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Evaluation of scale-up from analytical to preparative supercritical fluid chromatography
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Engineering and Chemical Sciences. Karlstad Univ, INTERACT, Dept Engn & Chem Sci, SE-65188 Karlstad, Sweden..
AstraZeneca R&D, Resp Inflammat & Autoimmun, Innovat Med, S-43183 Molndal, Sweden..
AstraZeneca R&D, Resp Inflammat & Autoimmun, Innovat Med, S-43183 Molndal, Sweden..
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2015 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1425, 280-286 p.Article in journal (Refereed) PublishedText
Abstract [en]

An approach for reliable transfer from analytical to preparative scale supercritical fluid chromatography was evaluated. Here, we accounted for the conditions inside the columns as well as to the fact that most analytical instruments are volume-controlled while most preparative scale units are mass-controlled. The latter is a particular problem when performing pilot scale experiments and optimizations prior to scaling up to production scale. This was solved by measuring the mass flow, the pressure and the temperature on the analytical unit using external sensors. Thereafter, it was revealed with a design of experiments approach that the methanol fraction and the pressure are the two most important parameters to control for preserved retention throughout the scale-up; for preserved selectivity the temperature was most important in this particular system. Using this approach, the resulting chromatograms from the preparative unit agreed well with those from the analytical unit while keeping the same column length and particles size. A brief investigation on how the solute elution volume varies with the volumetric flow rate revealed a complex dependency on pressure, density and apparent methanol content. Since the methanol content is a parameter of great importance to control during the scale up, we must be careful when changing operational and column design conditions which generates deviations in pressure, density and methanol content between different columns. (C) 2015 Elsevier B.V. All rights reserved.

Place, publisher, year, edition, pages
2015. Vol. 1425, 280-286 p.
Keyword [en]
SFC, Chiral separation, Transfer of method, Scale-up, Operational parameters, Design of experiments
National Category
Chemical Engineering
Research subject
Chemical Engineering
Identifiers
URN: urn:nbn:se:kau:diva-40985DOI: 10.1016/j.chroma.2015.11.001ISI: 000366770400032OAI: oai:DiVA.org:kau-40985DiVA: diva2:910104
Available from: 2016-03-08 Created: 2016-03-08 Last updated: 2016-03-08Bibliographically approved
In thesis
1. Fundamental Investigations of Supercritical Fluid Chromatography
Open this publication in new window or tab >>Fundamental Investigations of Supercritical Fluid Chromatography
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis aims at a deeper understanding of Supercritical Fluid

Chromatography (SFC). Although preparative SFC has started to replace Liquid Chromatography (LC) in the pharmaceutical industry - because of its advantages in speed and its less environmental impact - fundamental understanding is still lacking. Therefore there is no rigid framework to characterize adsorption or to understand the impact of changes in operational conditions.

 

In Paper I we demonstrated, after careful system verification, that most methods applied to determine adsorption isotherms in LC could not be applied directly in SFC. This was mainly due to operational differences and to the fact that the fluid is compressible which means that everything considered constant in LC varies in SFC.

 

In Paper II we showed that the most accurate methods for adsorption isotherm determination in LC, the so called plateau methods, do not work properly for SFC. Instead, methods based on overloaded profiles should be preferred.

 

In Paper III a Design of Experiments approach was successfully used to quantitatively describe the retention behavior of several solutes and the productivity of a two component separation system. This approach can be used to optimize SFC separations or to provide information about the separation system.

 

In Paper IV severe peak distortion effects, suspected to arise from injection solvent and mobile phase fluid mismatches, were carefully investigated using experiments and simulations. By this approach it was possible to examine the underlying reasons for the distortions, which is vital for method development.

 

Finally, in Paper V, the acquired knowledge from Paper I-IV was used to perform reliable scale-up in an industrial setting for the first time. This was done by carefully matching the conditions inside the analytical and preparative column with each other. The results could therefore provide the industry with key knowledge for further implementation of SFC.

Abstract [en]

This thesis aims at a deeper understanding of Supercritical Fluid

Chromatography (SFC). Although preparative SFC has started to replace Liquid Chromatography (LC) in the pharmaceutical industry - because of its advantages in speed and its less environmental impact - fundamental understanding is still lacking. Therefore there is no rigid framework to characterize adsorption or to understand the impact of changes in operational conditions.

 

In Paper I-II it was demonstrated why most methods applied to determine adsorption isotherms in LC could not be applied directly for SFC. Methods based on extracting data from overloaded profiles should be preferred.

 

In Paper III a Design of Experiments approach was successfully used to quantitatively describe the behavior of several solutes in a

separation system. This approach can be used to optimize SFC separations or to provide information about the separation system.

 

In Paper IV severe peak distortion effects often observed in SFC were carefully investigated and explained using experiments and simulations.

 

Finally, in Paper V, the prerequisites for performing reliable and predictable scale-up of SFC were investigated by small and large scale experiments.

Place, publisher, year, edition, pages
Karlstad: Karlstads universitet, 2015. 63 p.
Series
Karlstad University Studies, ISSN 1403-8099 ; 2015:45
Keyword
Supercritical Fluid Chromatography, SFC, Modeling, Adsorption Isotherms, Scale-up, Peak Distortion, Injection, Design of Experiments, Perturbation Peak Method, Elution by Characteristic Points Method, Method transfer
National Category
Analytical Chemistry Chemical Engineering
Research subject
Chemistry
Identifiers
urn:nbn:se:kau:diva-37913 (URN)978-91-7063-663-9 (ISBN)
Public defence
2015-10-16, Nyquistsalen 9C 203, Karlstads universitet, Karlstad, 10:15 (English)
Opponent
Supervisors
Note

Paper 4 ("Evaluation of scale-up from analytical to preparative...") ingick som manuskript med samma titel i avhandlingen. Nu publicerad. 

Available from: 2015-09-25 Created: 2015-09-11 Last updated: 2016-03-08Bibliographically approved

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Enmark, MartinAsberg, DennisSamuelsson, JorgenFornstedt, Torgny
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