Advances in Pharmaceutical Sciences Volume 7 This Page Intentionally Left Blank Advances in Pharmaceutical Sciences Volume 7 edited by David Ganderton King’s College, London Trevor Jones The Association of the British Pharmaceutical Industry, London and James McCinity College of Pharmacy, The University of Texas at Austin, USA ACADEMIC PRESS Harcourt Brace and Company, Publishers London San Diego . New York Tokyo . Toronto . Boston * Sydney ACADEMIC PRESS LIMITED 24-28 Oval Road London NWI 7DX United States Edition published by ACADEMIC PRESS INC. San Diego, CA 92101 Copyright 0 1995 by ACADEMIC PRESS LIMITED A// Rights Reserved No part of this book may be reproduced in any form by photostat, microfilm, or any other means, without the written permission from the publishers This book is printed on acid-free paper A catalogue record for this book is available from the British Library ISBN 0-12-032307-9 Filmset by Colset Pte Ltd and printed in Great Britain by Hartnolls Ltd, Bodmin, Cornwall CONTRIBUTORS J. G. Nairn Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada H. G. Kristensen Department of Pharrnaceutics, The Royal Danish School of Pharmacy, Copenhagen, Denmark R. J. Roberts ZENECA Pharmaceuticals, Macclesfield, Cheshire, UK R. C. Rowe ZENECA Pharmaceuticals, Macclesfield, Cheshire, UK A. Urtti Department of Pharmaceutical Technology, University of Kuopio, P.O. Box 7627, 70277 Kuopio, Finland This Page Intentionally Left Blank CONTENTS Contributors V Preface ix 1 The mechanical properties of powders 1 R. C. Rowe and R. 1. Roberts 2 Kinetic aspects in the design of prolonged action ocular drug delivery systems 63 A. Urtti 3 Coacervation-phase separation technology J. G. Nairn 4 Particle agglomeration 93 221 H. G. Kristensen Index 273 This Page Intentionally Left Blank PREFACE Like its predecessors, Volume 7 of Advances in Pharmaceutical Sciences presents critical evaluations of current research and development in selected fields of pharmaceutical technology. It reflects, in particular, two activities vital to the industry. The first is the provision of a better understanding of well-established processes. This provides both a rationale for further exploitation and a secure basis for the management of quality. The contributions of Rowe, Roberts and Kristensen, all world authorities in the field of powder technology, exemplify this principle with major contributions which displace much of the empiricism associated with the characterization of powders and agglomeration. The second major contribution of pharmaceutical technology lies in refined drug delivery. This is founded on a mastery of physico-chemical principles which are then related to clinical practice through pharmacokinetics. The first part of this sequence is illustrated in Nairn’s comprehensive review, which assesses the considerable contribution of coacervation techniques, and the second by Urtti’s account of the pharmacokinetics of ocular drug delivery. These accounts provide a strong base for rational product development and future invention. D. Ganderton Kings College, London T. M. Jones The Association of the British Pharmaceutical Industry J. W. McGinity The University of Texas at Austin ix This Page Intentionally Left Blank THE MECHANICAL PROPERTIES OF POWDERS R.C. Rowe and R.J. Roberts ZENECA Pharmaceuticals, Macclesfield, Cheshire, UK INTRODUCTION The vast majority of drugs, when isolated, exist as crystalline or amorphous solids. Subsequently, they may be either milled (comminuted) and/or admixed with other inac