Formulation and biopharmaceutical evaluation of transdermal patch containing benztropine

Benztropine (BZ) is a potent muscarinic receptor antagonist that has been used for the treatment of Parkinson disease. However, the oral administration of BZ is often limited because of its many dose-related side effects. In this study, BZ was formulated into drug-in adhesive (DIA) patches in an attempt to overcome these problems. The effects of the formulation factors including pressure-sensitive adhesive (PSA), enhancer, the loading amount of the drug and patch thickness on the skin permeation of the drug were evaluated using excised rat skin. The optimized patch contained 10% BZ in Duro-Tak (R) 2525 as a PSA at a thickness of 100 mu m. The pharmacokinetic characteristics of the optimized DIA patch were determined after the transdermal application to rabbits. The calculated relative bioavailability of BZ in the DIA patch was 54% compared to the oral administration of BZ mesylate. This suggests that the transdermal application of BZ in a DIA patch may be used for the treatment of Parkinson disease. (C) 2008 Elsevier B.V. All rights reserved.