Transdermal Drug Delivery - Technologies, Markets, and Companies

Table of Contents

0. Executive Summary 9

1. Basics of Transdermal Drug Delivery 11

• Introduction 11
• Historical landmarks in transdermal drug delivery 11
• Anatomy and physiology of skin 12
• Transcutaneous absorption 12
• Transdermal versus other methods of drug delivery 12
• Advantages of transdermal drug delivery 13
• First-Pass Effect 13
• Drawbacks of transdermal delivery 13
• Factors that influence transdermal drug delivery 13
• Events governing transcutaneous absorption 14
• Properties of the skin 14
• Properties of drugs 15
• The role of pH and pharmacokinetics 15
• Intradermal disposition of drugs after topical application 16

2. Transdermal Drug Delivery Technologies 17

• Introduction 17
• Local application formulations 18
• Crystalline topical formulations 18
• Microemulsions for transdermal drug delivery 18
• Transdermal gel technology 19
• Film forming polymeric solutions 20
• Biphasix system 20
• Penetration enhancers 21
• Chemical enhancers 21
• Nitric oxide-based transdermal drug delivery 23
• Vesicular transdermal carriers 23
• Liposomes 23
• Transfersomes 24
• Ethosomes 24
• Elastic vesicles for transdermal drug delivery 25
• Nanovesicles for transdermal drug delivery 25
• Transdermal patches 26
• Adhesives for transdermal patches 27
• Commercial development of transdermal patches 27
• Innovations in transdermal patches 28
• e-Patch"! controlled release micropump system 28
• Patchless Transdermal Delivery System 29
• Metered-dose transdermal system 29
• Use of physical modalities to facilitate transdermal transport 30
• Transdermal electrotransport 30
• Electroporation 30
• Drug delivery by electroporation 31
• Cryoelectrophoresis 32
• Iontophoresis 33
• Application of iontophoresis for drug delivery 34
• Companies with technologies for drug delivery by iontophoresis 35
• Combination of electrophoresis and iontophoresis 36
• Dermaportation 36
• Radiofrequency-driven transdermal delivery 36
• Microporation 37
• Electrode Scanning System 37
• Use of electrostatic force in skin patch technology 38
• Multiple Absorption Kinetic System 38
• Transdermal drug delivery facilitated by heat 38
• Controlled, heat-aided drug delivery 38
• Ultrasound 39
• Magnetophoresis 41
• Use of lasers for transdermal drug delivery 41
• Transdermal drug delivery by laser-induced pressure waves 41
• Transdermal drug delivery by laser-assisted changes in skin 41
• Transdermal delivery by gas under pressure 42
• Transdermal delivery with PowderJect gas gun 42
• Microscission induced by gas 42
• Microneedles and dermal microinjection technologies 43
• Microneedle patch 43
• Microneedle arrays for drug delivery 44
• MicroPyramid"! hollow microneedles 44
• Microstructured Transdermal Systems 44
• Microneedle Array Patch technology 45
• Macroflux microprojections technology 45
• Companies developing microneedles for transdermal drug delivery 45
• Needlefree injections 46
• Jet injection 46
• Mini-Ject needlefree delivery system 46
• MicroJet for painless injections 46
• Nanoliter-volume pulsed microjets 47
• Skin ablation or abrasion for drug delivery 47
• Nanotechnology-based transdermal drug delivery 48
• Nanoparticles and nanoemulsions for skin disorders 48
• Transdermal nanoparticle preparations for systemic effect 48
• Nanotechnology-based transdermal vaccination and immunotherapy 49
• Delivery of nanostructured drugs from transdermal patches 49
• NanoCyte transdermal drug delivery system 50
• Effect of mechanical flexion on penetration of bucky balls through the skin 50
• Safety issues of applications of nanomaterial carriers on the skin 50
• Comparison of transdermal drug delivery systems 51
• Role of microelectronics in transdermal drug delivery 51
• Transdermal drug design 51
• In vitro testing of transdermal drug delivery systems 52
• In vivo testing of drug delivery systems 53
• Infrared spectroscopy for evaluation of transdermal drug delivery 53
• Modeling of transport through the skin 53
• Concluding remarks on transdermal drug delivery technologies 54
• Future developments in transdermal drug delivery 55

3. Transdermal Therapeutics 57

• Introduction 57
• Drugs that can be administered transdermally 57
• Skin disorders 60
• Fungus infections of nails 60
• Topical penetrating applications for nail fungus infections 60
• Hair loss 60
• Cardiovascular disorders 60
• Angina pectoris 60
• Transdermal drug delivery for hypertension 62
• Transdermal beta blockers 62
• Transdermal anticoagulants 62
• Congestive heart failure 63
• Respiratory diseases 63
• Asthma 63
• Chronic obstructive pulmonary disease 64
• Neurological and psychiatric disorders 64
• Parkinson' s disease 64
• Transdermal drug delivery for Parkinson' s disease 65
• Transdermal dopamine agonists for Parkinson' s disease 65
• Rotigotine 66
• Transdermal administration of other drugs for Parkinson' s disease 67
• Depression 67
• Transdermal selegiline 67
• Bipolar disorder 68
• Transdermal lithium 68
• Restless legs syndrome 68
• Alzheimer' s disease 68
• Transdermal nicotine for Tourette syndrome 69
• Attention deficit hyperactivity disorder 69
• Transdermal methylphenidate 69
• Migraine 70
• Transdermal lidocaine 70
• Transdermal sumatriptan 70
• Epilepsy 70
• Tinnitus/Vertigo 71
• Transdermal nitroglycerin for vasospasm due to subarachnoid hemorrhage 71
• Musculoskeletal disorders 71
• Osteoporosis 71
• Transdermal hormonal therapy 71
• Osteoarthritis 72
• Transdermal insulin delivery in diabetes 72
• Male sexual disorders 73
• Erectile dysfunction 73
• Topical and transdermal preparation for erectile dysfunction 73
• Hypogonadism in the male 74
• Topical testosterone 74
• Women' s health 76
• Female sexual arousal disorder 76
• Menopause 77
• Hormone replacement therapy for menopause 77
• Effect of transdermal estradiol on bone density 79
• Transdermal testosterone for low libido in postmenopausal women 79
• Breast disorders 79
• Contraception 80
• Female contraception 80
• Male contraception 81
• Cancer 81
• Transcutaneous electroporation for anticancer drugs 81
• Pain 82
• Relief of pain associated with minor medical procedures 82
• Transdermal Lidoderm® for postherpectic neuralgia 82
• Nonsteroidal antiinflammatory drugs 83
• Topical NSAIDs 83
• Transdermal ketoprofen 84
• Topical opioids 85
• Cancer pain 85
• Transdermal fentanyl 85
• Transdermal nitroglycerine as an adjuvant to opioids 86
• Transdermal buprenorphine 86
• Chronic pain of non-malignant origin 87
• Postoperative pain 87
• Transdermal fentanyl for the management of postoperative pain 87
• Nausea and vomiting 88
• Motion sickness 88
• Postoperative vomiting 88
• Chemotherapy-induced nausea and vomiting 88
• Antiaging strategies 88
• Smoking cessation 89
• Transdermal nicotine replacement 89
• Other methods of nicotine replacement 90
• Other treatments for smoking cessation 90
• Miscellaneous uses of transdermal drug delivery 90
• Chronic fatigue syndrome 90
• Topical androgenic steroid therapy 91
• Fibromyalgia 91
• Dysmenorrhea 91
• Overactive bladder and urinary incontinence 91
• Transdermal oxybutynin 91
• Viral infections 92
• Transdermal nanoparticles for immune enhancement in HIV 92
• Transdermal gene therapy 92
• Transdermal antisense therapy 93
• Transdermal vaccination 94
• The skin as an immune organ 94
• Technologies for transdermal vaccination 94
• Dermal microinjection technology for delivery of vaccines 94
• Electroporation for administering DNA vaccines 94
• Intradermal delivery of cancer vaccines by adenoviral vectors 95
• PassPort system for needle free delivery of vaccines 95
• Transcutaneous immunization 95
• Applications of transdermal vaccination 96
• HIV/AIDS vaccination by topical application 96
• Transdermal DNA influenza vaccine 96
• Transdermal Aβ vaccination for Alzheimer' s disease 97
• Transdermal vaccination for traveller' s diarrhoea 97
• Complications of transdermal therapy 98
• Adverse effects of drugs 98
• Overdose effect 98
• Skin complications 98

4. Markets for Transdermal Drug Delivery 101

• Introduction 101
• Global markets for drug delivery 101
• Geographical distribution of transdermal drug delivery markets 102
• Emerging transdermal drug delivery markets in Asia 102
• Transdermal technology markets in therapeutic areas 102
• Angina pectoris 103
• Attention deficit hyperactivity disorder 103
• Erectile dysfunction 103
• Hypertension 104
• Pain therapeutics 104
• Parkinson' s disease 104
• Smoking cessation 104
• Transdermal hormone replacement therapy for menopause 104
• Transdermal testosterone replacement therapy for hypogonadism in the male 105
• Markets according to transdermal technologies 105
• Marketing strategies for transdermal drug delivery 105
• Marketing advantages of transdermal drug delivery 106
• Unmet needs in transdermal drug delivery 106
• Future prospects of transdermal drug delivery 107
• Prospects of transdermal delivery for drugs coming off patents 108
• Transdermal delivery of cosmetics 108

5. Companies involved in transdermal drug delivery 109

• Profiles of companies 109
• Collaborations 228

6. References 233

Tables

• Table 1 1: Historical landmarks in the development of transdermal drug delivery 11
• Table 1 2: Transdermal vs oral and intravenous drug delivery 13
• Table 2 1: Technologies for transdermal drug delivery 17
• Table 2 2: Chemical enhancers of skin penetration 21
• Table 2 3: Drug-in-adhesive versus reservoir type of transdermal patch 26
• Table 2 4: Companies developing transdermal patches for drug delivery 27
• Table 2 5: Companies with technologies for drug delivery by iontophoresis 35
• Table 2 6: Companies developing microneedles for transdermal drug delivery 45
• Table 2 7: Comparison of transdermal drug delivery systems 51
• Table 3 1: Approved categories of transdermal drugs 57
• Table 3 2: Current status of transdermal products 58
• Table 4 1: Worldwide drug delivery market growth 2008 to 2018 101
• Table 4 2: Transdermal drug delivery markets for geographical regions 2008 to 2018 102
• Table 4 3: Potential therapeutic markets for transdermal products 2008-2018 103
• Table 4 4: Marketing strategies based on transdermal drug delivery technologies 105
• Table 5 1: Collaborations in transdermal drug delivery 228

Figures

• Figure 1 1: Basic structure of the skin 12
• Figure 1 2: Events governing transcutaneous drug absorption 15
• Figure 2 1: Basic structure and function of transdermal drug delivery systems 26
• Figure 2 2: A schematic view of electroporation 31
• Figure 2 3: Depiction of breakdown of the stratum corneum during electroporation 32
• Figure 2 4: A schematic drawing of Iontophoresis 33
• Figure 2 5: SonoPrep ultrasonic skin permeation 40
• Figure 2 6: A schematic drawing of the microneedle patch 43
• Figure 3 1: Oral versus transdermal administration of a drug in Parkinson' s disease 66
• Figure 4 1: Unmet needs in transdermal drug delivery 107