Development of a transdermal patch for delivery of propafenone: preliminary studies in vitro

Propafenone, a well-known antiarrhythmic drug, has a low oral bioavailability due to extensive hepatic first-pass metabolism The present study was aimed at verifying, on a preliminary basis, feasibility of transdermal delivery of the drug. Propafenone is apparently unable to penetrate the skin in the absence of appropriate enhancers. Different prospective enhancers (terpenes, azone) for the drug hydrochloride and base were evaluated in vitro using hairless mouse skin. Propafenone hydrochloride and atone, the most favourable drug species and enhancer combination, were then incorporated into semisolid vehicles, designed to act as reservoirs in transdermal patches. The patches, with and without a microporous membrane and adhesive layer were then tested for transdermal release using the same in vitro model. Skin, not membrane permeation, was found to be the rate-limiting step in delivery from the final patches. These, after 5 to 6 h lag times, delivered propafenone hydrochloride at a constant rate (5.4 to 27.5 mu g/cm(2)/h) for over 48 h. Since the literature data on intravenous infusion of propafenone appear to indicate the need for higher rates, further research on more effective promoters and transdermal patches is in progress