Iontophoretic Delivery of Acyclovir: Intradermal Drug Monitoring Using Microdialysis and Quantification by Skin Extraction

Srujana Siddoju; Vishal Sachdeva; Phillip M. Friden; Ajay K. Banga

doi:10.5731/pdajpst.2011.00756

Abstract

The objective of this study was to investigate the effect of iontophoresis on the intradermal and transdermal delivery of acyclovir using hairless rat skin on a vertical Franz diffusion cell. In this study, cathodal iontophoretic delivery of acyclovir from a pH 11 formulation was explored. The effects of time of iontophoresis (10 min, 1 h, and 4 h) and current density (0.2, 0.3, and 0.5 mA/cm²) on skin permeation were examined. In vitro dermal microdialysis was performed to identify the drug depot formed in the dermis during iontophoresis. Acyclovir delivery into the receptor compartment was not influenced by current density or duration of current application. However, greater drug levels were delivered into the skin as a function of time of current application to form a drug depot. These results were further confirmed by in vitro dermal microdialysis in which higher drug levels were observed in dialysate in the 4 h iontophoresis group due to higher drug levels delivered into the skin layers as compared to 1 h iontophoresis group. Short duration iontophoresis enhanced acyclovir delivery into the skin layers rapidly and thus may be beneficial to improve treatment for cold sores (herpes labialis infection). Microdialysis could be used as a tool to simultaneously monitor drug levels in the tissue's interstitial fluid in real time in an in vitro setting.

LAY ABSTRACT: The objective of this study was to investigate the effect of current on the delivery of acyclovir into and across the skin using hairless rat skin mounted on glass diffusion cells. Acyclovir was delivered under negative polarity from a formulation with a very basic pH. The effect of current intensity and duration of application on delivery of acyclovir was investigated. The amount in the skin was also determined by inserting a probe into the skin with a semipermeable membrane that allows sampling of the drug that has entered the skin. When the current intensity or duration was increased, greater drug levels were seen in the skin but not across the skin. It was found that even short duration of current application can deliver acyclovir into the skin and this has potential use for treatment of cold sores.

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