For and Against

To Iontophorise or not to Iontophorise? That is the question

Holler to the blogosphere! After previously discussing the history, dosage and safety topics, the literature that has evaluated iontophoresis must now be reviewed. The pros and cons will be discussed from a range of papers on iontophoretic drug delivery.

For

First we will look at the merits of iontophoresis. The fact that it is a non-invasive technique is beneficial in terms of patients that are trypanophobic (have a phobia of needles) and need their analgesic delivered to treat the source of pain. Several papers compared Iontophoresis to traditional transdermal delivery system (TDDS) without electrical stimulation. Bodde, Verhoef & Ponec (1989) measured the half-life of a peptide drug in plasma and in the dermis and epidermis. The study showed that the half-life of the drug was significantly longer in the epidermis and dermis than in plasma. Therefore by enhancing the flux through iontophoresis there will be increased drug delivery and the bioavailability of the drug will be higher. The use of the electrical gradient instead of the chemical gradient to drive the flux across the stratum corneum also has its merits according to the same study. The chemical gradient requires higher concentrations of the drug to create a stronger gradient. This is in contrast to iontophoresis that can deliver smaller quantities just as fast but without the side effects that may occur with overdosing of the drug. Bodde et al. (1989) also found that the absorption rate of drugs varied without current application (due to changes in the concentration gradient over time) but this variation did not occur in iontophoresis. The faster diffusion rate of ionized drugs with iontophoresis when compared to TDDS (limited by the chemical gradient) was supported by Srinivasan, Higuchi, Sims, Ghanem & Behl (1989).

Against

Iontophoresis obviously has some great advantages on other drug delivery systems, however there is literature that highlights the limitations of this technique. Sanderson, de Riel & Dixon (1989) brings to light that iontophoresis may be a good system for applications requiring a short period of drug delivery, but has unwanted side effects for applications requiring continuous or long time periods of delivery. These effects were examined in the study of Singh, Gross, Sage, Davis & Maibach (2000), which observed skin irritation in all subjects from four ethnic groups who were treated with saline iontophoresis for four hours. In the Moliton & Fernandez (1939) review of iontophoresis, burns caused by iontophoresis are discussed. However, this is only when a DC current is applied. In this situation hydrogen ions build up in the anode whilst hydroxide ions accumulate in the cathode causing pH changes that lead to electrochemical burns (Howard, Drake & Kellogg, 1995). Howard et al. hypothesized that when an alternating current is applied, hydrogen ions and hydroxide ions will be generated at alternate phases, avoiding the pH change which causes skin burns. Howard’s study observed that no burns occurred on patients for a two or four hour treatment time, so burns need not be caused by iontophoresis. There have been related reports of pain due to iontophoresis mentioned in literature (Khan et al., 2011) but there is no evidence to support these claims.

As you can see, iontophoresis has significant evidence to suggest it is a safe, viable method of drug delivery in situations requiring brief treatment times.

Until next time, you stay classy planet Earth.

References

Singh, J., Gross, M., Sage, B., Davis, H. & Maibach, H. (2000). Effect of saline iontophoresis on skin barrier function and cutaneous irritation in four ethnic groups. Food Chem Toxiology, 38(8), 717-726.

Khan, A., Yasir, M., Asif, M., Chauhan, I., Singh, A., Sharma, R., Singh, P. & Rai, S. (2011). Iontophoretic drug delivery: History and applications. Journal of Applied Pharmaceutical Science, 1(3), 11-14.

Bodde, H., Verhoef, J. & Ponec, M. (1989). Transdermal Peptide Delivery. Biochemical Society Transactions, 17(5), 943-945.

Srinivasan, V., Higuchi, W., Sims, S., Ghanem, A. & Behl, C. (1989). Transdermal iontophoretic drug delivery: mechanistic analysis and application to polypeptide delivery. Journal of Pharmaceutical Science, 78(5), 370-375.

Sanderson, J., de Riel, S. & Dixon, R. (1989). Iontophoretic delivery of nonpeptide drugs: formulation optimization for maximum skin permeability. Journal of Pharmaceutical Science, 78(5), 361-364.

Howard, J., Drake, T. & Kellogg, D. (1995). Effects of Alternating Current Iontophoresis on Drug Delivery. Archives of Physical Medicine and Rehabilitation, 76(1), 463-466.

Moliton, H. & Fernandez, L. (1939). Experimental studies on the causes and prevention of iontophoretic burns. The American Journal of the Medical Sciences, 198(6), 778-784.