Transdermal Drug Delivery - Technologies, Markets, and Companies

• Publication date: February 2012

This report deals with transdermal drug delivery - an approach used to deliver drugs through the skin for therapeutic use as an alternative to oral,intravascular, subcutaneous and transmucosal routes. Various transdermal drug delivery technologies are described including the use of suitable formulations, carriers and penetration enhancers. The most commonly used transdermal system is the skin patch using various types of technologies. Nanoparticl...

This report deals with transdermal drug delivery - an approach used to deliver drugs through the skin for therapeutic use as an alternative to oral,intravascular, subcutaneous and transmucosal routes. Various transdermal drug delivery technologies are described including the use of suitable formulations, carriers and penetration enhancers. The most commonly used transdermal system is the skin patch using various types of technologies. Nanoparticles as well as the use of physical agents to facilitate transcutaneous drug delivery is described. Microneedle and needleless technologies are also described. Transdermal technologies may be applied for several categories of pharmaceuticals used for the treatment of disorders of the skin or for systemic effect to treat diseases of other organs. Several transdermal products and applications include hormone replacement therapy, contraception, management of pain, angina pectoris, smoking cessation and neurological disorders such as Parkinson's disease. The market for transdermal drug delivery is analyzed according to technologies and therapeutic areas from 2011 to 2021. This market is analyzed according to geographical regions as well.

Drug Delivery Technology Industry

TABLE OF CONTENTS

0. Executive Summary 11
1. Basics of Transdermal Drug Delivery 13
Introduction 13
Historical landmarks in transdermal drug delivery 13
Anatomy and physiology of skin 14
Transcutaneous absorption 14
Transdermal versus other methods of drug delivery 14
Advantages of transdermal drug delivery 15
First-Pass Effect 15
Drawbacks of transdermal delivery 15
Factors that influence transdermal drug delivery 15
Events governing transcutaneous absorption 16
Properties of the skin 16
Properties of drugs 17
The role of pH and pharmacokinetics 17
Intradermal disposition of drugs after topical application 18
2. Transdermal Drug Delivery Technologies 19
Introduction 19
Local application formulations 20
Crystalline topical formulations 20
Microemulsions for transdermal drug delivery 20
Nanoemulsions for transdermal drug delivery 21
Transdermal gel technology 21
Film forming polymeric solutions 22
Biphasix system 23
Penetration enhancers 23
Chemical enhancers 23
Nitric oxide-based transdermal drug delivery 25
Vesicular transdermal carriers 25
Liposomes 26
Transfersomes 26
Ethosomes 27
Elastic vesicles for transdermal drug delivery 27
Nanovesicles for transdermal drug delivery 28
Transdermal patches 28
Adhesives for transdermal patches 29
Commercial development of transdermal patches 30
Innovations in transdermal patches 31
e-Patch™ controlled release micropump system 31
Patchless Transdermal Delivery System 32
Metered-dose transdermal system 32
Use of physical modalities to facilitate transdermal transport 33
Transdermal electrotransport 33
Electroporation 33
Drug delivery by electroporation 34
Cryoelectrophoresis 35
Iontophoresis 36
Iontophoresis compared with electrophoresis 37
Application of iontophoresis for drug delivery 37
Companies with technologies for drug delivery by iontophoresis 38
Combination of electrophoresis and iontophoresis 39
Dermaportation 39
Radiofrequency-driven transdermal delivery 39
Microporation 40
Transcutaneous drug delivery by electropulsation 40
Companies involved in electroporation-based drug delivery 41
Electrode Scanning System 41
Use of electrostatic force in skin patch technology 41
Multiple Absorption Kinetic System 42
Transdermal drug delivery facilitated by heat 42
Controlled, heat-aided drug delivery 42
Ultrasound 43
Magnetophoresis 45
Use of lasers for transdermal drug delivery 45
Transdermal drug delivery by laser-induced pressure waves 45
Transdermal drug delivery by laser-assisted changes in skin 45
Transdermal delivery by gas under pressure 46
Transdermal delivery with PowderJect gas gun 46
Microscission induced by gas 46
Role of microelectronics in transdermal drug delivery 47
Microneedles and dermal microinjection technologies 47
Microneedle patch 47
AdminPatch® microneedle array 48
Biodegradable microneedles 49
Ceramic microneedle arrays 49
Dissolvable microneedle patches 50
Microneedle arrays for drug delivery 50
MicroPyramid™ microneedles 51
Microstructured Transdermal Systems 51
Microneedle Array Patch technology 51
Microneedle transdermal chip 52
Microneedle applicator device 52
Nanoject™ microneedle technology 53
Silk microneedles 53
ZP Patch microprojections technology 53
Companies developing microneedles for transdermal drug delivery 54
Needlefree injections 54
Glide SDI® solid dose injector 55
Jet injection 55
Mini-Ject needlefree delivery system 55
MicroJet for painless injections 55
Nanoliter-volume pulsed microjets 56
SUMAVEL™ DosePro™ needle-less injection 56
Skin ablation or abrasion for drug delivery 56
Nanotechnology-based transdermal drug delivery 57
Nanoparticles and nanoemulsions for skin disorders 57
Transdermal nanoparticle preparations for systemic effect 58
Nanotechnology-based transdermal vaccination and immunotherapy 58
Delivery of nanostructured drugs from transdermal patches 59
NanoCyte transdermal drug delivery system 59
Effect of mechanical flexion on penetration of bucky balls through the skin 60
Safety issues of applications of nanomaterial carriers on the skin 60
Comparison of transdermal drug delivery systems 60
Transdermal drug design 60
In vitro testing of transdermal drug delivery systems 61
In vivo testing of drug delivery systems 62
Infrared spectroscopy for evaluation of transdermal drug delivery 62
Modeling of transport through the skin 62
Concluding remarks on transdermal drug delivery technologies 63
Future developments in transdermal drug delivery 64
3. Transdermal Therapeutics 65
Introduction 65
Drugs that can be administered transdermally 65
Skin disorders 68
Psoriasis 68
Nanoemulsions for paclitaxel delivery in psoriasis 68
Iontophoresis for treatment of psoriasis 68
Hair loss 68
Cardiovascular disorders 69
Angina pectoris 69
Transdermal drug delivery for hypertension 70
Transdermal beta blockers 70
Transdermal anticoagulants 71
Congestive heart failure 71
Respiratory diseases 71
Asthma 71
Chronic obstructive pulmonary disease 72
Neurological and psychiatric disorders 72
Parkinson's disease 72
Transdermal drug delivery for Parkinson's disease 73
Transdermal dopamine agonists for Parkinson's disease 73
Rotigotine 74
Transdermal administration of other drugs for Parkinson disease 76
Depression 76
Transdermal selegiline 76
Bipolar disorder 77
Transdermal lithium 77
Restless legs syndrome 77
Alzheimer's disease 77
Transdermal nicotine for Tourette syndrome 78
Attention deficit hyperactivity disorder 78
Transdermal methylphenidate 78
Migraine 79
Transdermal lidocaine 79
Transdermal sumatriptan 79
Epilepsy 80
Tinnitus/Vertigo 80
Transdermal nitroglycerin for vasospasm due to subarachnoid hemorrhage 80
Musculoskeletal disorders 81
Osteoporosis 81
Transdermal alendronate 81
Transdermal estrogen 81
Transdermal human parathyroid hormone 82
Osteoarthritis 82
Transdermal therapy of diabetes 82
Transdermal insulin delivery in diabetes 82
Transdermal GLP1 agonist 83
Male sexual disorders 84
Erectile dysfunction 84
Topical and transdermal preparation for erectile dysfunction 84
Hypogonadism in the male 84
Topical testosterone 84
Women's health 86
Female sexual arousal disorder 86
Menopause 87
Hormone replacement therapy for menopause 87
Effect of transdermal estradiol on bone density 89
Transdermal PTH for postmenopausal osteoporosis 89
Transdermal testosterone for low libido in postmenopausal women 89
Breast disorders 90
Dysmenorrhea 90
Female infertility 90
Contraception 91
Female contraception 91
Ortho Evra™ 91
BAY86-5016 92
Male contraception 92
Transdermal progestin plus testosterone 92
Cancer 92
Nanoemulsion-based delivery of caffeine for skin cancer 93
Transcutaneous electroporation for anticancer drugs 93
Transdermal drug delivery for prostate cancer 93
Transdermal nitroglycerine for prostate cancer 93
Transdermal estradiol gel for prostate cancer 94
Transdermal drug delivery for breast cancer 94
Afimoxifene topical gel for breast cancer 94
Pain 94
Relief of pain associated with minor medical procedures 94
Transdermal Lidoderm? for postherpectic neuralgia 95
Nonsteroidal antiinflammatory drugs 95
Topical NSAIDs 95
Transdermal ketoprofen 96
Topical opioids 97
Cancer pain 98
Transdermal fentanyl 98
Transdermal nitroglycerine as an adjuvant to opioids 99
Transdermal buprenorphine 99
Chronic pain of non-malignant origin 99
Transdermal local anesthetics 100
Postoperative pain 100
Transdermal fentanyl for the management of postoperative pain 100
Fibromyalgia 100
Nausea and vomiting 101
Motion sickness 101
Postoperative vomiting 101
Chemotherapy-induced nausea and vomiting 101
Antiaging strategies 101
Smoking cessation 102
Transdermal nicotine replacement 102
Other methods of nicotine replacement 103
Other treatments for smoking cessation 103
Miscellaneous uses of transdermal drug delivery 104
Chronic fatigue syndrome 104
Topical androgenic steroid therapy 104
Overactive bladder and urinary incontinence 104
Transdermal oxybutynin 104
Viral infections 105
Transdermal nanoparticles for immune enhancement in HIV 105
Transdermal gene therapy 105
Transdermal delivery of plasmid DNA by electroporation 106
Transdermal antisense therapy 106
Transdermal vaccination 107
The skin as an immune organ 107
Technologies for transdermal vaccination 107
Electroporation for administering DNA vaccines 107
Intradermal delivery of cancer vaccines by adenoviral vectors 108
Microneedles for dermal delivery of vaccines 108
Needle-free delivery of vaccines 109
Transcutaneous immunization 109
Applications of transdermal vaccination 109
HIV/AIDS vaccination by topical application 109
Transdermal DNA influenza vaccine 110
Transdermal A? vaccination for Alzheimer’s disease 110
Transdermal vaccination for traveller’s diarrhoea 111
Transdermal neutraceuticals 111
Complications of transdermal therapy 112
Adverse effects of drugs 112
Overdose effect 112
Skin complications 112
4. Markets for Transdermal Drug Delivery 115
Introduction 115
Global markets for drug delivery 115
Geographical distribution of transdermal drug delivery markets 116
Emerging transdermal drug delivery markets in Asia 116
Transdermal technology markets in therapeutic areas 116
Angina pectoris 117
Attention deficit hyperactivity disorder 117
Erectile dysfunction 117
Hypertension 118
Pain therapeutics 118
Parkinson's disease 118
Smoking cessation 118
Transdermal hormone replacement therapy for menopause 118
Transdermal testosterone replacement therapy for hypogonadism in the male 119
Transdermal contraceptive market 119
Markets according to transdermal technologies 119
Markets for microneedle-based transdermal drug delivery 120
Marketing strategies for transdermal drug delivery 120
Marketing advantages of transdermal drug delivery 120
Unmet needs in transdermal drug delivery 121
Future prospects of transdermal drug delivery 122
Prospects of transdermal delivery for drugs coming off patents 122
Transdermal delivery of cosmetics 123
5. Companies involved in transdermal drug delivery 125
Profiles of companies 125
Collaborations 264
6. References 269

List of Tables
Table 1 1: Historical landmarks in the development of transdermal drug delivery 13
Table 1 2: Transdermal vs oral and intravenous drug delivery 15
Table 2 1: Technologies for transdermal drug delivery 19
Table 2 2: Chemical enhancers of skin penetration 24
Table 2 3: Drug-in-adhesive versus reservoir type of transdermal patch 29
Table 2 4: Companies developing transdermal patches for drug delivery 30
Table 2 5: Companies with technologies for drug delivery by iontophoresis 38
Table 2 6: Companies involved in electroporation-based drug delivery 41
Table 2 7: Companies developing microneedles for transdermal drug delivery 54
Table 2 8: Comparison of transdermal drug delivery systems 60
Table 3 1: Approved transdermal products 65
Table 3 2: Transdermal drugs in clinical trials or approval process 67
Table 4 1: Worldwide drug delivery market growth 2011 to 2021 115
Table 4 2: Transdermal drug delivery markets for geographical regions 2011 to 2021 116
Table 4 3: Potential therapeutic markets for transdermal products 2011-2021 117
Table 4 4: Markets according to transdermal technologies 119
Table 4 5: Marketing strategies based on transdermal drug delivery technologies 120
Table 5 1: Collaborations in transdermal drug delivery 264

List of Figures
Figure 1 1: Basic structure of the skin 14
Figure 1 2: Events governing transcutaneous drug absorption 17
Figure 2 1: Basic structure and function of transdermal drug delivery systems 29
Figure 2 2: A schematic view of electroporation 34
Figure 2 3: Depiction of breakdown of the stratum corneum during electroporation 35
Figure 2 4: A schematic drawing of Iontophoresis 36
Figure 2 5: SonoPrep ultrasonic skin permeation 44
Figure 2 6: A schematic drawing of the microneedle patch 48
Figure 3 1: Oral versus transdermal administration of a drug in Parkinson's disease 75
Figure 4 1: Unmet needs in transdermal drug delivery 122