Modeling the performance of pilot-scale countercurrent chromatography: Scale-up predictions and experimental verification of erythromycin separation
Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large‐scale purification of these antibiotics by conventional high‐performance liquid chromatography (HPLC) c...
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| Veröffentlicht in: | Biotechnology and bioengineering 2003-03, Vol.81 (6), p.640-649 |
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| creator | Booth, A.J. Sutherland, I. A. Lye, G. J. |
| description | Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large‐scale purification of these antibiotics by conventional high‐performance liquid chromatography (HPLC) can be prohibitively expensive due to the large volume of both solvent and adsorbent required. This study examines the feasibility of using a novel pilot‐scale countercurrent chromatography (CCC) machine as an alternative to HPLC. CCC is a low‐pressure (typically |
| doi_str_mv | 10.1002/bit.10508 |
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A. ; Lye, G. J.</creator><creatorcontrib>Booth, A.J. ; Sutherland, I. A. ; Lye, G. J.</creatorcontrib><description>Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large‐scale purification of these antibiotics by conventional high‐performance liquid chromatography (HPLC) can be prohibitively expensive due to the large volume of both solvent and adsorbent required. This study examines the feasibility of using a novel pilot‐scale countercurrent chromatography (CCC) machine as an alternative to HPLC. CCC is a low‐pressure (typically <4000 kN m−2) liquid–liquid chromatographic technique that allows the separation of solutes on the basis of their partitioning between two immiscible liquid phases. The effects of mobile phase flow rate, column rotational speed, and sample injection volume on the attainable yield and purity of EA were investigated. Our results show that, at a mobile phase flow rate of 40 mL min−1, a rotational speed of 1200 rpm, and an injection volume of 100 mL (10 g total erythromycin), EA could be satisfactorily fractionated with a purity of ∼92% (w/w) and a recovery yield of ∼100% (w/w). The total solute throughput was estimated to be 0.41 kg day−1. More importantly, we demonstrated simple and predictive linear scale‐up of the CCC separation based on data obtained from a single laboratory‐scale CCC chromatogram, and verified this experimentally. The retention time and peak width of the target compound at the pilot scale could be predicted to within 4% for operation at a range of mobile‐phase flow rates and injection volumes. This predictable nature of CCC separations, unlike HPLC methods, can greatly reduce process development times and enable a complete process‐scale operating scenario to be planned. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 640–649, 2003.</description><identifier>ISSN: 0006-3592</identifier><identifier>EISSN: 1097-0290</identifier><identifier>DOI: 10.1002/bit.10508</identifier><identifier>PMID: 12529878</identifier><identifier>CODEN: BIBIAU</identifier><language>eng</language><publisher>New York: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Biological and medical sciences ; Biotechnology ; Chromatography, Liquid - instrumentation ; Chromatography, Liquid - methods ; Computer Simulation ; Equipment Design ; erythromycin ; Erythromycin - analogs & derivatives ; Erythromycin - chemistry ; Erythromycin - isolation & purification ; Fundamental and applied biological sciences. Psychology ; Methods. Procedures. Technologies ; Models, Chemical ; Others ; Pilot Projects ; pilot-scale countercurrent chromatography ; predictive scale-up ; Quality Control ; Sensitivity and Specificity ; Various methods and equipments</subject><ispartof>Biotechnology and bioengineering, 2003-03, Vol.81 (6), p.640-649</ispartof><rights>Copyright © 2003 Wiley Periodicals, Inc.</rights><rights>2003 INIST-CNRS</rights><rights>Copyright 2003 Wiley Periodicals, Inc. 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A.</creatorcontrib><creatorcontrib>Lye, G. J.</creatorcontrib><title>Modeling the performance of pilot-scale countercurrent chromatography: Scale-up predictions and experimental verification of erythromycin separation</title><title>Biotechnology and bioengineering</title><addtitle>Biotechnol. Bioeng</addtitle><description>Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large‐scale purification of these antibiotics by conventional high‐performance liquid chromatography (HPLC) can be prohibitively expensive due to the large volume of both solvent and adsorbent required. This study examines the feasibility of using a novel pilot‐scale countercurrent chromatography (CCC) machine as an alternative to HPLC. CCC is a low‐pressure (typically <4000 kN m−2) liquid–liquid chromatographic technique that allows the separation of solutes on the basis of their partitioning between two immiscible liquid phases. The effects of mobile phase flow rate, column rotational speed, and sample injection volume on the attainable yield and purity of EA were investigated. Our results show that, at a mobile phase flow rate of 40 mL min−1, a rotational speed of 1200 rpm, and an injection volume of 100 mL (10 g total erythromycin), EA could be satisfactorily fractionated with a purity of ∼92% (w/w) and a recovery yield of ∼100% (w/w). The total solute throughput was estimated to be 0.41 kg day−1. More importantly, we demonstrated simple and predictive linear scale‐up of the CCC separation based on data obtained from a single laboratory‐scale CCC chromatogram, and verified this experimentally. The retention time and peak width of the target compound at the pilot scale could be predicted to within 4% for operation at a range of mobile‐phase flow rates and injection volumes. This predictable nature of CCC separations, unlike HPLC methods, can greatly reduce process development times and enable a complete process‐scale operating scenario to be planned. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 640–649, 2003.</description><subject>Biological and medical sciences</subject><subject>Biotechnology</subject><subject>Chromatography, Liquid - instrumentation</subject><subject>Chromatography, Liquid - methods</subject><subject>Computer Simulation</subject><subject>Equipment Design</subject><subject>erythromycin</subject><subject>Erythromycin - analogs & derivatives</subject><subject>Erythromycin - chemistry</subject><subject>Erythromycin - isolation & purification</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Methods. Procedures. Technologies</subject><subject>Models, Chemical</subject><subject>Others</subject><subject>Pilot Projects</subject><subject>pilot-scale countercurrent chromatography</subject><subject>predictive scale-up</subject><subject>Quality Control</subject><subject>Sensitivity and Specificity</subject><subject>Various methods and equipments</subject><issn>0006-3592</issn><issn>1097-0290</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFu1DAURSMEokNhwQ8gb0DqItR27NhhV1qYVhpg0UEsLcd56RiSONgONP_BB-N0BrpCrPysd-69erpZ9pzg1wRjelrbmAaO5YNsRXAlckwr_DBbYYzLvOAVPcqehPA1fYUsy8fZEaGcVlLIVfbrg2ugs8MNijtAI_jW-V4PBpBr0Wg7F_NgdAfIuGmI4M3kPQwRmZ13vY7uxutxN79B1wuUTyMaPTTWROuGgPTQILhNprZPGt2hH2lsrdHLegkAP8fFaDZ2QAFG7e9WT7NHre4CPDu8x9nn9--255f55tP66vxskxvGhczrhrVUCsFKyRkppGgAYykLSYuKi7ZhjEMrNCF1rZlmJSMguGwwMGBcF7Q4zl7tfUfvvk8QouptMNB1egA3BSVoJRbn_4JECow5Jwk82YPGuxA8tGpMx2s_K4LV0pVKXam7rhL74mA61T009-ShnAS8PAB66aD1qRcb7jnGiWC0TNzpnvtpO5j_najeXm3_ROd7hQ0Rbv8qtP-mSlEIrr58XCu8uay2dH2hrovfCEW9FQ</recordid><startdate>20030320</startdate><enddate>20030320</enddate><creator>Booth, A.J.</creator><creator>Sutherland, I. A.</creator><creator>Lye, G. J.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20030320</creationdate><title>Modeling the performance of pilot-scale countercurrent chromatography: Scale-up predictions and experimental verification of erythromycin separation</title><author>Booth, A.J. ; Sutherland, I. A. ; Lye, G. J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4578-bd4f2877468541387de00883823957fd445ef7a11bba4a4641e758d0e4e45a323</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Biological and medical sciences</topic><topic>Biotechnology</topic><topic>Chromatography, Liquid - instrumentation</topic><topic>Chromatography, Liquid - methods</topic><topic>Computer Simulation</topic><topic>Equipment Design</topic><topic>erythromycin</topic><topic>Erythromycin - analogs & derivatives</topic><topic>Erythromycin - chemistry</topic><topic>Erythromycin - isolation & purification</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Methods. Procedures. Technologies</topic><topic>Models, Chemical</topic><topic>Others</topic><topic>Pilot Projects</topic><topic>pilot-scale countercurrent chromatography</topic><topic>predictive scale-up</topic><topic>Quality Control</topic><topic>Sensitivity and Specificity</topic><topic>Various methods and equipments</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Booth, A.J.</creatorcontrib><creatorcontrib>Sutherland, I. A.</creatorcontrib><creatorcontrib>Lye, G. 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J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Modeling the performance of pilot-scale countercurrent chromatography: Scale-up predictions and experimental verification of erythromycin separation</atitle><jtitle>Biotechnology and bioengineering</jtitle><addtitle>Biotechnol. Bioeng</addtitle><date>2003-03-20</date><risdate>2003</risdate><volume>81</volume><issue>6</issue><spage>640</spage><epage>649</epage><pages>640-649</pages><issn>0006-3592</issn><eissn>1097-0290</eissn><coden>BIBIAU</coden><abstract>Biosynthesis of polyketide antibiotics, such as erythromycin A (EA), can result in the formation of analogues of the main compound that are chemically and structurally extremely similar. The large‐scale purification of these antibiotics by conventional high‐performance liquid chromatography (HPLC) can be prohibitively expensive due to the large volume of both solvent and adsorbent required. This study examines the feasibility of using a novel pilot‐scale countercurrent chromatography (CCC) machine as an alternative to HPLC. CCC is a low‐pressure (typically <4000 kN m−2) liquid–liquid chromatographic technique that allows the separation of solutes on the basis of their partitioning between two immiscible liquid phases. The effects of mobile phase flow rate, column rotational speed, and sample injection volume on the attainable yield and purity of EA were investigated. Our results show that, at a mobile phase flow rate of 40 mL min−1, a rotational speed of 1200 rpm, and an injection volume of 100 mL (10 g total erythromycin), EA could be satisfactorily fractionated with a purity of ∼92% (w/w) and a recovery yield of ∼100% (w/w). The total solute throughput was estimated to be 0.41 kg day−1. More importantly, we demonstrated simple and predictive linear scale‐up of the CCC separation based on data obtained from a single laboratory‐scale CCC chromatogram, and verified this experimentally. The retention time and peak width of the target compound at the pilot scale could be predicted to within 4% for operation at a range of mobile‐phase flow rates and injection volumes. This predictable nature of CCC separations, unlike HPLC methods, can greatly reduce process development times and enable a complete process‐scale operating scenario to be planned. © 2003 Wiley Periodicals, Inc. Biotechnol Bioeng 81: 640–649, 2003.</abstract><cop>New York</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>12529878</pmid><doi>10.1002/bit.10508</doi><tpages>10</tpages></addata></record> |
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| subjects | Biological and medical sciences Biotechnology Chromatography, Liquid - instrumentation Chromatography, Liquid - methods Computer Simulation Equipment Design erythromycin Erythromycin - analogs & derivatives Erythromycin - chemistry Erythromycin - isolation & purification Fundamental and applied biological sciences. Psychology Methods. Procedures. Technologies Models, Chemical Others Pilot Projects pilot-scale countercurrent chromatography predictive scale-up Quality Control Sensitivity and Specificity Various methods and equipments |
| title | Modeling the performance of pilot-scale countercurrent chromatography: Scale-up predictions and experimental verification of erythromycin separation |
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