Mf. Lu et al., THE EFFECTS OF FORMULATION VARIABLES ON IONTOPHORETIC TRANSDERMAL DELIVERY OF LEUPROLIDE TO HUMANS, Drug development and industrial pharmacy, 19(13), 1993, pp. 1557-1571
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.