Methods for treating alzheimer's disease with donepezil transdermal system

Abstract

A transdermal delivery system for systemic delivery of donepezil is described, where the system comprises an adhesive matrix drug reservoir layer comprised of a copolymer of acrylic acid/vinyl acetate, triethyl citrate, and donepezil base generated in situ by reaction of donepezil HCl and an alkaline salt. The system is provided for treatment of Alzheimer's disease, and achieves transdermal delivery of the therapeutic agent at steady state that is bioequivalent to administration of the therapeutic agent orally.

It is claimed: 
     
         1 . A method for treating Alzheimer's disease, comprising:
 providing a transdermal delivery system comprising a drug reservoir comprising donepezil HCl and an alkaline salt, and   applying the transdermal delivery system to the skin of a subject, thereby administering to the subject donepezil base generated in the drug reservoir by reaction of donepezil HCl and the alkaline salt.   
     
     
         2 . The method of  claim 1 , wherein the applying comprises applying once weekly. 
     
     
         3 . The method of  claim 1 , wherein providing comprises providing a transdermal delivery system that comprises an amount of donepezil HCl that generates an amount of donepezil base that is between about 1-25 mg in 24 hours. 
     
     
         4 . The method of  claim 3 , wherein the amount of donepezil base is generated for a period of at least about 3 days. 
     
     
         5 . The method of  claim 4 , wherein the amount of donepezil base is a therapeutically effective for amount for treating Alzheimer's disease in a human subject. 
     
     
         6 . The method of  claim 1 , wherein providing comprises providing a transdermal delivery system that further comprises an adhesive in the drug reservoir. 
     
     
         7 . The method of  claim 6 , wherein the adhesive forms a matrix in which donepezil base is soluble. 
     
     
         8 . The method of  claim 1 , wherein providing comprises providing a transdermal delivery system comprising between about 5-25 wt % donepezil HCl. 
     
     
         9 . The method of  claim 1 , wherein donepezil base is administered to the subject in an amount to achieve a plasma concentration of donepezil that is bioequivalent to administration of donepezil hydrochloride orally at a dose of up to approximately 10 mg/day. 
     
     
         10 . The method of  claim 1 , wherein donepezil base is administered to the subject in an amount to achieve a plasma concentration of donepezil for up to a 7-day period that is bioequivalent to daily administration of donepezil hydrochloride orally at a dose of up to approximately 10 mg/day.