Varicol Process Research Articles

Evaluation of the optimal performance of ModiCon and ModiCon+VariCol simulated moving bed variants

The interest in the simulated moving bed (SMB) technology lies in its variants. Some of them that have a high potential to increase the performance in enantioseparations are the ModiCon and the ModiCon+VariCol. These variants are based on the modulation of feed concentration and a combination of feed concentration and length of zones modulations. The concept of the ModiCon process in the literature is that it can be applied only for systems described by nonlinear isotherms. However, there are no numerical or experimental studies that prove that. On the other hand, the hybrid operation of ModiCon+VariCol can be used in systems with a low number of columns due to the flexibility in the use of columns, but it has been little explored. In this work, the maximal performance of the ModiCon process was compared with the SMB process for a linear isotherm. Additionally, the ModiCon+VariCol process was evaluated in systems with a low number of columns. The enantioseparation of guaifenesin was considered as a case study. The result shows that the ModiCon process can also be applied with high performance in systems described by linear isotherms. In the evaluation of the ModiCon+VariCol process for unequal product purity, it was found that the hybrid operation with 3 columns showed a higher throughput and productivity than the SMB process with 6 columns. The productivity of the ModiCon+VariCol was more than three times higher than the conventional operation.

Optimal performance comparison of the simulated moving bed process variants based on the modulation of the length of zones and the feed concentration

The VariCol and ModiCon processes are two variants of the simulated moving bed (SMB) process, characterized by the modulation of the length of zones of the chromatographic column train and the feed concentration. These features give more flexibility than the conventional operation, leading to essential improvements in the separation and purification of mixtures. The optimal performance comparison of these two variants, the hybrid formed by their combination, and the conventional SMB process are scarce in the literature. This comparison helps discover new characteristics of each single and combined operation mode and creates guidelines to select the appropriate operation mode for possible real applications. In this work, the performance comparison of the ModiCon, VariCol, ModiCon+VariCol, and SMB processes is carried out in terms of maximal throughput for specific product purity values. Particular emphasis is placed on both the ModiCon and the hybrid ModiCon+VariCol processes characteristics. A strategy for combining and optimizing the ModiCon and the VariCol processes was determined. As a case study, the enantioseparation of guaifenesin was considered. In the ModiCon process, more than two modulation subintervals did not improve the performance in the separation. The optimal pattern, based on two subintervals, has zero feed concentration in the first subinterval and the maximal concentration in the second one. The best result for the hybrid operation (ModiCon+VariCol) was reached when the feed port moves simultaneously as the SMB process switching period. The optimal throughput of the ModiCon and the ModiCon+VariCol processes was almost doubled than that of the SMB process. These performances were based on larger zones I and II and not in zones II and III as occur with the SMB and VariCol process. The throughput in the hybrid operation increases more significantly than the ModiCon process when 5 columns were considered instead of 6. The hybrid operation could be more attractive for a system with a few numbers of columns.

One-step optimization strategy in the simulated moving bed process with asynchronous movement of ports: A VariCol case study

The VariCol process is a variant of the conventional simulated moving bed (SMB) process, distinguished by the asynchronous shifting of the inlet and outlet ports of the chromatographic column train. This feature allows for a more flexible operation in column utilization and can also achieve higher separation performances. However, to take full benefit out of it, the operating parameters, such as the strategy for port switching, must be optimal. in this paper, a novel methodology for optimizing those parameters, based on a single NLP (non-linear programming), is proposed. The main advantage of this approach is that it significantly reduces the complexity of the original MINLP (mixed-integer non-linear programming) formulation currently discussed in the literature. The proposed optimization problem is built, considering that the average column configuration of three zones provides the necessary and sufficient information to describe the VariCol process. Several optimization scenarios for the enantioseparation of 1,1´-bi-2-naphthol and aminoglutethimide were considered to evaluate the proposed methodology and to compare the performance of VariCol and SMB processes. The results have shown that with the single NLP approach, it is possible to explore the optimal solution in all the VariCol process domains with less computational effort than other optimization strategies reported in the literature. That is a great advantage, especially in the context of real-time applications.

Enantioseparation of racemic aminoglutethimide using asynchronous simulated moving bed chromatography

The separation of aminoglutethimide enantiomers by the continuous multicolumn chromatographic processes were investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenyl-carbamate stationary phase (brand name Chiralcel OD) and mobile phase was a mixture of n-hexane and ethanol with monoethanolamine additive. The continuous enantioseparation processes included a synchronous shifting process (SMB) and an asynchronous shifting process (VARICOL), which allowed reducing the column number (here from six-column SMB to five-column VARICOL process). Transport-dispersive model with the consideration of both intraparticle mass transfer resistance and axial dispersion was adopted to design and optimize the operation conditions for the separation of aminoglutethimide enantiomers by SMB process and VARICOL process. According to the optimized operation conditions, experiments were carried out on VARICOL-Micro unit using five-column VARICOL process with 1/1.5/1.5/1 configuration and six-column SMB process with 1/2/2/1 configuration. Products of R-aminoglutethimide (R-AG) enantiomer and S-aminoglutethimide (S-AG) enantiomer with more than 99.0% purity were obtained continuously from extract stream and raffinate stream, respectively. Furthermore, the experiemntal data obtained from five-column VARICOL process were compared with that from six-column SMB process, the feasibility and efficiency for the separation of guaifenesin enantiomers by VARICOL processes were evaluated.

Optimization of VARICOL SMB processes using hybrid modeling and nonlinear programming

The Varicol process exhibits continuous and discrete-time dynamics and can be represented by a hybrid model, where the continuous-time dynamics is described by mass-balance partial differential equations, whereas the discrete-time dynamics is described by a timed transition Petri net (TTPN). This hybrid model allows to simplify the solution of a normally difficult Mixed-Integer Non-Linear Programming problem for maximizing the productivity of a Varicol process subject to constraints on the desired purities of the extract and the raffinate components. Indeed, the coverability tree of the TTPN can be constructed to generate a set of candidate integer parameters, and the corresponding nonlinear problems are solved for a subset of candidates selected on the basis of an approximate evaluation using the (true moving bed) triangle theory. The optimal solution is the Varicol configuration (column sequence) for which the productivity is maximal. A repeatability and a robustness analysis show the feasibility of this approach.

Experiment and modeling for the separation of guaifenesin enantiomers using simulated moving bed and Varicol units

The separation of guaifenesin enantiomers by both simulated moving bed (SMB) process and Varicol process was investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenylcarbamate (Chiralcel OD) stationary phase and a mixture of n-hexane and ethanol was used as mobile phase. The operation conditions were designed based on the separation region with the consideration of mass transfer resistance and axial dispersion, and the experiments to separate guaifenesin enantiomers were carried out on VARICOL-Micro unit using SMB process with the column configuration of 1/2/2/1 and Varicol process with the column configuration of 1/1.5/1.5/1, respectively. Single enantiomer with more than 99.0% purity was obtained in both processes with the productivity of 0.42genantiomer/dcm3 CSP for SMB process and 054genantiomer/dcm3 CSP for Varicol process. These experimental results obtained from SMB and Varicol processes were compared with those reported from literatures. In addition, according to the numerical simulation, the effects of solid-film mass transfer resistance and axial dispersion on the internal profiles were discussed, and the effect of column configuration on the separation performance of SMB and Varicol processes was analyzed for a few columns system. The feasibility and efficiency for the separation of guaifenesin enantiomers by SMB and Varicol processes were evaluated.

Study on the number of decision variables in design and optimization of Varicol process

As a variant of simulated moving bed chromatography, Varicol process can realize flexible adsorbent allocation through asynchronous shifting of inlet and outlet ports. In this research, the switching strategies for achieving one certain average configuration were investigated. It was found the system performance depends on the total number of switches of the four ports during one switching period and Simple-Shifting-Scheme (SSS) with four switches brings out the best performance. More importantly, SSS could be different schemes, different by a parallel shifting, but all of them result in the same performance, demonstrating that only three instead of four switching times are decision variables while designing a Varicol process. To make the design of SSS more solid, a systematic method for derivation of SSS is proposed and applied on the optimization of a Varicol process for enantioseparation of 1,1′-bi-2-naphthol and reduce the solvent consumption by 17% comparing with SMB.

Varicol process optimization strategy based on the solution of a MINLP

Varicol is a continuous chromatographic separation process which is based on the simulated moving bed principle with an asynchronous commutation of the inlet and outlet streams. The objective of this work is to develop a systematic procedure to optimize the operating conditions of the Varicol process, including the commutation sequence and the internal flow rates. To this end, the continuous dynamics are represented using a conventional mass-balance partial differential equation model, whereas the discrete dynamics are described by a timed transition Petri net. A Mixed-Integer Non-Linear Problem (MINLP) is formulated to maximize the process productivity under constraints on the desired purities of both the extract and the raffinate components. The MINLP is solved by constructing a set of candidate integer parameters and solving the resulting nonlinear problem for a subset of candidates selected on the basis of an approximate evaluation using the (true moving bed) triangle theory. Numerical results show the feasibility of this approach.

Efficient Moving Horizon State and Parameter Estimation for the Varicol SMB Process

Abstract Abstract In this paper, a moving horizon state and parameter estimation (MHE) scheme for the Varicol process is presented. The Varicol process is an extension of the Simulated Moving Bed (SMB) process that realizes non-integer column distributions over the separation zones by an asynchronous switching of the inlet and outlet ports (the ports are shifted individually). These additional degrees of freedom can be used to yield an improvement in economical performance compared to SMB operation. The proposed estimation scheme is based on a rigorous SMB model that incorporates rigorous chromatographic columns and port switching. The absence of model simplifications allows the extension of the estimation scheme to the more complex Varicol process. The goal of the estimation scheme is to reconstruct the full state of the system, i.e. the concentration profiles along all columns, and to identify critical model parameters in the presence of noisy measurements. The estimation is based on measurements of the concentrations of the components at the two outlet ports (which are asynchronously switched from one column to the next) and at one fixed location between two columns. The state estimation scheme utilizes a deterministic model within the prediction horizon. State noise is only considered in the state and in the parameters up to the beginning of the horizon. By applying a multiple-shooting method and a real-time iteration scheme for solving the resulting optimization problem, the computation times are reduced and the scheme can be applied online. A numerical simulation for an enantiomer separation system with nonlinear adsorption isotherm is presented.

Optimal Economic Design and Operation of Single‐ and Multi‐column Chromatographic Processes

Single-column chromatography is widely used in the biopharmaceutical industries, although multi-column alternatives in the form of simulated moving bed (SMB) processes are now emerging. It may be difficult, however, to determine which column alternative will be best suited for a given application, and this work sets out to address this issue. A systematic approach is presented that is based on a full economic appraisal of each process alternative based on an optimization of the net annual profit. Single-column processes with and without recycling are considered, as are both the SMB and the Varicol process. The cyclic steady state for the SMB and Varicol processes is determined directly by complete discretization. The approach is applied to a case study based on a linear isotherm where it is found that for this particular system, a recycling policy is not necessary for the single column. When comparing the single-column process with the multi-column alternatives, the single column is the most economical provided the life time of the project is short; however, the economic benefits of the more capital-intensive multi-column processes are greater if the life time of the project is over 5 years. The SMB process is found to perform marginally better than the Varicol process over 15 years; however, this may be because not all extra degrees of freedom for the Varicol process were considered.

Purification of Difluoromethylornithine by Global Process Optimization: Coupling of Chemistry and Chromatography with Enantioselective Crystallization

An industrial process for the purification of metric tons of enantiomerically pure difluoromethylornithine (DFMO HCl) is described. The amino acid DFMO HCl is cyclized to form the lactam, which is acylated with pivaloyl chloride to form rac-N-pivaloyl-DFMO lactam (4). The lactam 4 provides enhanced separation compared to a direct resolution of racemic DFMO HCl (1). A hybrid chiral resolution process is proposed to separate the enantiomers of 4. This process involves a multicolumn continuous enantioselective chromatographic process (VariCol) coupled with enantioselective crystallization of (d)-N-pivaloyl-DFMO lactam 5. The interest of this hybrid process is based on a favorable eutectic point providing a higher productivity of the VariCol process and lower purification costs than the chromatographic process alone. A final chemical modification (hydrolysis) is used to form the single enantiomers of both (d)-DFMO (6) and (l)-DFMO in high chemical purity and enantiomeric excess. A global optimization approach is applied to design an economical industrial process, which is based on a parametric study of the VariCol process and enantioselective crystallization to obtain maximum recovery and purity while significantly lowering the cost of manufacturing the single enantiomers. A detailed description of the global process optimization is presented.

Optimization of reactive simulated moving bed and Varicol systems for hydrolysis of methyl acetate

In this article, multi-objective optimization technique was applied to improve the performance of simulated moving bed reactor (SMBR) and its modification, Varicol process for hydrolysis of methyl acetate. The optimization problems of interest considered are simultaneous maximization of purity and yield of acetic acid and methanol, respectively, in the raffinate and extract streams. The effect of distributed feed flow rate on the performance of SMBR and the applicability of reactive Varicol systems were also investigated. The non-dominated sorting genetic algorithm (NSGA) was used in obtaining Pareto optimal solutions. It was observed that reactive Varicol performs better than SMBR due to non-synchronous switching and its increased flexibility in distributing columns in various sections.

Optimal Operation of an Industrial-Scale Parex Process for the Recovery of p-Xylene from a Mixture of C8 Aromatics

Multi-objective optimization for the operation and design of an industrial-scale Parex process for the recovery of p-xylene from a mixture of C8 aromatics has been studied using a state-of-the-art optimization technique: the Elitist Nondominated Sorting Genetic Algorithm with Jumping Genes (NSGA-II-JG, binary coded). An industrial-scale Parex process, which is based on simulated moving bed (SMB) technology, was simulated using an available mathematical model. The simulation results were verified with the reported industrial data. Subsequently, few two-objective optimization problems were solved to determine the optimum number of columns, the length of each column, and the column distribution in different zones. Significant improvement in the recovery of p-xylene using less solvent was obtained when a suitable column length and appropriate distribution of columns in various zones was chosen. Optimization study was also extended for the Varicol operation mode, which is based on a nonsynchronous switching, contrary to the synchronous switching used in traditional SMB systems. It was observed that the performance of the Varicol process is much superior to that of a SMB process, in terms of recovering more p-xylene while consuming less eluent. Results are presented and discussed in detail. The optimum results are also explained using equilibrium theory by locating them in the pure separation region.

Multiobjective Optimization of Simulated Moving Bed Reactor and its Modification — Varicol Process

AbstractA comprehensive optimization study on a Simulated Moving Bed Reactor (SMBR) system is reported in this article for the direct synthesis of Methyl Tertiary Butyl Ether (MTBE). In addition, the SMB technology, which is based on synchronous switching of ports, was modified to a new more flexible Varicol process based on non‐synchronous switching. Multi‐objective optimization has been performed for both SMBR and Varicol and their efficiencies were compared. A state‐of‐the‐art optimization technique, viz., Non‐dominated Sorting Genetic Algorithm (NSGA) that allows handling of these complex optimization problems is employed in this study.

Optimization of reactive SMB and Varicol systems

A comprehensive optimization study on a simulated moving bed reactor (SMBR) system is reported in this article for the direct synthesis of methyl tertiary butyl ether (MTBE) from tertiary butyl alcohol (TBA) and methanol. The applicability of the Varicol process, which is based on non-synchronous shift of the inlet and outlet ports, is explored for the first time for a reactive system. Multi-objective (two and three objective functions) optimization has been performed for both existing as well as design stage for SMBR and Varicol systems and their efficiencies are compared. The optimization problem involves relatively large number of decision variables; both continuous variables, such as flow rates in various sections and length of the columns and discrete variables, such as number of columns and column configuration. Pareto optimal solutions are obtained. It is observed that a five-column Varicol performs better than an equivalent five-column SMBR and its performance is nearly equal to that of a six-column SMBR in terms of purity and yield of MTBE and minimal eluent consumption. This is an important inference as it enables the reduction of fixed and operating costs while at the same time helps to achieve high purity and yield of the desired product and conversion of the limiting reactant. A state-of-the-art optimization technique, viz., non-dominated sorting genetic algorithm (NSGA), which allows handling of these complex optimization problems, is employed for this study. This is the first time that, not only the separating potential of Varicol has been extended to reaction systems, but also was optimized for multiple objectives.

PowerFeed operation of simulated moving bed units: changing flow-rates during the switching interval

A possible way to improve the separation performance of simulated moving bed (SMB) units is to change the internal and external liquid flow-rates during the switching period. This operation mode, referred to as PowerFeed, is examined in this work through a model analysis. Similar to the Varicol process, which allows for the asynchronous movement of the ports, the PowerFeed process exhibits more degrees of freedom than the classical SMB process and therefore allows more room for optimization. Using an optimization technique based on a genetic algorithm, all three processes have been optimized for a few case studies in order to determine their relative potentials. It is found that PowerFeed and Varicol provide substantially equivalent performances, which are however significantly superior to those of the classical SMB process.

Design of simulated moving bed and Varicol processes for preparative separations with a low number of columns

Simulated moving bed (SMB) chromatography has received significant attention in the last decade, particularly as regards the production of very valuable products, such as enantiomerically pure pharmaceutical compounds. Recent applications in the pharmaceutical industry use SMB systems containing a low total number chromatographic columns, usually four to eight. This paper deals with the modeling and simulation of SMB systems with only four, five and six columns. In particular, two modeling strategies, the equivalent true moving bed and the real SMB models, are compared for these units in terms of separation regions and system productivity. Also, the recently proposed Varicol process is analyzed and compared with the classical SMB operation, and the advantages of this new operation mode are shown for systems using a low number of columns.

Optimization of Simulated Moving Bed and Varicol Processes for Glucose–Fructose Separation

A comprehensive optimization study was carried out to evaluate the performance of a simulated moving bed (SMB) system and its modification, Varicol process, for an industrially important separation problem, the isolation of fructose (which is of interest in the food industry as sweetener) from a mixture of glucose and fructose solution. Contrary to the operation of SMB, where the inlet and outlet ports are switched synchronously at a predetermined time interval, the Varicol system is based on a non-synchronous shift of these ports. An existing model that can predict published pilot-scale experimental results of the system is used in the optimization study. The optimization problem is complex owing to the complex interplay of relatively large number of decision variables that include continuous variables like flow rates in different sections and column length, and discrete variables like column number and configuration. Several two-objective functions optimization was performed both for existing system and for systems at the design stage. A typical example is simultaneous maximization of productivity and purity of the desired fructose product or simultaneous maximization of productivity of both the products. An adaptation of the state-of-the-art artificial intelligence-based non-traditional optimization method known as non-dominated sorting genetic algorithm (NSGA) is used in obtaining Pareto optimal solution. It was observed that, after performing rigorous optimization, significant improvement in terms of performance is possible for both SMB and Varicol process.

Optimization of simulated moving bed and Vari col processes

A new continuous chromatographic process (Vari col) has been presented recently. Its basic principle consists, in contrast to the traditional simulated moving bed (SMB) technology, of an asynchronous shift of the inlet/outlet lines in a multi-column system with a recycle loop. Due to the stronger influence of the discrete dynamics on the plant behavior, the design of a Vari col process requires the use of model-based optimization to take advantage of the very high flexibility of this process. The equilibrium theory which has been successfully applied to SMB by many practitioners fails to predict the region of complete separation accurately. In this paper, we present a rigorous model-based optimization framework, which can handle the SMB and the novel Vari col process in a systematic manner. The feasibility of the approach is demonstrated by the separation of a mixture of propranolol isomers which exhibits a highly non-linear multi-component adsorption behavior. Experimental results are presented and discussed.

Optimal operation of reactive simulated moving bed and Varicol systems

AbstractIn this article, the performance of a reactive Simulated Moving Bed (SMB) and its modification, the more flexible Varicol process, is improved for the synthesis of methyl acetate (MeOAc) ester by multi‐objective optimization using Non‐dominated Sorting Genetic Algorithm (NSGA). The Varicol process is based on a non‐synchronous shift of the inlet and outlet ports instead of the synchronous one used in the traditional SMB technology. The optimization problems considered are both two‐ and three‐objective function problems. In one case, optimization was aimed at simultaneous maximization of the purity of MeOAc and minimization of adsorbent (and catalyst) requirement for the reactive SMB; while in the other case, maximization of purity and yield of MeOAc together with minimization of eluent (methanol) consumption for both reactive SMB and Varicol systems were considered. When the optimal solutions were compared, it was found that reactive Varicol systems could produce a higher purity product for a fixed yield, and consume slightly less eluent in the high purity region than more rigid SMB systems.© 2003 Society of Chemical Industry