Encapsulation and controlled release of pharmaceuticals with biodegradable hyperbranched polyesters [Elektronische Ressource] / vorgelegt von Rajendar Reddy Mallepally

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• Publié par: friedrich-alexander-universitat_erlangen-nurnberg
• Publié le: 01 janvier 2009
• Nombre de lectures: 37
• Langue: English
• Poids de l'ouvrage: 6 Mo

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Encapsulation and Controlled Release of Pharmaceuticals with
Biodegradable Hyperbranched Polyesters





Der Technischen Fakultät der
Universität Erlangen-Nürnberg
zur Erlangung des Grades




DOKTOR-INGENIEUR







vorgelegt von
M.Sc. Rajendar Reddy Mallepally
aus Hyderabad, INDIA









Erlangen - 2009























Als Dissertation genehmigt von
der Technischen Fakultät der
Universität Erlangen-Nürnberg


Tag der Einreichung: 11.11.2008
Tag der Promotion: 13.03.2009
Dekan: Prof. Dr. Johannes Huber

1. Berichterstatter: Prof. Dr. Wolfgang Arlt
2. Berichterstatter: Prof. Dr. Irina Smirnova
3. Berichterstatter: Prof. Dr. Geoffrey Lee


II
Acknowledgements

This research work was carried out at the chair for separation science and technology,
Friedrich-Alexander University, Erlangen-Nürnberg, Germany, during the years 2005 - 2009.

First and foremost, I would like to sincerely thank Prof. Dr. Wolfgang Arlt for giving me the
great opportunity to do my Ph.D. in his group, for his help, support and for the fine
corrections of my thesis.

I am indebted to my advisor Dr. Irina Smirnova at the chair for separation science and
technology, Erlangen (now Professor at the Technical University of Hamburg-Harburg) for
her excellent guidance, patient hearings and long sessions of discussions which were so great
and help to me for completing this work in time. Her support, also on personal level, has been
very valuable during many difficult situations. I am very thankful for her careful corrections
of the dissertation by reading line by line.

It was a great experience for me to work with Dr. Matthias Seiler, Dr. Saskia Klee-Laquai,
and Dr. Geoffrey Hills in a cooperation project with Evonik Degussa GmbH. Their innovative
discussions concerning the work helped me a lot. And moreover many thanks for giving me
the valuable suggestions regarding the publication of the research work.

I would also thank Suresh Gorle for his fruitful discussions, especially regarding analytical
problems. To all my colleagues: I am deeming myself very fortunate in having had the
possibility of working with you. Special thanks to Alexander Buchele who shared the office
with me.

I express my sincere thanks to Petra Kiefer for UV-Vis and GC measurements and Margeret
Leucker for HPLC measurements for performing hundreds of experiments in the laboratory.
Edelguard Schumann, Philipp Wolf, and Christa Genslein for their help in the laboratory as
well as performing few release kinetic measurements.

I would especially like to express my sincere gratitude to the following people for their help
either by doing the experiments for me or by providing me the necessary apparatus:
IIIMadhu Mallembakam for the viscosity and surface tension measurements and Prem Gorle, for
the laser light scattering measurements at the chair for particle science and technology. Dr.
Jochen Kaschta and Michelle Malter for SEC measurements at the institute of polymer
materials and Ulrike Marten-Jahns for XRD measurements, at the chair for surface science
and corrosion of the department of material science. Thanks to Jorge Wang for DSC
measurements at the chair for separation science and technology. Harish Vidya, Sucre
Cumana, Khaled, Sebastian Werner, Muhammad Irfan, Wei Wang for performing
microparticles preparation and release kinetic measurements.

The financial support from Evonik Degussa GmbH, while carrying this work is greatly
acknowledged.

I would not have made any progress without the support of my parents. The credit for my
study and research in Germany goes to my best friends Ganga Reddy, Praveen Reddy,
Rajashekar Reddy, and Ram Reddy.

Finally, I would like to express my deepest gratitude to my wife, Roopa Reddy Mallepally,
for sharing and enriching my life experiences, and for her love, affection and support.
IV

Index
1 INTRODUCTION AND OBJECTIVE......................................................................................................1
1.1 OBJECTIVE OF THE WORK...................................................................................................................... 2
2 THEORETICAL BACKGROUND ........................................................................................................... 4
2.1 MICROENCAPSULATION........................................................................................................................ 4
2.2 CONTROLLED RELEASE SYSTEMS.......................................................................................................... 6
2.2.1 Other applications of microencapsulation ...................................................................................... 7
2.3 MICROENCAPSULATION METHODS........................................................................................................ 7
2.4 TECHNIQUES USING ORGANIC SOLVENTS .............................................................................................. 9
2.4.1 Solvent evaporation method....... 9
2.4.2 Coacervation................................................................................................................................... 9
2.5 TECHNIQUES USING SUPERCRITICAL FLUIDS ....................................................................................... 10
2.5.1 Particles from gas saturated solutions..........................................................................................12
2.6 TECHNIQUES WITHOUT ORGANIC SOLVENTS 13
2.6.1 Melt dispersion method ................................................................................................................. 13
2.6.1.1 Droplet formation................................................................................................................................ 15
2.6.1.2 Properties of hyperbranched polymers ................................................................................................ 16
2.7 BIODEGRADABLE POLYMERS FOR DRUG DELIVERY............................................................................. 19
2.8 HYPERBRANCHED POLYMERS IN PHARMACEUTICAL AND BIOMEDICAL APPLICATIONS ....................... 20
2.8.1 Encapsulation with hyperbranched polymers ............................................................................... 20
2.8.2 Biodegradable polymers...... 23
2.8.2.1 Mechanism of biodegradation ............................................................................................................. 25
2.8.3 Biocompatibility ............................................................................................................................ 26
2.9 IN VITRO RELEASE KINETICS 27
2.9.1 Mechanisms of drug release.......................................................................................................... 27
2.9.2 Release of drug from erodible and biodegradable polymeric systems.......................................... 29
2.9.3 Mathematical modelling of the release kinetic data...................................................................... 30
2.10 GOAL OF THE THESIS........................................................................................................................... 31
3 MATERIALS AND METHODS.............................................................................................................. 32
3.1 MATERIALS ........................................................................................................................................ 32
3.1.1 Polymers........................................................................................................................................ 32
3.1.2 Drug substances............................................................................................................................ 33
3.1.3 Emulsifiers and surfactants........................................................................................................... 33
3.1.4 Solvents.................. 33
3.1.5 Lipases ........................................................................................................................ 33
3.2 EXPERIMENTAL METHODS .................................................................................................................. 34
3.2.1 Physicochemical properties determination ................................................................................... 34
3.2.2 Microparticles preparation and characterization......................................................................... 37
3.2.2.1 Preparation methods............................................................................................................................ 37
3.2.2.2 Characterization .................................................................................................................................. 39
3.2.3 In vitro release studies ...............................................................................................................