Pharmaceutical Emulsions

Acronyms and abbreviations xiii

Preface xv

Acknowledgements xvii

About the companion website xix

I Product considerations: medicinal formulations 1

1 Historical perspective 5

1.1 Landmarks 5

1.2 Significant discoveries 7

1.3 Difficulties 8

1.4 Traditional uses 10

1.5 Product regulation 13

2 What is an emulsion? 15

2.1 States of matter 24

2.2 Summary thermodynamics 34

2.3 Interfacial tension and wetting 36

2.4 Shear and size reduction 46

2.5 Raw materials 47

3 Stability, metastability and instability 49

3.1 Stokesâ law 51

3.2 Derjaguinâ"Landauâ"Verweyâ"Overbeek (DLVO) theory 52

3.3 Interfacial rheology 56

4 Manufacture 63

4.1 Premixing 63

4.2 High-shear mixers and size reduction 64

4.3 Multiple and microemulsions 65

4.4 Hot melt (steriles) 65

4.5 Filling 66

II Forms, uses and applications: biopharmaceutics 67

5 Creams and ointments 69

5.1 Nutraceuticals and cosmeceuticals 71

5.2 Medicinals 71

6 Pastes and bases 77

6.1 Emolliency 77

6.2 Suppositories 78

6.3 Pessaries 79

7 IV colloids 81

7.1 Needle free 86

7.2 Ocular therapy 87

7.3 Cancer 88

7.4 Antimicrobials 90

7.5 Temperature-sensitive matrices and release forms 93

7.6 Targeted endosomal use 94

7.7 Solid lipid nanoparticles 95

7.8 Diagnostic emulsions 98

8 Transdermal patches: semisolids 99

8.1 Hormones 104

8.2 Analgesia 104

8.3 Anaesthesia 104

8.4 Nicotine 105

8.5 Inserts: vaginal rings 105

9 Gels 107

9.1 Micro- and nanogels 107

9.2 Semisolids 107

10 Implants 109

10.1 Plastics and glasses 109

10.2 Thermoresponsive materials 110

11 De novo science, sustainable novel products and platform applications 111

11.1 Tablets 113

11.2 Metered-dose inhalers 113

11.3 Blood substitutes 114

III Tests: chemistry to control the quality, efficacy and fitness for purpose of a product 117

12 Physicochemical properties 119

12.1 Thermal evaluation (differential scanning calorimetry) and lipid polymorphs 124

12.2 Drug form, log P and Lipinski rules 129

12.3 Skin and epithelial models 133

12.4 Drug delivery routes 134

13 Sizing and microscopy 137

13.1 ζ -potential 137

13.2 Hydrodynamic diameter 139

14 Rheology, texture, consistency and spreadability 141

14.1 Bulk properties 141

14.2 Solid-state and nanorheological properties 144

14.3 Interfacial properties 144

15 Quality control, process analytical technology and accelerated testing 149

15.1 Preformulation, high-throughput screening 150

15.2 Industrial concerns 151

15.3 Rancimat and other methods 152

Questions 155

Guide for readers 155

Specimen 'test' questions 155

Answers 168

References 173

Index 181