Physical Pharmacy by David Attwood

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