Modulated delivery of donepezil using a combination of skin microporation and iontophoresis

The present study investigated the transdermal delivery of donepezil hydrochloride across dermatomed porcine ear skin using passive and physical enhancement techniques. In vitro permeation studies were performed on Franz diffusion cells. Microneedles were fabricated in the lab using a polymeric blend of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP). The fabricated microneedles were characterized using SEM. Effect of PVA-PVP microneedles and ablative laser (P.L.E.A.S.E) alone, and in combination with anodal iontophoresis on the delivery of donepezil hydrochloride was investigated. Scanning electron microscopy, histology, methylene blue staining, and confocal laser microscopy were used to characterize the microchannels created in the skin. Permeation of donepezil after passive delivery was found to be 26.87 +/-.97 mu g/sq.cm. Microneedles, laser, and iontophoresis significantly increased the permeation to 282.23 +/- 8.28 mu g/sq.cm, 1562 +/- 231.8 mu g/sq.cm and 623.4 +/- 21.3 mu g/sq.cm. Also, a significantly higher permeation was achieved with microneedles and laser in combination with iontophoresis (1000 +/- 160.9 mu g/sq.cm and 1700.4 +/- 189.43 pg/sq.cm respectively). A sharp increase in flux was observed with a combination of skin microporation and iontophoresis, however, the same was not observed for iontophoretic delivery alone. Thus, flux can be successfully tailored with a combination of skin microporation and iontophoresis to suit patient needs.