Iontophoresis transdermal delivery

Transdermal delivery is suitable for small, generally lipophilic, potent molecules that require low input rates to achieve effective plasma concentrations. There may be a slow rate of increase of concentration if the drug forms a depot in the skin. Depot formation will also result in a slow decrease in concentration when the system is removed from the skin. These disadvantages can be overcome by the use of iontophoresis, by which the molecules are actively carried across the skin by a small electrical current. This provides a faster and more controllable transfer of drug. Intramuscular/Subcutaneous... 

The use of skin permeation enhancers in combination for synergistic effects has been studied in the transdermal literature (70). Such synergistic methods can be grouped in three categories (i) combination of two physical methods, e.g., ultrasound and iontophoresis (71-75) (ii) combination of a physical method with a chemical enhancer, e.g., use of ultrasound with sodium lauryl sulfate or isopropyl myristate (76-80) and (iii) combination of two chemicals, e.g., terpenes and propylene glycol (46,81-88). Numerous studies have been published on using combination of two physical methods or use of a physical method in conjunction with a chemical enhancer. Use of a physical method, by itself or in combination with another physical method, increases application cost for delivery purposes as mentioned before. In addition, there are unexplored safety and membrane recovery issues associated with these methods. A few reports have also been published on the use of a mixture of chemical enhancers for enhancing transdermal delivery. Typically, such studies use... 

Singh J, Roberts M. Transdermal delivery of drugs by iontophoresis a review. Drug Delivery 1989 4 1-12. 

Denet A, Ucakar B, Preat V. Transdermal delivery of timolol and atenolol using electroporation and iontophoresis in combination a mechanistic approach. Pharm Res 2003 20 1946-1951. 

Transdermal iontophoresis involves the application of an electric field across the skin to facilitate (primarily) ionic transport across the membrane. Iontophoresis, it is important to point out, is differentiated from electroporation [14], another electrical approach to enhance transdermal transport, by the low fields employed. Whereas iontophoresis has achieved commercialization, there is (to our knowledge) no active development in progress of a transdermal delivery system employing electroporation. 

Scott, E.R., et al. 2000. Electrotransport systems for transdermal delivery A practical implementation of iontophoresis. In Handbook of pharmaceutical controlled release technology, ed. D.L. Wise. New York Marcel Dekker, chap. 31. 

Jadoul and Preat [56] have also proposed a similar explanation for the lack of synergistic effects on transdermal delivery of domperidone with combined electroporation (1 pulse of 1000 V with a time constant of 4 ms) and iontophoresis (0.4 mA/cm2) despite the fact that iontophoresis was switched on within a few seconds after electroporation. Combined pulsing and iontophoresis also did not improve penetration of sodium nonivamide acetate through nude mouse skin [51], Therefore, when combing the two protocols, it should be more efficient to use a system that delivers current during or immediately after pulsing without delay. 

Fang, J.Y., et al. 2002. The effects of iontophoresis and electroporation on transdermal delivery of buprenorphine from solutions and hydrogels. J Pharm Pharmacol 54 1329. 

Iontophoresis techniques (i.e., the use of electric current to facilitate transdermal delivery) have also been advocated as a way to enhance transdermal opioid delivery to the systemic circulation.11 By varying the amount of electric current, iontophoresis may ultimately allow the patient to control the rate of transdermal administration of the opioid.10,76,78 Finally, certain opioids such as fentanyl can be administered systemically via lozenges or a lollipop that dissolves in the mouth (transmucosal delivery), or via nasal spray (intranasal administration).21,54 It will be interesting to see if these newer methods of administration will gain widespread acceptance in the future. 

Badkar AV, Smith AM, Eppstein JA, Banga AK. Transdermal delivery of interferon alpha-2B using microporation and iontophoresis in hairless rats. Pharmaceutical Research 2007, 24, 1389-1395. 

Kanikkannan, N. 2002. Iontophoresis-based transdermal delivery systems. BioDrugs 16 339-347. 

Ointments, creams, and plasters are used for transdermal drug delivery. In the latter case, sustained release is accomplished by diffusion from a reservoir through a microporous membrane and into the skin [26,48,49]. Iontophoresis and electroporation has been reported to successfully promote transdermal delivery rates [50-52]. 

Leduc, S. Electric Ions and Their Use in Medicine. London, Robman Ltd, 1908. Singh, J. and Roberts, M. S. Transdermal delivery of dmgs by iontophoresis A review. Drug Design Delivery 4 1, 1989. 

Knoblauch, R and Moll. R In vitro pulsatile and continuous transdermal delivery of buserelin by iontophoresis. J. Controlled Rel. 26 203, 1993. 

Phipps, J.B. Electrode and reservoir design for optimal transdermal delivery by iontophoresis. In Transdermal Administration, A Case Study, Iontophoresis APGI/CRS European Symposium, Couvreur, P., Duchene, D., Green, P., Junginger, H.E., Eds. 3-4 March 1997, Paris, France Editions de Sante Paris, 1997 30-39. 

Jadoul, A. Regnier, V. Preat, V. Influence of ethanol and propylene glycol addition on the transdermal delivery by iontophoresis and electroporation. Pharm. Res. 1997, 14, S308-S309. 

The application of high-voltage electrical pulses to the skin (so-called electroporation) is another approach that has also been used to increase peptide delivery across the epidermal barrier. Several reviews of the application of electroporation to increase transdermal delivery have been published within the last few years. Unlike iontophoresis, which employs small currents (0.5mA/cm ) for relatively long periods of time (many minutes to hours), electroporation involves exposure of the skin to relatively high voltages (on the order of 30-100 V imposed across the skin) for rather short times, typically one to several hundred millise-conds.t ... 

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