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This book reviews the history, regulatory status, pharmacopeial specifications, and harmonization of pharmaceutical excipients in the United States and Europe, and provides a comprehensive understanding of the current scientific basis for safety evaluation and risk assessment. Examines excipients as a unique class of products and explores new procedures for determining toxicity! A timely and unique addition to the pharmaceutical literature, containing over 570 citations that support and enhance the text, Excipient Toxicity and Safety ·identifies the differences between excipients (inactive ingredients), food ingredients, and drug products ·evaluates issues of dose administration, species selection, and study design for various routes of exposure ·provides detailed information on the historical uses of excipients in drug formulations ·clarifies the Safety Committee of the International Pharmaceutical Excipients Council's (IPEC) guidelines and technical specifications for conducting tests for each route of exposure ·explains how data generated in toxicity models are applied to identify hazards in drug formulations ·details exposure assessment to link hazard identification with risk ·considers the requirements and importance of purity specifications ·and much more! Excipient Toxicity and Safety is a blue-ribbon reference ideal for pharmacists; toxicologists; pharmacologists; analytical chemists; quality control, quality assurance, and regulatory compliance managers; and upper-level undergraduate and graduate students in these disciplines.
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ISBN: 0-8247-8210-0 This book is printed on acid-free paper. Headquarters Marcel Dekker, Inc. 270 Madison Avenue, New York, NY 10016 tel: 212-696-9000; fax: 212-685-4540 Eastern Hemisphere Distribution Marcel Dekker AG Hutgasse 4, Postfach 812, CH-4001 Basel, Switzerland tel: 41-61-261-8482; fax: 41-61-261-8896 World Wide Web http:/ /www.dekker.com The publisher offers discounts on this book when ordered in bulk quantities. For more information, write to Special Sales/Professional Marketing at the headquarters address above. Copyright 2000 by Marcel Dekker, Inc. All Rights Reserved. Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, microfilming, and recording, or by any information storage and retrieval system, without permission in writing from the publisher. Current printing (last digit): 10 9 8 7 6 5 4 3 2 1 PRINTED IN THE UNITED STATES OF AMERICA Foreword Since the 1960s the producers of excipients and the drug dosage form formulation industry and regulators have slowly gained an appreciation of excipients and their specialized needs as distinct entities. There is a growing appreciation of the role that pharmaceutical excipients play in the production, shelf stability, dispensability, patient dosage acceptability, bioavailability, and delivery of the active pharmaceutical ingredient to the target organ. As the late Dr. Shangraw, Professor of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, pointed out (Pharmaceutical Technology, June 1997), when I was starting out in the field, years ago, virtually all excipients were of natural origin—as either foods, food additives, or simple inorganics. They were supplied primarily by food producers or chemical suppliers. During the 1950s and 1960s development of excipients began to accelerate in the industry. The need for reproducible disintegration, dissolution, and bioavailability began to be recognized. Since available excipients were natural or well-known compounds, without obvious physiological activity, excipients were universally considered inactive and inert. Work during the 1960s alerted us to tablets, which transversed the gastrointestinal tract intact. Thus, the ‘‘reproducible’’ rate and extent of disi