Transdermal and topical drug delivery : from theory to clinical practice / Adrian Williams.

Transdermal and Topical Drug Delivery is a comprehensive text that addresses all aspects of how to deliver drugs to the skin for local effects or across the skin for systemic therapy. Starting with a clear discussion of the principles underlying the area, the text expands into strategies used to deliver drugs effectively. An invaluable practical guide for the clinical delivery of drugs is included.

Author Biography Adrian C Williams is a professor of biophysical pharmaceutics at the University of Bradford, UK, and has considerable experience in academic research in transdermal drug delivery.

Includes bibliographical references and index.

Structure and function of human skin -- theoretical aspects of transdermal drug delivery -- experimental design -- chemical modulation of skin permeation -- physical and technological modulation of transdermal permeation -- topical and transdermal formulation -- clinical principles.

Table of Contents Preface pages xi Acknowledgements pages xiii About the author pages xiv 1 Structure and function of human skin pages 1 1.1 Introduction pages 1 1.2 Healthy skin structure and function pages 1 1.2.1 The subcutaneous fat layer pages 2 1.2.2 The dermis pages 2 1.2.3 The epidermis pages 5 1.2.4 Epidermal enzyme systems pages 13 1.3 Physiological factors affecting transdermal and topical drug delivery pages 14 1.3.1 Skin age pages 14 1.3.2 Body site pages 16 1.3.3 Race pages 17 1.3.4 Other factors pages 17 1.4 Pathological disorders pages 18 1.4.1 Eruptions pages 19 1.4.2 Infections pages 21 1.4.3 Ichthyoses pages 22 1.4.5 Tumours pages 23 1.5 References pages 23 2 Theoretical aspects of transdermal drug delivery pages 27 2.1 Terminology pages 27 2.2 The transdermal permeation process pages 28 2.3 Permeation pathways through the stratum corneum pages 30 2.3.1 Transappendageal transport pages 31 2.3.2 Transcellular route pages 32 2.3.3 Intercellular pathway pages 33 2.4 Influence of permeant physico-chemical properties on route of absorption pages 35 2.4.1 Partition coefficient pages 35 2.4.2 Molecular size pages 36 2.4.3 Solubility/melting point pages 37 2.4.4 Ionisation pages 38 2.4.5 Other factors pages 39 2.5 Mathematics of skin permeation pages 40 2.5.1 Pseudo-steady-state permeation (infinite dosing) pages 41 2.5.2 Transient permeation (finite dosing) pages 46 2.6 References pages 48 3 Experimental design pages 51 3.1 Introduction pages 51 3.2 In-vivo or in-vitro studies? pages 51 3.2.1 In-vitro tissue; potential problems pages 53 3.3 Alternative membranes for in-vitro studies pages 54 3.3.1 Animal membranes pages 54 3.3.2 Artificial membranes pages 56 3.4 Selection of membrane layers for in-vitro studies pages 59 3.4.1 Preparation of skin membranes pages 60 3.5 Selection of diffusion cell for in-vitro experiments pages 62 3.6 Formulation application considerations pages 64 3.6.1 Finite or infinite dose? pages 64 3.6.2 Vehicle effects pages 65 3.6.3 Ionisation pages 68 3.6.4 Permeant detection pages 70 3.6.5 Donor solution concentration pages 73 3.7 Receptor solution for in-vitro studies pages 73 3.8 Integrity checks pages 75 3.9 Temperature pages 76 3.10 Experimental duration pages 76 3.11 In-vitro experimental replicates pages 77 3.12 Mass balance pages 77 3.13 Expression of results pages 77 3.14 Current regulatory guidelines pages 79 3.15 References pages 79 4 Chemical modulation of topical and transdermal permeation pages 83 4.1 Introduction pages 83 4.2 Water pages 84 4.3 Chemical penetration enhancers pages 86 4.3.1 Sulfoxides and similar chemicals pages 87 4.3.2 Azone pages 89 4.3.3 Pyrrolidones pages 91 4.3.4 Fatty acids pages 92 4.3.5 Alcohols, fatty alcohols and glycols pages 94 4.3.6 Surfactants pages 96 4.3.7 Urea pages 98 4.3.8 Terpenes pages 98 4.3.9 Phospholipids pages 102 4.3.10 General comments on penetration enhancers pages 102 4.4 Chemical permeation retarders pages 104 4.4.1 Barrier creams pages 104 4.4.2 Permeation retarders pages 105 4.4.3 Cyclodextrins pages 106 4.5 Drug and formulation manipulation strategies pages 108 4.5.1 Prodrugs pages 108 4.5.2 Ion pairing pages 110 4.5.3 Eutectic systems/depression of permeant melting point pages 112 4.5.4 Supersaturation pages 114 4.6 References pages 116 5 Physical and technological modulation of topical and transdermal drug delivery pages 123 5.1 Introduction pages 123 5.2 Vesicles pages 123 5.2.1 Liposomes pages 124 5.2.2 Non-ionic surfactant vesicles (niosomes) pages 128 5.2.3 Highly deformable (or elastic) liposomes pages 130 5.2.4 Ethosomes pages 134 5.2.5 'Othersomes' pages 135 5.3 Needleless injection pages 136 5.3.1 Particles pages 137 5.3.2 Liquids pages 138 5.4 Physical avoidance of stratum corneum pages 139 5.4.1 Laser ablation pages 139 5.4.2 Other ablation methods pages 140 5.4.3 Microneedles pages 141 5.5 Ultrasound pages 142 5.6 Electrical methods pages 144 5.6.1 Iontophoresis pages 145 5.6.2 Electroporation pages 152 5.6.3 Other 'electrical' enhancement strategies pages 154 5.7 Combined enhancement strategies pages 155 5.7.1 Iontophoresis with chemical penetration enhancers pages 156 5.7.2 Iontophoresis with physical avoidance of the barrier pages 157 5.7.3 Electroporation with chemical penetration enhancers pages 158 5.7.4 Electroporation with iontophoresis pages 158 5.7.5 Other combinations pages 159 5.8 References pages 159 6 Topical and transdermal formulations pages 169 6.1 Introduction pages 169 6.2 Formulation options pages 169 6.2.1 Liquid formulations pages 171 6.2.2 Semi-solid formulations pages 172 6.2.3 Solid formulations pages 178 6.3 Transdermal patches pages 178 6.3.1 Types of transdermal patches pages 180 6.3.2 Transdermal patch components pages 183 6.4 Some general formulation 'rules' pages 187 6.4.1 Select a good drug candidate pages 187 6.4.2 Estimate drug flux pages 188 6.4.3 Use thermodynamics pages 190 6.4.4 Be realistic pages 191 6.4.5 Alcohol helps pages 192 6.4.6 How to keep the drug localised? pages 193 6.5 References pages 194 7 Clinical principles pages 195 7.1 Introduction pages 195 7.2 What quantities are necessary? pages 195 7.3 Which formulation type to select? pages 196 7.4 Formulation is more important than concentration pages 197 7.5 What can be delivered to and through the skin? pages 198 7.6 Occlusion or not? pages 203 7.7 Dilution of preparations pages 203 7.8 Ensuring formulation equivalence pages 204 7.9 Drug delivery through a repairing barrier pages 213 7.10 Case studies pages 215 7.10.1 Case 1: Permethrin treatment of scabies pages 215 7.10.2 Case 2: PUVA therapy pages 216 7.10.3 Case 3: Salicylic acid pages 217 7.10.4 Case 4: Errors with patches pages 219 7.11 References pages 220 Glossary pages 223 Index pages 229