Novel Delivery Systems for Transdermal and Intradermal Drug Delivery
Herausgegeben von Donnelly, Ryan F.; Singh, Thakur Raghu Raj
Novel Delivery Systems for Transdermal and Intradermal Drug Delivery
Herausgegeben von Donnelly, Ryan F.; Singh, Thakur Raghu Raj
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This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery. It provides a review of transdermal and intradermal drug delivery, including the history of the field and the various methods employed to produce delivery systems from different materials such as device design, construction and evaluation, so as to provide a sound background to the use of novel systems in enhanced delivery applications.
Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with…mehr
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This research book covers the major aspects relating to the use of novel delivery systems in enhancing both transdermal and intradermal drug delivery. It provides a review of transdermal and intradermal drug delivery, including the history of the field and the various methods employed to produce delivery systems from different materials such as device design, construction and evaluation, so as to provide a sound background to the use of novel systems in enhanced delivery applications.
Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with a focus on microneedle arrays, needle-free injections, nanoparticulate systems and peptide-carrier-type systems. It also covers conventional physical enhancement strategies, such as tape-stripping, sonophoresis, iontophoresis, electroporation and thermal/suction/laser ablation Discussions about the penetration of the stratum corneum by the various novel strategies highlight the importance of the application method. Comprehensive and critical reviews of transdermal and intradermal delivery research using such systems focus on the outcomes of in vivoanimal and human studies. The book includes laboratory, clinical and commercial case studies featuring safety and patient acceptability studies carried out to date, and depicts a growing area for use of these novel systems is in intradermal vaccine delivery. The final chapters review recent patents in this field and describe the work ongoing in industry.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Furthermore, it presents in-depth analyses of recent developments in this exponentially growing field, with a focus on microneedle arrays, needle-free injections, nanoparticulate systems and peptide-carrier-type systems. It also covers conventional physical enhancement strategies, such as tape-stripping, sonophoresis, iontophoresis, electroporation and thermal/suction/laser ablation Discussions about the penetration of the stratum corneum by the various novel strategies highlight the importance of the application method. Comprehensive and critical reviews of transdermal and intradermal delivery research using such systems focus on the outcomes of in vivoanimal and human studies. The book includes laboratory, clinical and commercial case studies featuring safety and patient acceptability studies carried out to date, and depicts a growing area for use of these novel systems is in intradermal vaccine delivery. The final chapters review recent patents in this field and describe the work ongoing in industry.
Hinweis: Dieser Artikel kann nur an eine deutsche Lieferadresse ausgeliefert werden.
Produktdetails
- Produktdetails
- Advances in Pharmaceutical Technology
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 296
- Erscheinungstermin: 28. September 2015
- Englisch
- Abmessung: 244mm x 170mm x 20mm
- Gewicht: 635g
- ISBN-13: 9781118734513
- ISBN-10: 1118734513
- Artikelnr.: 42397669
- Advances in Pharmaceutical Technology
- Verlag: Wiley & Sons
- 1. Auflage
- Seitenzahl: 296
- Erscheinungstermin: 28. September 2015
- Englisch
- Abmessung: 244mm x 170mm x 20mm
- Gewicht: 635g
- ISBN-13: 9781118734513
- ISBN-10: 1118734513
- Artikelnr.: 42397669
Dr Ryan Donnelly is Reader in Pharmaceutics at Queen's University Belfast. Dr Donnelly's research is centred on design and physicochemical characterisation of advanced polymeric drug delivery systems for transdermal and topical drug delivery, with a strong emphasis on improving therapeutic outcomes for patients. He is also a technical director at Swedish Pharma AB. Still at a relatively early stage of his career, he has authored over 300 peer-reviewed publications, including 3 patent applications, 3 textbooks, 16 book chapters and approximately 100 full papers. He's the holder of many awards including the current GSK Emerging Scientist Award. Dr Raj Thakur is Lecturer in Pharmaceutics at Queen's University Belfast. He obtained his PhD in polymer science in 2009 from Queens University Belfast and his MSc in drug delivery in 2006 from University Science Malaysia. He has a BSc in Pharmacy from Jawaharlal Nehru Technological University, India. Dr Thakur's research interests are in development and evaluation of novel in situ forming controlled release implants and ocular and transdermal drug delivery using novel minimally-invasive devices. He has published a textbook and over 30 scientific papers.
About the Editors xiii Contributors xv Advances in Pharmaceutical
Technology: Series Preface xvii Preface xix 1 Introduction 1 Gary P.J. Moss
1.1 The Subcutis (Subcutaneous Fat Layer) 1 1.2 The Dermis 2 1.3 Skin
Appendages 2 1.4 The Subcutaneous Sensory Mechanism 3 1.5 The Epidermis 5
1.6 The stratum germinativum 5 1.7 The stratum spinosum 5 1.8 The stratum
granulosum 6 1.9 The stratum lucidum 6 1.10 The stratum corneum 6 1.10.1
Routes of Absorption 9 1.10.2 Transdermal Permeation - Mechanisms of
Absorption 9 1.11 Theoretical Considerations 11 1.12 Physicochemical
Properties of the Penetrant 13 1.12.1 Partition Coefficient 13 1.12.2
Molecular Size and Shape 14 1.12.3 Applied Concentration/Dose 15 1.12.4
Solubility and Melting Point 15 1.12.5 Ionisation 15 1.12.6 Physiological
Factors Affecting Percutaneous Absorption 16 1.13 Physiological Properties
of the Skin 16 1.13.1 Skin Condition 16 1.13.2 Skin Hydration and Occlusion
17 1.13.3 Skin Age 17 1.13.4 Regional Variation (Body Site) 18 1.13.5 Race
19 1.13.6 Skin Temperature 19 1.14 Vehicle Effects 19 1.15 Modulation and
Enhancement of Topical and Transdermal Drug Delivery 20 1.15.1 Chemical
Modulation of Permeation 21 1.15.2 Physical Methods of Enhancement 26 2
Application of Spectroscopic Techniques to Interrogate Skin 41 Jonathan
Hadgraft, Rita Mateus and Majella E. Lane 2.1 Introduction 41 2.2
Vibrational Spectroscopic Methods 42 2.3 Electronic Spectroscopic Methods
46 2.3.1 UV and Fluorescence 46 2.3.2 Nuclear Magnetic Resonance 47 2.4
Miscellaneous Spectroscopic Methods 48 2.4.1 Opto?]Thermal Transient
Emission Radiometry 48 2.4.2 Electron Spin Resonance 48 2.4.3 Impedance
Spectroscopy 49 2.4.4 Laser?]Induced Breakdown Spectroscopy 49 2.4.5
Photoacoustic Spectroscopy 50 2.4.6 Mass Spectrometry Imaging 50 2.5
Conclusions and Future 50 3 Analysis of the Native Structure of the Skin
Barrier by Cryo?]TEM Combined with EM?]Simulation 57 Lars Norlén 3.1
Introduction 57 3.2 Our Approach: In Situ Biomolecular Structure
Determination in Near?]Native Skin 58 3.2.1 Step 1: Cryo?]Electron
Microscopy of Vitreous Sections 60 3.2.2 Steps 2-3: Molecular Model
Building and Electron Microscopy Simulation 66 3.2.3 Step 4: Confrontation
of Observed Data with Simulated Data 66 3.3 Molecular Organisation of the
Horny Layer's Fat Matrix 67 3.4 Molecular Organisation of the Horny Layer's
Keratin Filament Matrix 67 3.5 Final Remark 68 4 Intradermal Vaccination 71
Marija Zaric and Adrien Kissenpfennig 4.1 Vaccination 71 4.1.1
Disadvantages Associated with Conventional Vaccination 72 4.2 Dendritic
Cells Immunobiology 73 4.3 Skin Anatomy and Physiology 74 4.3.1 The Role of
Skin in Vaccine Delivery 75 4.4 The Skin Dendritic Cell Network 76 4.4.1
Langerhans Cells and the 'Langerhans Cell Paradigm' 76 4.4.2 Dermal
Dendritic Cell Network 77 4.4.3 Dendritic Cell Subsets in the
Skin?]Draining Lymph Node 79 4.4.4 Human Dendritic Cells in the Skin 80
4.4.5 The Role of Skin Dendritic Cells Subsets in Transdermal Immunisation
81 4.5 The DTR?]DT Depletion System 82 4.5.1 Langerin?]DTR Mouse Models 83
4.6 Dendritic Cells and the Differentiation of T Lymphocytes 84 4.6.1 CD8+
T Cell Activation 85 4.6.2 CD4+ T Cell Polarisation 85 4.7 Summary 88 5
Film?]Forming and Heated Systems 97 William J. McAuley and Francesco
Caserta 5.1 Film?]Forming Systems 97 5.1.1 The Design of Film?]Forming
Systems 98 5.1.2 Advantages of Using Film?]Forming Systems for Drug
Delivery 99 5.1.3 Production of a Supersaturated State 101 5.1.4 Use with
Chemical Penetration Enhancers 103 5.1.5 Advantages of Film?]Forming
Systems for Patient Use 105 5.1.6 Therapeutic Applications 105 5.2 Heated
Systems 107 5.2.1 Mechanisms of Drug Penetration Enhancement 107 5.2.2
Partitioning 108 5.2.3 Effects of Heat on Skin 110 5.2.4 Dermal Clearance
111 5.2.5 The Effects of Heat on the Permeation of Drugs Across Skin 112
5.2.6 Strategies for Generating Heat 113 5.2.7 Therapeutic Applications 115
5.3 Conclusions 116 6 Nanotechnology?]Based Applications for Transdermal
Delivery of Therapeutics 125 Venkata K. Yellepeddi 6.1 Introduction 125
6.1.1 Skin Structure 126 6.1.2 Skin Sites for Nanoparticle Delivery 127
6.1.3 Skin as a Barrier for Nanoparticle Penetration 128 6.1.4
Physicochemical Characteristics of NPs for Penetration through Skin 129 6.2
Nanocarriers for Topical and Transdermal Delivery 129 6.2.1 Polymeric
Nanoparticles 130 6.2.2 Lipid Based Nanocarriers 134 6.2.3 Metallic and
Mineral Nanoparticles 135 6.2.4 Carbon?]Based Nanomaterials 137 6.3
Interactions of Nanoparticles with the Skin 137 6.4 Limitations of
Nanotechnology for Skin Delivery 138 6.5 Conclusions 139 7 Magnetophoresis
and Electret?]Mediated Transdermal Delivery of Drugs 147 Abhijeet Maurya,
Cui Lili and S. Narasimha Murthy 7.1 Introduction 147 7.2 Physical
Permeation Enhancement Techniques 149 7.3 Magnetophoresis 150 7.3.1 Drug
Delivery Applications 151 7.3.2 Mechanism of Permeability Enhancement 152
7.3.3 Magnetophoretic Transdermal Patch 154 7.3.4 Conclusion 154 7.4
Electret?]Mediated Drug Delivery 155 7.4.1 Electrets for Cutaneous Drug
Delivery 156 7.4.2 Electret Layer in a Patch 158 7.4.3 Mechanism of
Permeability Enhancement 158 7.4.4 Conclusion 159 8 Microporation for
Enhanced Transdermal Drug Delivery 163 Thakur Raghu Raj Singh and Chirag
Gujral 8.1 Introduction 163 8.2 High?]Pressure Gas or Liquid Microporation
164 8.3 Ultrasound (Phonophoresis and Sonophoresis) Microporation 166 8.4
Iontophoresis 168 8.5 Electroporation 169 8.6 Laser Microporation 170 8.7
Thermal Microporation 171 8.8 RF Microporation 173 8.9 Microneedles 173
8.10 Conclusion 174 9 Microneedle Technology 179 Helen L. Quinn, Aaron J.
Courtenay, Mary?]Carmel Kearney and Ryan F. Donnelly 9.1 Introduction 179
9.2 MN Materials and Fabrication 182 9.3 MN?]Mediated Drug Delivery 185
9.3.1 Combinational Approaches 187 9.4 MN Vaccination 188 9.4.1 Polymeric
MNs and Vaccination 188 9.4.2 Solid MNs and Vaccination 189 9.4.3 Hollow
MNs and Vaccination 190 9.4.4 MN Vaccination Moving Forwards 190 9.5
Further MN Applications 191 9.5.1 Therapeutic Drug Monitoring 192 9.5.2
Cosmetic Applications 193 9.5.3 Other Potential Applications 194 9.6
Patient Factors Relating to MN Use 194 9.6.1 Effects of MN Insertion on the
Skin 194 9.6.2 Patient Safety 196 9.6.3 Acceptability to Patients and
Healthcare Providers 197 9.6.4 Patient Application 197 9.7 The Next Steps
in MN Development 198 9.7.1 Manufacturing Considerations 199 9.7.2
Regulatory Considerations 199 9.7.3 Commercialisation of MN Technologies
200 9.8 Conclusion 201 10 Intradermal Delivery of Active Cosmeceutical
Ingredients 209 Andrzej M. Bugaj 10.1 Introduction 209 10.2 Emulsions 210
10.2.1 Microemulsions 211 10.2.2 Nanoemulsions 212 10.2.3 Quick?]Breaking
Emulsions 213 10.2.4 Pickering Emulsions 214 10.2.5 Gel Emulsions 214
10.2.6 Liquid Crystal Emulsions 214 10.2.7 Multiple Emulsions 215 10.3
Vesicular Systems 216 10.3.1 Liposomes 216 10.3.2 Niosomes 221 10.3.3
Sphingosomes 221 10.3.4 Multiwalled Delivery Systems 221 10.4 Solid
Particulate Systems 222 10.4.1 Microparticles 222 10.4.2 Solid
Nanoparticles 225 10.4.3 Fullerenes 228 10.4.4 Cyclodextrins 228 10.4.5
Fibrous Matrices 229 10.5 Cosmetic Foams 229 10.6 Cosmetic Patches 230 10.7
Cosmeceuticals: The Future 230 11 Commercial and Regulatory Considerations
in Transdermal and Dermal Medicines Development 243 Marc. B. Brown, Jon
Lenn, Charles Evans and Sian Lim 11.1 Introduction 243 11.2 Dermal and
Transdermal Product/Device Development 245 11.2.1 Drug Candidate Selection
246 11.2.2 Dosage/Device Form 246 11.2.3 Pre?]formulation and
Formulation/Device Development 248 11.2.4 Performance Testing 250 11.3
Product Scale?]Up and Process Optimisation, Validation and Stability
Testing 253 11.3.1 Product Scale?]Up, Process Optimisation and
Specification Development 253 11.3.2 Analytical Method Validation 253
11.3.3 ICH Stability Testing 254 11.4 The Commercial Future of Transdermal
Devices 254 Index 259
Technology: Series Preface xvii Preface xix 1 Introduction 1 Gary P.J. Moss
1.1 The Subcutis (Subcutaneous Fat Layer) 1 1.2 The Dermis 2 1.3 Skin
Appendages 2 1.4 The Subcutaneous Sensory Mechanism 3 1.5 The Epidermis 5
1.6 The stratum germinativum 5 1.7 The stratum spinosum 5 1.8 The stratum
granulosum 6 1.9 The stratum lucidum 6 1.10 The stratum corneum 6 1.10.1
Routes of Absorption 9 1.10.2 Transdermal Permeation - Mechanisms of
Absorption 9 1.11 Theoretical Considerations 11 1.12 Physicochemical
Properties of the Penetrant 13 1.12.1 Partition Coefficient 13 1.12.2
Molecular Size and Shape 14 1.12.3 Applied Concentration/Dose 15 1.12.4
Solubility and Melting Point 15 1.12.5 Ionisation 15 1.12.6 Physiological
Factors Affecting Percutaneous Absorption 16 1.13 Physiological Properties
of the Skin 16 1.13.1 Skin Condition 16 1.13.2 Skin Hydration and Occlusion
17 1.13.3 Skin Age 17 1.13.4 Regional Variation (Body Site) 18 1.13.5 Race
19 1.13.6 Skin Temperature 19 1.14 Vehicle Effects 19 1.15 Modulation and
Enhancement of Topical and Transdermal Drug Delivery 20 1.15.1 Chemical
Modulation of Permeation 21 1.15.2 Physical Methods of Enhancement 26 2
Application of Spectroscopic Techniques to Interrogate Skin 41 Jonathan
Hadgraft, Rita Mateus and Majella E. Lane 2.1 Introduction 41 2.2
Vibrational Spectroscopic Methods 42 2.3 Electronic Spectroscopic Methods
46 2.3.1 UV and Fluorescence 46 2.3.2 Nuclear Magnetic Resonance 47 2.4
Miscellaneous Spectroscopic Methods 48 2.4.1 Opto?]Thermal Transient
Emission Radiometry 48 2.4.2 Electron Spin Resonance 48 2.4.3 Impedance
Spectroscopy 49 2.4.4 Laser?]Induced Breakdown Spectroscopy 49 2.4.5
Photoacoustic Spectroscopy 50 2.4.6 Mass Spectrometry Imaging 50 2.5
Conclusions and Future 50 3 Analysis of the Native Structure of the Skin
Barrier by Cryo?]TEM Combined with EM?]Simulation 57 Lars Norlén 3.1
Introduction 57 3.2 Our Approach: In Situ Biomolecular Structure
Determination in Near?]Native Skin 58 3.2.1 Step 1: Cryo?]Electron
Microscopy of Vitreous Sections 60 3.2.2 Steps 2-3: Molecular Model
Building and Electron Microscopy Simulation 66 3.2.3 Step 4: Confrontation
of Observed Data with Simulated Data 66 3.3 Molecular Organisation of the
Horny Layer's Fat Matrix 67 3.4 Molecular Organisation of the Horny Layer's
Keratin Filament Matrix 67 3.5 Final Remark 68 4 Intradermal Vaccination 71
Marija Zaric and Adrien Kissenpfennig 4.1 Vaccination 71 4.1.1
Disadvantages Associated with Conventional Vaccination 72 4.2 Dendritic
Cells Immunobiology 73 4.3 Skin Anatomy and Physiology 74 4.3.1 The Role of
Skin in Vaccine Delivery 75 4.4 The Skin Dendritic Cell Network 76 4.4.1
Langerhans Cells and the 'Langerhans Cell Paradigm' 76 4.4.2 Dermal
Dendritic Cell Network 77 4.4.3 Dendritic Cell Subsets in the
Skin?]Draining Lymph Node 79 4.4.4 Human Dendritic Cells in the Skin 80
4.4.5 The Role of Skin Dendritic Cells Subsets in Transdermal Immunisation
81 4.5 The DTR?]DT Depletion System 82 4.5.1 Langerin?]DTR Mouse Models 83
4.6 Dendritic Cells and the Differentiation of T Lymphocytes 84 4.6.1 CD8+
T Cell Activation 85 4.6.2 CD4+ T Cell Polarisation 85 4.7 Summary 88 5
Film?]Forming and Heated Systems 97 William J. McAuley and Francesco
Caserta 5.1 Film?]Forming Systems 97 5.1.1 The Design of Film?]Forming
Systems 98 5.1.2 Advantages of Using Film?]Forming Systems for Drug
Delivery 99 5.1.3 Production of a Supersaturated State 101 5.1.4 Use with
Chemical Penetration Enhancers 103 5.1.5 Advantages of Film?]Forming
Systems for Patient Use 105 5.1.6 Therapeutic Applications 105 5.2 Heated
Systems 107 5.2.1 Mechanisms of Drug Penetration Enhancement 107 5.2.2
Partitioning 108 5.2.3 Effects of Heat on Skin 110 5.2.4 Dermal Clearance
111 5.2.5 The Effects of Heat on the Permeation of Drugs Across Skin 112
5.2.6 Strategies for Generating Heat 113 5.2.7 Therapeutic Applications 115
5.3 Conclusions 116 6 Nanotechnology?]Based Applications for Transdermal
Delivery of Therapeutics 125 Venkata K. Yellepeddi 6.1 Introduction 125
6.1.1 Skin Structure 126 6.1.2 Skin Sites for Nanoparticle Delivery 127
6.1.3 Skin as a Barrier for Nanoparticle Penetration 128 6.1.4
Physicochemical Characteristics of NPs for Penetration through Skin 129 6.2
Nanocarriers for Topical and Transdermal Delivery 129 6.2.1 Polymeric
Nanoparticles 130 6.2.2 Lipid Based Nanocarriers 134 6.2.3 Metallic and
Mineral Nanoparticles 135 6.2.4 Carbon?]Based Nanomaterials 137 6.3
Interactions of Nanoparticles with the Skin 137 6.4 Limitations of
Nanotechnology for Skin Delivery 138 6.5 Conclusions 139 7 Magnetophoresis
and Electret?]Mediated Transdermal Delivery of Drugs 147 Abhijeet Maurya,
Cui Lili and S. Narasimha Murthy 7.1 Introduction 147 7.2 Physical
Permeation Enhancement Techniques 149 7.3 Magnetophoresis 150 7.3.1 Drug
Delivery Applications 151 7.3.2 Mechanism of Permeability Enhancement 152
7.3.3 Magnetophoretic Transdermal Patch 154 7.3.4 Conclusion 154 7.4
Electret?]Mediated Drug Delivery 155 7.4.1 Electrets for Cutaneous Drug
Delivery 156 7.4.2 Electret Layer in a Patch 158 7.4.3 Mechanism of
Permeability Enhancement 158 7.4.4 Conclusion 159 8 Microporation for
Enhanced Transdermal Drug Delivery 163 Thakur Raghu Raj Singh and Chirag
Gujral 8.1 Introduction 163 8.2 High?]Pressure Gas or Liquid Microporation
164 8.3 Ultrasound (Phonophoresis and Sonophoresis) Microporation 166 8.4
Iontophoresis 168 8.5 Electroporation 169 8.6 Laser Microporation 170 8.7
Thermal Microporation 171 8.8 RF Microporation 173 8.9 Microneedles 173
8.10 Conclusion 174 9 Microneedle Technology 179 Helen L. Quinn, Aaron J.
Courtenay, Mary?]Carmel Kearney and Ryan F. Donnelly 9.1 Introduction 179
9.2 MN Materials and Fabrication 182 9.3 MN?]Mediated Drug Delivery 185
9.3.1 Combinational Approaches 187 9.4 MN Vaccination 188 9.4.1 Polymeric
MNs and Vaccination 188 9.4.2 Solid MNs and Vaccination 189 9.4.3 Hollow
MNs and Vaccination 190 9.4.4 MN Vaccination Moving Forwards 190 9.5
Further MN Applications 191 9.5.1 Therapeutic Drug Monitoring 192 9.5.2
Cosmetic Applications 193 9.5.3 Other Potential Applications 194 9.6
Patient Factors Relating to MN Use 194 9.6.1 Effects of MN Insertion on the
Skin 194 9.6.2 Patient Safety 196 9.6.3 Acceptability to Patients and
Healthcare Providers 197 9.6.4 Patient Application 197 9.7 The Next Steps
in MN Development 198 9.7.1 Manufacturing Considerations 199 9.7.2
Regulatory Considerations 199 9.7.3 Commercialisation of MN Technologies
200 9.8 Conclusion 201 10 Intradermal Delivery of Active Cosmeceutical
Ingredients 209 Andrzej M. Bugaj 10.1 Introduction 209 10.2 Emulsions 210
10.2.1 Microemulsions 211 10.2.2 Nanoemulsions 212 10.2.3 Quick?]Breaking
Emulsions 213 10.2.4 Pickering Emulsions 214 10.2.5 Gel Emulsions 214
10.2.6 Liquid Crystal Emulsions 214 10.2.7 Multiple Emulsions 215 10.3
Vesicular Systems 216 10.3.1 Liposomes 216 10.3.2 Niosomes 221 10.3.3
Sphingosomes 221 10.3.4 Multiwalled Delivery Systems 221 10.4 Solid
Particulate Systems 222 10.4.1 Microparticles 222 10.4.2 Solid
Nanoparticles 225 10.4.3 Fullerenes 228 10.4.4 Cyclodextrins 228 10.4.5
Fibrous Matrices 229 10.5 Cosmetic Foams 229 10.6 Cosmetic Patches 230 10.7
Cosmeceuticals: The Future 230 11 Commercial and Regulatory Considerations
in Transdermal and Dermal Medicines Development 243 Marc. B. Brown, Jon
Lenn, Charles Evans and Sian Lim 11.1 Introduction 243 11.2 Dermal and
Transdermal Product/Device Development 245 11.2.1 Drug Candidate Selection
246 11.2.2 Dosage/Device Form 246 11.2.3 Pre?]formulation and
Formulation/Device Development 248 11.2.4 Performance Testing 250 11.3
Product Scale?]Up and Process Optimisation, Validation and Stability
Testing 253 11.3.1 Product Scale?]Up, Process Optimisation and
Specification Development 253 11.3.2 Analytical Method Validation 253
11.3.3 ICH Stability Testing 254 11.4 The Commercial Future of Transdermal
Devices 254 Index 259
About the Editors xiii Contributors xv Advances in Pharmaceutical
Technology: Series Preface xvii Preface xix 1 Introduction 1 Gary P.J. Moss
1.1 The Subcutis (Subcutaneous Fat Layer) 1 1.2 The Dermis 2 1.3 Skin
Appendages 2 1.4 The Subcutaneous Sensory Mechanism 3 1.5 The Epidermis 5
1.6 The stratum germinativum 5 1.7 The stratum spinosum 5 1.8 The stratum
granulosum 6 1.9 The stratum lucidum 6 1.10 The stratum corneum 6 1.10.1
Routes of Absorption 9 1.10.2 Transdermal Permeation - Mechanisms of
Absorption 9 1.11 Theoretical Considerations 11 1.12 Physicochemical
Properties of the Penetrant 13 1.12.1 Partition Coefficient 13 1.12.2
Molecular Size and Shape 14 1.12.3 Applied Concentration/Dose 15 1.12.4
Solubility and Melting Point 15 1.12.5 Ionisation 15 1.12.6 Physiological
Factors Affecting Percutaneous Absorption 16 1.13 Physiological Properties
of the Skin 16 1.13.1 Skin Condition 16 1.13.2 Skin Hydration and Occlusion
17 1.13.3 Skin Age 17 1.13.4 Regional Variation (Body Site) 18 1.13.5 Race
19 1.13.6 Skin Temperature 19 1.14 Vehicle Effects 19 1.15 Modulation and
Enhancement of Topical and Transdermal Drug Delivery 20 1.15.1 Chemical
Modulation of Permeation 21 1.15.2 Physical Methods of Enhancement 26 2
Application of Spectroscopic Techniques to Interrogate Skin 41 Jonathan
Hadgraft, Rita Mateus and Majella E. Lane 2.1 Introduction 41 2.2
Vibrational Spectroscopic Methods 42 2.3 Electronic Spectroscopic Methods
46 2.3.1 UV and Fluorescence 46 2.3.2 Nuclear Magnetic Resonance 47 2.4
Miscellaneous Spectroscopic Methods 48 2.4.1 Opto?]Thermal Transient
Emission Radiometry 48 2.4.2 Electron Spin Resonance 48 2.4.3 Impedance
Spectroscopy 49 2.4.4 Laser?]Induced Breakdown Spectroscopy 49 2.4.5
Photoacoustic Spectroscopy 50 2.4.6 Mass Spectrometry Imaging 50 2.5
Conclusions and Future 50 3 Analysis of the Native Structure of the Skin
Barrier by Cryo?]TEM Combined with EM?]Simulation 57 Lars Norlén 3.1
Introduction 57 3.2 Our Approach: In Situ Biomolecular Structure
Determination in Near?]Native Skin 58 3.2.1 Step 1: Cryo?]Electron
Microscopy of Vitreous Sections 60 3.2.2 Steps 2-3: Molecular Model
Building and Electron Microscopy Simulation 66 3.2.3 Step 4: Confrontation
of Observed Data with Simulated Data 66 3.3 Molecular Organisation of the
Horny Layer's Fat Matrix 67 3.4 Molecular Organisation of the Horny Layer's
Keratin Filament Matrix 67 3.5 Final Remark 68 4 Intradermal Vaccination 71
Marija Zaric and Adrien Kissenpfennig 4.1 Vaccination 71 4.1.1
Disadvantages Associated with Conventional Vaccination 72 4.2 Dendritic
Cells Immunobiology 73 4.3 Skin Anatomy and Physiology 74 4.3.1 The Role of
Skin in Vaccine Delivery 75 4.4 The Skin Dendritic Cell Network 76 4.4.1
Langerhans Cells and the 'Langerhans Cell Paradigm' 76 4.4.2 Dermal
Dendritic Cell Network 77 4.4.3 Dendritic Cell Subsets in the
Skin?]Draining Lymph Node 79 4.4.4 Human Dendritic Cells in the Skin 80
4.4.5 The Role of Skin Dendritic Cells Subsets in Transdermal Immunisation
81 4.5 The DTR?]DT Depletion System 82 4.5.1 Langerin?]DTR Mouse Models 83
4.6 Dendritic Cells and the Differentiation of T Lymphocytes 84 4.6.1 CD8+
T Cell Activation 85 4.6.2 CD4+ T Cell Polarisation 85 4.7 Summary 88 5
Film?]Forming and Heated Systems 97 William J. McAuley and Francesco
Caserta 5.1 Film?]Forming Systems 97 5.1.1 The Design of Film?]Forming
Systems 98 5.1.2 Advantages of Using Film?]Forming Systems for Drug
Delivery 99 5.1.3 Production of a Supersaturated State 101 5.1.4 Use with
Chemical Penetration Enhancers 103 5.1.5 Advantages of Film?]Forming
Systems for Patient Use 105 5.1.6 Therapeutic Applications 105 5.2 Heated
Systems 107 5.2.1 Mechanisms of Drug Penetration Enhancement 107 5.2.2
Partitioning 108 5.2.3 Effects of Heat on Skin 110 5.2.4 Dermal Clearance
111 5.2.5 The Effects of Heat on the Permeation of Drugs Across Skin 112
5.2.6 Strategies for Generating Heat 113 5.2.7 Therapeutic Applications 115
5.3 Conclusions 116 6 Nanotechnology?]Based Applications for Transdermal
Delivery of Therapeutics 125 Venkata K. Yellepeddi 6.1 Introduction 125
6.1.1 Skin Structure 126 6.1.2 Skin Sites for Nanoparticle Delivery 127
6.1.3 Skin as a Barrier for Nanoparticle Penetration 128 6.1.4
Physicochemical Characteristics of NPs for Penetration through Skin 129 6.2
Nanocarriers for Topical and Transdermal Delivery 129 6.2.1 Polymeric
Nanoparticles 130 6.2.2 Lipid Based Nanocarriers 134 6.2.3 Metallic and
Mineral Nanoparticles 135 6.2.4 Carbon?]Based Nanomaterials 137 6.3
Interactions of Nanoparticles with the Skin 137 6.4 Limitations of
Nanotechnology for Skin Delivery 138 6.5 Conclusions 139 7 Magnetophoresis
and Electret?]Mediated Transdermal Delivery of Drugs 147 Abhijeet Maurya,
Cui Lili and S. Narasimha Murthy 7.1 Introduction 147 7.2 Physical
Permeation Enhancement Techniques 149 7.3 Magnetophoresis 150 7.3.1 Drug
Delivery Applications 151 7.3.2 Mechanism of Permeability Enhancement 152
7.3.3 Magnetophoretic Transdermal Patch 154 7.3.4 Conclusion 154 7.4
Electret?]Mediated Drug Delivery 155 7.4.1 Electrets for Cutaneous Drug
Delivery 156 7.4.2 Electret Layer in a Patch 158 7.4.3 Mechanism of
Permeability Enhancement 158 7.4.4 Conclusion 159 8 Microporation for
Enhanced Transdermal Drug Delivery 163 Thakur Raghu Raj Singh and Chirag
Gujral 8.1 Introduction 163 8.2 High?]Pressure Gas or Liquid Microporation
164 8.3 Ultrasound (Phonophoresis and Sonophoresis) Microporation 166 8.4
Iontophoresis 168 8.5 Electroporation 169 8.6 Laser Microporation 170 8.7
Thermal Microporation 171 8.8 RF Microporation 173 8.9 Microneedles 173
8.10 Conclusion 174 9 Microneedle Technology 179 Helen L. Quinn, Aaron J.
Courtenay, Mary?]Carmel Kearney and Ryan F. Donnelly 9.1 Introduction 179
9.2 MN Materials and Fabrication 182 9.3 MN?]Mediated Drug Delivery 185
9.3.1 Combinational Approaches 187 9.4 MN Vaccination 188 9.4.1 Polymeric
MNs and Vaccination 188 9.4.2 Solid MNs and Vaccination 189 9.4.3 Hollow
MNs and Vaccination 190 9.4.4 MN Vaccination Moving Forwards 190 9.5
Further MN Applications 191 9.5.1 Therapeutic Drug Monitoring 192 9.5.2
Cosmetic Applications 193 9.5.3 Other Potential Applications 194 9.6
Patient Factors Relating to MN Use 194 9.6.1 Effects of MN Insertion on the
Skin 194 9.6.2 Patient Safety 196 9.6.3 Acceptability to Patients and
Healthcare Providers 197 9.6.4 Patient Application 197 9.7 The Next Steps
in MN Development 198 9.7.1 Manufacturing Considerations 199 9.7.2
Regulatory Considerations 199 9.7.3 Commercialisation of MN Technologies
200 9.8 Conclusion 201 10 Intradermal Delivery of Active Cosmeceutical
Ingredients 209 Andrzej M. Bugaj 10.1 Introduction 209 10.2 Emulsions 210
10.2.1 Microemulsions 211 10.2.2 Nanoemulsions 212 10.2.3 Quick?]Breaking
Emulsions 213 10.2.4 Pickering Emulsions 214 10.2.5 Gel Emulsions 214
10.2.6 Liquid Crystal Emulsions 214 10.2.7 Multiple Emulsions 215 10.3
Vesicular Systems 216 10.3.1 Liposomes 216 10.3.2 Niosomes 221 10.3.3
Sphingosomes 221 10.3.4 Multiwalled Delivery Systems 221 10.4 Solid
Particulate Systems 222 10.4.1 Microparticles 222 10.4.2 Solid
Nanoparticles 225 10.4.3 Fullerenes 228 10.4.4 Cyclodextrins 228 10.4.5
Fibrous Matrices 229 10.5 Cosmetic Foams 229 10.6 Cosmetic Patches 230 10.7
Cosmeceuticals: The Future 230 11 Commercial and Regulatory Considerations
in Transdermal and Dermal Medicines Development 243 Marc. B. Brown, Jon
Lenn, Charles Evans and Sian Lim 11.1 Introduction 243 11.2 Dermal and
Transdermal Product/Device Development 245 11.2.1 Drug Candidate Selection
246 11.2.2 Dosage/Device Form 246 11.2.3 Pre?]formulation and
Formulation/Device Development 248 11.2.4 Performance Testing 250 11.3
Product Scale?]Up and Process Optimisation, Validation and Stability
Testing 253 11.3.1 Product Scale?]Up, Process Optimisation and
Specification Development 253 11.3.2 Analytical Method Validation 253
11.3.3 ICH Stability Testing 254 11.4 The Commercial Future of Transdermal
Devices 254 Index 259
Technology: Series Preface xvii Preface xix 1 Introduction 1 Gary P.J. Moss
1.1 The Subcutis (Subcutaneous Fat Layer) 1 1.2 The Dermis 2 1.3 Skin
Appendages 2 1.4 The Subcutaneous Sensory Mechanism 3 1.5 The Epidermis 5
1.6 The stratum germinativum 5 1.7 The stratum spinosum 5 1.8 The stratum
granulosum 6 1.9 The stratum lucidum 6 1.10 The stratum corneum 6 1.10.1
Routes of Absorption 9 1.10.2 Transdermal Permeation - Mechanisms of
Absorption 9 1.11 Theoretical Considerations 11 1.12 Physicochemical
Properties of the Penetrant 13 1.12.1 Partition Coefficient 13 1.12.2
Molecular Size and Shape 14 1.12.3 Applied Concentration/Dose 15 1.12.4
Solubility and Melting Point 15 1.12.5 Ionisation 15 1.12.6 Physiological
Factors Affecting Percutaneous Absorption 16 1.13 Physiological Properties
of the Skin 16 1.13.1 Skin Condition 16 1.13.2 Skin Hydration and Occlusion
17 1.13.3 Skin Age 17 1.13.4 Regional Variation (Body Site) 18 1.13.5 Race
19 1.13.6 Skin Temperature 19 1.14 Vehicle Effects 19 1.15 Modulation and
Enhancement of Topical and Transdermal Drug Delivery 20 1.15.1 Chemical
Modulation of Permeation 21 1.15.2 Physical Methods of Enhancement 26 2
Application of Spectroscopic Techniques to Interrogate Skin 41 Jonathan
Hadgraft, Rita Mateus and Majella E. Lane 2.1 Introduction 41 2.2
Vibrational Spectroscopic Methods 42 2.3 Electronic Spectroscopic Methods
46 2.3.1 UV and Fluorescence 46 2.3.2 Nuclear Magnetic Resonance 47 2.4
Miscellaneous Spectroscopic Methods 48 2.4.1 Opto?]Thermal Transient
Emission Radiometry 48 2.4.2 Electron Spin Resonance 48 2.4.3 Impedance
Spectroscopy 49 2.4.4 Laser?]Induced Breakdown Spectroscopy 49 2.4.5
Photoacoustic Spectroscopy 50 2.4.6 Mass Spectrometry Imaging 50 2.5
Conclusions and Future 50 3 Analysis of the Native Structure of the Skin
Barrier by Cryo?]TEM Combined with EM?]Simulation 57 Lars Norlén 3.1
Introduction 57 3.2 Our Approach: In Situ Biomolecular Structure
Determination in Near?]Native Skin 58 3.2.1 Step 1: Cryo?]Electron
Microscopy of Vitreous Sections 60 3.2.2 Steps 2-3: Molecular Model
Building and Electron Microscopy Simulation 66 3.2.3 Step 4: Confrontation
of Observed Data with Simulated Data 66 3.3 Molecular Organisation of the
Horny Layer's Fat Matrix 67 3.4 Molecular Organisation of the Horny Layer's
Keratin Filament Matrix 67 3.5 Final Remark 68 4 Intradermal Vaccination 71
Marija Zaric and Adrien Kissenpfennig 4.1 Vaccination 71 4.1.1
Disadvantages Associated with Conventional Vaccination 72 4.2 Dendritic
Cells Immunobiology 73 4.3 Skin Anatomy and Physiology 74 4.3.1 The Role of
Skin in Vaccine Delivery 75 4.4 The Skin Dendritic Cell Network 76 4.4.1
Langerhans Cells and the 'Langerhans Cell Paradigm' 76 4.4.2 Dermal
Dendritic Cell Network 77 4.4.3 Dendritic Cell Subsets in the
Skin?]Draining Lymph Node 79 4.4.4 Human Dendritic Cells in the Skin 80
4.4.5 The Role of Skin Dendritic Cells Subsets in Transdermal Immunisation
81 4.5 The DTR?]DT Depletion System 82 4.5.1 Langerin?]DTR Mouse Models 83
4.6 Dendritic Cells and the Differentiation of T Lymphocytes 84 4.6.1 CD8+
T Cell Activation 85 4.6.2 CD4+ T Cell Polarisation 85 4.7 Summary 88 5
Film?]Forming and Heated Systems 97 William J. McAuley and Francesco
Caserta 5.1 Film?]Forming Systems 97 5.1.1 The Design of Film?]Forming
Systems 98 5.1.2 Advantages of Using Film?]Forming Systems for Drug
Delivery 99 5.1.3 Production of a Supersaturated State 101 5.1.4 Use with
Chemical Penetration Enhancers 103 5.1.5 Advantages of Film?]Forming
Systems for Patient Use 105 5.1.6 Therapeutic Applications 105 5.2 Heated
Systems 107 5.2.1 Mechanisms of Drug Penetration Enhancement 107 5.2.2
Partitioning 108 5.2.3 Effects of Heat on Skin 110 5.2.4 Dermal Clearance
111 5.2.5 The Effects of Heat on the Permeation of Drugs Across Skin 112
5.2.6 Strategies for Generating Heat 113 5.2.7 Therapeutic Applications 115
5.3 Conclusions 116 6 Nanotechnology?]Based Applications for Transdermal
Delivery of Therapeutics 125 Venkata K. Yellepeddi 6.1 Introduction 125
6.1.1 Skin Structure 126 6.1.2 Skin Sites for Nanoparticle Delivery 127
6.1.3 Skin as a Barrier for Nanoparticle Penetration 128 6.1.4
Physicochemical Characteristics of NPs for Penetration through Skin 129 6.2
Nanocarriers for Topical and Transdermal Delivery 129 6.2.1 Polymeric
Nanoparticles 130 6.2.2 Lipid Based Nanocarriers 134 6.2.3 Metallic and
Mineral Nanoparticles 135 6.2.4 Carbon?]Based Nanomaterials 137 6.3
Interactions of Nanoparticles with the Skin 137 6.4 Limitations of
Nanotechnology for Skin Delivery 138 6.5 Conclusions 139 7 Magnetophoresis
and Electret?]Mediated Transdermal Delivery of Drugs 147 Abhijeet Maurya,
Cui Lili and S. Narasimha Murthy 7.1 Introduction 147 7.2 Physical
Permeation Enhancement Techniques 149 7.3 Magnetophoresis 150 7.3.1 Drug
Delivery Applications 151 7.3.2 Mechanism of Permeability Enhancement 152
7.3.3 Magnetophoretic Transdermal Patch 154 7.3.4 Conclusion 154 7.4
Electret?]Mediated Drug Delivery 155 7.4.1 Electrets for Cutaneous Drug
Delivery 156 7.4.2 Electret Layer in a Patch 158 7.4.3 Mechanism of
Permeability Enhancement 158 7.4.4 Conclusion 159 8 Microporation for
Enhanced Transdermal Drug Delivery 163 Thakur Raghu Raj Singh and Chirag
Gujral 8.1 Introduction 163 8.2 High?]Pressure Gas or Liquid Microporation
164 8.3 Ultrasound (Phonophoresis and Sonophoresis) Microporation 166 8.4
Iontophoresis 168 8.5 Electroporation 169 8.6 Laser Microporation 170 8.7
Thermal Microporation 171 8.8 RF Microporation 173 8.9 Microneedles 173
8.10 Conclusion 174 9 Microneedle Technology 179 Helen L. Quinn, Aaron J.
Courtenay, Mary?]Carmel Kearney and Ryan F. Donnelly 9.1 Introduction 179
9.2 MN Materials and Fabrication 182 9.3 MN?]Mediated Drug Delivery 185
9.3.1 Combinational Approaches 187 9.4 MN Vaccination 188 9.4.1 Polymeric
MNs and Vaccination 188 9.4.2 Solid MNs and Vaccination 189 9.4.3 Hollow
MNs and Vaccination 190 9.4.4 MN Vaccination Moving Forwards 190 9.5
Further MN Applications 191 9.5.1 Therapeutic Drug Monitoring 192 9.5.2
Cosmetic Applications 193 9.5.3 Other Potential Applications 194 9.6
Patient Factors Relating to MN Use 194 9.6.1 Effects of MN Insertion on the
Skin 194 9.6.2 Patient Safety 196 9.6.3 Acceptability to Patients and
Healthcare Providers 197 9.6.4 Patient Application 197 9.7 The Next Steps
in MN Development 198 9.7.1 Manufacturing Considerations 199 9.7.2
Regulatory Considerations 199 9.7.3 Commercialisation of MN Technologies
200 9.8 Conclusion 201 10 Intradermal Delivery of Active Cosmeceutical
Ingredients 209 Andrzej M. Bugaj 10.1 Introduction 209 10.2 Emulsions 210
10.2.1 Microemulsions 211 10.2.2 Nanoemulsions 212 10.2.3 Quick?]Breaking
Emulsions 213 10.2.4 Pickering Emulsions 214 10.2.5 Gel Emulsions 214
10.2.6 Liquid Crystal Emulsions 214 10.2.7 Multiple Emulsions 215 10.3
Vesicular Systems 216 10.3.1 Liposomes 216 10.3.2 Niosomes 221 10.3.3
Sphingosomes 221 10.3.4 Multiwalled Delivery Systems 221 10.4 Solid
Particulate Systems 222 10.4.1 Microparticles 222 10.4.2 Solid
Nanoparticles 225 10.4.3 Fullerenes 228 10.4.4 Cyclodextrins 228 10.4.5
Fibrous Matrices 229 10.5 Cosmetic Foams 229 10.6 Cosmetic Patches 230 10.7
Cosmeceuticals: The Future 230 11 Commercial and Regulatory Considerations
in Transdermal and Dermal Medicines Development 243 Marc. B. Brown, Jon
Lenn, Charles Evans and Sian Lim 11.1 Introduction 243 11.2 Dermal and
Transdermal Product/Device Development 245 11.2.1 Drug Candidate Selection
246 11.2.2 Dosage/Device Form 246 11.2.3 Pre?]formulation and
Formulation/Device Development 248 11.2.4 Performance Testing 250 11.3
Product Scale?]Up and Process Optimisation, Validation and Stability
Testing 253 11.3.1 Product Scale?]Up, Process Optimisation and
Specification Development 253 11.3.2 Analytical Method Validation 253
11.3.3 ICH Stability Testing 254 11.4 The Commercial Future of Transdermal
Devices 254 Index 259