Enhancement of nortriptyline penetration through human epidermis: influence of chemical enhancers and iontophoresis.

Different known percutaneous chemical enhancers and iontophoresis have been tested in-vitro to study their ability to increase transdermal absorption of nortriptyline hydrochloride (20 mg mL(-1)). The chemicals 1-dodecanol, Span 20, Azone, (R)-(+)-limonene or isopropyl myristate were used as an overnight pretreatment at 5% (w/w) in ethanol. Furthermore, isopropyl myristate (20%, w/w) and propylene glycol (15%, w/w) were tested in the same vehicle. Iontophoresis was applied directly to the nortriptyline hydrochloride donor solution for three different concentrations (20, 2 and 0.5 mgmL(-1)). The chemical enhancers slightly increased the nortriptyline transdermal flux but iontophoresis was more efficient. In this case, nortriptyline transdermal flux was concentration dependent, having a higher flux when the concentration was lowered. Therefore, iontophoresis was the most suitable technique to increase transdermal absorption of nortriptyline and it could be an alternative method to provide therapeutic concentrations of this drug in smoking cessation treatment.