Iontophoretic delivery of nonpeptide drugs: formulation optimization for maximum skin permeability

Although the technique of transdermal iontophoretic drug delivery has been known for many years, its use has been limited clinically to those applications for which a brief drug delivery period is adequate (e.g., delivery of pilocarpine in the diagnosis of cystic fibrosis). For most therapeutic applications, however, it is necessary to have an extended, if not continuous, drug delivery regimen. The use of iontophoresis has been limited in these applications by side effects, primarily skin trauma, associated both with the current density and the total amount of current passed. A mechanism for these side effects will be proposed and techniques to mitigate them will be presented. Many of these techniques involve ways in which the drug formulation can be designed to maximize the fraction of current carried by the drug species. These methods include the following: control of the pH in the bulk solution and in the boundary layer without using conventional buffers; taking advantage of polarization effects; and enhancing the permselectivity of skin. In this way, the therapeutic dose or optimal infusion rate of drug can be achieved with the minimum current and, therefore, the minimum number of side effects.