THE EFFECTS OF FORMULATION VARIABLES ON IONTOPHORETIC TRANSDERMAL DELIVERY OF LEUPROLIDE TO HUMANS

Feasibility of applying iontophoresis to facilitate the transdermal pe rmeation of leuprolide acetate was investigated. Because of the comple xity of the factors involved in the process of iontophoresis, theoreti cal predictions of the combination effects from formulation variables are difficult. This study incorporated the formulation variables, drug levels and buffer concentrations, in a device prepared by Drug Delive ry System, Inc., to assess the feasibility for leuprolide delivery. St eady state serum leuprolide concentrations were achieved within 30 min utes of patch application, and were maintained for the duration of the study period. An increase in LH levels was observed for each formulat ion. The serum leuprolide concentrations were higher with lower drug c oncentration and more dilute buffer solutions. Increasing drug concent ration in the patch appeared to inhibit delivery of leuprolide. A mean steady state serum concentration, 0.8 ng/ml, was achieved by a formul ation composed of 10 mg/ml leuprolide acetate and 0.05 M acetate buffe r at pH 5.0. Competitive reaction of ions possibly involved in the del ivery mechanism will be discussed.