Simulated Moving Bed Chromatography (SMB) C E R T I F I Q • E D U DIN • A EN ISO L T I T 900 N Y 1 E M M E A N A G SMB The next step in chromatography Simulated Moving Bed Chromatography (SMB) SMB Pilot Unit CSEP® C9116 System for the production of up to 100 kg of pure compounds per year! The SMB System CSEP® C9116 is used for the extraction of pure substances in a semi-preparative scale. Similar to the ”big” system, CSEP® C9812, the pilot facility enables continuous operation with high efficiency. The system operates with a thermostat and can hold up to 16 SMB columns of equal type. The patented Multi-Port Valve with 64 ports guarantees a compact design that maintains an incredibly small total dead volume. The continuous product feed covers almost all of the surface of the stationary phase. Thus, the extraction yields maximum results. There is no need for small particle sizes or large plate numbers. This keeps the column packing inexpensive! Software for process simulation and optimization is available. Refer to next page for more details. Important Due to the individual requirements, columns are excluded from the standard delivery. We will gladly suggest appropriate columns and packing materials to suit your particular needs. Order No. Article Quantity A28701 SMB Pilot Unit CSEP® C9116 1 Consisting of: WellChrom HPLC Pump K-501 1 with 10 ml or 50 ml pump head, inert, with ceramic inlays, stainless steel 4 64-Port Multi-Function Valve, Hastelloy (stainless steel), 1/16” connectors, pressure stability 80 bar, for up to 16 equal SMB columns with either max. length of 300 mm, max. OD 22 mm or max. weight of 20 kg 1 Column Thermostat (up to 60°C) 1 Rack on castors, 30 x 35 cm 1 Set of capillaries, fittings, and accessories (1/16”) 1 PC including pre-configured ValveChrom software 1 2 SMB Production Unit CSEP® C9812 System for the production of up to 1,000 kg of pure compounds per year! The SMB System CSEP® C9812 stands out for its continous operation and high productivity. The continous delivery of feed and desorbent enables the permanent extraction of two fractions at high concentrations. The thermostated system can hold up to 12 SMB columns of similar type in terms of column packing, column dimensions etc. The patented Multi-Port Valve with its 48 ports plays the role of the ”heart” in the system. The compact design of CSEP® C9812 drama-tically reduces the total dead volume compared to other available SMB concepts. The product covers almost the complete surface of the stationary phase. Thus, the system is highly efficient. When peak recycling is practiced, one can save up to 90% of eluent consumption! With column packing another savings of up to 80% can be achieved. How? It’s simple: There is no need for small particle sizes or large plate numbers. This keeps the column packing inexpensive! Software for process simulation and optimization is available. Refer to next page for more details. Important Due to the individual requirements, columns are excluded from the standard delivery. We will gladly suggest appropriate columns and packing materials to suit your particular needs. Order No. Article Quantity A28706 SMB Production Unit CSEP® C9812 1 Consisting of: WellChrom Preparative Pump K-1800, 1 with 100 ml, 250 ml, or 1,000 ml pump head, stainless steel 4 48-Port Multi-Function Valve, Hastelloy, 1/8’’ connectors, pressure stability of 50 bar, for up to 12 equal SMB columns with either max. length of 1,000 mm or max. weight of 120 kg 1 Column Thermostat (up to 60°C) 1 Rack on castors 50 x 50 cm 1 Set of capillaries, fittings, and accessories (1/8’’) 1 PC including pre-configured ValveChrom software 1 3 Pilot SMB System CSEP® C9116S System for the production of up to 100 kg of pure substance extraction each year! The Pilot SMB System CSEP® C9116S, a modification of the CSEP® C9116 system, is designed for the extraction of pure substances out of a two component mixture in the semi-preparative range. The system works thermostatically and can be operated with up to 16 SMB separating columns of the same type. The patented multifunctional valve drastically reduces the dead volume and provides for the compact design. The system is very efficient due to the continuously fed product being distributed over the entire stationary phase. CSEP® C9116S is additionally equipped with 8 electrically driven valve drives with 6-port/3-channel valves. The drives enable samples to be withdrawn in each zone before and after the separation column for offline analysis. Order No. Article Quantity A28707 Pilot SMB System CSEP® 9116S with 8 WellChrom electrical valve drives K-6, with a 6-Port/3-Channel Switching Valve (A1484), maximum 16 columns, up to 80 bar, 1/16’’ 1 Pilot SMB System CSEP® C91168 The System is optimized for three component separation. The Pilot SMB System CSEP® C91168, a modification of the CSEP® C9116 system, is designed for the extraction of pure substances out of a three component mixture in the semi-preparative range. The system works thermostatically and can be operated with up to 16 SMB separating columns of the same type. The patented multifunctional valve drastically reduces the dead volume and provides for the compact design. CSEP® C91168 has been modified so that an 8 zone SMB process can be less expensively simulated in compairson to the classical 4 zone. Therefore, three component separations are possible with only one SMB system. Order No. Article Quantity A28708 Pilot SMB System CSEP® C91168 eight zone configuration, for maximum 16 columns, up to 80 bar, 1/16’’ 1 4 Simulated Moving Bed Chromatographie (SMB) SMB_Guide® for Windows With the design and simulation software, SMB_Guide® for Windows, it is possible to simulate and optimize an isocratic separation and SMB process PC based within the shortest amount of time. The calculations refer to the rapid and established algo-rithms from Prof. Guiochon (University of Tennessee, USA) and Prof. Seidel-Morgenstern (Max-Planck-Institute for dynamically complex technical systems, Germany). The calculations have made the long and empirical series of tests finally expendable. The SMB_Guide® helps you to thoroughly understand the inner process of a SMB system. This is due to the clear representation of the internal and external concentration profiles in the software. It is only necessary to specify the system configuration and the feed current, the SMB_Guide® will calculate all of the process parameters that have to be set. Then analyze the desired SMB configurations in reference to the number of columns, the dimensions, as well as distribution in the various SMB separation zones. The optional eluent recycling or a solid regeneration are more features adding further flexibility to the SMB_Guide®. Another helpful characteristic is the outstanding visual aid (i.e. assists in employee training). The SMB_Guide® will help you to get your SMB system up and running in the shortest amount of time! IsothermFit® for Windows Since knowledge of the thermodynamic functions is the most essential prerequisite for optimizing preparative separations, the determination of non-linear adsorption isotherms in high concentration ranges have been simplified with IsothermFit®. The software is able to apply different measurement methods (i.e. ECP, perturbation method) and evaluates the parameters of various single and competitive isotherm equations to non-linear Screenshot taken from the SMB_Guide® software regression methods. The competitive behavior is described by generally required to find optimal conditions such as flow rates extensions of the Langmuir equation such as linear isotherm, or the proper injection amount. Langmuir isotherm, and bi-Langmuir isotherm; or by the theory of the ideal adsorbed solution (IAS). The powerful ChromSim® software ... IsothermFit® supports the following four most suitable methods: • Reveals the consequences if chromatographic columns are overloaded • Linear Isotherm Method (Retention Time Method) • Simulates how peak profiles and separation performance are • Adsorption Desorption Method (ADM) affected after relevant parameters have been altered • ”Elution by a Characteristic Point” Method (ECP) • Implements various peak recycling modes with and without • Minor Disturbance Method (MDM, Perturbation Method) peak-sharing The results are essential input parameters for the simulation of • Calculates the cut times for fraction collection systems with elution profiles, recycling chromatography, and for setting up respect to the predefined purity requirements SMB processes that can be simulated using the powerful • Evaluates and compares the standard elution mode with ChromSim® and SMB_Guide® software. other modes such as frontal chromatography Ordering information ChromSim® for Windows Order No. Article Quantity A2865 SMB_Guide® for Windows™. Software for simulation Over several years a detailed theoretical analysis of non-linear and optimization of SMB separations 1 and preparative chromatography was performed by well known A2867 IsothermFit® for Windows™ Software for determination scientists such as Prof. Guiochon and his numerous co-workers. of non-linear adsorption isotherms when working with The presented theory has made the calculation of the migra-high concentrations 1 tion concentration dependence velocities in chromatographic A2866 ChromSim® for Windows™. Simulation software for peak recycling and fraction collection 1 columns possible. ChromSim® reduces the experimental work 5 Why SMB? Operation scheme for Preparative chromatography (Simulated Moving Bed chroma- interpreting and carrying out a SMB separation tography) is increasingly applied as a separation technique in the 1. Determine the phase volume ratio or porosity between pharmaceutical industry, production of fine chemicals, and in the stationary and mobile phase. the field of bioengineering. Simulated Moving Bed is a method 2. Determine the adsorption isotherms for each component in process chromatography that enables substance mixtures based on the overload chromatogram from each com-to be continuously separated and extracted in two fractions. ponent or the mixture. By repeated use of the SMB process each partial fraction can be 3. Determine the isotherm parameters using the IsothermFit® separated into a further fraction – up to binary substance mix-software. tures. Typically, the SMB process is set up in advance for a two 4. Definition of the process (hardware). component mixture. Following this, both substances can be im-5. Simulation of the process and optimization of the inter-mediately extracted in pure form – up to 1,000 kg per year. pretation using the SMB_Guide® simulation software. 6. Carry out a continuous ”SMB separation”. 7. Optimize the productivity. Where can a SMB separation be used? The SMB principle for continuous extraction of pure substances Comparison between on a preparative scale is successfully used in several areas of chemistry and biochemistry. The yearly production of the offered a SMB and a preparative HPLC system systems is between 100 and 1,000 kg of pure substance. Parameters Preparative System SMB System Range of application Separation and extraction of ... Separation process Batch method Continuous, higher Pharmaceutical chemistry Chiral compound (i.e. cis-trans phytol, productivity steroids, peptides, antibiotics) Stationary phase Only effective to a Maximum charge Food chemistry Fatty acids, carbohydrate mixture fractional part (i.e. sucrose/molasses or fructose/glucose) Mobile phase Higher consumption 90% less consumption Biochemistry Citric acid, phenylalanine by solvent recycling Petrochemistry C8-Hydrocarbon (i.e.xylene/toluene) Separation Several components 2–3 components Fractionation Individual substances Separation of a fraction from a mixture (can even be a mixture again) Operating mode Isocratic or gradient Isocratic operation When is a suitable time to set up operation a SMB process? Process simulation Feasible Feasible The extraction of pure substances (valuable substances) using a SMB system is offered after the required amount of a respective substance has been reached. Furthermore, the application of a SMB process is linked to the following prerequisites: KNAUER SMB • Two-component mixture (binary mixture) • Good solubility in the liquid phase Systems ”in use” – References • It must be possible to carry out an isocratic separation Schering Plough Corp., New Jersey, USA (since 2002) • Retention time of the substance must be under 20 min. Merck Rahway, New Jersey, USA (since 2001) • Knowledge of the adsorption isotherms Dow Chemicals Midland, Michigan, USA (since 2001) • Selectivity of 2.0 > d > 1.2 EISAI Research Institute, Massachusetts, USA (since 2001) Pfizer, Holland, Michigan, USA (since 2001) Wuxi University, Wuxi, China (since 2000) Advantages of SMB technology Roche Diagnostics Mannheim, Germany (since 1999) compared to classical batch chromatography Max-Planck-Institut Magdeburg, Germany (since 1999) • The entire stationary phase is continuously covered with Goedecke Parke Davis (Pfizer) Freiburg, Germany (since 1998) the mixture to be separated which produces a much higher productivity. • A 90% reduction in the demand for solvent due to solvent recycling. selmann Berlin • High plate counts or particle sizes are no longer required, Wissenschaftliche Gerätebau e reducing packing material costs by 80%. Dr. Ing. Herbert Knauer GmbH • Extract and raffinate are extracted in high concentration Hegauer Weg 38 · D-14163 Berlin-Zehlendorf, Germany which make it easier to remove solvent. Telephone: +49 (0)30 / 80 97 27- 0 • The patented multi-function valve enables an extremely Telefax: +49 (0)30 / 8 01 50 10 small dead volume. E-Mail: info@knauer.net · Internet: www.knauer.net KN 32/02/05.02/5.0 W 6