Gradient injection in preparative chromatography [Elektronische Ressource] : exploitation of sample solvents different than the mobile phase / von Knut Gedicke

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Informations

• Publié par: otto-von-guericke-universitat_magdeburg
• Publié le: 01 janvier 2010
• Nombre de lectures: 56
• Langue: Deutsch
• Poids de l'ouvrage: 6 Mo

Extrait

Gradient Injection in Preparative Chromatography –
Exploitation of Sample Solvents Different than the Mobile Phase


Dissertation
zur Erlangung des akademischen Grades


Doktoringenieur
(Dr.Ing.)



von: DiplomIngenieur Knut Gedicke
geboren am: 25. Feb. 1975
in: Magdeburg

genehmigt durch die Fakultät für Verfahrens und Systemtechnik
der OttovonGuerickeUniversität Magdeburg

Gutachter:
Prof. Dr.Ing Andreas SeidelMorgenstern
Prof. Dr.Ing. Dorota Antos

eingereicht am: 7. Januar 2010
Promotionskolloquium am: 22. Juli 2010 Abstrakt
Die vorliegende Arbeit soll einen Beitrag zum besseren Verständnis der präparativen
BatchFlüssigkeitsChromatographie leisten. Es wird die Verwendung eines anderen
Lösungsmittels für die Injektion als für die Elution in dieser Arbeit untersucht – die
Gradienteninjektion. Besonderes Augenmerk gilt dabei einer in der
pharmazeutischen Industrie weit verbreiteten Methode, der Nutzung eines stärkeren
Lösungsmittels für die Injektionen.
In einer theoretischen Untersuchung der Gradienteninjektion wurden Lösungen der
Gleichgewichtstheorie für die Gradienteninjektion angewandt und erweitert. Dadurch
konnten prinzipielle Effekte einer solchen Verfahrensführung abgeleitet werden. Die
theoretisch ermittelten Resultate wurden in zwei experimentellen Studien bestätigt.
Anhand einer experimentellen Fallstudie wurde eine einfache und effiziente Methode
vorgeschlagen, anhand derer das Potential einer Prozessintensivierung durch den
Einsatz der Gradienteninjektion überprüft werden kann. Es konnte gezeigt werden,
dass die Gradienteninjektion Potential zur Verbesserung der BatchChromatographie
besitzt. Randbedingen, lohnende Einsatzgebiete und Grenzen der Gradienten
injektion wurden identifiziert

Abstract
This work is meant as a contribution to increase the understanding of preparative
batch liquid chromatography. It investigates on the use of a different sample solvent
for injection than for the elution – the gradient injection. The use of a stronger sam
ple solvent for injection, as often used in pharmaceutical industry, has been given
special consideration.
For theoretical investigation of the gradient injection, solutions of the equilibrium
theory have been applied and extended. This led to identification and derivation of
general elution effects of such an injection method. The theoretical results have been
verified in two experimental studies. Based on a experimental case study a rather
simple and effective methodology has been suggested, suitable for process design
and evaluation. It has been shown, that gradient injections have potential for process
intensification. Suitable application areas and limits of the gradient injection have
been identified. Acknowledgement
Primarily I thank my supervisor Andreas SeidelMorgenstern. His ongoing confi
dence helped me through all my struggles. Greatly I appreciate, that he has given me
the freedom, the trust and the patience to perform studies beyond my actual job.
Gratitude is also expressed to Prof. Dorota Antos. She was the one who first brought
up the idea to scientifically examine a wellestablished method in industry. The out
standing work of Magdalena Tomusiak is the reason why Chapter 4 has become a
reality. Her restless effort allowed the numerous experiments in such a limited time.
The contribution of Isabella Poplewska on chapter 5 is gratefully acknowledged. I
would like to thank Jadwiga Novak and all the other folks at the university of
Rzeszów for their hospitality and inspiration.
I thank all my colleagues at the OttovonGuericke University a nd the MaxPlanck
Institute Magdeburg for their assistance and friendship. Special thanks go at this
point to Bert Vollbrecht and Volker Zahn for their critical comments. The discus
sions with Malte Kaspereit, Tuomo Saino and Achim Kienle on the subject of the
equilibrium theory are greatly appreciated. After all: “It is as simple as a simple
wave.”
Last but not least: Ich danke meinen Eltern und meiner Familie, dass sie mir ihre
Unterstützung gegeben haben und somit erst das Umfeld geschaffen haben, dass ich
mich einer solchen Herausforderung stellen konnte. Meiner Frau, Elina, danke ich
für Ihre unermüdliche Motivation und Hilfe.

Table of Contents
1. Introduction........................................................................................................ 1
2. Background 5
2.1. Literature Survey ......................................................................................... 5
2.2. Definitions.................................................................................................... 9
2.3. Modelling Batch Chromatography ............................................................ 12
2.3.1. Equilibrium Loadings – Adsorption Isotherms ................................. 13
2.3.2. Ideal Model of Chromatography........................................................ 16
2.3.3. Models with Mass Transfer Effects ................................................... 20
2.3.4. Modelling Gradient Elution............................................................... 23
2.3.5. Determination of Adsorption Isotherms ............................................ 25
2.3.5.1. Frontal Analysis......................................................................... 26
2.3.5.2. Perturbation Method .................................................................. 26
2.3.5.3. Inverse Method .......................................................................... 28
2.4. Introduction to Solutions of the Ideal Model and the Hodograph Space .. 29
3. Application of Equilibrium Theory for the Analysis of Solvent$Solute
Interactions during Gradient Injection ................................................................. 41
3.1. Analysis of Systems with Linear Linear Isotherms.................................. 44
3.1.1. Binary System – General Effects for a Single Solute........................ 46
3.1.1.1. Modifier is the Least Retained Component Case a)................ 47
3.1.1.2. Modifier is the Strongest Retained Component Case b) ......... 55
3.1.1.3. Mixed Elution Order Case c)................................................... 59
3.1.1.4. Summary of Binary Systems with Linear Linear Isotherms....63
3.1.2. Ternary System – Application of Gradient Injections to Separation..65
3.2. Analysis of Systems with Linear Langmuir Isotherms .............................72
3.2.1. Binary System General Effects for a Single Solute .........................72
3.2.1.1. Modifier is the Least Retained Component Case a).................76
3.2.1.2. Modifier is the Strongest Retained Component Case b)..........83
3.2.2. Summary of Binary Systems with Linear Langmuir Isotherms.......87
3.3. Summary .....................................................................................................88
st4. Gradient Injection and the Effect of Solvent$Solute Interactions – 1 Case
Study ..........................................................................................................................91
4.1. Chemicals and Experimental Procedures ..................................................92
4.2. Results.........................................................................................................93
4.2.1. Solubility of DLthreonine in the Mobile phases and in the Injection
Media ..................................................................................................93
4.2.2. Elution Profiles...................................................................................95
4.2.3. Determination of Adsorption Isotherm...............................................97
4.2.4. Column model ....................................................................................99
4.3. Discussion.................................................................................................100
4.4. Summary ...................................................................................................104
nd
5. Effect of Gradient Injection on Separation – 2 Case Study.....................107
5.1. Theoretical Methods Applied ...................................................................108
5.1.1. Process model...................................................................................108
5.1.2. Adsorption Isotherm of the Solvent .................................................109
5.1.3. Adsorption Isotherm of the Solutes..................................................110
5.2. Chemicals and Experimental Procedures ................................................111
5.2.1. Chemicals and Apparatus .................................................................111
5.2.2. Experimental Procedures..................................................................112
5.3. Results and Discussion ............................................................................ 113
5.3.1. Analysis of the Experimental Data .................................................. 113
5.3.2. Adsorption Isotherm of the Solvent................................................. 113
5.3.3. Adsorption isother