Evaluation of acyclovir cream and gel formulations for transdermal iontophoretic delivery.

BACKGROUND: Efficient iontophoretic transdermal delivery of hydrophilic drug molecules requires selection of appropriate aqueous formulation. In this study, oil/water cream and gel formulations were investigated for iontophoretic transdermal delivery of acyclovir (ACV), a model hydrophilic small-drug molecule, across hairless rat skin on Franz diffusion cells. RESULTS: Iontophoresis (0.2 mA/cm2) enhanced ACV delivery from both 5% cream (pH 6.8) and 4% gel (pH II) formulations. However, sixfold higher drug levels were delivered across the skin using gel formulation (12.25 +/- 4.04 microg/cm2) as compared with cream formulation (2.03 +/- 0.05 microg/cm2). Significantly higher drug levels were delivered when iontophoresis was performed at higher current density (0.32 mA/cm2; p < 0.05). Influence of formulation co-solvents (glycerin and propylene glycol) on drug delivery was also investigated in vitro using Franz cells and in vivo in hairless rats using microdialysis. CONCLUSION: Iontophoretic transdermal delivery of ACV was feasible and dependent on the selection of formulation components and delivery parameters.

Acyclovir skin depot characterization following in vivo iontophoretic delivery.

BACKGROUND/PURPOSE: Current Herpes labialis infection treatment by oral, parenteral or topical routes is inefficient. The objective of this study was to investigate the use of iontophoresis for improved topical delivery of acyclovir (ACV) in vivo in hairless rat. METHODS: Iontophoresis was performed for 10 min using a 5% ACV gel formulation. Tape stripping and skin extractions were performed at different time points following treatment for drug quantification in stratum corneum (SC) and underlying skin, respectively. RESULTS: Fourfold more ACV was detected in the SC immediately following 10-min iontophoresis as compared with passive delivery. Similarly, high ACV levels (29.27±3.52 µg/cm(2)) were achieved in the underlying skin following a single 10-min iontophoretic treatment while no drug detected following passive delivery (P<0.05). At 24-h post-iontophoresis, ACV levels in the SC decreased with a corresponding increase in the underlying skin due to drug migration. After 24-h post-iontophoresis, drug levels gradually decreased in both skin compartments until no ACV was detected at 72-h post-iontophoresis. CONCLUSION: Iontophoretic delivery of ACV resulted in high drug levels in skin layers to form a drug depot, which persisted over 2-3 days.

Iontophoretic delivery of acyclovir: intradermal drug monitoring using microdialysis and quantification by skin extraction.

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/cm(2)) 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.

Transdermal iontophoretic delivery of terbinafine hydrochloride: quantitation of drug levels in stratum corneum and underlying skin.

The objective of this study was to determine the effect of iontophoresis on the delivery of terbinafine hydrochloride (4%, w/w) into and across hairless rat skin. In vitro skin uptake and permeation studies were performed using Franz diffusion cells. Anodal iontophoresis was applied for 1h at current densities of 0.2, 0.3 and 0.4mA/cm(2). In addition, iontophoresis was applied for 15, 30, 45 and 60min. Studies were conducted in which the formulation was either removed or left in contact with the skin following iontophoresis and then passive delivery was assessed 23h later. Tape stripping and skin extraction were performed to quantify drug levels in the stratum corneum and the underlying skin, respectively. The samples were analyzed using HPLC. The amount of drug delivered into the stratum corneum following iontophoresis was not significantly different from the amount delivered passively (p>0.05). However, drug levels in the underlying skin were significantly higher for the iontophoretic group. The amount of terbinafine delivered into the skin layers was influenced by current density and duration of current application. Leaving the drug formulation in contact with the skin during the post-iontophoretic period had a significant effect on drug levels delivered into skin layers. Iontophoresis enhanced the delivery of terbinafine hydrochloride into the skin layers and, therefore, may be used to improve the treatment of skin fungal infections.