Unlike SFC and HPLC, multicolumn continuous chromatography is a continuous process and is typically 2 to 10 times more productive than a batch chromatography process. MCC processes, such as simulated moving bed (SMB) and Varicol® are designed for the separation of binary mixtures and are, thus, perfectly adapted to the resolution of racemates and diastereomeric mixtures.
In multicolumn continuous chromatography processes, one long column is replaced by a loop of 4 to 6 shorter columns, optimizing the usage of the stationary phase. Only pure fractions are collected, leaving mixed fractions to re-circulate through the columns.
In the early 1990’s, Novasep pioneered the SMB chromatography in the pharmaceutical industry, and successfully scaled it up for multi-ton separations of optical isomers. The Varicol process, more recently developed by Novasep, is an improvement of SMB chromatography, optimizing both the stationary phase usage and the process productivity. In most cases, Varicol® is 15 to 25% more productive than SMB chromatography and typically 5 or 6 columns are used in Varicol whereas 6 to 8 columns are used in SMB chromatography.
Using Novasep proprietary computer modelling tools, the development time is almost as quick as with preparative HPLC. Everything is designed to minimize operating costs and to optimize both robustness and productivity. With automated solvent recycling, MCC makes the perfect tool to minimize the environmental impact of industrial-scale chromatography. Although exceptions exist, HPLC with integrated solvent recycling is often preferred for complex mixture separations, from multi-kg to multi-ton scale.
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Solvent recycling is a key aspect in preparative chromatography which can be designed as a unit operation that includes complete solvent recycling with the dry feed mixture being injected while dry separated compounds are recovered.
During a separation, the solvent is recovered from evaporators and dryers while pure dry compounds are recovered. The recycled solvent is reused as eluent of the continuous chromatography system and to dissolve the dry feed mixture. Only a small amount of fresh solvent is automatically added to the recycled one in order to adjust the eluent composition, using a technology patented by Novasep.
Organic solvent recycling of up to 99.97% and solvent consumption as low as 130 mL/kg of purified product for commercial scale applications has been reported by UCB Pharma using Novasep’s integrated Varicol® technology.
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