Contents
Cover
Companion website
Title Page
Copyright
Dedication
Preface
List of Abbreviations
Chapter 1: Basic Principles of Preformulation Studies
1.1 Introduction
1.2 Assay design
1.3 Concentrations
1.4 UV spectrophotometry
1.5 Thin-layer chromatography (TLC)
1.6 High-performance liquid chromatography
1.7 Differential scanning calorimetry
1.8 Dynamic vapour sorption
1.9 Summary
References
Answer to study question
Additional study questions
Chapter 2: Ionisation Constants
2.1 Introduction
2.2 Ionisation
2.3 Buffers
2.4 Determination of pKa
2.5 Summary
References
Answers to study questions
Additional self-study questions and answers
Chapter 3: Partition Affinity
3.1 Introduction
3.2 Partitioning
3.3 Summary
References
Answers to study questions
Chapter 4: Solubility
4.1 Introduction
4.2 Intrinsic solubility
4.3 Summary
References
Answer to study question
Additional self-study questions and answers
Chapter 5: Dissolution
5.1 Introduction
5.2 Models of dissolution
5.3 Dissolution testing
5.4 Summary
References
Answers to study questions
Chapter 6: Salt Selection
6.1 Introduction
6.2 Salt formation
6.3 Salt solubility
6.4 Dissolution of salts
6.5 Partitioning of salts
6.6 Summary
References
Answers to study questions
Chapter 7: Physical Form I – Crystalline Materials
7.1 Introduction
7.2 Crystal formation
7.3 Crystal structure
7.4 Polymorphism
7.5 Pseudopolymorphism
7.6 Polymorph screening
7.7 Characterisation of physical form
7.8 Summary
References
Answers to study questions
Chapter 8: Physical Form II – Amorphous Materials
8.1 Introduction
8.2 Formation of amorphous materials
8.3 Ageing of amorphous materials
8.4 Characterisation of amorphous materials
8.5 Processing and formation of amorphous material
8.6 Amorphous content quantification
8.7 Summary
References
Answers to study questions
Chapter 9: Stability Assessment
9.1 Introduction
9.2 Degradation mechanisms
9.3 Reaction kinetics
9.4 The temperature dependence of reaction kinetics
9.5 Stress testing
9.6 Summary
References
Answers to study questions
Chapter 10: Particle Properties
10.1 Introduction
10.2 Microscopy
10.3 Particle shape
10.4 Summary
References
Answer to study question
Chapter 11: Powder Properties
11.1 Introduction
11.2 Powder flow and consolidation
11.3 Compaction properties
11.4 Summary
References
Answers to study questions
Index
This edition first published 2013
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Library of Congress Cataloging-in-Publication Data
Gaisford, Simon.
Essentials of pharmaceutical preformulation / Simon Gaisford and Mark Saunders.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-0-470-97635-7 (cloth) – ISBN 978-0-470-97636-4 (paper)
I. Saunders, Mark, 1976 Sept. 18- II. Title.
[DNLM: 1. Drug Compounding–methods. 2. Drug Discovery–methods. QV 779]
615.1′9–dc23
2012027538
A catalogue record for this book is available from the British Library.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Cover design: Gary Thompson
First Impression 2013
For Yasmina and Oliver
Preface
The inspiration for this book came when Michael Aulton asked me to take over his preformulation module on the PIAT course of the University of Manchester. The existing module was based on the excellent textbook (Pharmaceutical Preformulation) written by Jim Wells in 1988 and thus a perfect opportunity to write both an updated module and an updated book presented itself.
The majority of the text was written while I was on sabbatical leave at the Monash Institute for Pharmaceutical Sciences (MIPS) in Melbourne, Australia, in the summer of 2011. I am hugely grateful to Prof. Bill Charman, Prof. Peter Stewart, Marian Costelloe and Marian Glennon for arranging the visit and to MIPS as a whole for the welcoming, friendly and stimulating environment they provided. I would also like to mention many of the wonderful people that I met, including Anne, Ben, Carolyn, Chris, Colin, David, Ian, Hywel, Iliana, Joe, Laurence, Mercedes and Michelle. Special thanks are reserved for Richard Prankerd, who took the time and effort to talk with me about many aspects of the text while I was at MIPS and also to review the whole text before publication; the book is immeasurably better for his input and advice. Thermal analysts are indeed a special breed!
Equally, the book would never have been finished were it not for several other special people. Nicole Hunter undertook the weighty tasks of reviewing the whole text and providing constant support and encouragement while Hamid Merchant cast his expert eye over the dissolution chapter. My group of amazing PhD students (Alice, Asma, Garima, Jawal, Jip, Luis, Mansa, Mustafa and Rin) provided many of the data and examples that populate the text while my academic colleagues, particularly Prof. Abdul Basit, Prof. Anthony Beezer and Prof. Kevin Taylor, have been constant sources of advice and support. I also acknowledge all of the wonderful students who I have taught on the MSc in Drug Delivery and who are such an inspiration to me.
Of course, no book would be possible without a publisher, and I am extremely grateful to Fiona Seymour and Lucy Sayer for editorial advice and encouragement.
Finally, I must acknowledge the constant support of my family, especially Joanne and Oliver, who keep me sane!
S Gaisford
April 2012
List of Abbreviations
Abbreviation | Meaning |
![]() |
Molar absorption coefficient |
θ | Angle of repose |
σ | Normal stress |
τ | Shear stress |
A | Surface area |
AFM | Atomic force microscopy |
AR | Aspect ratio |
BCS | Biopharmaceutical Classification System |
BP | British Pharmacopoeia |
C | Concentration |
CRM | Certified reference material |
D | Diffusion coefficient |
DSC | Differential scanning calorimetry |
ESEM | Environmental scanning electron |
microscopy | |
F | Dilution factor |
FaSSIF | Fasted state simulated intestinal fluid |
FDA | US Food and Drug Administration |
FeSSGF | Fed state simulated gastric fluid |
FeSSIF | Fed state simulated intestinal fluid |
FTIR | Fourier transform infrared |
G | Gibb's free energy |
GRAS | Generally regarded as safe |
h | Thickness of boundary layer |
H | Enthalpy |
HPLC | High-performance liquid chromatography |
HSM | Hot-stage microscopy |
ICH | International Conference on Harmonisation |
IDR | Intrinsic dissolution rate |
IR | Infrared |
IUPAC | International Union of Pure and Applied |
Chemistry | |
k | Rate constant |
K | Equilibrium constant or stress ratio |
MTDSC | Modulated temperature DSC |
n | Reaction order |
NA | Numerical aperture |
NIR | Near infrared |
p | Negative logarithm |
PhEur | European Pharmacopoeia |
RI | Refractive index |
S | Entropy |
So | Intrinsic solubility |
SEM | Scanning electron microscopy |
SGF | Simulated gastric fluid |
T | Temperature |
TEM | Transmission electron microscopy |
TGA | Thermogravimetric analysis |
TLC | Thin-layer chromatography |
UHPLC | Ultra high-performance liquid chromatography |
USP | United States Pharmacopoeia |
UV | Ultraviolet |
V | Volume |
W | Weight |
x | Mole fraction |
XRPD | X-ray powder diffraction |