of acetic acid from the biomass hydrolyzate, i.e., sugars. However, the previous study on the Amberchrom-CG161C SMB with the aforementioned separation goal has been limited to only a theoretical work, including some batch-chromatography tests. The experimental validation of such an Amberchrom-CG161C SMB process, including its optimal design, was attempted in this article. This task began by assembling the experimental unit of the SMB process with three zones. Its operating conditions were then optimized by using genetic algorithm. Under the optimized operating conditions, the relevant three-zone SMB experiment was conducted. The assay of all the resultant product samples verified that the SMB separation of interest was performed successfully as designed. The experimental data were also found to agree closely with the model predictions. Finally, a partial-discard strategy was applied to maintain the sugar product concentration as high as possible.

Practical Aspects of Integrated Operation of Biotransformation and SMB Separation for Fine Chemical Synthesis

Integrated operation of biotransformation and simulated moving bed (SMB) separation is an attractive option for high-yield manufacturing of commercially relevant compounds such as rare sugars and sialic acids from equilibrium-limited isomerase- or aldolase-catalyzed reactions. Here, we present the first lab-scale implementation of such a process using the production of d-psicose, which is currently under consideration as low calorie sweetener, by d-tagatose epimerase-catalyzed epimerization from d-fructose as a model system. While a typical batchwise eprimerization of d-fructose would stop at 25%, a yield of 97% was obtained when operating the fully integrated process consisting of SMB, enzyme membrane reactor (EMR) and nanofiltration (NF) for a number of days with absolute product purities. Next to the proof of principle, important process characteristics such as startup time, stability and robustness were investigated. By pre-equilibrating the NF unit to the projected conditions, startup times could be ...

Chiral separation of flurbiprofen enantiomers by preparative and simulated moving bed chromatography

This study presents the chiral resolution of flurbiprofen enantiomers by preparative liquid chromatography using the simulated moving bed (SMB) technology. Flurbiprofen enantiomers are widely used as nonsteroidal anti-inflammatory drugs, and although demonstrate different therapeutic actions, they are still marketed as a racemic mixture. The results presented here clearly show the importance of the selection of the proper solvent composition for the preparative separation of flurbiprofen enantiomers. Chiral SMB separation is carried out using a laboratory-scale unit (the FlexSMB-LSRE®) with six columns, packed with the Chiralpak AD® stationary phase (20 μm). Results presented include the experimental measurement of equilibrium and kinetic data for two very different solvent compositions, a traditional high hydrocarbon content [10%ethanol/90%n-hexane/0.01% trifluoroacetic acid (TFA)] and a strong polar organic composition (100%ethanol/0.01%TFA). Experimental data, obtained using the two mobile phase compositions, are used to predict and optimize the SMB operation. After selecting 10%ethanol/90%n-hexane/0.01%TFA as the most appropriate solvent composition, three feed concentrations of racemic flurbiprofen were considered. Using 40 g/l of racemic flurbiprofen feed solution, the purities for both outlet streams were above 99.4%, the productivity was 13.1 g(feed) /(L(bed) h), and a solvent consumption of 0.41 L(solvent) /g(feed) was achieved.

Parametric uncertainties and influence of the dead volume representation in modelling simulated moving bed separation processes

In this study, a systematic numerical procedure for identifying the model parameters of simulated moving bed (SMB) separation processes is developed. The parameters are first estimated by minimizing a weighted least-squares criterion using experimental data from batch experiments, e.g. the time evolution of the concentration of elution peaks. Then, a cross-validation is achieved using data from experiments in SMB operation. At this stage, the importance of a careful modelling of the dead volumes within the SMB process is highlighted. In addition, confidence intervals on the estimated parameters and on the predicted concentration profiles are evaluated.

Experimental Optimizing Control of the Simulated Moving Bed Separation of Tröger’s Base Enantiomers

Simulated moving bed (SMB) chromatography has become a well-established technique in the pharmaceutical industry and biotechnology for the separation of enantiomers. However, exploiting the full economic potential of the process is not trivial, and therefore, we developed a “cycle-to-cycle” optimizing controller to facilitate the operation of SMB units close to the economic optimum. The proposed controller only requires the information about the linear adsorption behavior and the average porosity of the columns. This paper presents the different steps required to set up our controller for a given separation problem, namely the separation of Tröger’s Base enantiomers. For the investigated system, the complete adsorption isotherm is available which allows us to carry out detailed simulations and to compare them to the actual experiments. Hence, one can judge how well the simulations can predict both the dynamic and the steady state behavior of the controller at different feed concentrations. The paper demonstrates that the control concept is simple enough to be implemented quickly and reliably for a new separation campaign within three days. Furthermore, the experimental results clearly show that despite process disturbances the controller is able to fulfill the product specifications and to improve the process performance.

PARTNERSHIPS DEBUT AT INFORMEX

EXHIBITORS at the annual Informex trade show in San Francisco last week put a positive spin on business in the fine chemicals sector, pointing to a continuing trend toward pharmaceutical outsourcing and signs of an upturn in the general economy. Several companies announced partnerships they claim will position them to take advantage of new opportunities to supply active pharmaceutical ingredients (APIs) and intermediates. Dishman Group and Ampac Fine Chemicals announced collaborations with Codexis under which both companies will have access to Codexis’ enzymebased biocatalysis technology. Nick Green, president of Dishman Contract Research & Manufacturing Services, says the firm will manufacture products for Codexis and will also use the technology in its own contract production of APIs and intermediates. Aslam Malik, president of Ampac, says the agreement will allow his firm to add enzyme biocatalysis to its tools for chiral chemistry, which include simulated moving bed separations. Meanwhile, Albemarle’s...