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Preparative Separat...
Preparative Separation of Omeprazole: Predictions of the Optimal Experimental Conditions by Computer Simulations
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- Enmark, Martin (författare)
- Karlstads universitet,Avdelningen för kemi och biomedicinsk vetenskap
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- Samuelsson, Jörgen, 1971- (författare)
- Karlstads universitet,Avdelningen för kemi och biomedicinsk vetenskap
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- Fornstedt, Torgny, 1957- (författare)
- Karlstads universitet,Avdelningen för kemi och biomedicinsk vetenskap
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- Forssén, Patrik, 1966- (författare)
- Karlstads universitet,Avdelningen för kemi och biomedicinsk vetenskap
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(creator_code:org_t)
- 2011
- 2011
- Engelska.
- Relaterad länk:
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http://www.separatio...
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https://urn.kb.se/re...
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Abstract
Ämnesord
Stäng
- In this study, omeprazole was used as a model compound. Omeprazole and other related sulfoxide benzimidazoles are used against gastric ulcers and have been extensively studied regarding chromatographic resolution techniques using several different chiral stationary phases.First, AstraZeneca launched Losec, a racemic mixture of RS-omeprazole. Facing loss of patent, the more potent S-enantiomer was developed and marketed as Nexium. Now the patent of Nexium is close expiration why methods for isolation of the pure S-enantiomer will be of importance for the generic pharmaceutical companies.The experimental model separation system represents a system with good selectivity and high solubility of the solute in the eluent. In this investigation the productivity optima for three different particle sizes (5, 10 and 25 µm) at maximum system pressure ranging from 50 to 400 bars are studied. Two different optimizations cases were studied in depth. First,a process optimization with fixed column geometry is studied. The results clearly show that larger packing materials have higher productivity at low pressure drops on the analytical size column.With increasing allowed pressure drops, over 200 bar, the smaller packing materials have substantially higher productivity.The results also show that smaller packing material will always have much lower solvent consumption compared to larger particles.The second process optimization was performed with a fixed column volume, but the column geometry was variable. The results shows that the productivity obtained for the smaller packing particles materials was higher compared to the large for all allowed pressure drops. The productivity obtained for the small particle compared to the large increased by 25-300 % while maintaining 50-300 % less solvent consumption for the purification of the first enantiomer.The addition of TEA seems to be unfavorable for all tested conditions.In conclusion, the optimization of the enantioseparation of omeprazole has been shown to be dependent on column packing particle size as well as column geometry. It has been demonstrated that all parameters need to be simultaneously optimized to reach a global productivity optima.
Ämnesord
- NATURVETENSKAP -- Kemi (hsv//swe)
- NATURAL SCIENCES -- Chemical Sciences (hsv//eng)
Nyckelord
- Kemi
- Chemistry
Publikations- och innehållstyp
- ref (ämneskategori)
- kon (ämneskategori)