/Nimlaeceyeltcas(elamcomn Celltatcer)| Pharmaceutics Alexander T Florence An Introduction to Clinical Pharmaceutics An Introduction to Clinical Pharmaceutics Alexander T. Florence Emeritus Professor “The Schoo! of Pharmacy, University of London, UK P) lenin «Cheose Pharmaceutical Press Published by Pharmaceutical Press 1 Lambeth High Stret, London SE1 7JN, UK 1559 St Paul Avenve, Gurnee, IL 60031, USA (© Pharmaceutical Press 2010 (BP) is a tcade mark of Pharmaceutical Press Pharmaceutical Press the publishing division of the Royal Pharmaceutical Society of Great Britain First published 2010 ‘Typeset by Thomson Digital, Noida, India Printed in Great Britain by'T} International, Padstow, Cornwall ISBN 978 0 85369 6919 Allright reserved, No par of this publication may be reproduced, sored ina retrieval system, or transmitted in any form of by any means, without the prior writen permission ofthe copyright holder. “The publisher makes no epresentation, express or implied, with regacd to the sccuracy ofthe information contained inthis book and eaanot accept aay legal responsibility or ibility for any errors or omissions that may be made. The right of Alexander T Florence tobe identified as the author of this work has been aserted by him in accordance with the Copyright, Designs and Patents Act, 1988. A catalogue record for this book is availabe from the British Library. Preface ix Introduction xi Book outline ~ ‘About the author >i 1. Whats clinical pharmaceutics? 1 Introduction 1 Physical concepts 2 ‘The nature of the dosage form and outcomes 18 Quality of effect 19 Ingredients in dosage forms and their influence on outcomes 22 Conclusion B References 24 2 Excipients: Not always inert 2 Introduction 7 Usually but not always inert 7 E-numbers 31 Cross-reactivity 33 Dyes used in lymph node identification 3 Norvionic surfactants 33 Polyoxyethylene glycols (PEGs) 35 “Adjuvants as therapeutic substances 35 Talc 2s therapeutic agent and excipient 37 Active excipients in muitioe therapies 39 Conclusions 39 References 39 3° Thinking chemically a Introduction 41 ‘The chemistry of drugs and clinical pharmaceutics 2 | Contents Chemical nomenclature Surface-active drugs ‘Acids and bases Structural similarities between drugs Cross-reactivity Betalactam antibiotics and the formation of oligomers The bisphosphonates Hydrophobic and hydrophilic statins Photochemical reactions and photoinduced reactions Chelation and tetracyclines Sugammedex: a cyclodextrin derivative Conclusions References Looking at formulations Introduction Protein drugs and formulations Monoclonal antibodies (MAbs) ‘Amphotericin 8 formulations ‘A doxorubicin formulation: Doxil ‘A propofol formulation: Diprivan Long-acting depot injections Raft-producing oral formulations Etoposide (Vepesid, VP 16 and etoposide phosphate) Paclitaxel Eutectic mixtures of local anaesthetics iclospotin (cyclosporin) Lupron Depot; Prostap SR and Prostap 3 Zoladex Fluoroquinolone eye drops lonsys: lontophoretic transdermal device for fentanyl Parenterals Chloramphenicol Materials used in drug delivery Conclusions References ‘Adverse events and formulations and devices Introduction Dosage form type Reactions to impurities Contents | il Abnormal bioavailability, high or low "4 Testing for adverse effects 14 Nanosysters 116 Conclusions 18 References 19 6 Paediatric, geriatric and special formulations 121 Introduction 121 Extemporaneous formulations 122 Effect of formulation and presentation: a case from the literature 124 Extemporaneous formulations and performance 126 ‘The elderly and their medication 126 Enteral feeding 128 Drug interactions with nutrient formulations 131 Conclusions 131 References 131 7 Generic medicines: Conventional drugs and biologicals 133 Introduction 133 Regulatory statements on generic products 134 Generics: A question of quality 135 Specific conditions and generics 137 Reading and deconstructing the Iterature on bioequivalence 139, Antiretroviral drugs 139 Bioequivalence of ophthalmic products 141 The case of sevoflurane 141 Generic biolagicals (biologics) 144 Conclusions 146 References 148 8 The future: Delivery systems for modern therapeutics 151 Introduction 151 Personalised medicine and medicines 151 Drug delivery and personalised medicines 152 Technologies 155 Nanotechnology 160 Call-based therapies 165 Gene therapy 168 Conclusions 169 References 169 Index 173 ‘This book has had a long period of gestation. I made a proposal for such as this in 1982 to Robert Campbell of Blackwell Scientific Publi Ltd. He encouraged me to write it, provided it was ‘reasonably short and inexpensive.’ Over the intervening years in collaboration with David Attwood, four editions of Physicochemical Principle of Pharmacy appeared, the latest in 2006 and the concise version, FASTerack: Physical Pharmacy in 2008. We also co-wrote Surfactant Systems published in 1983. These and ‘other activities took over and the present book obviously did not materialise. But it has always remained an ambition to complete it, especially as the pharmacy scene has been changing and some subjects are now under pressure of one kind and another, in spite of the four-year degree programme. A few subjects such as pharmaceuties and pharmaccutial chemistry appear to nota {ew students to be too far away from real practice. Well it depends on how we define practice and what practice will look like in the future. ‘Themain premise ofthe bookis that the subject matter of pharmaceutics is relevant far beyond the confines of the laboratory and pharmaceutical indus- ty. Undergraduate and postgraduate lectures that Ihave given over the years incorporated many of the concepts espoused in this book. Ie was not until retirement from the Deanship of the School of Pharmacy, University of London in 2006 that there was some more time to write this book. Itis not meant to be a compendium, nor is it for advanced practitioners, but more a primer that I hope will encourage readers to think about the principles of applying basic scientific facts to solving problems in medication. If it provides ‘a single insight to any student or practitioner that enables the solution of one ‘medication conundrum, i wll have been worth it. A warning itis not written inthat linear style that has been the bane of many subject, as ittakes too long from the very frst principle o get to the application or the problem. The basics are covered in AT Florence and D Attwood, Pharmaceutical Principles of Pharmacy, 4th edition, 2006 or D Attwood and AT Florence, Physical Pharmacy 2007, both published by the Pharmaceutical Press.