Routes of Drug Administration

Routes of Drug Administration Edited by A. T. Florence PhD, DSc, FRSC, FRSE, FRPharmS The School of Pharmacy, University of London, London, UK and E. G. Salole BSc, PhD, MRPharmS Department of Pharmacy, University of Strathclyde, Glasgow, UK WRIGHT London Boston Singapore Sydney Toronto Wellington Wright is an imprint of Butterworth Scientific @l PART OF REED INTERNATIONAL RL.C. All rights reserved. No part of this publication may be reproduced in any material form (including photocopying or storing it in any medium by electronic means and whether or not transiently or incidentally to some other use of this publication) without the written permission of the copyright owner except in accordance with the provisions of the Copyright, Designs and Patents Act 1988 or under the terms of a licence issued by the Copyright Licensing Agency Ltd, 33-34 Alfred Place, London, England WCIE 7DP. Applications for the copyright owner's written permission to reproduce any part of this publication should be addressed to the Publishers. Warning: The doing of an unauthorised act in relation to a copyrigbht work may result in both a civil claim for damages and criminal prosecution. This book is sold subject to the Standard Conditions of Sale of Net Books and may not be re-sold in the UK below the net price given by the Publishers in their current price list. First published 1990 © Butterworth & Co. (Publishers) Ltd, 1990 British Library Cataloguing in Publication Data Routes of drug administration. 1. Medicine. Drug therapy I. Florence, A. T. (Alexander Taylor) II. Salole, E.G. (Eugene G) III. Series 615.6 ISBN 0-7236-0922-5 Library of Congress Cataloging-in-Publication Data Routes of drug administration/edited by A. T. Florence and E.G. Salole. p. cm.—(Topics in pharmacy; v. 2) Includes bibliographical references. ISBN 0-7236-0922-5 1. Drugs—Administration. I. Florence, A. T. (Alexander Taylor) II. Salole, E. G. III. Series. [DNLM: 1. Drug Administration Routes. QV 785 R869] RM147.R68 1990 615'.6—dc20 Composition by Genesis Typesetting, Laser Quay, Rochester, Kent Printed and bound in England by Page Bros. Ltd, Norwich, Norfolk Series preface There is, in our view, an important need to draw the attention of both students and practitioners concerned with drug therapy to recent and continuing developments in the pharmaceutical sciences. The purpose of the Topics in Pharmacy series is to fulfil this need by providing up-to-date, concise, readable accounts of current aspects of pharmacy - with particular emphasis on those aspects of the pharmaceutical sciences related to clinical practice. In this endeavour we have been fortunate in securing the collaboration of academics and practitioners recognized as experts in the subjects of their contributions. Each volume in the series has a theme, and each constituent chapter provides a concise account of a particular area; the accounts are intended to be introductions to a topic rather than comprehensive and complete reviews, and hence, wherever possible, each chapter is appended with a short bibliography for further study. The series is aimed at a readership comprising senior undergraduate and postgraduate students in pharmacy, medi cine, nursing and allied health sciences, and practitioners in these fields. However, it is our hope that the series will also be generally useful to other professionals concerned with the preparation and administration of medicines and the monitor ing of drug therapy. Alexander T. Florence, London Eugene G. Salole, Glasgow Preface Oral administration, the commonest and most convenient route for delivery of drugs to the systemic circulation, is not always the most suitable, for example in the elderly or the seriously ill. Indeed, the oral route may not be an option for systemic action of a range of drugs which are poorly absorbed from the gastrointestinal tract, through inappropriate intrinsic physical properties, degradation or metabolism. This volume, the second in the Topics in Pharmacy series, describes a number of parenteral routes of administration, some of which, such as the transder mal route, are increasingly finding favour as viable alternatives to the enterai route. Others such as the nasal and buccal routes will possibly find a place in therapy with a more limited group of drugs. The theme of Volume 1 of this series, the interaction of formulations with the biological milieu, is continued in this volume, as individual chapters review the anatomy and physiology of administration sites, the formulation and design of delivery systems and other relevant aspects of biopharma- ceutics. Dosage form behaviour in vivo has to be taken into account in the design of the delivery system. The success or failure of a system can depend on the anatomy of the route and the tailoring of the formulation to it. Nowhere is this better illustrated than in pulmonary delivery. This route and the nasal, buccal and transdermal routes of administration for systemic delivery are considered in this volume, as are a number of systems for more localized therapy with antibiotics. We are indebted to Professor Lawrence Danziger, Dr Stephen Farr, Professor Ian Kellaway, Dr Philip Lamey, Dr Michael Lewis, Dr Graham Parr, Dr Alan Rogerson, Professor Jill Shwed, Dr Glyn Taylor and Dr Kenneth Walters for their sustained interest and contributions to this book. Alexander T. Florence, London Eugene G. Salole, Glasgow vi Contributors L. H. Danziger, PharmD Assistant Professor of Pharmacy Practice, The University of Illinois at Chicago, USA S. J. Farr, BSc, PhD, MRPharmS Lecturer in Pharmaceutics, Welsh School of Pharmacy, University of Wales College of Cardiff, Cardiff, UK I. W. Kellaway, BPharm, PhD, MRPharmS Professor of Pharmaceutics, Welsh School of Pharmacy, University of Wales College of Cardiff, Cardiff, UK P.-J. Lamey, BSc, BDS, MBChB, DDS, FDS Senior Lecturer and Honorary Consultant in Oral Medicine & Pathology, University of Glasgow, Glasgow, UK; Visiting Professor of Stomatology, Baylor College of Dentistry, Dallas, Texas, USA M. A. O. Lewis, BDS, PhD, FDS Lecturer in Oral Medicine and Pathology, University of Glasgow, Glasgow, UK G. D. Parr, BSc, PhD, MRPharmS Group Head, Pharmaceutical Development, Reckitt & Colman Products Ltd, Hull, UK A. Rogerson, BSc, PhD, MRPharmS Senior Section Manager, Prescription Product Development, Reckitt & Colman Products Ltd, Hull, UK J. A. Shwed, PharmD Assistant Professor of Hospital Pharmacy Practice and Administration, Medical University of South Carolina, Charleston, USA vii viii Contributors G. Taylor, BSc, PhD, MRPharmS Lecturer in Pharmaceutics, Welsh School of Pharmacy, University of Wales College of Cardiff, Cardiff, UK K. A. Walters, PhD Director of Research & Development, Pharmaserve Ltd, Swinton, Manchester, UK 1 Nasal drug delivery A. Roger son and G. D. Parr Introduction In most mammals the major function of the nose is as an olfactory organ, and sense of smell has a vital role in activities as diverse as hunting, and recognizing young. In man, although its function is no longer vital to survival, the importance of the nose should not be underestimated: in the seventeenth century Blaise Pascal noted that 'if Cleopatra's nose had been shorter, the whole history of the world would have been different'! In its simplest form the nose is a passage through which air must pass en route to the lungs, and thus the modification of inspired air is probably its most important function in man. The nose consists of three distinguishable regions (Figures 1.1 and 1.2). The nostrils act to gather and direct air. Behind the nostrils lies the region which contains the convoluted turbinâtes and the nasal epithelium. This region leads into the nasopharynx, where the septum (which divides the nasal cavity into two halves) ends and the cavity becomes one. From the nostrils to the nasopharynx is generally a distance of c. 12-15 cm. When air is inspired it travels in an approximately parabolic pattern from the nostrils, upwards through the middle meatus, generally bypassing the turbinâtes, then downwards again through the nasopharynx (Figure 1.1). To pass into the nasal cavity, air must first be inspired with sufficient linear velocity to pass through the constriction of the nasal valve just beyond the nostrils. Within the central region of the nasal cavity lie the ciliated nasal epithelial cells. This region presents a barrier to the absorption of drugs and contaminants that is relatively thin (and unkeratinized, despite its continuity with the exterior) and well perfused by nasal blood vessels. However, any drug substance applied nasally would rarely come into prolonged intimate contact with the epithelial cell surface owing to the presence of mucus glands and goblet cells (Figure 1.3). Mucus is a glycoprotein which is stored within goblet cells in its dehy drated form (containing c. 5% water), and is then hydrated as it 1 Figure 1.1 A side view of the upper respiratory tract. In the diagram, the left-hand dashed line (just behind the nostrils) indicates the region of the nasal valve; the intermediate dashed line indicates the approximate region of the ciliated epithelial mucosa, which ends near the termination of the nasal septum at the pharynx (indicated by the right-hand dashed line) Figure 1.2 A frontal view of the nasal tract. The upper olfactory region (stippled area) is generally free from inspired air. The clear areas either side of the central nasal septum indicate the zone which is lined with absorptive epithelial cells and most accessible to inspired air Nasal drug delivery 3 Mucus Figure 1.3 Schematic representation of ciliated epithelium overlaid with discontinuous mucus and periciliary fluid. The cilia beat in periciliary fluid, with a velocity gradient which is greatest at their apex is released, swelling rapidly to form a layer (which may or may not be continuous) on top of the ciliated epithelial cells. Thus, mucus, which contains 95% water when fully hydra ted, is responsible for the protection of the nasal epithelium, as it normally prevents intimate contact of epithelial cells with inspired material.

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