Transdermal delivery of therapeutic compounds by iontophoresis

Therapeutic administration of pharmaceuticals requires that safe and controlled delivery rates be achieved. Iontophoresis is a promising technique for delivering ionic drugs across the skin. Topical delivery of therapeutic agents by iontophoresis is attractive because the large surface area of skin provides for easy access. The top-most skin layer, the stratum corneum, does not favor the transport of most therapeutically active compounds under normal physiological conditions. Iontophoresis takes advantage of the negative background charge of skin which favors delivery of positively charged species. During iontophoresis a driving force for enhanced transport across skin is provided by an applied electric field. A limitation of the approach is that skin may be altered during the process.; The object of this work was to identify the influence of electric fields on the physicochemical properties of skin. The effect of electrolyte solution composition on these properties was also studied. Electrochemical impedance spectroscopy was applied to monitor the properties of skin before, during and after iontophoresis. Statistical models were regressed to the data to identify nonstationary and nonlinear behavior. Results indicated that skin properties began to change as the potential across the skin exceeded a critical value. An adaptive modulation strategy was developed to prevent alterations to membrane properties during the impedance experiment.; The delivery rate of lidocaine across the skin was studied by UV-vis absorption spectroscopy. A customized dual-beam diffusion cell was developed to account for the mildly nonstationary behavior of the spectroscopy system. The work indicated that applied current enhanced the transdermal flux of lidocaine.; An additional goal of this work was to identify the influence of controlled variables on concentration and flux profiles within the skin. A one-dimensional steady-state mathematical model was developed to provide insight into the coupled phenomena that occur in the stratum corneum. The governing equations for the model account for diffusion and migration, homogeneous reactions in the electrolyte and the negative background charge of skin. Sample calculations are provided to demonstrate the complex nature of the interactions among the species in the system during iontophoresis.