Microsystems for Pharmatechnology

Microsystems for Pharmatechnology

Andreas Dietzel Editor Microsystems for Pharmatechnology Manipulation of Fluids, Particles, Droplets, and Cells

Editor Andreas Dietzel Institute of Microtechnology Technische Universität Braunschweig PVZ Center of Pharmaceutical Engineering Technische Universität Braunschweig ISBN 978-3-319-26918-4 ISBN 978-3-319-26920-7 (ebook) DOI 10.1007/978-3-319-26920-7 Library of Congress Control Number: 2015958783 Springer Cham Heidelberg New York Dordrecht London Springer International Publishing Switzerland 2016 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. Printed on acid-free paper Springer International Publishing AG Switzerland is part of Springer Science+Business Media (www.springer.com)

Preface As the world becomes increasingly concerned about affordable health care, fast and effective screening methods for drugs in different formulations are required in the course of their development. Moreover, a more personalized medicine demands production of drugs in very small volumes. For both, the microfluidic approach seems ideally suited. With miniaturized systems that can be realized by microfabrication processes, new tools for research and development but also new products become available. New and better technologies for screening, for production by micro-reaction technology and micro-bioreactors, for small-scale processing of drug formulations, as well as for drug delivery are under development. Interdisciplinary research involving typical engineering disciplines and life science disciplines is the key for a further development of this field. This challenge has been accepted by the Center of Pharmaceutical Engineering (PVZ) of the TU Braunschweig established in 2012 where research groups from the pharmaceutical sciences, from biology, from process engineering, and from microtechnology intensively collaborate. Many but not all chapters of this book are written by authors active in this research center. The book shall provide a comprehensive state-of-the-art review of microfluidic approaches and applications in pharma technology. It shall help students and postgraduate students with an interdisciplinary interest from both the pharmaceutical field and the engineering field but also process developers in the pharmaceutical industry and scientists with an overview of technologies and applications in this growing field of research. I am grateful to all the authors for their excellent contributions to this book. I want to thank the management team of the PVZ, in particular Christel Müller- Goymann and Arno Kwade, the key persons to bring their vision and ideas into the reality of the new research center PVZ and Heike Bunjes, with whom I enjoy leading the postgraduate program μ-props in which topics of this book continue in ongoing research. Special thanks go to Sabine Kral-Aulich who far in excess of what I could expect helped me in completing the book by keeping contact with the v

vi Preface authors and with the publisher and by working on all the details and adjustments necessary to bring the manuscripts and this book into a suitable format without losing her patience. September 2015 Andreas Dietzel

Contents 1 A Brief Introduction to Microfluidics... 1 A. Dietzel 2 Fabrication of Microfluidic Devices... 23 M. Leester-Schädel, T. Lorenz, F. Jürgens, and C. Richter 3 Surface Functionalization of Microfluidic Devices... 59 M. Eichler, C.-P. Klages, and K. Lachmann 4 Microbioreactors... 99 R. Krull, S. Llad o Maldonado, T. Lorenz, S. Demming, and S. Büttgenbach 5 Microsystems for Emulsification... 153 H. Bunjes and C.C. Müller-Goymann 6 On-Chip Fabrication of Drug Delivery Systems... 181 M. Windbergs 7 Microsystems for Dispersing Nanoparticles... 197 C. Schilde, T. Gothsch, S. Beinert, and A. Kwade 8 Particles in Microfluidic Systems: Handling, Characterization, and Applications... 221 T.P. Burg 9 Respiratory Drug Delivery... 257 H. Wachtel vii

viii Contents 10 Drug Delivery Through Microneedles... 275 R. Luttge 11 Organ on Chip... 299 N. Beißner, T. Lorenz, and S. Reichl Index... 341

Contributors S. Beinert TU Braunschweig, Institut für Partikeltechnik, Braunschweig, Germany N. Beißner Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, H. Bunjes Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, T.P. Burg Max Planck Institute for Biophysical Chemistry, G ottingen, Germany S. Büttgenbach IMT Institute of Microtechnology, Technische Universität Braunschweig, S. Demming IMT Institute of Microtechnology, Technische Universität Braunschweig, Global Technology Chemical Intermediates, BASF SE, Ludwigshafen, Germany A. Dietzel IMT Institute of Microtechnology, Technische Universität Braunschweig, Braunschweig, M. Eichler Fraunhofer IST Institute for Surface Engineering and Thin Films, T. Gothsch TU Braunschweig, Institut für Partikeltechnik, Braunschweig, Germany ix

x Contributors F. Jürgens IMT Institute of Microtechnology, Technische Universität Braunschweig, C.-P. Klages IOT Institute of Surface Technology, Technische Universität Braunschweig, Braunschweig, R. Krull IBVT Institute of Biochemical Engineering, Technische Universität Braunschweig, A. Kwade TU Braunschweig, Institut für Partikeltechnik, Braunschweig, Germany Braunschweig, K. Lachmann Fraunhofer IST Institute for Surface Engineering and Thin Films, M. Leester-Schädel IMT Institute of Microtechnology, Technische Universität Braunschweig, T. Lorenz IMT Institute of Microtechnology, Technische Universität Braunschweig, R. Luttge Department of Mechanical Engineering, Microsystems Group and ICMS Institute for Complex Molecular Systems, Eindhoven University of Technology, Eindhoven, The Netherlands MESA+ Institute for Nanotechnology, University of Twente and MyLife Technologies BV, Enschede, The Netherlands S. Llad o Maldonado IBVT Institute of Biochemical Engineering, Technische Universität Braunschweig, C.C. Müller-Goymann Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, S. Reichl Institut für Pharmazeutische Technologie, Technische Universität Braunschweig, Braunschweig, C. Richter IMT Institute of Microtechnology, Technische Universität Braunschweig, C. Schilde TU Braunschweig, Institut für Partikeltechnik, Braunschweig, Germany

Contributors xi H. Wachtel Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany M. Windbergs Department for Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany Helmholtz Centre for Infection Research (HZI), Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Saarbrücken, Germany