Inhaler devices © Woodhead Publishing Limited, 2013 Related titles: Drug- device combination products: Delivery technologies and applications (ISBN 978-1-84569-470-8) Coatings for biomedical applications (ISBN 978-1-84569-568-2) Bioactive materials in medicine: Design and applications (ISBN 978-1-84569-624-5) D etails of these books and a complete list of titles from Woodhead Publishing can be obtained by: • visiting our web site at www.woodheadpublishing.com • contacting Customer Services (e- mail: [email protected]; fax: +44 (0) 1223 832819; tel.: +44 (0) 1223 499140 ext. 130; address: Woodhead Publishing Limited, 80, High Street, Sawston, Cambridge CB22 3HJ, UK) • in North America, contacting our US offi ce (e- mail: usmarketing@ woodheadpublishing.com; tel.: (215) 928 9112; address: Woodhead Publishing, 1518 Walnut Street, Suite 1100, Philadelphia, PA 19102-3406, USA) If you would like e-v ersions of our content, please visit our online platform: www. woodheadpublishingonline.com . 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Library of Congress Control Number: 2013930801 ISBN 978-0-85709-496-4 (print) ISBN 978-0-85709-869-6 (online) ISSN 2049-9485 Woodhead Publishing Series in Biomaterials (print) ISSN 2049-9493 Woodhead Publishing Series in Biomaterials (online) The publisher’s policy is to use permanent paper from mills that operate a sustainable forestry policy, and which has been manufactured from pulp which is processed using acid- free and elemental chlorine- free practices. Furthermore, the publisher ensures that the text paper and cover board used have met acceptable environmental accreditation standards. Typeset by Refi neCatch Limited, Bungay, Suffolk Printed by MPG Printgroup, UK © Woodhead Publishing Limited, 2013 Contents Contributor contact details ix Woodhead Publishing Series in Biomaterials xi Preface xv Part I Fundamentals and considerations of inhaler devices 1 1 Anatomy and pathophysiology of the respiratory system 3 E. CA LLARD P REEDY and P. P ROKOPOVICH , Cardiff University, UK 1.1 Introduction 3 1.2 Functional anatomy 4 1.3 Pathophysiology 7 1.4 Analysis of pathophysiology 10 1.5 References 12 2 History of inhaler devices 13 E. CA LLARD P REEDY and P. P ROKOPOVICH , Cardiff University, UK 2.1 Introduction 13 2.2 Structure and function of the lungs 15 2.3 Inhalers and successful therapy 17 2.4 Nebulisers 19 2.5 Pressurised metered-dose inhalers (pMDIs) 22 2.6 Dry powder inhalers 25 2.7 Future trends 26 2.8 References 27 3 Tribology of inhaler devices and components 29 P. P ROKOPOVICH , Cardiff University, UK 3.1 Introduction 29 3.2 Design and principles of pressurised metered-dose inhalers (pMDIs) 30 3.3 Friction and lubrication within inhaler devices 30 3.4 Measuring friction between pMDI components 33 3.5 References 35 v © Woodhead Publishing Limited, 2013 vi Contents 4 Novel coatings and biotechnology trends in inhaler devices 37 E. CA LLARD P REEDY and P. P ROKOPOVICH , Cardiff University, UK 4.1 Introduction 37 4.2 Current trends in inhaler devices 39 4.3 Novel coatings 41 4.4 Biotechnology 43 4.5 References 48 5 Microbial control and safety in inhalation devices 51 S. P ERNI , University of Birmingham, UK 5.1 Microbial cells 51 5.2 Growth of microorganisms in the environment 51 5.3 Microbial inactivation 63 5.4 Microbial contamination control 69 5.5 Keeping inhalers microbiologically safe 71 5.6 References 72 Part II Drug formulations for inhaler devices 75 6 Chitosan and inhalers: a bioadhesive polymer for pulmonary drug delivery 77 R. H ARRIS , N. A COSTA and A. H ERAS , Complutense University of Madrid, Spain 6.1 Introduction 77 6.2 Chitosan- based inhaler drug delivery systems 78 6.3 The absorption enhancing effect of chitosan 79 6.4 Types of particle systems used in inhalers 81 6.5 Inhaler formulations based on chitosan and chitosan derivatives 82 6.6 Conclusions 88 6.7 References 89 7 Polyelectrolyte assemblies for drug storage and delivery: multilayers, nanocapsules and multicapsules 94 E. G UZMÁN , National Research Council, Italy and M. RU ANO , R. G. RU BIO and F. O RTEGA , Complutense University of Madrid, Spain 7.1 Introduction 94 7.2 Layer-by-layer (LbL) multilayers for drug delivery applications: planar polyelectrolyte multilayers and capsules 97 7.3 Assembling of layer-by-layer multilayers 99 7.4 Variables affecting the electrostatic self- assembling 111 © Woodhead Publishing Limited, 2013 Contents vii 7.5 Properties of polyelectrolyte multilayers of interest in drug delivery 116 7.6 Encapsulation approximations 118 7.7 Encapsulating bioactive molecules 121 7.8 Strategies for releasing encapsulated drugs 124 7.9 Layer-by-layer capsules in drug delivery applications 128 7.10 Layer-by-layer capsules and inhalers 131 7.11 Conclusions 131 7.12 Acknowledgements 132 7.13 References 132 8 Functionalized core- shell nanoparticles for medical applications 146 E. M ILEVA and B. S OKLEV , Bulgarian Academy of Sciences, Bulgaria, V. M ICHAILOVA , Medical University, Bulgaria and D. A RABADZHIEVA , Bulgarian Academy of Sciences, Bulgaria 8.1 Introduction 146 8.2 New insights into copolymer–NSAID interactions 148 8.3 Materials and methods of interfacial and bulk studies of copolymer– drug aqueous systems 149 8.4 Experimental results and implications for intake and release mechanisms 150 8.5 Conclusions 166 8.6 Acknowledgements 167 8.7 References 167 Index 171 © Woodhead Publishing Limited, 2013 Contributor contact details (* = main contact) Editor and Chapter 3 Chapter 5 Dr Polina Prokopovich Dr Stefano Perni School of Pharmacy and School of Chemical Engineering Pharmaceutical Sciences University of Birmingham Cardiff University Edgbaston Redwood Building Birmingham King Edward VII Avenue B15 2TT Cardiff UK CF10 3NB Email: [email protected] UK Email: [email protected] Chapter 6 Ruth Harris, Niuris Acosta and Chapters 1, 2 and 4 Angeles Heras* Emily Callard Preedy and Dr Polina Institute for Biofunctional Studies Prokopovich* Department of Physical Chemistry School of Pharmacy and Faculty of Pharmacy Pharmaceutical Sciences Complutense University of Madrid Cardiff University Paseo Juan XXIII, 1 Redwood Building Madrid 28040 King Edward VII Avenue Spain Cardiff Email: [email protected] CF10 3NB UK Email: [email protected] and Dr Polina Prokopovich School of Engineering Cardiff University UK ix © Woodhead Publishing Limited, 2013