Physical Pharmacy by David Attwood

University education is about acquiring knowledge, not just passing examinations. The latter is of course a necessary marker of progress, and as a result many students feel that examinations dominate their academic years. In our experience, as teachers of pharmaceutics and physical pharmacy over many years, many students do not adopt proper modes of study for any of their subjects, or even devote enough time to revision. No textbook substitutes for students’ own notes gathered during lectures, annotated later with more information from textbooks and a timetable of revision leading up to examinations. Reading notes at intervals of days is much more effective than re-reading the notes several times in one day.  The FASTtrack series is intended not as an alternative to textbooks but as an aid to revision, providing the key points of each topic and questions with which progress in learning can be gauged. But, like past examination papers, these can only give clues as to what might come in the examination which you are to sit. What you must always ask as a user of this book is: what kind of question might I be asked about topic A and topic B? 

This book is derived unashamedly from the fourth edition of our textbook Physicochemical Principles of Pharmacy, published by the Pharmaceutical Press in 2006. It is not a substitute for it but should be used alongside it for those revision periods when time is short. In many cases you will need to refer to the full text for more detail. You will fi nd fewer equations here. How can we have a physical pharmacy text without equations? There are few drug structures, yet an understanding of structures is essential for understanding physical pharmacy, formulation and drug behaviour. Hence for a complete understanding of some areas you must refer to drug structures. In examination answers it is important to include appropriate drug structures, equations and diagrams not only but especially in this subject. Physicochemical Principles of Pharmacy has structures, diagrams and equations; Martindale in its latest edition includes structural formulae.

Pharmaceutics is one of the fundamental bases of pharmacy. Few, if any, other disciplines study the subject. Knowledge of the essentials which we have put down in this FAST track book are, in our view, very important if pharmacists are to continue to know about drugs and formulations and to contribute something special to healthcare. We hope that this book helps in preparing not only for examinations but also for the future.

CONTENTS 

Introduction to the FASTtrack series vii

Preface viii

About the authors ix

1. Solids . . . . . . . . . . . . . . . . . . . . . . . . . . 1

Crystal structure and external appearance 1

Polymorphism 3

Crystal hydrates 5

Wetting of solid surfaces and powders 6

Dissolution of drugs 7

Solid dispersions 7

Multiple choice questions 8

2. Solubility and solution properties

of drugs . . . . . . . . . . . . . . . . . . . . . . 11

Solvents for pharmaceutical aerosols 11

Factors infl uencing solubility 13

Ionisation of drugs in solution 16

pH of drug solutions 19

Buffers 20

Thermodynamic properties of drugs in

solution 21

Osmotic properties of drugs in solution

– isotonic solutions 22

Partitioning of drugs between immiscible

solvents 24

Diffusion of drugs in solution 25

Multiple choice questions 26

3. Drug stability . . . . . . . . . . . . . . . . . . . 29

The chemical breakdown of drugs 29

Kinetics of chemical decomposition in

solution 31

Factors infl uencing drug stability of liquid

dosage forms 34

Factors infl uencing drug stability of solid

dosage forms 39

Stability testing and calculation of

shelf-life 40

Multiple choice questions 40

4. Surfactants . . . . . . . . . . . . . . . . . . . . 43

Some typical surfactants 43

Reduction of surface and interfacial

tension 45

Insoluble monolayers 46

Adsorption at the solid–liquid interface 48

Micellisation 51

Formation of liquid crystals and vesicles 54

Solubilisation 58

Multiple choice questions 60

5. Emulsions, suspensions and other

dispersed systems . . . . . . . . . . . . . . 63

Colloid stability 63

Emulsions 69

Suspensions 75

Foams and defoamers 78

Multiple choice questions 79

6. Polymers . . . . . . . . . . . . . . . . . . . . . . 81

Polymer structure 81

Solution properties of polymers 84

Properties of polymer gels 86

Some water-soluble polymers used in

pharmacy and medicine 88

Water-insoluble polymers 90

Application of polymers in drug delivery 92

Multiple choice questions 95

7. Drug absorption . . . . . . . . . . . . . . . . . 97

Biological membranes and drug transport 97

Routes of administration 102

The oral route and oral absorption 102

Buccal and sublingual absorption 106

Intramuscular and subcutaneous

injection 106

Transdermal delivery 109

The eye 113

The ear 114

Absorption from the vagina 115

Inhalation therapy 115

The nasal route 117

Rectal absorption of drugs 118

Intrathecal drug administration 120

Multiple choice questions 121

8. Physicochemical drug interactions

and incompatibilities . . . . . . . . . . . . 125

Solubility problems 125

pH effects in vitro and in vivo 126

Dilution of mixed solvent systems 128

Cation–anion interactions 128

Ion-pair formation 129

Chelation and other forms of

complexation 130

Adsorption of drugs 132

Drug interactions with plastics 132

Protein binding of drugs 133

Multiple choice questions 135

9. Peptides, proteins and other

biopharmaceuticals . . . . . . . . . . . . . 137

Structure and solution properties of

peptides and proteins 137

The stability of proteins and peptides 140

Protein formulation and delivery 145

Therapeutic proteins and peptides 146

DNA and oligonucleotides 148

Multiple choice questions 148

10. In vitro assessment of dosage

forms. . . . . . . . . . . . . . . . . . . . . . . . 151

Dissolution testing of solid dosage forms 151

In vitro evaluation of non-oral systems 154

Rheological characteristics of products 154

Adhesivity of dosage forms 155

Particle size distribution in aerosols 156

In vitro–in vivo correlations 159

Multiple choice questions 159

Answers to self-assessment 161

Memory diagrams 163

Index 169