Solvent gradient operation of simulated moving beds. 2. Langmuir isotherms

Simulated Moving Bed separations of enantiomers or fine chemicals are usually carried out in the isocratic mode, i.e. by applying the same operating conditions (temperature, pressure, mobile phase composition, pH) in the whole SMB unit. However, it has been recently recognized that by properly modulating operating conditions in the SMB sections. i.e. Sections 1-4 normally, separation performance in terms of productivity and solvent consumption can be significantly improved. In this work, we study solvent gradient SMB (SG-SMB) operation, where the concentration of a modifier in the main solvent constituting the mobile phase is adjusted along the SMB unit, so as to have weaker retention of the species to be separated in the first two sections, and stronger retention in Sections 3 and 4. Overload chromatographic conditions are considered, where the adsorption behavior is characterized by a nonlinear competitive adsorption isotherm, e.g. a binary Langmuir isotherm. Design criteria to achieve complete separation are developed in the frame of the equilibrium theory of chromatography. The theoretical findings are discussed in view of typical effects of the modifier concentration on retention times and solubility of the species to be separated, and an overall assessment of the SG-SMB technology is attempted.     

Optimizing control of simulated moving bed separations of mixtures subject to the generalized Langmuir isotherm

Simulated moving bed (SMB) is a cost-efficient separation technique that offers high productivity and low solvent consumption. SMB has gained importance in the pharmaceutical and fine chemical industry to perform complex separation tasks. However, an open and challenging problem is the optimal, robust operation of the SMB process. We have developed a control scheme that integrates the optimization and control of the SMB unit. A significant feature of the controller is that only minimal information of the system has to be provided, i.e. the linear adsorption behavior of the mixture to be separated and the average void fraction of the columns. Therefore, a full characterization of the adsorption behavior of the mixture and the columns is no longer required. In this ‘cycle to cycle’ control scheme, the measurements, optimization and control actions are performed once in every cycle. This paper presents simulation results of the control scheme applied to the separation of binary mixtures characterized by generalized Langmuir isotherms. The results are presented and analyzed in the frame of the triangle theory that has been recently extended to encompass these types of isotherms. Besides, online optimum performance of the SMB unit is compared with off-line optimization carried out using genetic algorithm. The results show that the controller fulfills the product and process specifications while operating the SMB unit optimally, regardless of the different types of Langmuir isotherms that the systems exhibit.     

Enantioseparation of 1-phenyl-1-propanol by simulated moving bed under linear and nonlinear conditions

Approximately optimum operating conditions needed to separate 1-phenyl-1-propanol (PP) enantiomers by simulated moving bed (SMB) were determined using the "safety margin" approach in the linear case and the "triangle theory" in the nonlinear case. Previous results showed the adsorption isotherm data to fit well to the competitive Langmuir model. This allowed the use of the triangle theory approach that applies straightforwardly to Langmuir systems. Experimentally, the operating conditions under nonlinear isotherm behavior were determined for a feed solution with a total concentration of 5 g/l. The purity of the products exceeded 98% for the raffinate and 95% for the extract. Failing to reach complete purity while the experimental conditions were chosen inside the separation zone is explained by the nonideality of the system used, which violates one of the triangle theory assumptions. The computed overall daily production rate was 11.6 g of racemic PP processed per day per kg of stationary phase, a result that compares favorably with previous ones.     

Optimization of simulated moving bed and Varicol processes

A new continuous chromatographic process (Varicol) 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 Varicol 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 Varicol 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.     

Recombinant protein purification using gradient assisted simulated moving bed hydrophobic interaction chromatography. Part II: process design and experimental validation

In the first part of this work adsorption isotherm parameters were acquired to describe the migration of recombinant streptokinase in Butyl Sepharose columns at different salt concentrations. Based on these results, a simulated moving bed (SMB) chromatographic process was designed and realised, which exploits a two-step salt gradient and allows the continuous separation of streptokinase from contaminants present in a clarified Escherichia coli cell lysate solution. This second part describes the design of the three-zone open-loop gradient SMB process applying both equilibrium theory and an equilibrium stage model and presents results of a series of experiments aiming to obtain pure streptokinase. Moreover, the potential of the SMB process and the design approach are evaluated.     

Solvent gradient operation of simulated moving beds. I. Linear isotherms

The simulated moving bed (SMB) is a multi-column chromatographic separation process, which--with respect to the single-column preparative batch process--allows for a continuous separation with larger productivity and smaller solvent consumption at the same time. The benefits of this process have been shown for several different applications in fine chemistry, particularly for the separation of enantiomers. In general, SMBs are operated under isocratic conditions. However, separation performance can be further improved by applying some sort of gradient mode operation, in order to optimize the operating conditions of each individual section of the unit. This can be achieved by tuning the retention behavior of the solutes to be separated along the unit, namely by enforcing weak adsorption conditions in sections 1 and 2, and strong adsorption conditions in sections 3 and 4. This can be achieved by applying a temperature gradient (high temperature in section 1, and low temperature in section 4), a pressure gradient (e.g. in the supercritical SMB, when pressure is high in section 1, and low in section 4), or a solvent gradient, which is the aim of this work. In the solvent gradient mode the mobile phase consists of a mixture of two or more solvents. To different mobile phase compositions corresponds a different retention behavior of the solutes, i.e. different adsorption isotherms. In this work we study a closed loop SMB unit with solvent mixtures of two different compositions entering the unit at the feed and desorbent inlet ports, respectively. Thereby two different mobile phase compositions are established in sections 1 and 2, and sections 3 and 4, respectively. To optimize this process the equilibrium theory design criteria for non-linear SMBs are extended to describe this operation mode. It is shown how the region of separation is derived and how the optimal operating conditions can be found. Finally the solvent gradient mode is compared with the isocratic mode in terms of productivity and solvent consumption.     

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.     

Adsorption behavior of the (+/-)-Tröger's base enantiomers in the phase system of a silica-based packing coated with amylose tri(3,5-dimethyl carbamate) and 2-propanol and molecular modeling interpretation

The binary adsorption isotherms of the enantiomers of Tr?ger's base in the phase system made of Chiral Technologies ChiralPak AD [a silica-based packing coated with amylose tri(3,5-dimethyl carbamate)] as the chiral stationary phase (CSP) and 2-propanol as the mobile phase were measured by the perturbation method. The more retained enantiomer exhibits a S-shaped adsorption isotherm with a clear inflection point, the concentration of the less retained enantiomer having practically no competitive influence on this isotherm: In the entire range of concentrations studied, dq2/dC1 approximately 0. By contrast, the less retained enantiomer has a Langmuir adsorption isotherm when pure. At constant mobile phase concentrations, however, its equilibrium concentration in the adsorbed phase increases with increasing concentration of the more retained enantiomer and dq1/dC2 > 0. This cooperative adsorption behavior, opposed to the classical competitive behavior, is exceedingly rare but was clearly demonstrated in this case. Two adsorption isotherm equations that account for these physical observations were derived. They are based on the formation of an adsorbed multi-layer, as suggested by the isotherm data. The excellent agreement between the experimental overloaded elution profiles of binary mixtures and the profiles calculated with the equilibrium-dispersive model validates this binary isotherm model. The adsorption energies calculated by molecular mechanics (MM) and by molecular dynamics (MD) indicate that the chiral recognition arising from the different interactions between the functional groups of the CSP and the molecules of the Tr?ger's base enantiomers are mainly driven by their Van der Waals interactions. The MD data suggest that the interactions of the (-)-Tr?ger's base with the CSP are more favored by 8+/-(5) kJ/mol than those of (+)-Tr?ger's base. This difference seems to be a contributing factor to the increased retention of the - enantiomer on this chromatographic system. The modeling of the data also indicates that both enantiomers can form high stoichiometry complexes while binding onto the stationary phase, in agreement with the results of the equilibrium isotherm studies.     

Mechanism and equilibrium modeling of Re and Mo adsorption on a gel type strong base anion resin

A static-batch technique was used to demonstrate the adsorption behavior of Re (VII) and Mo ions onto Dowex 21K at equilibrium in single and binary component systems. The single equilibrium adsorption data were modeled through a linear form of four widely used equilibrium isotherm equations. The results indicated that Freundlich and D-R models for Re, and Temkin and D–R isotherms for Mo fitted the obtained data satisfactorily. Binary adsorptions of Re and Mo ions onto Dowex 21K were also analyzed using Extended Langmuir, Modified Langmuir, Extended Freundlich and Langmuir–Freundlich models. The competitive Extended Freundlich model fitted the binary adsorption equilibrium data adequately. Studies on mutual interference effects of Mo ions on Re adsorption capacity indicated that the adsorption of perrhenate ions is always suppressed. In this perspective, the results from EDX studies confirmed the rhenium atom decrease in the simulated Re–Mo adsorption. However, under the studied conditions the affinity of the Dowex 21K for rhenium ions is marginally greater than that of molybdenum ions.     

Intermittent simulated moving bed chromatography: 1. Design criteria and cyclic steady-state

The intermittent SMB (I-SMB) process is a multi-column chromatographic process, which is a modification of the conventional SMB process, has been applied so far only in the sugar industry and is claimed to achieve higher productivity. In the I-SMB process the time interval between two port switches is divided in two sub-intervals, and only during the first the product streams are collected. The potential of the I-SMB technology is demonstrated in the case of the separation of a binary mixture subject to the linear isotherm by using both the equilibrium theory of chromatography and detailed simulations. It is shown that a I-SMB with only four columns can achieve much higher separation performance than a SMB unit with four columns.     

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%.     

The significance of a second adsorption phase with weakly adsorbed species for the calculation of the surface concentrations of a mixture: methanol–DME and methanol–ethene adsorption in SAPO-34

With the calorimetric (adsorption heat versus coverage) curve also measured together with the adsorption isotherm, the simultaneous use of both curves showed that there were two phases of adsorption in the adsorption of methanol, dimethyl ether, ethene and propane in SAPO-34. The dual-site Langmuir equation gave good fits to the adsorption data to support the interpretation that a second (type 2) adsorption phase occurred in the high-pressure region in addition to a first (type 1) adsorption phase on the acid sites at lower pressures. Adsorption experiments and calculations using binary gas mixtures showed that due to the existence of two types of adsorption, the multicomponent Langmuir isotherm equation (Langmuir competitive adsorption model) calculated incorrect surface concentrations when the concentrations were high. In contrast, the ideal adsorbed solution theory (IAST) calculated correct surface concentrations in the adsorption of mixtures.     

Retention of ionizable compounds in high-performance liquid chromatography. 14. Acid-base pK values in acetonitrile-water mobile phases

Using competitive frontal analysis, the binary adsorption isotherms of the enantiomers of 1-phenyl-l-propanol were measured on a microbore column packed with a chiral stationary phase based on cellulose tribenzoate. These measurements were carried out using only the racemic mixture. The experimental data were fitted to four different isotherm models: Langmuir, BiLangmuir, Langmuir-Freundlich and Tóth. The BiLangmuir and the Langmuir-Freundlich models accounted best for the competitive adsorption data. An excellent agreement between the experimental and the calculated overloaded band profiles for various samples of racemic mixture was obtained when the equilibrium dispersive model of chromatography was used together with the BiLangmuir competitive isotherm. The isotherm parameters measured under competitive conditions were used to calculate the overloaded band profiles of large samples of the pure S- and R-enantiomers, too. A satisfactory agreement between the experimental and calculated band profiles was observed when using in the computation the corresponding single component BiLangmuir isotherm derived from the binary isotherm previously determined. Thus oniy data derived from the racemic mixture are required for computer optimization of the preparative chromatography separation of the enantiomers.     

Enantioseparation of 1-phenyl-1-propanol by supercritical fluid-simulated moving bed chromatography

The enantioseparation of 1-phenyl-1-propanol through the supercritical fluid-simulated moving bed (SF-SMB) process is studied. Non-linear isotherms were measured on an analytical column, and used together with the triangle theory for SMB design to select operating conditions for the SF-SMB. Experiments were carried out on a pilot-scale SF-SMB plant at conditions that corresponded to the non-linear range of the isotherm. Under conditions of low feed concentration, complete separation (extract purity = 99.5%; raffinate purity = 98.4%) was achieved. Under conditions of larger feed concentration, the best separation corresponded to an extract purity of 98.0% and a raffinate purity of 94.0%, and yielded a productivity of 110 g of racemate per kg stationary phase per day.     

Competitive adsorption isotherm modelling of heterocyclic nitrogenous compounds,pyridine and quinoline,onto granular activated carbon and bagasse fly ash

In the present study, simultaneous adsorption of quinoline and pyridine onto adsorbents such as granular activated carbon (GAC) and bagasse fly ash (BFA) from pyridine–quinoline binary aqueous solution was studied at various temperatures (288–318 K). Gathered equilibrium adsorption data were further analysed using various multicomponent competitive isotherm models such as non-modified and modified competitive Langmuir isotherms, extended-Langmuir isotherm, extended-Freundlich model, Sheindorf–Rebuhn–Sheintuch (SRS) model, and non-modified and modified competitive Redlich–Peterson isotherm model. It was observed that increase in pyridine concentration decreased the total adsorption yield and the individual adsorption yield for both the quinoline and pyridine for both the adsorbents GAC and BFA at all the temperatures studied. Identical trend was observed during the equilibrium uptake of pyridine on to GAC and BFA with an increase in quinoline concentration. The extended-Freundlich model satisfactorily represented the binary adsorption equilibrium data of quinoline and pyridine onto GAC and BFA.     

胺修饰酚醛树脂对酸性橙Ⅱ的吸附性能研究

研究了自制胺修饰酚醛树脂(AMPF)对水溶性染料酸性橙II的吸附性能,探讨了pH值、温度、浓度等因素对酸性橙吸附性能的影响。结果表明,AMPF与市售大孔树脂D296和D301相似,对酸性橙均具有较强的吸附能力。温度升高有利于AMPF对酸性橙的吸附;酸性橙浓度升高,吸附量增大。AMPF对酸性橙的吸附符合Boyd液膜扩散控制。各种树脂对酸性橙的平衡吸附数据符合Langmuir方程和Freundlich等温式,其相关系数大于0.98,n均大于1,表明为优惠吸附。     

Nonlinear chromatography Recent theoretical and experimental results

The theory of nonlinear chromatography has been advanced by the incorporation of recent results obtained by the theory of partial differential equations. The system of equations of the ideal model has been solved analytically in the case of a single component for which the equilibrium isotherm between the mobile and the stationary phases is given by a Langmuir equation. A series of computer programs has been written which permits the calculation of numerical solutions of the semi-ideal model. The properties of the solutions obtained are described and discussed for a one-component system (profile of high concentration bands of a pure compound eluted by a pure solvent), several two-component systems (elution of a pure compound band by a binary mobile phase, separation of a binary mixture eluted by a pure mobile phase), and three-component systems (separation of a binary mixture eluted by a binary solvent, displacement and separation of a binary mixture). Experimental results are reported which validate the conclusions derived from the numerical integration of the model. The conclusions of the work apply to all high-performance chromatographic procedures, i.e., to those where the kinetics of mass transfer are fast enough for the mobile and stationary phases always to be near equilibrium. More specifically, the contribution from the kinetics of the retention mechanism to the mass transfer resistance must itself be negligible. This clearly excludes affinity chromatography.     

Enantioseparation of 1-phenyl-1-propanol on cellulose-derived chiral stationary phase by supercritical fluid chromatography II. Non-linear isotherm

The separation of the enantiomers of 1-phenyl-1-propanol by supercritical fluid chromatography on a chiral stationary phase, which consists of cellulose tris (3,5-dimethylphenylcarbamate) coated on a silica support (Chiralcel-OD), is studied under overloaded, non-linear chromatographic conditions. Pulse experiments are performed at a temperature of 30 degrees C using supercritical CO(2) modified with methanol as a mobile phase. The parameters of the binary Langmuir adsorption isotherm are determined by the inverse method, comparing experimental and simulated peak responses. Isotherm parameters are derived for modifier concentrations between 1 and 5% (w/w) and operating pressures between 125 and 185 bar, and the dependency of the isotherm parameters, namely the Henry constant and the saturation capacity, on operating conditions is investigated.