Comparison of configurations of a four-column simulated moving bed process by multi-objective optimization

Configurations of a four-column simulated moving bed chromatographic process are investigated by multi-objective optimization. Various existing column configurations are compared through a multi-objective optimization problem. Furthermore, an approach based on an SMB superstructure is applied to find novel configurations which have been found to outperform the standard SMB configuration. An efficient numerical optimization technique is applied to the mathematical model of the SMB process. It has been confirmed that although the optimal configuration highly depends on the purity requirement, the superstructure approach is able to find the most efficient configuration without exploring various existing configurations.     

A novel pseudo simulated moving bed with solvent gradient for ternary separations

A novel pseudo simulated moving bed was suggested to separate a ternary mixture. A solvent gradient was created to make the solvent strength decreasing from zone II to zone III. Under suitable conditions, the least retained solute A moved forward and the most retained solute C moved backward in zones II and III whereas the medium retained solute B moved forward in zone II but backward in zone III to be trapped in the two zones consequently. Once the columns in zones II and III were saturated with solute B, the solvent dissolving the feed was introduced at the feed port to remove solute A from the raffinate-port and solute C from the extract-port. Finally, solute B was recovered from the extract port by stopping the liquid flow in zone II. This scheme was validated by the successful separation of dihydrocapsaicin from capsaicinoids.     

Improving performance of a five-zone simulated moving bed chromatography for ternary separation by simultaneous use of partial-feeding and partial-closing of the product port in charge of collecting the intermediate-affinity solute molecules

The performance of a five-zone simulated moving bed (SMB) chromatographic process for ternary separation has been improved to a certain extent in previous researches by applying either a partial-feeding (PF) or a partial-closing of the extract-2 port (PCE(2)) to its operation. To make a further improvement, the strategy of applying both PF and PCE(2) simultaneously to the five-zone SMB operation was proposed in this study. The results from both equilibrium-theory analysis and detailed simulation proved that the proposed strategy, which was called PF-PCE(2) in this article, had the benefit of a synergy between the individual merits of PF and PCE(2) in the five-zone SMB performance. As a consequence, the PF-PCE(2) mode could surpass the PF and the PCE(2) modes by a wide margin and the standard mode by a much wider margin in the aspects of ternary-separation performance and throughput. For the separation system considered, the PF-PCE(2) mode was found to achieve more than 100% improvement, compared to the standard mode. Furthermore, such advantage of the PF-PCE(2) over all the other modes was greater as the selectivity between the intermediate-affinity and the highest-affinity components was reduced.     

Bi-level optimizing control of a simulated moving bed process with nonlinear adsorption isotherms

A bi-level optimizing control scheme originally proposed for a simulated moving bed (SMB) with linear isotherms has been extended to an SMB with nonlinear isotherms. Cyclic steady state optimization is performed in the upper level to determine the optimum switching period and time-varying feed/desorbent flow rates, and repetitive model predictive control is run in the lower level for purity regulation, taking the decision variables from the upper level as feed-forward information. Experimental as well as numerical study for an SMB process separating a high-concentration mixture of aqueous L-ribose and L-arabinose solutions showed that the proposed scheme performs satisfactorily against various disturbances. In contrast, an alternative scheme based on an SMB model with linear isotherms showed a limitation in the control performance; this scheme was apt to fail in purity regulation.     

Transmission analysis in ultrafiltration of ternary protein mixture through a hydrophilic membrane

One of the main reasons for the underutilization of ultrafiltration has been the lack of experimental data on transmission of proteins for complex systems and its corresponding theoretical analysis. Of course, the presence of fouling coupled with concentration polarization have had their share in making ultrafiltration operation a difficult one to understand. In the present study, the systematic ultrafiltration of 3-protein mixture, namely lysozyme, myoglobin and ovalbumin, has been carried out using a hydrophilic 30,000 molecular weight cut off membrane. The experimental data of individual protein transmission in ternary mixture showed a very low transmission (as low as 3% for ovalbumin) to a very high transmission (as high as 90% for lysozyme) of proteins for different operating conditions. This behaviour of each protein in the mixture was analyzed using combined concentration polarization and irreversible thermodynamics model. The parameters of the modeled values gave a very good fit with experimental data and the resulting analysis indicated some interesting findings, which are discussed in this paper. The comparison of parameters obtained for single protein solution and the ternary protein solution showed some unusual results that point to the presence of the protein–protein and protein–membrane interactions.     

Simulated moving bed chromatography for the separation of enantiomers

Simulated moving bed (SMB) chromatography, a continuous multi-column chromatographic process, has become one of the preferred techniques for the separation of the enantiomers of a chiral compound. Several active pharmaceutical ingredients, including blockbuster drugs, are manufactured using the SMB technology. Compared to single column preparative chromatography, SMB separations achieve higher productivity and purity, while reducing the solvent consumption. The SMB technology has found applications both at small and large scales. Design methods have been developed for robust operation and scale-up, using data obtained from analytical experiments. In the last few years, rapid developments have been made in the areas of design, improved process schemes, optimization and robust control. This review addresses these developments, as well as both the fundamentals of the SMB science and technology and some practical issues concerning the operation of SMB units. Particular emphasis is placed on the consolidation of the “triangle theory”, a design tool that is used both in the academia and industry for the design of SMB processes.     

H-point standard addition method for simultaneous determination of phenylephrine hydrochloride,chlorpheniramine maleate,and paracetamol as a ternary mixture in pharmaceutical formulations

The simultaneous analysis of a ternary mixture containing paracetamol (PAR), phenylephrine hydrochloride (PHE), and chlorpheniramine maleate (CPM) was conducted without prior separation and using an advanced spectrophotometric method. The H-point standard addition and absorbance correction methods were selected to determine the compounds, which are highly overlapped spectra in pharmaceutical formulations. The method is based on the use of three different wavelengths of 296, 272, and 227 nm for the ternary mixture. The concentration of PAR was calculated directly at 296 nm because no interferences existed. Absorbance correction method was used to remove the role of PAR at 272 and 227 nm. The concentrations of the PHE and CPM compounds in the mixture were determined by using the H-point standard addition method. The results showed that simultaneous determination of PAR, PHE, and CPM could be conducted within the range of 1–33 μg/mL, 1–23 μg/mL, and 1–36 μg/mL, respectively. The relative standard deviations for the simultaneous determination of PHE, CPM, and PAR were 0.617, 2.76, and 1.71, respectively. The proposed method was implemented successfully for the simultaneous determination of PAR, PHE, and CPM in pharmaceutical formulations.     

A simple procedure for the rapid optimization of reversed-phase separations with ternary mobile phase mixtures

Summary A simple rapid procedure is described for estimating optimum compositions of ternary mobile phase mixtures for the separation of samples by reversed-phase liquid chromatography (RPLC). Retention data in two iso-eluotropic binary mobile phase mixtures (mixtures with equal retention times) are required to initiate the procedure. The logarithm of the capacity factor is assumed to vary linearly with the composition of isoeluotropic ternary mixtures formed by mixing the two limiting binaries. Using the product of resolution factors of adjacent peaks as the criterion, an optimum ternary composition is then calculated. After a chromatogram has been obtained with the predicted optimum ternary mobile phase, the procedure is repeated until no further improvement can be achieved. Examples of the application of the present procedure are described to illustrate its effectiveness.     

Experimental validation of a new integrated simulated moving bed process for the production of single enantiomers

A new integrated 3-zone simulated moving bed (SMB) concept with internal racemization reaction was suggested recently for the production of single enantiomers from racemic mixtures [1,2]. The process utilizes an internal gradient to trigger the racemization within a single zone. It can deliver the pure enantiomer and outperforms conventional technologies. In this contribution, the concept is validated experimentally for the separation of a model system compound. The results demonstrate that the new concept is capable of producing a single enantiomer with purity, yield and conversion of 100%.     

Continuous chromatographic separation process: simulated moving bed allowing simultaneous withdrawal of three fractions

Continuous counter-current chromatographic separation has been carried out in a simulated moving bed system (SMB). We have worked with a SMB pilot plant (8 columns, 4.4 litres of resin each) which allows the continuous withdrawal of two different fractions. A mixture of glucose-fructose has been separated. To calculate the concentration profile within the separator an axial dispersed plug flow model and an equilibrium stage model have been employed; software has been created to simulate the behaviour of the separator. The necessary parameters of the mode: the adsorption equilibrium constant, the height equivalent to a theoretical plate and the bed voidage, have been acquired experimentally from elution chromatography measurements. The results calculated by simulation give a good representation of the experimental concentration profiles; other separations like xylitol-arabitol have been simulated. The influence of some factors like desorbent flow-rate, feed flow-rate and the bed voidage have been studied using the software. Once the system has worked in a two withdrawal way, an extension of the pilot plant has been constructed so as to obtain a third one. The necessary parameters of the three withdrawal model will be studied.     

Flow-through fluorescence-based optosensor with on-line solid-phase separation for the simultaneous determination of a ternary pesticide mixture

A rapid and selective method was developed for the simultaneous determination of 3 widely used pesticides, carbendazim (CBZ), carbofuran (CF), and benomyl (BNM). The method utilized a single continuous-flow, solid surface fluorometric multioptosensor implemented with a previous separation of the analytes on a minicolumn, placed just before the sensor, that was packed with the same solid support (C18 silica gel) as the flow-through cell. The separation was achieved because of the different kinetics of retention/elution of the pesticides on the solid support in the minicolumn, enabling the sequential arrival of the analytes at the sensing zone. With a single injection of the mixture, 2 of them were more strongly retained in the minicolumn (CF and BNM) while the other (CBZ) passed through the system towards the sensing material where it developed its fluorescence transitory signal. Then, CF and BNM were successively eluted from the solid support using 2 different eluting solutions, and they sequentially reached the sensing zone and developed their respective signals. A multiwavelength fluorescence detection mode was used, recording the signals of each pesticide at its maximum excitation/emission wavelength; therefore, the sensitivity was increased. The system was calibrated using a sample volume of 2000 microL. The linear dynamic range was 80-1400, 250-2400, and 150-2000 ng/mL with detection limits of 15, 68, and 35 ng/mL and relative standard deviation values of 3.5, 3.2, and 2.4% for CBZ, CF, and BNM, respectively. A recovery study was applied to spiked environmental water samples, and recoveries ranged from 96 to 104%.     

Continuous separation of copper ions from a mixture of heavy metal ions using a three-zone carousel process packed with metal ion-imprinted polymer

In this study, a three-zone carousel process based on a proper molecular imprinted polymer (MIP) resin was developed for continuous separation of Cu(2+) from Mn(2+) and Co(2+). For this task, the Cu (II)-imprinted polymer (Cu-MIP) resin was synthesized first and used to pack the chromatographic columns of a three-zone carousel process. Prior to the experiment of the carousel process based on the Cu-MIP resin (MIP-carousel process), a series of single-column experiments were performed to estimate the intrinsic parameters of the three heavy metal ions and to find out the appropriate conditions of regeneration and re-equilibration. The results from these single-column experiments and the additional computer simulations were then used for determination of the operating parameters of the MIP-carousel process under consideration. Based on the determined operating parameters, the MIP-carousel experiments were carried out. It was confirmed from the experimental results that the proposed MIP-carousel process was markedly effective in separating Cu(2+) from Mn(2+) and Co(2+) in a continuous mode with high purity and a relatively small loss. Thus, the MIP-carousel process developed in this study deserves sufficient attention in materials processing industries or metal-related industries, where the selective separation of heavy metal ions with the same charge has been a major concern.     

A new hybrid double divisor ratio spectra method for the analysis of ternary mixtures

A new spectrophotometric method was developed for the simultaneous determination of ternary mixtures, without prior separation steps. This method is based on convolution of the double divisor ratio spectra, obtained by dividing the absorption spectrum of the ternary mixture by a standard spectrum of two of the three compounds in the mixture, using combined trigonometric Fourier functions. The magnitude of the Fourier function coefficients, at either maximum or minimum points, is related to the concentration of each drug in the mixture. The mathematical explanation of the procedure is illustrated. The method was applied for the assay of a model mixture consisting of isoniazid (ISN), rifampicin (RIF) and pyrazinamide (PYZ) in synthetic mixtures, commercial tablets and human urine samples. The developed method was compared with the double divisor ratio spectra derivative method (DDRD) and derivative ratio spectra-zero-crossing method (DRSZ). Linearity, validation, accuracy, precision, limits of detection, limits of quantitation, and other aspects of analytical validation are included in the text.     

Ethylene-vinyl acetate semi-batch emulsion copolymerization: Use of factorial experiments for process optimization

The application of factorial experiments to optimize the ethylene-vinyl acetate emulsion polymerization process is described herein. A prior extensive experimental phase identified those variables that are most important for ethylene-vinyl acetate emulsion copolymer production. The effects of temperature, pressure, added co-solvent, vinyl acetate feed rate and emulsifier type, and concentration on the rate of polymerization, cumulative copolymer composition, molecular weight averages, and particle size and number are described in this article. The primary objectives of this research were to increase the amount of ethylene that could be incorporated into the copolymer at reduced temperatures and pressures (our target was a copolymer with an ethylene content of 30% by weight at 500 psig and 20°C versus the commonly employed industrial conditions in excess of 1000 psig), to achieve an improved process understanding, and to accumulate reliable data for modelling purposes. A copolymer containing 34% by weight of ethylene has been achieved at a pressure of 500 psig and a temperature of 20°C. The confusion present in the literature surrounding emulsifier effects has also been clarified. A discussion of hydrolysis, experimental reproducibility, and glass transition temperatures is also included. The sequential nature of the experimental process is illustrated throughout these optimizing experiments. © 1994 John Wiley & Sons, Inc.     

Experiment planning,mathematical modelling,and nonlinear optimization of the ion-nitriding process in a glow-discharge plasma

A new, efficient method for investigating and optimizing the ion-nitriding process in a glow-discharge plasma is proposed and worked out in detail for the mass kinetics of Rp-3 steel. This method, which is based on the concepts of experiment planning, mathematical modelling, and nonlinear optimization, is quite general and potentially applicable to a wide class of technological and other processes depending on several parameters.     

Experimental and predicted viscosities of the binary system (n-hexane + 1,3-dioxolane) and for the ternary system (n-hexane + 1,3-dioxolane + 1-butanol) at 298.15 and 313.15 K

Viscosities of the ternary system n-hexane+1,3-dioxolane+1-butanol and the binary system n-hexane+1,3-dioxolane have been measured at atmospheric pressure at 298.15 and 313.15 K. Viscosity deviations for the binary and ternary systems were calculated from experimental data and fitted to Redlich–Kister and Cibulka equations, respectively. The group contribution method proposed by Wu has been used to predict the viscosity of all mixtures.     

Evaluation of the potential of nonlinear gradients for separating a ternary mixture

The potential of applying nonlinear gradients in preparative chromatography is evaluated theoretically and experimentally. The second eluting component of a ternary model mixture is considered as the target component. Systematic gradient resolution experiments were conducted for this mixture using reversed phase chromatography. In preliminary experimental investigations the effect of the mobile phase composition on the specific distribution equilibria was quantified. Concave and convex solvent strength gradients were analysed and compared with conventional linear gradients. Main result of the study is the fact that significant improvement in productivity can be achieved if the gradient shapes are designed carefully.     

Measurements and analysis of excess molar volumes for the ternary mixture MTBE + 1-pentanol + decane

Summary Densities at 298.15 K and atmospheric pressure have been measured, using a DMA 4500 Anton Paar densimeter, for the ternary mixture methyl tert-butyl ether (MTBE)+1-pentanol+decane and for the involved binary mixtures MTBE+1-pentanol and 1-pentanol+decane. The excess molar volumes for the binary mixture MTBE+decane was reported in an earlier work [1]. In addition, excess molar volumes were determined from the densities of the pure liquids and mixtures. Suitable fitting equations have been used in order to correlate adequately the excess molar volumes. The empirical expressions of Kohler [18], Jacob and Fitzner [19], Colinet [20], Knobeloch and Schwartz [21], Tsao and Smith [22], Toop [23], Scatchard et al. [24], Hillert [25], Mathieson and Thynne [26] were applied to estimate ternary properties from binary results.     

Statistical mixture design optimization of extraction media and mobile phase compositions for the characterization of green tea

The influence of different solvents on the extraction medium and the RP-HPLC mobile phase composition were investigated by statistical mixture designs to optimize solvent proportions to prepare the fingerprint of a medicinal herbal extract. For modeling, the number of peaks was used as a measure of fingerprint information. The optimum compositions of solvent to extract chemical substances from green tea and for mobile phase chromatographic analysis were ethyl acetate/ ethanol/dichloromethane (20:5:75 v/v/v) and MeOH/ACN/water (7.5:57.5:35 v/v/v), respectively. This system results in 26 peaks in the chromatographic fingerprint. These results show that an incorrect choice of modifiers for mobile phase composition and solvent extraction hampers the detection of a maximum number of peaks and produces a poor chromatographic fingerprint.     

Experimental evaluation of the effect of a modified port‐location mode on the performance of a three‐zone simulated moving‐bed process for the separation of valine and isoleucine

The removal of isoleucine from valine has been a key issue in the stage of valine crystallization, which is the final step in the valine production process in industry. To address this issue, a three‐zone simulated moving‐bed (SMB) process for the separation of valine and isoleucine has been developed previously. However, the previous process, which was based on a classical port‐location mode, had some limitations in throughput and valine product concentration. In this study, a three‐zone SMB process based on a modified port‐location mode was applied to the separation of valine and isoleucine for the purpose of making a marked improvement in throughput and valine product concentration. Computer simulations and a lab‐scale process experiment showed that the modified three‐zone SMB for valine separation led to >65% higher throughput and >160% higher valine concentration compared to the previous three‐zone SMB for the same separation.