Transdermal iontophoresis: combination strategies to improve transdermal iontophoretic drug delivery.

For several decades, there has been interest in using the skin as a port of entry into the body for the systemic delivery of therapeutic agents. However, the upper layer of the skin, the stratum corneum, poses a barrier to the entry of many therapeutic entities. Given a compound, passive delivery rate is often dependent on two major physicochemical properties: the partition coefficient and solubility. The use of chemical enhancers and modifications of the thermodynamic activity of the applied drug are two frequently employed strategies to improve transdermal permeation. Chemical enhancers are known to enhance drug permeation by several mechanisms which include disrupting the organized intercellular lipid structure of the stratum corneum , 'fluidizing' the stratum corneum lipids , altering cellular proteins, and in some cases, extracting intercellular lipids . However, the resulting increase in drug permeation using these techniques is rather modest especially for hydrophilic drugs. A number of other physical approaches such as iontophoresis, sonophoresis, ultrasound and the use of microneedles are now being studied to improve permeation of hydrophilic as well as lipophilic drugs. This article presents an overview of the use of iontophoresis alone and in conjunction with other approaches such as chemical enhancement, electroporation, sonophoresis, and use of microneedles and ion-exchange materials.