Transdermal iontophoretic delivery of [3H]-betamethasone sodium phosphate to the hind knee joints of rabbits: visualization of drug permeation routes and distributions

We used semimicro autoradiographs (ARGs) to investigate how tritium-labeled betamethasone sodium phosphate (beta-Na-phos) permeates the skin and is delivered to deeper tissues when it was transdermally administered to the hind knee joints of rabbits with and without iontophoresis. In passive transdermal administration, ARGs revealed the presence of beta-Na-phos only in the epidermis immediately beneath the site of drug administration. In active administration using iontophoresis, on the other hand, the plasma concentrations of beta-Na-phos after 30- and 120-min iontophoretic administrations were 0.090 and 12 μg eq./mL, respectively. Furthermore, ARGs indicated that beta-Na-phos was non-uniformly distributed from the skin to tissues surrounding the joint capsule (pericapsular tissues). The procedure suggested that beta-Na-phos reached pericapsular tissues via the perimysium. These results indicated the marked effect of iontophoresis to enhance the skin permeation of beta-Na-phos and that at least 30-min iontophoretic administration allowed its delivery to pericapsular tissues.