Transdermal Iontophoretic Delivery of Thyrotropin-Releasing Hormone Across Excised Rabbit Pinna Skin

Enhanced transport of a model peptide drug thyrotropin-releasing hormone (TRH), a tripeptide of molar mass 362 g and a pK_a 6.2, through excised rabbit pinna skin was achieved by means of iontophoresis with continuous current or monophase periodically pulsed current. The resulting flux in the steady state was proportional to the applied current density. In the transdermal iontophoretic delivery of TRH, the pulsed iontophoretic flux exceeded that obtained with a continuous current. At a low ionic strength, an increased degree of protonation in TRH increased the rate of permeation. The flux of TRH in a buffer at pH 4 is greater than that at pH 8 when the ionic strength is 0.1 M. At a greater ionic strength, the trend is reversed. The enhanced flux of unprotonated TRH during transdermal iontophoresis is attributed largely to electro-osmotic volume flow. An increased rate of permeation of TRH crossing the skin is achieved at low ionic strength, moderate pH, and a large duly cycle of current; the frequency of pulsed current had no significant influence on the rate of transdermal iontophoretic delivery of TRH.