Effects of fatty acids and iontophoresis on the delivery of midodrine hydrochloride and the structure of human skin

Purpose. The purpose of this work was to investigate if fatty acids can increase the iontophoretic delivery of midodrine hydrochloride through human dermatomed skin and to observe the effects of iontophoresis and fatty acids on skin using SEM. Methods. After prehydration for 1 h, human dermatomed skin was treated with 0 - 0.3 M fatty acids ( oleic acid, linoleic acid, decanoic acid, and lauric acid) in propylene glycol ( PG) for 1 h. Then the fatty acid solution was replaced by 1% midodrine hydrochloride aqueous solution, and 0.1 mA/cm(2) constant current was applied. Samples were taken over 24 h and analyzed by HPLC. After the treatments outlined above, the epidermis was separated, fixed with glutaraldehyde, and dehydrated for SEM. Results. SEM studies revealed that only 1 h of treatment with fatty acids opened up the tightly compact stratum corneum cell layer, and the permeation study showed a significant increase of the permeability of skin to midodrine hydrochloride after fatty acid treatment. Conclusions. Using 5% oleic acid pretreatment, with the electrical current offset at 0.1 mA/cm(2), the daily delivery of midodrine hydrochloride can provide an adequate clinical application. The enhancement of passive and iontophoretic delivery by fatty acids may be occurring through the same mechanism.