Effect of penetration enhancers on the transdermal delivery of isradipine through excised rabbit skin

ABSTRACT

Transdermal delivery is proposed for the calcium channel blocker isradipine, to overcome its poor oral bioavailability caused mainly by extensive first pass metabolism. This drug is approved for the treatment of angina pectoris and hypertension. In this study, the effect of penetration enhancers on the permeation of isradipine through rabbit skin was studied utilizing improved Franz diffusion cells. Three penetration enhancers including oleic acid, azone and 1, 8-cineole at three concentrations [2.5, 5.0 and 10% w/v] were investigated at drug concentration of 20 mg/ml in presence of propylene glycol as a vehicle. Results of the penetration enhancer permeability studies revealed that for all enhancers studied, increasing the enhancer concentration lead to a linear increase in the amount diffused. In addition, at 10% penetration enhancer concentration, the cumulative amount diffused over 24 hour period [Mean +/- SEM] was calculated to be 22965 +/- 4490, 12617 +/- 902, 10917 +/- 950 ng for oleic acid, azone and cineole, respectively compared to the control calculated to be 794 +/- 75 ng. This clearly shows that among the different enhancers studied, oleic acid at a concentration of 10% resulted in the highest amount of isradipine diffusing through the rabbit skin. Permeation parameters namely steady state flux, enhancement factor and permeability coefficient were also calculated in presence and absence of enhancers [control]. Results showed enhancement factors [Mean +/- SEM] of 28.9 +/- 8.08, 14.3 +/- 1.09 and 12.7 +/- 1.47 for oleic acid, azone and cineole, respectively with oleic acid showing highest diffusion enhancement. The permeability coefficient [P] data revealed similar trend. These results clearly indicate that the penetration enhancers tested succeeded in significantly increasing diffusion of isradipine through skin which affirms the feasibility of using a transdermal delivery system for isradipine for treatment of angina pectoris and hypertension