Preface |
|
xiii | |
About the Author |
|
xv | |
|
Chapter 1 Percutaneous Absorption and Enhancement Strategies |
|
|
1 | (26) |
|
|
1 | (4) |
|
1.2 Structure and Enzymatic Activity of the Skin |
|
|
5 | (3) |
|
|
5 | (2) |
|
1.2.1.1 Hair Follicles in the Skin |
|
|
7 | (1) |
|
1.2.2 Enzymatic Activity of the Skin |
|
|
8 | (1) |
|
1.3 Percutaneous Absorption |
|
|
8 | (2) |
|
1.3.1 Mechanisms of Percutaneous Absorption |
|
|
8 | (1) |
|
1.3.2 Theoretical Basis of Percutaneous Absorption |
|
|
9 | (1) |
|
1.4 Passive Permeation Enhancement Strategies |
|
|
10 | (5) |
|
1.4.1 Chemical Penetration Enhancers |
|
|
10 | (2) |
|
|
12 | (1) |
|
1.4.3 Nanocarriers for Intradermal or Transdermal Delivery |
|
|
13 | (1) |
|
|
13 | (1) |
|
|
13 | (2) |
|
|
15 | (1) |
|
1.5 Active Enhancement Strategies for Percutaneous Absorption |
|
|
15 | (3) |
|
|
16 | (1) |
|
|
16 | (1) |
|
|
17 | (1) |
|
|
17 | (1) |
|
1.6 Applications in Veterinary Medicine |
|
|
18 | (9) |
|
|
19 | (8) |
|
Chapter 2 Experimental Methods and Tools for Transdermal Delivery by Physical Enhancement Methods |
|
|
27 | (26) |
|
|
27 | (1) |
|
2.2 Considerations in Selecting the Skin Model |
|
|
27 | (6) |
|
2.2.1 Animal Models for Transdermal Delivery |
|
|
27 | (2) |
|
|
29 | (1) |
|
2.2.3 Isolated Perfused Porcine Skin Flap Model |
|
|
30 | (1) |
|
2.2.4 Artificial Skin Equivalents |
|
|
31 | (1) |
|
|
31 | (1) |
|
2.2.6 Use of Synthetic Membranes |
|
|
32 | (1) |
|
|
33 | (5) |
|
2.3.1 Diffusion Cells: Vertical Configuration |
|
|
33 | (2) |
|
2.3.2 Diffusion Cells: Horizontal Configuration |
|
|
35 | (1) |
|
2.3.3 Devices Used with Skin Enhancement Techniques |
|
|
35 | (1) |
|
2.3.4 Typical Experimental Setup |
|
|
36 | (1) |
|
2.3.5 Variability of Percutaneous Absorption |
|
|
37 | (1) |
|
|
38 | (3) |
|
|
39 | (1) |
|
|
40 | (1) |
|
2.5 Instrumental Tools Used to Characterize Transdermal Transport |
|
|
41 | (12) |
|
|
44 | (9) |
|
Chapter 3 Microporation-Mediated Transdermal Drug Delivery |
|
|
53 | (28) |
|
|
53 | (1) |
|
3.2 Skin Microporation by Microneedles |
|
|
53 | (13) |
|
3.2.1 Potential Advantages of a Microneedle Patch |
|
|
53 | (1) |
|
3.2.2 Fabrication of Microneedles |
|
|
54 | (2) |
|
3.2.3 Mechanisms of Delivery and Type of Microneedles |
|
|
56 | (1) |
|
3.2.3.1 Solid Microneedles |
|
|
56 | (3) |
|
3.2.3.2 Hollow Microneedles |
|
|
59 | (2) |
|
3.2.4 Factors Influencing Microneedle Insertion |
|
|
61 | (1) |
|
3.2.4.1 Insertion Kinetics |
|
|
61 | (1) |
|
3.2.4.2 Microneedle Length and Density |
|
|
62 | (1) |
|
3.2.4.3 Microneedle Geometry |
|
|
63 | (1) |
|
3.2.4.4 Depth of Insertion and Pain |
|
|
63 | (1) |
|
3.2.5 Pore Closure and Safety Following Microporation |
|
|
64 | (1) |
|
3.2.6 Delivery of Particulates through Hair Follicles and through Microporated Skin |
|
|
65 | (1) |
|
3.3 Skin Microporation by Other Approaches |
|
|
66 | (4) |
|
|
66 | (1) |
|
3.3.2 Laser Microporation |
|
|
67 | (1) |
|
3.3.3 Radio-Frequency Ablation |
|
|
68 | (2) |
|
3.3.4 Other Means of Skin Microporation |
|
|
70 | (1) |
|
3.4 Combination Approaches |
|
|
70 | (1) |
|
3.5 Applications of Microporation |
|
|
71 | (10) |
|
3.5.1 Delivery of Small Drug Molecules |
|
|
71 | (1) |
|
3.5.2 Photodynamic Therapy |
|
|
71 | (1) |
|
3.5.3 Delivery of Lipophilic Drugs |
|
|
72 | (1) |
|
3.5.4 Delivery of Macromolecules |
|
|
72 | (1) |
|
3.5.5 Diagnostic and Other Applications |
|
|
72 | (1) |
|
|
73 | (8) |
|
Chapter 4 Iontophoretic Intradermal and Transdermal Drug Delivery |
|
|
81 | (50) |
|
|
81 | (1) |
|
4.1.1 Historical Origin of Iontophoresis |
|
|
81 | (1) |
|
4.2 Electrical Properties of Skin |
|
|
82 | (1) |
|
4.3 Pathways of Iontophoretic Drug Delivery |
|
|
83 | (2) |
|
4.4 Theoretical Basis of Iontophoresis |
|
|
85 | (2) |
|
4.5 Factors Affecting Iontophoretic Delivery |
|
|
87 | (6) |
|
|
87 | (2) |
|
4.5.2 Modality of Current |
|
|
89 | (1) |
|
4.5.3 Physicochemical Properties of the Drug |
|
|
90 | (2) |
|
4.5.4 Formulation Factors |
|
|
92 | (1) |
|
|
93 | (1) |
|
4.6 pH Control in Iontophoresis Research |
|
|
93 | (4) |
|
4.6.1 Selection of Electrode Material |
|
|
93 | (1) |
|
4.6.2 Silver/Silver Chloride Electrodes |
|
|
94 | (1) |
|
4.6.3 Preparation and Care of Silver/Silver Chloride Electrodes |
|
|
95 | (1) |
|
4.6.4 Alternative Methods for pH Control |
|
|
96 | (1) |
|
|
97 | (2) |
|
4.7.1 Theoretical Treatment of Electroosmotic Flow |
|
|
99 | (1) |
|
4.8 Reverse Iontophoresis |
|
|
99 | (2) |
|
4.9 Treatment Protocols and Formulations |
|
|
101 | (1) |
|
4.10 Combined Use of Iontophoresis and Other Enhancement Techniques |
|
|
102 | (1) |
|
4.11 Applications of Iontophoresis |
|
|
102 | (4) |
|
4.11.1 Iontophoretic Delivery to the Nail |
|
|
102 | (1) |
|
|
103 | (1) |
|
4.11.3 Synthetic Narcotics: Sufentanil |
|
|
104 | (1) |
|
4.11.4 Iontophoretic Delivery of Dopamine Agonists |
|
|
104 | (1) |
|
|
105 | (1) |
|
4.11.6 Alternate Applications for Iontophoresis |
|
|
106 | (1) |
|
4.12 Clinical Applications of Iontophoresis for Intradermal Delivery |
|
|
106 | (25) |
|
4.12.1 Delivery of Dexamethasone |
|
|
107 | (2) |
|
4.12.2 Delivery of Other Steroids |
|
|
109 | (1) |
|
4.12.3 Treatment of Hyperhidrosis |
|
|
109 | (1) |
|
4.12.4 Diagnosis of Cystic Fibrosis |
|
|
110 | (2) |
|
4.12.5 Iontophoresis of Histamine and Antihistamines |
|
|
112 | (1) |
|
4.12.6 Delivery of Antiviral Agents |
|
|
112 | (1) |
|
4.12.7 Delivery of Antibiotic/Anti-Infective Agents |
|
|
113 | (1) |
|
4.12.8 Other Applications of Iontophoresis |
|
|
113 | (1) |
|
|
114 | (17) |
|
Chapter 5 Skin Electroporation and Its Applications |
|
|
131 | (22) |
|
|
131 | (2) |
|
5.2 Electropermeabilization of the Skin |
|
|
133 | (2) |
|
5.3 Electroporation Equipment |
|
|
135 | (1) |
|
5.4 Factors Affecting Delivery by Electroporation |
|
|
136 | (3) |
|
5.5 Skin Toxicology of Electroporation |
|
|
139 | (2) |
|
5.6 Electroporation for Cancer Chemotherapy |
|
|
141 | (2) |
|
5.7 Delivery of Drugs by Electroporation |
|
|
143 | (10) |
|
5.7.1 Luteinizing Hormone-Releasing Hormone |
|
|
145 | (1) |
|
|
145 | (1) |
|
|
146 | (1) |
|
|
146 | (7) |
|
Chapter 6 Sonophoresis for Intradermal and Transdermal Drug Delivery |
|
|
153 | (18) |
|
|
153 | (1) |
|
6.2 Factors Affecting Sonophoresis |
|
|
153 | (2) |
|
6.3 Mechanisms of Ultrasound-Mediated Transdermal Delivery |
|
|
155 | (1) |
|
6.4 Delivery of Lipophilic Drugs |
|
|
156 | (1) |
|
|
157 | (1) |
|
6.6 Skin Irritation and Electrical Properties |
|
|
158 | (1) |
|
6.7 Transdermal Delivery Application of Sonophoresis |
|
|
159 | (5) |
|
6.7.1 Delivery of Small Molecules |
|
|
160 | (1) |
|
6.7.2 Delivery of Insulin |
|
|
161 | (1) |
|
6.7.3 Delivery of Other Macromolecules |
|
|
161 | (2) |
|
|
163 | (1) |
|
6.8 Combination Approaches |
|
|
164 | (7) |
|
|
165 | (6) |
|
Chapter 7 How to Go about Selecting the Optimal Enhancement Method for Transdermal Delivery of a Specific Drug Molecule: Case Studies |
|
|
171 | (24) |
|
|
171 | (1) |
|
7.2 Technology Comparison and Limitations |
|
|
172 | (1) |
|
7.3 Passive versus Active Patches for Transdermal and Intradermal Delivery |
|
|
173 | (1) |
|
|
174 | (21) |
|
7.4.1 Moderately Lipophilic |
|
|
174 | (1) |
|
|
175 | (1) |
|
|
176 | (1) |
|
|
176 | (1) |
|
|
176 | (1) |
|
7.4.3 Hydrophilic Small Molecules |
|
|
177 | (1) |
|
|
177 | (1) |
|
|
178 | (1) |
|
7.4.4 Hydrophilic Macromolecules |
|
|
179 | (1) |
|
|
180 | (3) |
|
7.4.5 Therapeutic Categories |
|
|
183 | (1) |
|
7.4.5.1 Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) |
|
|
183 | (2) |
|
7.4.5.2 Antihypertensive/Cardiovascular Agents |
|
|
185 | (2) |
|
|
187 | (8) |
|
Chapter 8 Transdermal Delivery of Peptides and Proteins |
|
|
195 | (24) |
|
|
195 | (2) |
|
8.2 Structural Considerations of Polypeptides Relevant to Transdermal Delivery |
|
|
197 | (1) |
|
8.3 Protease Inhibitors and Permeation Enhancers for Transdermal Protein Delivery |
|
|
198 | (2) |
|
8.3.1 Proteolytic Activity of Skin |
|
|
198 | (1) |
|
8.3.2 Protease Inhibitors |
|
|
199 | (1) |
|
8.3.3 Permeation Enhancers |
|
|
199 | (1) |
|
8.4 Iontophoretic Delivery of Peptides |
|
|
200 | (2) |
|
8.5 Transdermal Delivery of Peptides and Proteins: Examples |
|
|
202 | (17) |
|
|
202 | (1) |
|
|
203 | (1) |
|
8.5.3 Vasopressin and Analogs |
|
|
204 | (2) |
|
8.5.4 Luteinizing Hormone-Releasing Hormones and Analogs |
|
|
206 | (2) |
|
|
208 | (3) |
|
|
211 | (1) |
|
8.5.7 Other Peptide/Protein Candidates |
|
|
211 | (1) |
|
|
212 | (7) |
|
Chapter 9 Transcutaneous Immunization via Physical Methods |
|
|
219 | (24) |
|
|
219 | (1) |
|
9.2 Immunology of the Skin |
|
|
220 | (1) |
|
9.3 Transcutaneous Immunization by Passive Approaches |
|
|
221 | (1) |
|
9.4 Microneedle-Based Intradermal Injection |
|
|
221 | (2) |
|
9.5 Microneedle-Mediated Vaccination |
|
|
223 | (4) |
|
|
227 | (1) |
|
9.6.1 Particle-Mediated Immunization |
|
|
227 | (1) |
|
9.7 Delivery of DNA Vaccines, Genes, and Oligonucleotides |
|
|
228 | (15) |
|
9.7.1 DNA Vaccination by Electroporation |
|
|
229 | (1) |
|
|
230 | (1) |
|
9.7.3 Delivery of Oligonucleotides |
|
|
231 | (2) |
|
|
233 | (10) |
|
Chapter 10 Commercial Development of Devices and Products for Transdermal Physical Enhancement Technologies |
|
|
243 | (40) |
|
|
243 | (1) |
|
10.2 What Can Be Learned from the Passive Patches on the Market? |
|
|
244 | (1) |
|
10.3 Safety Issues and Effect of Heat |
|
|
245 | (3) |
|
10.4 Skin Irritation Testing |
|
|
248 | (3) |
|
10.5 Commercial Development of Microporation Devices |
|
|
251 | (8) |
|
10.5.1 Challenges for Commercial Development of a Microneedle-Based Patch |
|
|
251 | (2) |
|
10.5.2 Microneedle-Based Transdermal Products in Development |
|
|
253 | (1) |
|
10.5.2.1 Marketed Products |
|
|
253 | (2) |
|
10.5.2.2 Products in Clinical Development |
|
|
255 | (2) |
|
10.5.2.3 Products in Preclinical Development |
|
|
257 | (2) |
|
10.6 Commercial Development of Iontophoretic Devices |
|
|
259 | (8) |
|
|
259 | (2) |
|
10.6.2 Iontophoresis Devices |
|
|
261 | (3) |
|
|
264 | (1) |
|
10.6.4 Iontophoresis-Based Transdermal Products on Market or in Clinical Development |
|
|
265 | (2) |
|
10.7 Formulation Considerations |
|
|
267 | (2) |
|
10.8 Patch Design and Regulatory Issues |
|
|
269 | (4) |
|
10.9 Dose and Bioavailability |
|
|
273 | (10) |
|
|
274 | (9) |
Index |
|
283 | |