Cover Page

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


Companion website
This book is accompanied by a companion website at:
http://www.wiley.com/go/gaisford/essentials
Visit the website for:

Title Page

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