Table of Contents
1.0 Executive Summary 17
1.1 Objectives of Report 17
1.2 Data Sources & Methodology 18
1.3 Key Findings & Observations 19
1.3.1 The Global Drug Delivery Market has a Growth Rate of 5% 19
1.3.2 The Transdermal Drug Delivery Market is Growing Vertically 20
1.3.3 Who are the Leading Players in the Market? 20
1.3.4 Neurodegenerative Disorders Such as Alzheimer’s and Parkinson’s Disease Will Propel the Future Market 21
1.3.5 Why is the Transdermal Drug Delivery Market so Promising? 21
1.3.6 What are the Main Drivers of the Market? 21
1.3.7 First, Second and Third Generation Drug Delivery Systems 22
1.3.8 The Niche Market of Commercially Available Skin Models 22
1.3.9 Transdermal Drug Delivery Technologies are Providing the Market with Niche Spaces 22
1.3.10 Nanotechnology is Transforming Transdermal Drug Delivery 23
1.3.11 Can Transdermal Drug Delivery be Applied to Cancer Vaccination? 23
1.3.12 Gene Therapy Advancement Using Transdermal Delivery 23
2.0 Transdermal Drug Delivery 24
2.1 Introduction 24
2.2 Developments of Transdermal Drug Delivery to Date 24
2.3 The Skin – Anatomy and Physiology 27
2.3.1 Drug Administration via the Intracellular Pathway 28
2.3.2 Drug Administration via the Intercellular Pathway 29
2.3.3 Fick’s Law 29
2.4 Factors that Influence Transdermal Drug Delivery 29
2.4.1 Parameters Influencing Skin Permeability 29
2.4.1.1 The Vehicle 29
2.4.1.2 Drug Concentration 30
2.4.1.3 Partition Coefficient 30
2.4.1.4 Variations in Skin Type 30
2.5 Strategies to Enhance Transdermal Drug Delivery 30
2.5.1 1st Generation Delivery Systems 30
2.5.2 2nd Generation Delivery Systems 31
2.5.2.1 Chemical Enhancers 31
2.5.2.2 Physical Enhancers 32
2.5.3 3rd Generation Delivery Systems 32
2.6 Comparison of Transdermal Delivery with Other Methods 34
2.7 Advantages of Transdermal Drug Delivery 35
2.7.1 First-Pass Metabolism 35
2.8 Disadvantages of Transdermal Delivery 36
2.9 Complications of Transdermal Therapy 36
2.9.1 Overdose 37
2.9.2 Skin Sensitivity and Reactions 37
- MRI-Induced Skin Burns 38
3.0 Biomechanical & Pharmacological Elements Effecting Transdermal Drug Delivery 39
3.1 Factors That Influence Transdermal Drug Delivery 39
3.1.1 Rate of Permeation Across the Skin 39
3.1.2 Skin Characteristics 39
3.1.3 Drug Characteristics 39
3.1.4 pH and Pharmacokinetics 39
3.2 Transdermal Drug Design 40
3.2.1 Factors That Affect the Absorption of the Drug 40
3.2.1.1 Hydration and Temperature 40
3.2.1.2 Biotransformation of the Drug in the Skin 40
3.2.2 Selecting Drug and Vehicle 40
3.2.3 Drug Modification 40
3.2.3.1 Ion-Pair Formation 40
3.2.3.2 Pro-Drug 40
3.2.3.3 Drug Complexation 41
3.2.4 Thermodynamic Activity of the Drug within the Vehicle 41
3.2.4.1 Eutectic Systems 41
3.2.4.2 Vehicle Formulation 41
3.2.4.3 Modification of the Stratum Corneum 41
3.3 In Vitro Testing of Transdermal Drug Delivery Systems 41
3.3.1 Static Franz Diffusion Cell 42
3.3.2 Side-Bi-Side Cells 42
3.4 Commercially Available Skin Models for Transdermal Drug Testing 43
3.5 In vivo Testing of Transdermal Drug Delivery Systems 43
3.5.1 In vivo Testing of Drug Delivery Systems 44
3.5.2 Modelling of Transport Through the Skin 44
4.0 Transdermal Drug Delivery Technologies 46
4.1 Introduction 46
4.1.1 Local Application Formulations 46
4.1.2 Liquid Crystals for Transdermal Drug Delivery 46
4.1.3 Microemulsions for Transdermal Drug Delivery 47
4.1.4 Nanoemulsions for Transdermal Drug Delivery 49
4.1.5 Transdermal Gel Technology 50
4.1.6 Biphasix System 51
4.1.7 Penetration Enhancers 51
4.1.8 Chemical Enhancers 52
4.1.9 Nitric Oxide-Based Transdermal Drug Delivery 52
4.2 Vesicular Transdermal Carriers 52
4.2.1 Liposomes 53
4.2.2 Transfersomes 54
4.2.3 Ethosomes 55
4.2.4 Elastic Vesicles 55
4.3 Transdermal Patch 56
4.3.1 Types of Transdermal Patch 57
4.3.1a Single-layer Drug-in-Adhesive 57
4.3.1b Multi-layer Drug-in-Adhesive 58
4.3.1c Reservoir 58
4.3.1d Matrix Patch 58
4.3.1e Vapour Patch 59
4.3.2 Transdermal Patches Adhesives 59
4.3.3 h-Patch™ Controlled Release Micropump System 60
4.4 Patchless Transdermal Delivery System 60
4.5 Metered-Dose Transdermal System 60
4.6 Polymers for Transdermal Drug Delivery 61
4.6.1 Film Forming Polymeric Solutions 61
4.7 Physical Methods to Promote Transdermal Delivery 62
4.7.1 Electrotransport 62
4.7.2 Electroporation 62
4.7.2.1 Drug delivery by Electroporation 63
4.7.2.2 Electrochemotherapy 63
4.7.3 Cryoelectrophoresis 64
4.7.4 Iontophoresis 64
4.7.4.1 Application of Iontophoresis for Drug Delivery 64
4.7.4.2 Companies with Technologies for Drug Delivery by Iontophoresis 65
4.8 How Combining Electrophoresis and Iontophoresis Impacts Drug Delivery 66
4.9 Dermaportation 66
4.10 Radiofrequency-Driven Transdermal Delivery 67
4.11 Transcutaneous Drug Delivery by Electropulsation 67
4.11.1 Skin Patch Systems and Electrostatic Force 67
4.12 Heat-Aided Drug Delivery 67
4.13 Ultrasound 68
4.14 Magnetophoresis 69
4.15 Use of Lasers for Transdermal Drug Delivery 69
4.15.1 Laser-Induced Microporation 70
4.15.2 Painless Laser Injection 70
4.15.3 Laser-Induced Pressure Waves 70
4.15.3.1 Transdermal Drug Delivery by Laser-Assisted Changes in Skin 71
4.16 How Pressurized Gas is Transforming Transdermal Drug Delivery 72
4.17 Microscission Induced by Gas 72
4.18 Role of Microelectromechanical Systems (MEMS) in Transdermal Drug Delivery 72
4.19 Microneedles and Dermal Microinjection 74
4.20 Microneedle Arrays for Drug Delivery 75
4.20.1 Microneedle Patch 75
4.20.2 Applications of Microneedles 75
4.20.3 AdminPatch® Microneedle Array 75
4.20.4 Dissolving Microneedles 76
4.21 Biodegradable Microneedles 76
4.22 Ceramic Microneedle Arrays 77
4.23 Dissolvable Microneedle Patches 77
4.23.1 MicorCor 78
4.23.2 MicroPyramid™ 78
4.24 Microstructured Transdermal Systems 78
4.25 Microneedle Transdermal Chip 79
4.26 Microneedle Applicator Device 80
4.27 DebioJect ™ Microneedle Technology 80
4.28 Silk Microneedles 81
4.29 Tattooing 82
4.30 ZP Patch Microprojections Technology 82
4.31 Other Microneedle Products Currently Available 83
4.32 Needlefree injections 83
4.33 Glide SDI® Solid Dose Injector 84
4.34 Jet Injection 84
4.34.1 Why is Needle-Free so Important? 85
4.34.2 Mini-Ject Needlefree Delivery System 85
4.34.3 PharmaJet Stratis 86
4.34.4 MicroJet for Painless Injections 86
4.34.5 Nanoliter-Volume Pulsed Microjets 86
4.35 SUMAVEL™ DosePro™ Needle-Less Injection 86
4.36 Skin Abrasion 87
5.0 How Nanotechnology is Transforming Transdermal Drug Delivery 88
5.1 Overview 88
5.2 Nanotechnology-Based Transdermal Drug Delivery 89
5.2.1 Nanobiotechnology for Transdermal Application 89
5.3 Nanoparticles and Nanoemulsions for Skin Disorders 90
5.4 Nanopatches 91
5.4.1 Vaxxas Nanopatch Technology 91
5.4.2 Effect of Mechanical Flexion on Penetration of Bucky Amino Acids Through the Skin 91
5.5 Inocyte™ Epidermal Drug Delivery System 91
5.6 Ionic Nanoparticle Technology 92
5.7 Solid Lipid Nanoparticles (SLN) Gels 93
5.8 siRNA- Nanoparticle Conjugates 93
5.9 Transdermal Nanoparticle Preparations for Systemic Effect 94
5.10 Micellar Nanoparticle Estradiol Emulsion (MNPEE) 94
5.11 Transferosomes 95
5.12 Nanocarriers 95
5.13 Nanotechnology for Vaccination and Immunotherapy 95
5.14 Safety Issues of Applications of Nanomaterial Carriers on the Skin 96
5.15 Comparison of Current Transdermal Drug Delivery Systems 96
6.0 Transdermal Drug Delivery and Disease States 98
6.1 Antiaging Products 98
6.2 Cancer 98
6.2.1 δ-Amino Levulinic Acid 98
6.2.2 Breast Cancer & Afimoxifene Gel 99
6.2.3 Cervical Cancer & Interferon α2b 99
6.2.4 Prostate Cancer & Nitroglycerine 99
6.2.5 Prostate Cancer & Estradiol Gel 100
6.2.6 Prostate Cancer & Leuprolide Acetate 100
6.2.7 Skin Cancer & Caffeine 100
6.2.8 Cancer Vaccines 101
6.2.8.1 Intradermal Delivery Using Adenoviral Vectors 101
6.2.8.2 Peptide Cancer Vaccines 101
6.2.8.3 Electroporation of Anticancer Agents 102
6.3 Cardiovascular Disease 102
6.3.1 Transdermal Anticoagulants 102
6.3.2 Angina Pectoris 103
6.3.3 Atherosclerotic Cardiovascular Disease 103
6.3.3.1 Transdermal Oestrogen for Prevention of Atherosclerotic Cardiovascular Disease 103
6.3.4 Congestive Heart Failure 104
6.3.5 Hypertension 105
6.3.5.1 Clonidine 105
6.3.5.2 β-Blockers 105
6.3.5.3 Calcium Channel Blockers 106
6.4 Chronic Fatigue Syndrome 109
6.5 Contraception 109
6.5.1 Female Contraception 109
6.5.1.1 Agile Therapeutics AG200-15 109
6.5.1.2 BAY86-5016 / FC Patch Low BAY86-5016 110
6.5.1.3 Desogestrel 110
6.5.1.4 Ortho Evra™ 111
6.5.2 Male Contraception 111
6.5.2.1 Transdermal Progestin Plus Testosterone 112
6.6 Diabetes 112
6.6.1 Insulin Drug Delivery 112
6.6.1.1 V-Go 112
6.6.1.2 GLP1 Agonist 113
6.7 Men’s Health 113
6.7.1 Benign Prostatic Hypertrophy 113
6.7.1.2 Tamsulosin Transdermal Drug Delivery System 114
6.7.2 Erectile Dysfunction 114
6.7.2.1 Topical and Transdermal Preparation for Erectile Dysfunction 115
6.7.3 Hypogonadism 115
6.7.3.1 Topical Testosterone 116
6.8 Musculoskeletal Disease 117
6.8.1 Osteoarthritis 117
6.8.2 Osteoporosis 117
6.8.2.1 Alendronate 118
6.8.2.2 Estrogen 118
6.8.2.3 Human Parathyroid Hormone 118
6.9 Nausea and Vomiting 119
6.9.1 Chemotherapy-Induced 119
6.9.2 Motion Sickness 119
6.9.3 Postoperative Vomiting 119
6.10 Neurological Disease 120
6.10.1 Alzheimer’s Disease 120
6.10.1.1 Arecoline 120
6.10.1.2 Rivastigmine 120
6.10.1.3 Donepezil 120
6.11 Attention Deficit Hyperactivity Disorder 121
6.11.1 Methylphenidate 121
6.12 Bipolar Disorder 121
6.12.1 Lithium 121
6.13 Depression 122
6.13.1 Antidepressants 122
6.13.2 Selective Serotonin-Reuptake Inhibitors 122
6.13.3 Fluoxetine 123
6.13.4 Monoamine Oxidase Inhibitors 123
6.13.5 Selegiline 123
6.13.6 Trazodone Hydrochloride 124
6.13.7 Venlafaxine 124
6.13.8 Bupropion 124
6.14 Epilepsy 124
6.15 Migraine 125
6.15.1 Sumatriptan 125
6.15.2 Zolmitriptan 126
6.16 Parkinson’s Disease 126
6.16.1 Introduction 126
6.16.2 Dopamine Agonists 126
6.16.2.1 Levodopa 127
6.16.2.2 Rotigotine 127
6.16.3 Other Agents 128
6.17 Restless Leg Syndrome 128
6.17.1 Rotigotine 128
6.18 Schizophrenia 128
6.18.1 Haloperidol 129
6.18.2 Risperidone 129
6.18.3 Blonanserin 129
6.19 Tinnitus/Vertigo 130
6.20 Tourette syndrome 131
6.20.1 Nicotine 131
6.21 Multiple Sclerosis 131
6.22 Respiratory Diseases 131
6.22.1 Asthma and Chronic Obstructive Pulmonary Disease (COPD) 131
6.23 Skin disorders 132
6.23.1 Cutaneous Leishmaniasis 132
6.23.2 Hair Loss 132
6.23.3 Iontophoretic Drug Delivery for Nail Disorders 133
6.23.4 Psoriasis 133
6.23.4.1 Nanoemulsions for Paxitacel in Psoriasis 133
6.23.4.2 Iontophoresis for Treatment of Psoriasis 134
6.24 Overactive Bladder and Urinary Incontinence 134
6.24.1 Oxybutynin 134
6.25 Pain 134
6.25.1 Chronic Pain 134
6.25.2 Transdermal Local Anesthetics 135
6.25.3 Transdermal Fentanyl for the Management of Postoperative Pain 136
6.25.4 Fibromyalgia 136
6.25.5 Minor Medical Procedures 137
6.25.6 Neuralgia 137
6.25.6.1 Lidoderm 137
6.25.7 Nonsteroidal Anti-Inflammatory Drugs 137
6.25.7.1 Topical NSAIDs 137
6.25.8 Ketoprofen 138
6.25.9 Opioids 138
6.25.10 Cancer Pain 139
6.25.10.1 Fentanyl 139
6.25.10.2 Nitroglycerine 139
6.25.10.3 Buprenorphine 140
6.26 Smoking Cessation 140
6.26.1 Nicotine Replacement Therapy 140
6.26.2 Nicotine Patch in Pregnancy 140
6.27 Viral infections 142
6.27.1 Transdermal Nanoparticles for Immune Enhancement in HIV 142
6.28 Women’s Health 143
6.28.1 Dysmenorrhea 143
6.28.2 Female Infertility 143
6.28.3 Female Sexual Arousal Disorder 144
6.28.4 Menopause 145
6.28.4.1 Hormone Replacement Therapy 145
6.28.4.2 Estradiol 145
6.28.4.3 Parathyroid Hormone for Postmenopausal Osteoporosis 146
6.28.4.4 Testosterone and Low Libido 146
6.29 Transdermal Nutraceuticals 147
7.0 Gene Therapy and Transdermal Drug Delivery 148
7.1 Overview 148
7.2 Plasmid DNA and Electroporation 148
7.2.1 TriGrid™ Delivery System 149
7.2.2 CELLECTRA® 149
7.2.3 Magnetic Pulse Electroporation 150
7.3 Antisense Therapy 150
8.0 Vaccines and Transdermal Drug Technology 152
8.1 Introduction 152
8.1.1 The Skin as an Immune Organ 152
8.1.1.1 Langerhans Cells- Epidermal Antigen Presenting Cells 152
8.1.1.2 Keratinocytes- Immune Competent Epithelial cells 152
8.1.1.3 Dendritic Epidermal T Cells (DETC) γδ T cells -Specialised Resident Epithelial Cells 152
8.1.1.4 Epidermotropic T lymphocytes-Circulating T Cells that home to the Epidermis 153
8.1.1.5 Melanocytes-Epidermal Pigment Cells With Immune Properties 153
8.2 Current Technologies 153
8.2.1 Dissolvable Microneedle Array 153
8.2.2 Electroporation for Administering DNA Vaccines 154
8.2.3 Microneedles for Transdermal Vaccine Delivery 154
8.2.4 Needle-Free Delivery of Vaccines 155
8.3 Applications for Transdermal Vaccination 156
8.3.1 HIV/AIDS Vaccine 156
8.3.2 Transdermal DNA Influenza Vaccine 157
8.3.3 Transdermal Aβ Vaccine for Alzheimer’s Disease 157
8.3.4 Transdermal Vaccine for Traveller’s Diarrhoea 157
9.0 Global Drug Delivery Market 158
9.1 Overview and Analysis 158
9.2 USA Drug Delivery Market 160
9.3 European Drug Delivery Market 162
9.4 Emerging Drug Delivery Markets 164
9.5 The Advanced Drug Delivery Landscape 164
9.6 Transdermal Drug Delivery Market 166
9.7 Smoking Cessation Drug Market 169
9.7.1 Nicotine Replacement Therapeutics 171
9.7.2 Non-Nicotine Containing Therapeutics 171
9.7.3 Smoking Cessation Products in the Pipeline 171
9.8 Neurodegenerative Disorders Such as Alzheimer’s & Parkinson’s disease will Propel the Future Market 172
9.9 How Transdermal Systems Relate to the Global Pain Market 172
9.9.1 Neuropathic Pain Market (US, UK, France, Germany, Japan, Spain and Italy) 2014-2020 173
9.9.2 Transdermal Products Within the Neuropathic Pain Market 176
9.10 How Transdermal Systems Relate Within the Generic Market 176
9.11 Duragesic and Generic Fentanyl Transdermal System Competition 179
9.12 Lidocaine Market Analysis 181
9.13 Who are the Leading Players in the Market? 182
9.14 What is Driving the Transdermal Drug Delivery Market? 184
9.15 Increased Number of Geriatric and Pediatric Patients is Propelling the Market 184
9.16 Unmet Needs Within the Transdermal Drug Delivery Market 185
9.17 Women’s Health Market 185
10.0 Transdermal Drug Delivery Company Business Profiles and Strategic Evaluation 187
10.1 Actavis 187
10.2 Actelion 188
10.3 GlaxoSmithKline 189
10.4 Bayer 190
10.5 Mylan Pharmaceuticals 191
10.6 Novartis 191
10.7 Upsher-Smith 193
10.8 Ascend Therapeutics 195
10.9 AMAG Pharmaceuticals (Lumara Health, KV Pharma/Ther-Rx Corp) 195
10.10 Janssen Pharmaceuticals 195
10.11 Lavipharm 196
10.12 Noven Pharmaceuticals 197
10.13 ProStrakan 198
10.14 Shire 198
10.15 Hercon Pharmaceutical 199
10.16 Kremers Urban Pharmaceuticals 199
10.17 Nitto Denko 199
10.18 Teva Pharmaceutical Industries 199
10.19 Endo International 201
10.20 Teikoku USA 201
10.21 Boehringer Ingelheim 201
10.22 3M 203
10.23 UCB 204
10.24 ParPharm 204
11.0 Transdermal Drug Delivery Company Financial Analysis 208
11.1 Actavis 210
11.2 Actelion 212
11.3 GlaxoSmithKline 217
11.3.1 ViiV Healthcare 218
11.4 Bayer 218
11.5 Mylan Pharmaceuticals 224
11.6 Novartis 228
11.7 Janssen Pharmaceuticals (Johnson & Johnson) 232
11.8 Shire 236
11.9 Nitto Dento 237
11.10 Teva Pharmaceuticals 238
11.11 Endo International 243
11.12 Boehringer Ingelheim 246
11.13 3M 248
11.14 UCB 250
11.15 ParPharm 253
12.0 Current Transdermal Drug Delivery Products on the Market 255
12.1 Actavis 255
12.1.1 Androderm 255
12.1.2 Fentanyl Transdermal System 255
12.1.3 Lidocaine Topical Patch 255
12.1.4 Oxytrol 255
12.2 Actelion 256
12.2.1 Vachlor Gel (mechlorethamine) 256
12.3 GlaxoSmithKline 256
12.3.1 Niquitin/Nicoderm 257
12.4 Bayer 257
12.5 Mylan Pharmaceuticals 258
12.5.1 Clonidine Transdermal System 258
12.5.2 EMSAM (Selegiline Transdermal System) 258
12.5.3 Estradiol Transdermal System 258
12.5.4 Fentanyl Transdermal System 259
12.5.5 Nitroglycerin Transdermal System 259
12.5.6 XULANE (Norelgestromin / Ethinyl Estradiol Transdermal System) 259
12.6 Novartis 259
12.6.1 Exelon Patch (Rivastigmine Transdermal System) 261
12.6.2 Duragesic – Fentanyl Patches 261
12.6.3 Transderm Scop – Scopolamine Patches 262
12.7 Upsher-Smith 262
12.7.1 Vogelxo – Testosterone (1%) Gel 262
12.8 ASCEND Therapeutics 262
12.8.1 EstroGel® 262
12.9 AMAG Pharmaceuticals (Lumara Health) 262
12.9.1 Evamist® 262
12.10 Janssen Pharmaceuticals 262
12.10.1 OrthoEvra® 263
12.10.2 Duragesic® 263
12.11 Lavipharm 263
12.11.1 Fentadur 264
12.11.2 Nicotine Transdermal Patch 264
12.11.3 Acne Transdermal Patch 264
12.11.4 Trinipatch 264
12.12 Noven Pharmaceuticals 264
12.12.1 Minivelle® 264
12.12.2 CombiPatch® 264
12.12.3 Daytrana® 265
12.13 ProStraken 265
12.13.1 Sancuso® 265
12.14 Shire 265
12.14.1 Daytrana® CII 265
12.15 Hercon Pharmaceuticals 265
12.15.1 Nitroglycerin Transdermal System 265
12.16 Kremers Urban Pharmaceuticals 265
12.16.1 Nitroglycerin Transdermal System 265
12.17 Nitto Dento 265
12.17.1 Bisono Tape 265
12.17.2 Penles Tape 265
12.17.3 Passport Advanced Drug Delivery System 265
12.18 Teva Pharmaceuticals 266
12.18.1 Zecuity 266
12.18.2 Transdermal Fentanyl (generic) 266
12.18.3 Tev Tropin 266
12.19 Endo International 267
12.19.1 Lidoderm®Patch 267
12.19.2 Fortesa Gel 267
12.20 Teikoku 267
12.20.1 Lidoderm® 1 267
12.20.2 IontoPatch® 268
12.21 3M 268
12.21.1 3M Fentanyl Transdermal Delivery System 268
12.21.2 3M Rivastigmine Transdermal Delivery System 268
12.21.3 Microneedles 269
12.22 UCB 269
12.22.1 Neupro® 269
12.23 ParPharm 269
12.23.1 Fentanyl Transdermal System 269
13.0 In-Depth SWOT Analysis of the Transdermal Drug Delivery Market 270
13.1 Drivers of the Market 270
13.1.1 Will Patent Expirations and Introduction of Generics Drive the Short Term Transdermal
Market? 270
13.1.2 Increased Patient Compliance Rates 270
13.1.3 Increased Incidence of Chronic Conditions & Application of Patch Technology
to These Areas 271
13.1.3.1 Cancer 271
13.1.3.2 Cardiovascular Disease 273
13.1.3.3 Diabetes 273
13.1.3.4 Men’s Health 273
13.1.3.5 Neurological Disease 273
13.1.4 Increased Geriatric and Pediatric Drug Administration Requirements 274
13.2 Restraints and Weaknesses of the Transdermal Drug Delivery Market 274
13.2.1 Technical Restraints 274
13.2.2 Drug Adverse Reactions 275
13.2.3 Drug Failures 275
13.3 Opportunities Within the Market Place 275
13.3.1 High Number of Pharmaco & Drug Delivery Company Collaboration 276
13.3.4 Targeted Transdermal Drug Delivery 277
13.4 Challenges and Barriers to Market Entry 277
Appendix 1: Further Reading & Bibliography 279
