Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 Physiological Pharmaceutics Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 With all our love For Alexander and Sarina Physiological Pharmaceutics Barriers to drug absorption Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 Second Edition Neena Washington, Clive Washington and Clive G.Wilson First edition 1989 Second edition first published 2001 by Taylor and Francis 11 New Fetter Lane, London EC4P 4EE Simultaneously published in the USA and Canada by Taylor and Francis Inc, 29 West 35th Street, New York, NY 10001 Taylor and Francis is an imprint of the Taylor & Francis Group This edition published in the Taylor & Francis e-Library, 2003. Publisher’s Note Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 This book has been prepared from camera-ready copy provided by the authors. © 2001 Neena Washington, Clive Washington and Clive G.Wilson All rights reserved. No part of this book may be reprinted or reproduced or utilised in any form or by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying and recording, or in any information storage or retrieval system, without permission in writing from the publishers.
Every effort has been made to ensure that the advice and information in this book is true and accurate at the time of going to press. However, neither the publishers nor the authors can accept any legal responsibility or liability for any errors or omissions that may be made. In the case of drug administration, any medical procedure or the use of technical equipment mentioned within this book, you are strongly advised to consult the manufacturer’s guidelines. British Library Cataloguing in Publication Data A catalogue record is available for this book from the British Library Library of Congress Cataloguing in Publication Data Washington, Neena, 1961– Physiological pharmaceutics: barriers to drug absorption/Neena Washington, Clive Washington, and Clive George Wilson.
Physiological pharmaceutics: biological barriers to drug absorption/Clive George Wilson, Neena Washington. “Simultaneously published in the USA and Canada.” Includes bibliographical references and index. Drugs—Dosage forms. Drugs—Physiological transport.
Washington, Clive, 1957– II. Wilson, Clive George. Wilson, Clive George. Physiological pharmaceutics: biological barriers to drug absorption.7–dc21 ISBN 0-203-48370-7 Master e-book ISBN ISBN 0-203-79194-0 (Adobe eReader Format) ISBN 0-748-40610-7 (hbk) ISBN 0-748-40562-3 (pbk) PREFACE Considering the variety in the human race, height, weight, temperament, enzymatic capacity, it is amazing that pharmaceuticals work at all.
Add environmental factors, and personal preferences, and suddenly you begin to realise the scale of the problem. Some years ago I ran a clinical trial in patients with ulcerative colitis. When I was recruiting the subjects, I asked people to keep a diary of everything that they ate. Even within the catchment area of Queen’s Medical Centre in Nottingham, the diversity of food eaten, let alone the frequency of eating, was beyond comprehension.
This led me to think about the world outside Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 Nottingham, eating habits within the UK, the north/south divide (which we are assured by the Government does not exist) let alone what people eat in Africa, China, Fiji.?? Then remember that medication is designed for sick people, who by definition have a physiology disordered in some way. So how can one pill fit all? The development work is aimed at the “average” patient. Is there such a thing as an average patient? Is the “average” person really a 70 kg man? In the U. 41% of males and 20% of females are overweight.
Even the “average” healthy woman may be excluded from pharmacokinetic trials not only due to the risk of potential genetic damage to reproductive tissue but also a tacit admission that the menstrual cycle may affect not only gastrointestinal transit, but also a wide range of physiological processes. This leaves basic data concerning the behaviour of drugs in women largely undiscovered until they are treated as patients. The realisation that the USP dissolution test bore little resemblance to dosage form behaviour in the body, particularly for the new sophisticated dose forms, led to the first edition of this book being written ten years ago. Over the past 30 years, a predominant focus of drug delivery has been the development of sustained and controlled release formulations, whose interaction with the body is even more critical and complex than that of ‘ordinary’ tablets.
In 1996 there were 35 pharmaceutical products based on advanced drug delivery with a worldwide sales often million US dollars each or higher; this was 11 more than in 1994. In these two years total sales had increased from 5. Four products were responsible for more than half of the total sales in 1996; these were ProcardiaXL (nifedipine), Lupron (leuprolide), Cardizem (diltiazem) and Zoladex (goserelin). The primary goals are usually to minimise the dose of drug administered and to optimize the delivery of the drug, to achieve an ‘ideal’ plasma-concentration time profile.
An added advantage is that simplification of the dosage regimen leads to increased patient compliance by reducing the number of daily doses. With the new requirement to deliver drugs to precise locations of the gastrointestinal tract came the need to study physiological variations in gastrointestinal transit, such as those brought about by eating, levels of physical activity and chronobiological effects. The focus on once-a-day dosing necessitated larger payloads of drugs per unit than conventional counterparts. Premature release of the drug could have potentially disastrous effects, so prediction of dosage form behaviour needs to be accurate.
With the leap in the number of sophisticated technologies reaching the market place the amount of literature which has become available since 1990 is considerable, and hence the second edition of “Physiological Pharmaceutics” is a complete re-write and not just an update. We are very aware that people placed advance orders for this book and we would like to thank them for buying it on faith. We also would like to thank them for their patience and we hope that they feel that the wait was worthwhile. We would like to thank our v vi Preface publishers, who I am sure, at times, thought the manuscript was a figment of the imagination (either theirs or ours).
Ironically, the first draft of the manuscript was delivered to them 3 years to the day late. By way of an explanation for the tardiness of this book, I would like you to realise that this book was written in “our spare time”, as if scientists with full time jobs and a young family have “spare time”! The university obsession with the research assessment exercise has made the production of textbooks a rather low priority, so much of the volume has been written after 11 at night! For this very reason I would like to thank our children, Alex (9 years) and Sarina (4 years) for their patience whilst mummy was writing or daddy was drawing diagrams, and Alex for ‘helping’ with the diagrams…We are painfully aware that it is they who have suffered as we have had virtually no time for them, particularly over the last year. As I write Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 this, they know that the “end of book” promised trip to LegoLand is coming closer! I also must thank my friends and colleagues, Drs Caroline Herd, Mike Nassim, Gerry Hooper and Carol Astbury for their caring and support. I would also like to thank my husband, who saw the vast amount of work which needed to be done on the book and mucked in.
In acknowledgement of his substantial contribution,we made him a full author on this edition. Without him, the book would probably have been 6 years late! Neena Washington 14th February 2000 FIGURE ACKNOWLEDGEMENTS Fig 1.13 is reprinted from Volkheimer G et al. with the permission of the BMJ Publishing Group.4 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.5 is reprinted from Pimlott & Addy, Oral Surg. with the permission of Mosby.6 is reprinted from Squier CA & Johnson NW, British Medical Bulletin 1975; 31:169 with the Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 permission of Christopher A Squier.8 is reprinted from Wilson CG et al., Int J Pharm 1987; 40:119–123 with the permission of Elsevier Science.9 is reprinted from Davis SS et al, In: Modern Concepts in Nitrate Delivery Systems, Goldberg AAJ & Parson DG (eds) pp29–37 (1983) with the permission of Pharmaceutical Press.6 is reprinted from Wilson CG et al.
1988; 46:241–46 with the permission of Elsevier Science.7 is reprinted from Kikendall JW et al. 1983; 28:174–182 with the permission of Kluwer Academic/Plenum Publisher.8 is reprinted from Weinbeck M et al, Bailliere’s Clin. 1988; 2:263–274 with the permission of Harcourt Publishers Ltd.1 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.6 is reprinted from Johnson LR (ed), Gastrointestinal physiology, 3rd edition (1985) with the permission of W.7 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.11 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.13 is reprinted with thanks to Dr Wright of the Department of Surgery, Queen’s Medical Centre, Nottingham, UK.15 is reprinted from Goo RH et al, Gastroenterol. 1987; 93:515–518 with the permission of W.17 is reprinted from O’Reilly S et al.
1987; 34:213–216 with the permission of Elsevier Science.19 is reprinted from O’Reilly S et al. 1987; 34:213–216 with the permission of Elsevier Science.20 is reprinted from Meyer JH et al. 1985; 88:1502 with the permission of W.1 is reprinted from Moog F., The lining of the small intestine. Scientific American 1981; 245:154–158 with the permission of Carol Donner.2 is reprinted from Weiner D, Chapter 43 in: Biological Foundations of Biomedical Engineering, Kline J (ed) (1976) with the permission of Lippincott Williams & Wilkins and D Weiner.4 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.
vii viii Acknowledgements Fig 6.5 is reprinted from Johnson LR (ed), Gastrointestinal Physiology, 3rd edition (1985) with the permission of W.7 is reprinted from Davis SS et al. 1987; 34:253–8 with the permission of Elsevier Science.8 is reprinted from Davis SS et al., Gut 1986; 27:886–892 with the permission of the BMJ Publishing Group.10 is reprinted from Fischer W et al, Pharm. 1987; 4:480–485 with the permission of Kluwer Academic/Plenum Publisher.11 is reprinted from Bechgard H et al. 1985; 37:718–721 with the permission of Pharmaceutical Press.12 is reprinted from Schinkel AH, Adv.
Rev 1999; 36:179–194 with the Downloaded by [Saudi Digital Library] at 09:33 30 January 2014 permission of Elsevier Science.1 is reprinted from Sanford PA, Digestive System Physiology (1982) with the permission of Arnold.2 is reprinted from Krstic RV, Human Microscopic Anatomy (1991) with the permission of Springer-Verlag.3 is reprinted from Stephen AM et al. 1986; 56:349–361 with the permission of CABI Publishing.4 is reprinted from Washington N et al., Moderation of lactulose induced diarrhoea by psyllium: effects on motility and fermentation Am. 1998; 67:317–321 with the permission of The American Society for Clinical Nutrition.5 is reprinted from Davis et al., Relationship between the rate of appearance of oxprenolol in the systemic circulation and the location of an oxprenolol Oros 16/260 drug delivery system within the gastrointestinal tract as determined by scintigraphy. 1988; 26:435–443 with the permission of Sage Publications Inc.6 is reprinted from Hardy JG et al.
1985; 37:874–877 with the permission of Pharmaceutical Press.7 is reprinted from Hardy JG et al. 1985; 37:874–877 with the permission of Pharmaceutical Press.9 is reprinted from Tozer, T., Kinetic perspectives on colonic delivery. 1990; 17:126 with the permission of the Controlled Release Society.11 is reprinted from Tukker J, Ph.D thesis, University of Leiden 1983 with the permission of J Tukker.12 is reprinted from Wood E et al. 1985; 25:191–197 with the permission of Elsevier Science.13 is reprinted from van Hoogdalem E., Pharmacokinetics of rectal drug administration.
Part I—general considerations and clinical applications of centrally acting drugs.