Aulton's Pharmaceutics E-Book: The Design and Manufacture of Medicines

1627 Pages·2013·27.07 MB·english

by  Michael Aulton

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2015v1.0
Aulton’s Pharmaceutics
The Design and Manufacture
of Medicines
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Aulton’s
Pharmaceutics
The Design and Manufacture of Medicines
FIFTH EDITION
Edited by
Michael E. Aulton
BPharm PhD FAAPS FSP FRPharmS
Emeritus Professor, De Montfort University, Leicester, UK
Kevin M. G. Taylor
BPharm PhD FRPharmS
Professor of Clinical Pharmaceutics, UCL School of Pharmacy, London, UK
Edinburgh London New York Oxford Philadelphia St Louis Sydney Toronto 2018
© 2018 Elsevier Ltd. All rights reserved.
First edition 1988
Second edition 2002
Third edition 2007
Fourth edition 2013
Fifth edition 2018
No part of this publication may be reproduced or transmitted in any form or by any means, electronic
or mechanical, including photocopying, recording, or any information storage and retrieval system,
without permission in writing from the publisher. Details on how to seek permission, further
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organizations such as the Copyright Clearance Center and the Copyright Licensing Agency can be
found at https://www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the
publisher (other than as may be noted herein).
Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical treatment
may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described herein. In
using such information or methods, they should be mindful of their own safety and the safety of
others, including parties for whom they have a professional responsibility.
With respect to any drug or pharmaceutical products identified, readers are advised to check
the most current information provided (1) on procedures featured or (2) by the manufacturer of
each product to be administered to verify the recommended dose or formula, the method and
duration of administration, and contraindications. It is the responsibility of practitioners, relying
on their own experience and knowledge of their patients, to make diagnoses, to determine
dosages and the best treatment for each individual patient, and to take all appropriate safety
precautions.
To the fullest extent of the law, neither the publisher nor the authors, contributors, or editors
assume any liability for any injury and/or damage to persons or property as a matter of product
liability, negligence, or otherwise, or from any use or operation of any methods, products,
instructions, or ideas contained in the material herein.
ISBN 978-0-7020-7005-1
International Edition 978-0-7020-7003-7
Printed in China
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Contents
Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .viii
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xi
What is pharmaceutics? Michael E. Aulton and Kevin M. G. Taylor 1
1 Design of dosage forms Peter York 6
PART 1 Scientific principles of dosage form design
2 Dissolution and solubility Michael E. Aulton 18
3 Properties of solutions Michael E. Aulton 37
4 Surfaces and interfaces Graham Buckton 47
5 Disperse systems David Attwood 60
6 Rheology Christopher Marriott 93
7 Kinetics Gareth R. Williams 114
PART 2 Particle science and powder technology
8 Solid-state properties Graham Buckton 128
9 Particle size analysis Kevin M. G. Taylor 140
10 Particle size reduction and size separation Michael E. Aulton 158
11 Mixing Andrew M. Twitchell 172
12 Powder flow Michael E. Aulton 189
PART 3 Pharmaceutical microbiology and sterilization
13 Fundamentals of microbiology Geoffrey W. Hanlon 201
14 Pharmaceutical applications of microbiological techniques
Norman A. Hodges 227
15 Action of physical and chemical agents on microorganisms
Geoffrey W. Hanlon and Norman A. Hodges 250
16 Principles of sterilization Susannah E. Walsh and Jean-Yves Maillard 268
17 Sterilization in practice Jean-Yves Maillard and Susannah E. Walsh 278
PART 4 Biopharmaceutical principles of drug delivery
18 Introduction to biopharmaceutics Marianne Ashford 296
19 Gastrointestinal tract – physiology and drug absorption
Marianne Ashford 300
20 Bioavailability – physicochemical and dosage form factors
Marianne Ashford 319
v
Contents
21 Assessment of biopharmaceutical properties Marianne Ashford 339
22 Dosage regimens Soraya Dhillon, Nkiruka Umaru and John H. Collett 363
PART 5 Dosage form design and manufacture
23 Pharmaceutical preformulation Simon Gaisford 380
24 Solutions Sudaxshina Murdan 407
25 Clarification Andrew M. Twitchell 417
26 Suspensions Susan A. Barker 427
27 Emulsions and creams Gillian M. Eccleston 446
28 Powders, granules and granulation Michael E. Aulton 476
29 Drying Michael E. Aulton and Satyanarayana Somavarapu 498
30 Tablets and compaction Göran Alderborn and Göran Frenning 517
31 Modified-release oral drug delivery Emma L. McConnell and
Abdul W. Basit 564
32 Coating of tablets and multiparticulates Stuart C. Porter 580
33 Hard capsules Brian E. Jones 597
34 Soft capsules Keith G. Hutchison and Josephine Ferdinando 612
35 Dissolution testing of solid dosage forms Ana Cristina Freire and
Abdul W. Basit 626
36 Parenteral drug delivery Robert Lowe 638
37 Pulmonary drug delivery Kevin M. G. Taylor 653
38 Nasal drug delivery Gary P. Martin and Alison B. Lansley 671
39 Ocular drug delivery Hala Fadda, Ashkan Khalili, Peng Tee Khaw,
and Steve Brocchini 690
40 Topical and transdermal drug delivery Adrian C. Williams 715
41 Rectal and vaginal drug delivery Kalliopi Dodou 739
42 The formulation and manufacture of plant medicines
G. Brian Lockwood 758
43 Delivery of biopharmaceuticals Ijeoma F. Uchegbu and
Andreas G. Schätzlein 769
44 Pharmaceutical nanotechnology and nanomedicines Yvonne Perrie 784
45 Design and administration of medicines for paediatric and geriatric
patients Catherine Tuleu, Mine Orlu and David Wright 804
Part 6 Packaging and stability of pharmaceutical products
46 Packaging Sudaxshina Murdan 820
47 Chemical stability in dosage forms Andrew R. Barnes 836
48 Microbial contamination, spoilage and preservation of medicines
Norman A. Hodges 850
49 Product stability and stability testing Paul Marshall 862
Self Assessment Please check your eBook at https://studentconsult.inkling.
com/ for self-assessment questions. See inside cover for registration details.
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .886
vi
Preface
This is the fifth edition of Aulton’s Pharmaceutics: written by a new generation of experts. The new
The Design and Manufacture of Medicines. The first authorship reflects contemporary knowledge and
edition was published in 1988, the second in 2002, thinking in pharmaceutics.
the third in 2007 and the fourth in 2013. The pedigree The fourth edition of this book saw major restruc-
of the book is, however, actually much older. It was turing and revision of the text, with the addition of
originally known as Tutorial Pharmacy (which itself many new chapters and deletion of others. In this
went to six editions) and was initially edited by John edition, the changes have been less radical, but neces-
Cooper and Colin Gunn, and later by Sidney Carter. sary and important nonetheless. Every chapter has
Professor Mike Aulton and Professor Kevin Taylor received detailed attention and has been revised and
continue their editing role and have identified new updated appropriately to reflect modern thinking and
authors and fresh subject matter for this new edition. current university curricula worldwide. Some of the
The philosophy of this fifth edition remains basic science remains virtually unchanged – and will
unchanged from that of previous editions, i.e. it is always do so – but other areas, particularly biophar-
intentionally designed and written for newcomers to maceutics and some areas of drug delivery, have
the design of dosage forms (drug products). Other changed significantly in recent years. Several new
expert texts can take you into much greater detail authors have been included in this edition to ensure
for each of the subject areas considered here, once the comprehensive nature and currency of this text.
you have mastered these basics. The subject matter All purchasers of the print version of this new
of the book remains, in essence, the same but the edition receive the enhanced ebook, which can be
detail has changed significantly, because pharmaceutics used online or downloaded to their mobile device
has changed. Since the last edition there have been for convenient, any time access. The ebook includes
changes in the way that dosage forms are designed more than 400 self-assessment questions, based on
and manufactured and drugs are delivered. These the book, to check understanding and to help with
developments are reflected in this new edition. any examination preparation.
The involvement of a wide range of authors We wish you well in your studies if you are an
continues in this edition, all authors being a recognized undergraduate student, or with your career if you
expert in the field on which they have written. Just are working in industry, medicines regulation or the
as importantly, each author has experience of impart- hospital service. We sincerely hope that this book
ing that information to undergraduate pharmacy and helps you with your understanding of pharmaceutics
pharmaceutical science students, and to practitioners – the science of the design and manufacture of
in the pharmaceutical and associated industries and medicines.
those working in technical services within hospital
M. E. Aulton
pharmacy who are new to the subject. Many authors
K. M. G. Taylor
from the previous edition remain as they are still
world leaders in their field. Other chapters have been
vii
Contributors
Göran Alderborn PhD Soraya Dhillon BPharm, PhD
Professor in Pharmaceutical Technology, Uppsala Professor and Dean, Life and Medical Sciences,
University, Uppsala, Sweden University of Hertfordshire, Hatfield, UK
Marianne Ashford BSc (Pharm), PhD Kalliopi Dodou BSc (Pharm), PhD
Associate Principal Scientist Drug Delivery, AstraZeneca, Reader, Pharmacy Health and Wellbeing, University of
Macclesfield, UK Sunderland, Sunderland, UK
David Attwood BPharm, PhD, DSc, CChem, FRSC Gillian M. Eccleston BSc, PhD
Emeritus Professor, University of Manchester, Professor of Pharmacy, University of Strathclyde,
Manchester, UK Glasgow, UK
Michael E. Aulton BPharm, PhD, FAAPS, FSP, FRPharmS Hala Fadda MPharm, PhD
Emeritus Professor, De Montfort University, Leicester, Associate Professor of Pharmaceutics, College of
UK Pharmacy and Health Sciences, Butler University,
Indianapolis, USA
Susan A. Barker BPharm, PhD
Senior Lecturer in Pharmaceutics, UCL School of Josephine Ferdinando BSc, MSc, PhD
Pharmacy, London, UK Senior Vice President, Nonclinical Development, Shire
Research and Development, Basingstoke, UK
Andrew R. Barnes BSc (Pharm), PhD
Quality Assurance Specialist, Pharmacy Quality Ana Cristina Freire PhD
Assurance Specialist Services, Hellesdon Hospital, Development Manager, Kuecept, Potters Bar, UK
Norwich, UK
Göran Frenning
Abdul W. Basit BPharm, PhD Professor in Pharmaceutical Physics, Uppsala University,
Professor of Pharmaceutics, UCL School of Pharmacy, Uppsala, Sweden
London, UK
Simon Gaisford BSc, MSc, PhD
Steve Brocchini BA, PhD Professor in Pharmaceutics, UCL School of Pharmacy,
Professor of Chemical Pharmaceutics, UCL School of London, UK
Pharmacy, London, UK
Geoffrey W. Hanlon BSc, PhD
Graham Buckton BPharm, PhD, DSc Emeritus Professor of Pharmaceutical Microbiology,
Emeritus Professor of Pharmaceutics, UCL School of University of Brighton, Brighton, UK
Pharmacy, London, UK
Norman A. Hodges MPharm, PhD
John H. Collett PhD, DSC, FRPharmS Principal Lecturer in Pharmaceutical Microbiology,
Professor of Pharmaceutics, University of Manchester, School of Pharmacy and Biomolecular Sciences,
Manchester, UK University of Brighton, Brighton, UK
viii