Mechanism of Transdermal Controlled Nitroglycerin Administration (III) Control of Skin Permeation Rate and Optimization

Abstract

A mathematical model was developed to correlate the drug permeation rate through the skin with the drug release rate from a matrix-type drug delivery system. Experiments were carried out using hairless mouse abdominal skin mounted on a recently-developed and hydrodynamically well-calibrated Keshary-Chien skin permeation system. A matrix-type drug delivery system was designed to contain different loading doses of nitroglycerin and to study the effect of drug loading variation on the rate of drug release, the rate of skin permeation and the equilibrium concentration of nitroglycerin in the skin. Results indicated that the stratum corneum plays a significant rate-limiting role in the skin permeation of nitroglycerin across the intact skin, yielding a constant skin permeation profile. The permeation rate across the intact skin was observed to increase with the increase in the drug release flux initially and then levelled off in a hyperbolic fashion. Various constants were obtained from the reciprocal plot of skin permeation rate vs. drug release flux. These constants could be used for the prediction of the skin permeation rate. A very good correlation between the predicted and the observed values of skin permeation rates was observed. After the stratum corneum was removed by stripping technique, the mechanism and the rate of skin permeation became dominated by the mechanism and the release rate of the delivery system. A linear correlation was observed between the drug permeation rate through the skin and the equilibrium concentration of drug in the skin. This correlation was observed in both intact and viable skins.