Pharmaceutical companies interested in transdermal drug delivery
Pharmaceutical research institutes
Summary
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.
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
Nanoemulsions for transdermal drug delivery 19
Transdermal gel technology 19
Film forming polymeric solutions 20
Biphasix system 21
Penetration enhancers 21
Chemical enhancers 21
Nitric oxide-based transdermal drug delivery 23
Vesicular transdermal carriers 23
Liposomes 24
Transfersomes 24
Ethosomes 25
Elastic vesicles for transdermal drug delivery 25
Nanovesicles for transdermal drug delivery 26
Transdermal patches 26
Adhesives for transdermal patches 27
Commercial development of transdermal patches 28
Innovations in transdermal patches 29
e-Patch"! controlled release micropump system 29
Patchless Transdermal Delivery System 30
Metered-dose transdermal system 30
Use of physical modalities to facilitate transdermal transport 31
Transdermal electrotransport 31
Electroporation 31
Drug delivery by electroporation 32
Cryoelectrophoresis 33
Iontophoresis 34
Iontophoresis compared with electrophoresis 35
Application of iontophoresis for drug delivery 35
Companies with technologies for drug delivery by iontophoresis 36
Combination of electrophoresis and iontophoresis 37
Dermaportation 37
Radiofrequency-driven transdermal delivery 37
Microporation 38
Transcutaneous drug delivery by electropulsation 38
Companies involved in electroporation-based drug delivery 39
Electrode Scanning System 39
Use of electrostatic force in skin patch technology 39
Multiple Absorption Kinetic System 40
Transdermal drug delivery facilitated by heat 40
Controlled, heat-aided drug delivery 40
Ultrasound 41
Magnetophoresis 43
Use of lasers for transdermal drug delivery 43
Transdermal drug delivery by laser-induced pressure waves 43
Transdermal drug delivery by laser-assisted changes in skin 43
Transdermal delivery by gas under pressure 44
Transdermal delivery with PowderJect gas gun 44
Microscission induced by gas 44
Role of microelectronics in transdermal drug delivery 45
Microneedles and dermal microinjection technologies 45
Microneedle patch 46
AdminPatchR microneedle array 47
Biodegradable microneedles 47
Ceramic microneedle arrays 48
Dissolvable microneedle patches 48
Microneedle arrays for drug delivery 48
MicroPyramid"! microneedles 49
Microstructured Transdermal Systems 49
Microneedle Array Patch technology 50
Microneedle transdermal chip 50
Microneedle applicator device 51
Nanoject"! microneedle technology 51
Silk microneedles 51
ZP Patch microprojections technology 52
Companies developing microneedles for transdermal drug delivery 52
Needlefree injections 53
Glide SDIR solid dose injector 53
Jet injection 53
Mini-Ject needlefree delivery system 54
MicroJet for painless injections 54
Nanoliter-volume pulsed microjets 54
SUMAVEL"! DosePro"! needle-less injection 55
Skin ablation or abrasion for drug delivery 55
Nanotechnology-based transdermal drug delivery 55
Delivery of nanostructured drugs from transdermal patches 56
Effect of mechanical flexion on penetration of bucky balls through the ski
56
Nanoparticles and nanoemulsions for skin disorders 56
Nanotechnology-based transdermal vaccination and immunotherapy 56
NanoCyte transdermal drug delivery system 57
Safety issues of applications of nanomaterial carriers on the skin 57
Transdermal administration of lipid nanocapsules 58
Transdermal nanoparticle preparations for systemic effect 58
Comparison of transdermal drug delivery systems 59
Transdermal drug design 59
In vitro testing of transdermal drug delivery systems 59
In vivo testing of drug delivery systems 60
Infrared spectroscopy for evaluation of transdermal drug delivery 61
Modeling of transport through the skin 61
Concluding remarks on transdermal drug delivery technologies 62
Future developments in transdermal drug delivery 62
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 79
Migraine 79
Transdermal lidocaine 79
Transdermal sumatriptan 79
Epilepsy 80
Tinnitus/Vertigo 80
Transdermal nitroglycerin for vasospasm due to subarachnoid hemorrhage
81
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 85
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 93
Nanoemulsion-based delivery of caffeine for skin cancer 93
Transcutaneous electroporation for anticancer drugs 93
Transdermal drug delivery for prostate cancer 94
Transdermal nitroglycerine for prostate cancer 94
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 95
Transdermal Lidoderm® for postherpectic neuralgia 95
Nonsteroidal antiinflammatory drugs 95
Topical NSAIDs 96
Transdermal ketoprofen 97
Topical opioids 98
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 101
Nausea and vomiting 101
Motion sickness 101
Postoperative vomiting 101
Chemotherapy-induced nausea and vomiting 101
Antiaging strategies 102
Smoking cessation 102
Transdermal nicotine replacement 102
Use of nicotine patch for smoking cessation in pregnancy 103
Other methods of nicotine replacement 103
Other treatments for smoking cessation 104
Miscellaneous uses of transdermal drug delivery 104
Chronic fatigue syndrome 104
Topical androgenic steroid therapy 104
Overactive bladder and urinary incontinence 104
Transdermal oxybutynin 105
Viral infections 105
Transdermal nanoparticles for immune enhancement in HIV 105
Transdermal gene therapy 106
Transdermal delivery of plasmid DNA by electroporation 106
Transdermal antisense therapy 107
Transdermal vaccination 107
The skin as an immune organ 108
Technologies for transdermal vaccination 108
Electroporation for administering DNA vaccines 108
Intradermal delivery of cancer vaccines by adenoviral vectors 108
Microneedles for transdermal delivery of vaccines 109
Needle-free delivery of vaccines 110
Transcutaneous immunization 110
Applications of transdermal vaccination 110
HIV/AIDS vaccination by topical application 110
Transdermal DNA influenza vaccine 111
Transdermal Aβ vaccination for Alzheimer's disease 111
Transdermal vaccination for traveller's diarrhoea 112
Transdermal neutraceuticals 112
Complications of transdermal therapy 113
Adverse effects of drugs 113
Overdose effect 113
Skin complications 113
4. Markets for Transdermal Drug Delivery 116
Introduction 116
Global markets for drug delivery 116
Geographical distribution of transdermal drug delivery markets 117
Emerging transdermal drug delivery markets in Asia 117
Transdermal technology markets in therapeutic areas 117
Angina pectoris 118
Attention deficit hyperactivity disorder 118
Erectile dysfunction 118
Hypertension 119
Pain therapeutics 119
Parkinson's disease 119
Smoking cessation 119
Transdermal hormone replacement therapy for menopause 119
Transdermal testosterone replacement therapy for hypogonadism in the male
120
Transdermal contraceptive market 120
Markets according to transdermal technologies 120
Markets for microneedle-based transdermal drug delivery 121
Marketing strategies for transdermal drug delivery 121
Marketing advantages of transdermal drug delivery 121
Unmet needs in transdermal drug delivery 122
Future prospects of transdermal drug delivery 123
Prospects of transdermal delivery for drugs coming off patents 123
Transdermal delivery of cosmetics 124
5. Companies involved in transdermal drug delivery 126
Profiles of companies 126
Collaborations 264
6. References 268
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 22
Table 2-3: Drug-in-adhesive versus reservoir type of transdermal patch
27
Table 2-4: Companies developing transdermal patches for drug delivery
28
Table 2-5: Companies with technologies for drug delivery by iontophoresis
36
Table 2-6: Companies involved in electroporation-based drug delivery 39
Table 2-7: Companies developing microneedles for transdermal drug delivery
52
Table 2-8: Comparison of transdermal drug delivery systems 59
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 116
Table 4-2: Transdermal drug delivery markets for geographical regions 2011
to 2021 117
Table 4-3: Potential therapeutic markets for transdermal products
2011-2021 118
Table 4-4: Markets according to transdermal technologies 120
Table 4-5: Marketing strategies based on transdermal drug delivery
technologies 121
Table 5-1: Collaborations in transdermal drug delivery 264
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 27
Figure 2-2: A schematic view of electroporation 32
Figure 2-3: Depiction of breakdown of the stratum corneum during
electroporation 33
Figure 2-4: A schematic drawing of Iontophoresis 34
