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36449

36449

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Published by Himanshu Jha

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Published by: Himanshu Jha on Aug 21, 2012
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Cephalosporin C (CPC) belongs to the largest classof antibiotics, the beta-lactam antibiotics. The overallworld market for beta-lactam antibiotics is estimatedover $ 9 billion (in 2001).CPC is a bulk intermediate for many semi-synt-hetic antibiotics. After fermentation and purification,
Cephalosporin C purification usingSepTor technology
CPC is converted to 7-ACA, which serves as the beta-lactam nucleus for the majority of semi-synthetic anti-biotics available today.CPC is produced by specific high yield strains ofCephalosporium Acremonium, a filamentous strictlyaerobic fungus. Originally, the commercial recoveryprocesses were based on solvent extraction. Nowa-days, most processes are based on the more selectivecapabilities of polymeric media. This results in a betterrecovery and higher purity of CPC.In this application note, we will outline the reco-very of CPC by using continuous chromatography on anon-functionalized polymeric adsorbent. The continuo-us chromatography process involves multiple steps,which makes the SepTor chromatography system thesystem of choice.
 
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Design considerations
CPC is adsorbed on non-functionalized polystyreneadsorbents, such as Amberlite XAD-16 or equivalentresins. The adsorption is carried out near the iso-elec-tric point of CPC, typically at pH 2.Key issue in the purification of CPC is the remo-val of desacetyl cephalosporin (DCPC) and desacety-loxy cephalosporin (DOCPC). Typical breakthrough andelution profiles of the three main components in theseparation (CPC, DCPC and DOCPC) are shown in figu-re 2. The graph clearly shows that DCPC is displacedby CPC and that DOCPC binds stronger than CPC.Depending on the final form of the Cephalospo-rin that is produced (either its Na or its Zn salt), theelution is done with a water miscible solvent, such asIPA, or with a sodium acetate buffer.After the elution, the resin needs to be regene-rated with caustic, which is sometimes combined witha solvent. After the regeneration, some sulphuric acidis applied in order to bring the pH down to conditionscompatible with the adsorption.
Pilot test results
During pilot tests, the influence of various parameterson the separation performance has been investiga-ted and process conditions have been optimized. Thisincludes optimization of the settings to accommodatevariations in the feed composition.The recovery of CPC is 93 – 95% and the reduc-tion in DCPC and DOCPC are 28 and 3-fold. The colourremoval depends on the nature of the fermentationbroth. Even in case of very turbid fermentation broths(with a light transmission at 420 nm T420 < 75% after50 times dilution), the colour reduced with a factor 50– 60.
Commercial process flow diagram
A typical process flow diagram for the purification ofCPC from clarified fermentation broth is shown in figu-re above. The PFD shows a process with a productioncapacity of 850 tpa CPC.Most relevant system dimensions of the PFDshown in figure 3 are: Resin volume: 33 m³ in 30 co-lumns e.g. 1,1 m³ resin/column.The process shown in figure 2 would operate ata specific productivity of 26 tpa/m³. The performan-ce of large-scale systems is slightly better than forpilot-scale processes. Recoveries of 95% are normallyobtained and the reduction of DCPC and DOCPC is verysimilar or slightly better than in pilot trials. The colourremoval is normally in the same range as in the pilot
Figure 1. Molecular structure of Cephalosporin.

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