Transdermal iontophoretic delivery of hydrocortisone from cyclodextrin solutions

Enhanced skin penetration of hydrocortisone can be desirable for treatment of several diseases. Transdermal iontophoretic delivery of hydrocortisone solubilized in an aqueous solution of hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) was investigated and compared with chemical enhancement of co-solvent formulations. The passive permeation of hydrocortisone through human cadaver skin was higher when delivered from propylene glycol than when delivered after solubilization in an aqueous solution of HP-beta-CyD. However, the iontophoretic delivery of the 1% hydrocortisone-9% HP-beta-CyD solution was higher than the amount delivered passively by the 1% hydrocortisone-propylene glycol formulation, even if oleic acid was used as a chemical enhancer. Iontophoretic delivery of 1% hydrocortisone with 3% or 15% HP-beta-CyD was lower than that of the 9% HP-beta-CyD solution. These data suggest that free hydrocortisone rather than complexes is predominantly delivered iontophoretically through the skin and the HP-beta-CyD complex serves as a carrier to replenish depletion of hydrocortisone. HP-beta-CyD prevents hydrocortisone from forming a skin reservoir. Iontophoresis provides better enhancement of transdermal delivery of hydrocortisone than the chemical approach when just sufficient HP-beta-CyD is added to solubilize the hydrocortisone.