Percutaneous absorption of terodiline and the membrane-controlled transdermal therapeutic system

Abstract

In an attempt to prepare a transdermal dosage form of terodiline which is extensively metabolized in man, the absorption of terodiline, an anticholinergic and calcium antagonist, through rat skin was estimated in vitro and in vivo. Terodiline penetrated rapidly through the skin from the gel formulation without enhancers (penetration rate, 167.6 μg/h per cm 2). Laurocapram, a potent enhancer, did not enhance the absorption in vitro. When the gel formulation (0.9 g) was applied to rat abdominal skin (6 cm 2), high plasma concentrations ( C max, 8.8±3.4 μg/ ml) of terodiline were observed for 24 h, thereby resulting in a high bioavailability equivalent to that after intravenous injection. The application of a transdermal therapeutic system, prepared using the gel formulation and a microporous membrane, gave a constant plasma level of terodiline, 250–820 ng/ml, for about 48 h, indicating that the membrane-controlled systems may be an efficient drug delivery system for treatment of urinary urge incontinence.