The influence of anti-irritants on captopril hydrophilic gel.

In this study, we compared the irritation inhibition of various types of anti-irritants such as antihistamines (cyprohetadine, diphenhydramine, and promethazine), alpha-hydroxy acids (gluconolactone and gluco-delta-lactone), corticosteroids (betamethasone and clobetasol), and ion channel modulating agents (amiloride, ethacrynic acid, nifedipine, and verapamil) on the adverse dermatological reaction caused by captopril gel using noninvasive bioengineering methods including measuring the transepidermal water loss (TEWL) and the color change of skin surface [such as change chroma (delta C) and difference in color (delta E) between the gel-treated site and the untreated site]. In addition, the influence of these anti-irritants on the penetration capacity of captopril through the rabbit skin was also investigated. The results showed that the TEWL, change chroma (delta C), and difference in color (delta E) of skin were significantly reduced via incorporating diphenhydramine and clobetasol, indicating that both substances had potent irritation inhibition activity. Moreover, these substances had no effect on the percutaneous absorption of captopril gel. However, flux of the captopril with anti-irritants was about 480 microg/cm2/h and the required minimum administration area to obtain the minimum effective concentration was about 15 cm2, indicating that this formulation could possibly be developed for a transdermal drug delivery system.

Effect of antioxidants and anti-irritants on the stability, skin irritation and penetration capacity of captopril gel.

The effects of antioxidants and chelating agent on the stability of captopril in aqueous and semisolid were determined in this study. Then the influence of the combination of additives including antioxidants, anti-irritants and penetration enhancer on stability, skin irritation and penetration capacity of captopril in semisolid dosage form was investigated. In the stability study, the degradation of captopril followed the first-order kinetic. The chelating agent EDTA showed a potent stability effect and obviously increased the shelf-life up to 14-fold that of control gel. The anti-irritants such as clobetasol and diphenhydramine had potent inhibition irritation activity and the effect was not retarded by the addition of EDTA. Moreover, the captopril gel containing penetration enhancer, anti-irritants and chelating agent had a higher penetration capacity and the minimum therapeutic concentration could be obtained by applying about 13.24 cm(2) of administered area, indicating that the formulation can possibly be developed for a transdermal drug delivery system.