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Preparative chromatography (Simulated Moving Bed) is increasingly applied as a separation technique in the pharmaceutical industry, production of fine chemicals, and in the field of bioengineering.
Why Simulated Moving Bed?
Simulated Moving Bed is a method in process chromatography that enables substance mixtures to be continuously separated and extracted in two fractions. By repeated use of the SMB process each partial fraction can be separated into a further fraction - up to binary substance mixtures. Typically, the SMB process is set up in advance for a two component mixture. Following this, both substances can be immediately extracted in pure form - up to 1,000 kg per year.
Where can a SMB separation be used?
The SMB principle for continuous extraction of pure substances on a preparative scale is successfully used in several areas of chemistry and biochemistry. The yearly production of the offered systems is between 100 and 1,000 kg per year. SMB is applicable in:
| Pharmaceutical Chemistry |
Chiral compounds such as cis-trans phytol, steroids, antibiotics |
| Food chemistry |
Fatty acids, carbohydrate mixtures such as sucrose/molasses or fructose/glucose |
| Biochemistry |
Peptides, phenylalanine, citric acid |
| Petrochemistry |
C8-hydrocarbons such as xylene/toluene |
When is a suitable time to set up a SMB process?
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:
- Two-component mixture (binary mixture)
- Good solubility in the mobile phase
- It must be possible to make an isocratic separation
- Retention time of the substance must be under 20 minutes
- Knowledge of the adsorption isotherms
Advantages of SMB technology compared to classical batch chromatography
- The entire stationary phase is continuously covered with the mixture to be separated which produces a much higher productivity.
- A 90% reduction in the demand for solvent due to solvent recycling.
- High plate counts or particle sizes are no longer required, reducing packing material by 80%.
- Extract and raffinate are extracted (in high concentrations) which make it easier to remove solvent.
- The patented multifunctional valve enables an extremely low dead volume.
Operation scheme for interpreting and carrying out a SMB separation
- Determine the phase volume ratio or porosity between the stationary and mobile phase.
- Determine the adsorption isotherms for each component based on the overload chromatogram from each component or the mixture.
- Determine the isotherm parameters using the IsothermFit® software.
- Define the process (hardware).
- Simulate the process and optimize the interpretation using the SMB_Guide® simulation software.
- Carry out a continuous "SMB separation".
- Optimize the productivity.
Comparison between a SMB and preparative HPLC system
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| Parameters |
Preparative System |
SMB System |
| Separation process |
Batch method |
Continuous |
| Stationary phase |
Only effective to a fractional part |
Maximum charge |
| Mobile phase |
Higher consumption |
90% less consumption by recycling the solvent |
| 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 operation |
Isocratic |
| Process simulation |
Feasible |
Feasible |
KNAUER's SMB systems "in use" references:
In the past several years KNAUER has been able to win over the confidence of several large research and development corporations. This is specifically true with our efficient and reliable SMB systems. SMB systems are being operated daily, for example at:
IICT, Hyderabad, India (since 2006)
Technikrom, Evanston, Illinois, USA (since 2005)
Fluka Chemicals, Buchs, Switzerland (since 2004)
University of Applied Science, Winterthur, Switzerland (since 2004)
University of Shenjang, China (since 2003)
Gedeon Richter, Budapest, Hungary (since 2003)
NCL, Pune, India (since 2002)
Yonsei University, Seoul, Korea (since 2002)
Schering Plough Corp., New Jersey USA (since 2002)
Merck Rahway, New Jersey USA (since 2001)
Dow Chemicals Midland, Michigan USA (since 2001)
EISAI Research Institute, Andover, Massachusetts (since 2001)
Pfizer, Holland, Michigan, USA (since 2001)
Wuxi University, China (since 2000)
Roche Diagnostics, Mannheim, Germany (since 1999)
Goedecke Parke Davis, (Pfizer) Freiburg, Germany (since 1998)
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