Methodology, data interpretation and practical transfer of freeze dry microscopy [Elektronische Ressource] / vorgelegt von Eva Meister

Eva Meister

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• Gesundheit

Informations

• Publié par: friedrich-alexander-universitat_erlangen-nurnberg
• Publié le: 01 janvier 2009
• Nombre de lectures: 19
• Langue: English
• Poids de l'ouvrage: 5 Mo

Extrait

Methodology, Data Interpretation and
Practical Transfer
of Freeze-Dry Microscopy


Der Naturwissenschaftlichen Fakultät
der Friedrich-Alexander-Universität Erlangen-Nürnberg
zur
Erlangung des Doktorgrades



vorgelegt von
Eva Meister
aus Münchberg Als Dissertation genehmigt von der Naturwissenschaftlichen Fakultät
der Universität Erlangen-Nürnberg









Tag der mündlichen Prüfung: 12. März 2009
Vorsitzender
der Prüfungskommission: Prof. Dr. Eberhard Bänsch
Erstberichterstatter: Prof. Dr. Geoffrey Lee
Zweitberichterstatter: Prof. Dr. Wolfgang Frieß I





Es gibt auf der Welt einen einzigen Weg,
auf welchem niemand gehen kann,
außer dir: Wohin er führt?
Frage nicht, gehe ihn.

Friedrich Nietzsche


II
Acknowledgements III
Acknowledgements
The work for the present thesis has been performed between February 2005 and Sep-
tember 2008 at the Department of Pharmaceutics, University of Erlangen-Nuremberg,
Erlangen, Germany.

Prof. Dr. Geoffrey Lee is gratefully acknowledged for offering me the opportunity to work
at his department and for being my doctoral advisor. Many thanks to Prof. Dr. Wolfgang
Frieß, Department of Pharmaceutical Technology, University of Munich, for being co-
referee for this thesis.
Dr. Henning Gieseler is greatly acknowledged for giving me the chance to work in his
focus group freeze-drying and for being my supervisor. Thank you for your support dur-
ing this period, for research projects of significant interest, for the extensive discussions,
and your confidence in my work.

Special thanks go to Carsten Brenk for his encouragement and optimism, for highly so-
phisticated scientific discussions we shared and for distractions during our free time.
I would like to gratefully acknowledge Stefan Schneid and Dr. Jörg Kunze for proofread-
ing this thesis. Your support was great!

Thanks to Prof. Dr. Michael Pikal, School of Pharmacy, University of Connecticut, Storrs,
USA, and to Dr. Evgenyi Shalaev, Pfizer Global Research and Development, Groton,
USA, for the discussions and helpful advice. IV Acknowledgements
For their technical support during my thesis period, I would like to greatly acknowledge
LAT Labor- und Analysen-Technik GmbH, Garbsen, Germany, especially Thomas Wi-
chert, and Dr. Bernhard Dringenberg, as well as Dr. Thorsten Kern and Dr. Susanne
Klerner from Carl Zeiss AG, Oberkochen, Germany. Thank you very much for providing
me the high-end equipment, and for the great time we had at the tradeshow exhibitions!
Stephan Wasser from LAT Labor- und Analysen-Technik GmbH is kindly thanked for his
software solutions.
In the department of pharmaceutics I would like to thank all my colleagues, who helped
me with equipment or teaching issues, and with whom I shared a good time during my
thesis period. Thanks to my students Marek Ellnain, Stefan Schuster, and Elisabeth
Scheffel for supporting me during some of my experiments. I further thank Petra Neu-
barth for taking care of administrative issues, Josef Huber and Winfried Bauer for solving
technical problems, Dr. Stefan Seyferth for his IT support, Luise Schedl for the SEM pic-
tures, and Christiane Blaha for ordering excipients and lab equipment. Additionally, Dr.
Christian Führling and Dr. Heiko Schiffter are kindly acknowledged for their support.

During the period of this thesis, I had the great pleasure to make a lot of new friends, and
to share many magnificent moments and events. First of all, I want to thank Yolanda
Philipps-Gomez for her wonderful friendship, and all my other friends for their support.
Special thanks go to all my flamenco co-dancers. I enjoyed the dancing lessons and fes-
tivals with you very much! Further, I would like to thank all “co-Ms” with whom I had a lot
of fun participating in our annual meetings and other events.

Last, but not least, my parents Irene and Erich Meister are kindly acknowledged for lay-
ing the foundation for the path I followed. Publications V
Publications

Parts of this thesis were subject to articles, posters and invited talks:


1. Articles:
• E. Meister, S. Klerner, H. Gieseler. Gefriertrocknungsmikroskopie: Proteine und
Peptide zwischen Kollaps und Kristallisation. Deutsche Apotheker Zeitung: 146
(24): 2552-2557, 2006.
• E. Meister, B. Dringenberg, H. Gieseler. Die Schlüsselstellung
der Gefriertrocknungsmikroskopie in der Entwicklung parenteraler Formulierun-
gen. GIT Laborfachzeitschrift: 51 (6): 476-478, 2007.
• E. Meister, H. Gieseler. Freeze-Dry Microscopy of Protein/Sugar Mixtures: Dry-
ing Behavior, Interpretation of Collapse Temperatures and a Comparison to Cor-
responding Glass Transition Data. J. Pharm. Sci., in press, 2008.
• E. Meister, H. Gieseler. Evaluation of the Critical Formulation Temperature in
Freeze-Drying: A Comparison Between Collapse and Glass Transition Tempera-
tures. European Pharmaceutical Review, in press, 2008.



VI Publications
2. Poster presentations:
• E. Meister, H. Gieseler. Evaluation of Collapse Temperatures by Freeze-Dry Mi-
croscopy: Impact of Excipient Concentration on Measured Transition and the
thOverall Dependence on Measurement Methodology. Proc. 5 World Meeting on
Pharmaceutics and Pharmaceutical Technology, Geneva (SWITZERLAND),
March 27-30, 2006.
• E. Meister, H. Gieseler. Measurement of Collapse Temperature by Freeze-Dry
Microscopy: Dependence of Collapse Temperatures on Total Solid Content and
Correlation to Physical Properties of the Measured Excipient Solution. Proc.
CPPR Freeze-Drying of Pharmaceuticals and Biologicals, Garmisch-
Partenkirchen (GERMANY), Oct. 3-6, 2006.
• E. Meister, M. Ellnain, H. Gieseler. Collapse Temperature Measurement by
Freeze-Dry Microscopy and Transferability to Freeze Drying Processes: Influence
of Solute Concentration on Collapse Behavior and Effect on Cycle Design. Proc.
AAPS Annual Meeting and Exposition, San Antonio (USA), Oct. 29 - Nov. 2,
2006.
• E. Meister, H. Gieseler. Freeze-Dry Microscopy: Correlation between Physical
Properties and Collapse Behavior of Excipients Frequently Used for Freeze-
Drying. Proc. AAPS Annual Meeting and Exposition, San Diego (USA), Nov.
11-15, 2007.
• E. Meister, H. Gieseler. Freeze-Dry Microscopy: Drying and Collapse Behavior
of Human Serum Albumine and Bovine Serum Albumine Based Formulations.
Proc. AAPS Annual Meeting and Exposition, San Diego (USA), Nov. 11-15, 2007. Publications VII
• S. Schneid, E. Meister, H. Gieseler. Design Space in Freeze-Drying: A Robust-
ness Testing Procedure in the Laboratory to Delineate the Impact of Product
Temperature Variability on Product Quality Attributes. Proc. CPPR Freeze-Drying
of Pharmaceuticals and Biologicals, Breckenridge (USA), Aug. 6-9, 2008.

3. Invited talks:
• E. Meister. Freeze-Dry Microscopy – Investigation of Interplay between Physical
Properties of a Formulation and Collapse Behaviour. DPhG - Graduate Student
Symposium, Heroldsberg (GERMANY), Sept. 6-8, 2006
• E. Meister. Freeze-Dry Microscopy - A powerful Tool to Develop Optimized
Freeze-Drying Cycles. Lyophilization of Pharmaceuticals, Informa Life Science
Seminar, London (UK), Dec. 3-5, 2007
• E. Meister. Freeze-Dry Microscopy (FDM) – Measurement Methodology, Data In-
terpretation and Transfer to Cycle Development. Pfizer Global Research and De-
velopment, Groton (USA), Mar. 3, 2008
• E. Meister. The critical formulation temperature in freeze-drying. SP Industries,
Stone Ridge (USA), Mar. 6, 2008
• E. Meister. Analytical Tools I: Evaluation of the Critical Formulation Temperature
by DSC and Freeze-Dry Microscopy. Seminar on Freeze-Drying (SP Industries),
Mumbai, Ahmedabad, Delhi, Hyderabad (INDIA), Aug. 18-22, 2008
VIII