ABSTRACT
Introduction .................................................................................................................................... 178 Principles of Iontophoresis ............................................................................................................ 179
Mechanisms................................................................................................................................. 179 Electromigration...................................................................................................................... 180 Electroosmosis ........................................................................................................................ 181
Practical Considerations ............................................................................................................. 181 Electrode Choice..................................................................................................................... 181 Current .................................................................................................................................... 182 Drug Concentration in the Donor.......................................................................................... 182 pH............................................................................................................................................ 183
Exisiting Therapeutic Applications of Iontophoresis .................................................................... 184 FDA Approved Applications ...................................................................................................... 184
Pilocarpine Delivery for the Diagnosis of Cystic Fibrosis..................................................... 184 Tap Water Delivery for the Treatment of Hyperhidrosis ...................................................... 184 Lidocaine Delivery .................................................................................................................. 185 The GlucoWatch1 Biographer for Noninvasive Glucose Monitoring.................................. 187 E-TRANS1 Fentanyl HCl (Ionsyse
ˆ ) — Pending Approval from the FDA ........................... 189
Other Applications of Iontophoresis In Vivo ............................................................................ 190 Physical Medicine ................................................................................................................... 191 Dentistry and Other Oral Pathologies.................................................................................... 191 Ophthalmology....................................................................................................................... 192 Otorhinolaryngology .............................................................................................................. 192
Potential Candidates for Iontophoretic Delivery .......................................................................... 193 Animal Models ............................................................................................................................ 193
Cardiovascular Agents ............................................................................................................ 193 Dermal Applications ............................................................................................................... 193 Opioids.................................................................................................................................... 200 Antiinflammatory Agents ........................................................................................................ 201 Miscellaneous Nonpeptidic Drugs ......................................................................................... 201 Protein and Peptide Drugs ..................................................................................................... 201
Human Studies............................................................................................................................ 204 Dermal Applications ............................................................................................................... 204 Opioids.................................................................................................................................... 206 Antiinflammatory Agents ........................................................................................................ 207 Miscellaneous Nonpeptidic Drugs ......................................................................................... 207 Protein and Peptide Drugs ..................................................................................................... 208
Conclusions .................................................................................................................................... 208 Successes and Opportunities for the Future ............................................................................. 208 Limitations................................................................................................................................... 208 Remaining Challenges ................................................................................................................ 209
References....................................................................................................................................... 209
The first detailed descriptions of the use of transdermal iontophoresis to deliver molecules across the skin date back to the early 20th century. Leduc showed, to dramatic effect, that a potential difference could be used to deliver strychnine and cyanide to rabbits (with obvious results) from the anodal and cathodal electrode compartments, respectively.1,2
In the 1930s and 1940s, iontophoresis was frequently used to deliver molecules across the skin, but the technique did not gain scientific prominence until several decades later.2 The acceptance of transdermal delivery as a viable alternative administration route, together with the need to extend the range of drugs amenable to this approach, spurred a revival of scientific interest in iontophoresis during the 1980s. The constraints imposed by the skin’s barrier function meant that passive transdermal delivery was limited to a few select (highly potent) drugs with the appropriate physicochemical properties. This is illustrated by the concise list of available passive systems: clonidine, estradiol, fentanyl, nicotine, nitroglycerin, scopolamine, testosterone, oxybutinin, and the combination products norelgestromin or ethinyl estradiol and estradiol or norethindrone acetate.3 Numerous strategies have been developed in order to expand the range of drugs available for transdermal administration including the use of current application.
