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
2012 to 2022. 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
Role of nanobiotechnology in understanding basis of transdermal delivery
15
Properties of drugs 15
The role of pH and pharmacokinetics 16
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 21
Biphasix system 21
Penetration enhancers 21
Chemical enhancers 22
Nitric oxide-based transdermal drug delivery 24
Vesicular transdermal carriers 24
Liposomes 24
Transfersomes 25
Ethosomes 25
Elastic vesicles for transdermal drug delivery 26
Nanovesicles for transdermal drug delivery 26
Transdermal patches 27
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 32
Transdermal electrotransport 32
Electroporation 33
Drug delivery by electroporation 34
Cryoelectrophoresis 35
Iontophoresis 36
Iontophoresis compared with electrophoresis 36
Application of iontophoresis for drug delivery 36
Companies with technologies for drug delivery by iontophoresis 38
Combination of electrophoresis and iontophoresis 38
Dermaportation 39
Radiofrequency-driven transdermal delivery 39
Microporation 39
Transcutaneous drug delivery by electropulsation 40
Companies involved in electroporation-based drug delivery 40
Electrode Scanning System 41
Use of electrostatic force in skin patch technology 41
Multiple Absorption Kinetic System 41
Transdermal drug delivery facilitated by heat 42
Controlled, heat-aided drug delivery 42
Ultrasound 42
Magnetophoresis 44
Use of lasers for transdermal drug delivery 44
Laser-induced microporation 44
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
Delivery of nanostructured drugs from transdermal patches 57
Effect of mechanical flexion on penetration of bucky balls through the
skin 57
Nanomaterials for transdermal application 58
Nanoparticles and nanoemulsions for skin disorders 58
NanoCyte transdermal drug delivery system 58
Topical delivery of siRNA- nanoparticle conjugates 58
Transdermal nanoparticle preparations for systemic effect 59
Transferosomes for transdermal drug delivery 60
Transdermal administration of nanocarriers 60
Nanotechnology-based transdermal vaccination and immunotherapy 60
Safety issues of applications of nanomaterial carriers on the skin
61
Comparison of transdermal drug delivery systems 61
Transdermal drug design 61
In vitro testing of transdermal drug delivery systems 62
In vivo testing of drug delivery systems 63
Infrared spectroscopy for evaluation of transdermal drug delivery 63
Modeling of transport through the skin 63
Concluding remarks on transdermal drug delivery technologies 64
Future developments in transdermal drug delivery 65
3. Transdermal Therapeutics 66
Introduction 66
Drugs that can be administered transdermally 66
Skin disorders 69
Psoriasis 69
Nanoemulsions for paclitaxel delivery in psoriasis 69
Iontophoresis for treatment of psoriasis 69
Iontophoretic drug delivery for nail disorders 69
Hair loss 70
Cardiovascular disorders 70
Angina pectoris 70
Transdermal drug delivery for hypertension 71
Transdermal delivery of β-blockers for hypertension 72
Transdermal delivery of calcium channel blockers for hypertension 72
Transdermal drug delivery for congestive heart failure 73
Transdermal beta blockers 73
Transdermal anticoagulants 73
Respiratory diseases 73
Asthma 74
Chronic obstructive pulmonary disease 74
Neurological and psychiatric disorders 75
Parkinson's disease 75
Transdermal drug delivery for Parkinson's disease 75
Transdermal dopamine agonists for Parkinson's disease 76
Rotigotine 76
Transdermal administration of other drugs for Parkinson disease 78
Depression 78
Antidepressants 78
Selective serotonin-reuptake inhibitors 78
Transdermal fluoxetine 79
Monoamine oxidase inhibitors 79
Transdermal selegiline 79
Trazodone hydrochloride 80
Venlafaxine 80
Bupropion 81
Bipolar disorder 81
Transdermal lithium 81
Schizophrenia 82
Transdermal haloperidol 82
Transdermal risperidone for treatment of schizophrenia 82
Restless legs syndrome 83
Alzheimer's disease 83
Transdermal rivastigmine 83
Transdermal donepezil 84
Transdermal arecoline 84
Transdermal nicotine for Tourette syndrome 85
Attention deficit hyperactivity disorder 85
Transdermal methylphenidate 85
Migraine 85
Transdermal sumatriptan 85
Epilepsy 86
Tinnitus/Vertigo 87
Transdermal nitroglycerin for vasospasm due to subarachnoid hemorrhage
87
Musculoskeletal disorders 87
Osteoporosis 87
Transdermal alendronate 87
Transdermal estrogen 88
Transdermal human parathyroid hormone 88
Osteoarthritis 88
Transdermal therapy of diabetes 89
Transdermal insulin delivery in diabetes 89
Transdermal GLP1 agonist 89
Male sexual disorders 90
Erectile dysfunction 90
Topical and transdermal preparation for erectile dysfunction 90
Hypogonadism in the male 90
Topical testosterone 91
Women's health 92
Female sexual arousal disorder 92
Menopause 93
Hormone replacement therapy for menopause 93
Effect of transdermal estradiol on bone density 95
Transdermal PTH for postmenopausal osteoporosis 95
Transdermal testosterone for low libido in postmenopausal women 95
Breast disorders 96
Dysmenorrhea 96
Female infertility 96
Contraception 97
Female contraception 97
Ortho Evra™ 97
AG200-15 98
BAY86-5016 98
Male contraception 98
Transdermal progestin plus testosterone 98
Cancer 99
Delivery of the photosensitizer drug δ-amino levulinic acid
99
Intradermal delivery of cancer vaccines by adenoviral vectors 99
Nanoemulsion-based delivery of caffeine for skin cancer 100
Topical interferon α2b for cervical cancer and precancerous lesions
100
Transcutaneous electroporation for delivery of anticancer drugs 100
Transdermal delivery of peptide cancer vaccines 101
Transdermal drug delivery for prostate cancer 101
Transdermal nitroglycerine for prostate cancer 101
Transdermal estradiol gel for prostate cancer 101
Transdermal drug delivery for breast cancer 101
Afimoxifene topical gel for breast cancer 101
Pain 102
Relief of pain associated with minor medical procedures 102
Transdermal Lidoderm® for postherpectic neuralgia 102
Nonsteroidal antiinflammatory drugs 103
Topical NSAIDs 103
Transdermal ketoprofen 104
Topical opioids 105
Cancer pain 105
Transdermal fentanyl 105
Transdermal nitroglycerine as an adjuvant to opioids 106
Transdermal buprenorphine 106
Chronic pain of non-malignant origin 107
Transdermal local anesthetics 107
Postoperative pain 107
Transdermal fentanyl for the management of postoperative pain 107
Fibromyalgia 108
Nausea and vomiting 108
Motion sickness 108
Postoperative vomiting 108
Chemotherapy-induced nausea and vomiting 108
Antiaging strategies 109
Smoking cessation 109
Transdermal nicotine replacement 109
Use of nicotine patch for smoking cessation in pregnancy 110
Other methods of nicotine replacement 111
Other treatments for smoking cessation 111
Miscellaneous uses of transdermal drug delivery 111
Chronic fatigue syndrome 111
Overactive bladder and urinary incontinence 111
Transdermal oxybutynin 112
Viral infections 112
Transdermal nanoparticles for immune enhancement in HIV 113
Transdermal gene therapy 113
Transdermal delivery of plasmid DNA by electroporation 114
Transdermal antisense therapy 114
Transdermal vaccination 115
The skin as an immune organ 115
Technologies for transdermal vaccination 115
Dissolvable microneedle array for vaccine delivery 115
Electroporation for administering DNA vaccines 115
Microneedles for transdermal delivery of vaccines 116
Needle-free delivery of vaccines 117
Transcutaneous immunization 117
Applications of transdermal vaccination 118
HIV/AIDS vaccination by topical application 118
Transdermal DNA influenza vaccine 119
Transdermal Aβ vaccination for Alzheimer's disease 119
Transdermal vaccination for traveller's diarrhoea 119
Transdermal neutraceuticals 120
Complications of transdermal therapy 120
Adverse effects of drugs 120
Overdose effect 121
Skin complications 121
4. Markets for Transdermal Drug Delivery 122
Introduction 122
Global markets for drug delivery 122
Geographical distribution of transdermal drug delivery markets 123
Emerging transdermal drug delivery markets in Asia 123
Transdermal technology markets in therapeutic areas 123
Angina pectoris 124
Attention deficit hyperactivity disorder 124
Erectile dysfunction 124
Hypertension 125
Pain therapeutics 125
Parkinson's disease 125
Smoking cessation 125
Transdermal hormone replacement therapy for menopause 125
Transdermal testosterone replacement therapy for hypogonadism in the male
126
Transdermal contraceptive market 126
Markets according to transdermal technologies 126
Markets for microneedle-based transdermal drug delivery 127
Marketing strategies for transdermal drug delivery 127
Marketing advantages of transdermal drug delivery 127
Unmet needs in transdermal drug delivery 128
Future prospects of transdermal drug delivery 129
Prospects of transdermal delivery for drugs coming off patents 129
Transdermal delivery of cosmetics 130
5. Companies involved in transdermal drug delivery 132
Profiles of companies 132
Collaborations 261
6. References 266
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
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 61
Table 3-1: Approved transdermal products 66
Table 3-2: Transdermal drugs in clinical trials or approval process
68
Table 4-1: Worldwide drug delivery market growth 2012 to 2022 122
Table 4-2: Transdermal drug delivery markets for geographical regions 2012
to 2022 123
Table 4-3: Potential therapeutic markets for transdermal products
2012-2022 124
Table 4-4: Markets according to transdermal technologies 2012-2022
126
Table 4-5: Marketing strategies based on transdermal drug delivery
technologies 127
Table 5-1: Top ten companies in transdermal drug delivery 132
Table 5-2: Collaborations in transdermal drug delivery 261
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: Transdermal system for delivery of liquid drugs 29
Figure 2-3: A schematic view of electroporation 33
Figure 2-4: Depiction of breakdown of the stratum corneum during
electroporation 35
Figure 2-5: A schematic drawing of Iontophoresis 36
