University of Groningen

University of Groningen

Blends of trehalose and pullulan to stabilize biopharmaceuticals in alternative dosage forms:

orodispersible films and dissolving microneedles Tian, Yu

DOI:

10.33612/diss.135502200

IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below.

Document Version

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Publication date:

2020

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Tian, Y. (2020). Blends of trehalose and pullulan to stabilize biopharmaceuticals in alternative dosage forms: orodispersible films and dissolving microneedles. University of Groningen.

https://doi.org/10.33612/diss.135502200

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Blends of trehalose and pullulan to stabilize biopharmaceuticals in alternative dosage forms:

orodispersible films and dissolving microneedles

Yu Tian

Paranymphs Annemarie Broesder Mei Li

Cover design: Tingting Sun and Ridderprint BV Layout and printing: Yu Tian and Ridderprint BV

The research presented in this thesis was carried out at the Department pf Pharmaceutical Technology and Biopharmacy of the University of Groningen and financially supported by the China Scholarship Council (CSC). Printing of this thesis was financially supported from the University Library, the Graduate School of Science and Engineering of the University of Groningen.

©Copyright Yu Tian, 2020.

All rights reserved. No part of this publication may be reproduced, stored on a retrieval

system, or transmitted in any form or by any means, without permission of the author.

Blends of trehalose and pullulan to stabilize biopharmaceuticals in alternative dosage forms: orodispersible films and dissolving microneedles

PhD thesis

to obtain the degree of PhD at the University of Groningen

on the authority of the Rector Magnificus Prof. C. Wijmenga

and in accordance with the decision by the College of Deans.

This thesis will be defended in public on Friday 23 October 2020 at 9.00 hours

by

Supervisor

Prof. dr. H.W. Frijlink

Co-supervisor

Dr. W.L.J. Hinrichs

Assessment Committee

Prof. E. Mastrobattista

Prof. H.J. Heeres

Prof. H.J. Haisma

TABLE OF CONTENTS

Chapter 1

Introduction and outline of this thesis 7

Chapter 2

Oromucosal films: from patient centricity to production by printing techniques 17 Chapter 3

Addition of pullulan to trehalose glasses improves protein stability at high moisture conditions 55 Chapter 4

Orodispersible films based on blends of trehalose and pullulan for protein delivery 79 Chapter 5

Development of an orodispersible film containing stabilized influenza vaccine 101 Chapter 6

Trehalose and pullulan based dissolving microneedles for intradermal delivery of influenza vaccines 127 Chapter 7

Summary, concluding remarks and perspectives 145 Appendices 157 Nederlandse samenvatting

Curriculum vitae 169

list of publications 170

Acknowledgements 173

CHAPTER 1

General introduction and scope of the thesis