Formulation and biopharmaceutical evaluation of a transdermal patch containing letrozole

Abstract The purpose of this study was to formulate a drug‐in‐adhesive (DIA) transdermal patch containing letrozole, a third generation aromatase inhibitor for the treatment of breast cancer, using pressure‐sensitive‐adhesives (PSAs) and to evaluate the percutaneous penetration and pharmacokinetics of letrozole after transdermal administration, compared with that for the oral route. The formulation factors for such a patch, including the PSAs, enhancers and amount of drug loaded were investigated. Among the tested preparations, the formulation with DURO‐TAK 87‐4098, Azone and propylene glycol showed the highest letrozole permeation. The pharmacokinetic characteristics of an optimized DIA patch containing letrozole were determined using rats, while orally administered letrozole in solution was used as a control. The pharmacokinetic parameter, such as the mean residence time (MRT) was significantly ( p <0.05) different following transdermal administration compared with oral administration. The in vivo results observed with the patches in rats were in good agreement with the plasma concentrations predicted from the in vitro penetration data. As a patient‐friendly, convenient, high local drug concentration and sustained dosing therapeutic system, the transdermal patches incorporating letrozole provide a useful strategy for the prevention and treatment of breast cancer. Copyright © 2010 John Wiley & Sons, Ltd.