DONEPEZIL TRANSDERMAL DELIVERY SYSTEM
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.
1 . A transdermal delivery system for systemic delivery of donepezil base, comprising:
a skin contact adhesive layer to attach the system to the skin of a user, and
a drug reservoir comprised of a hydrophilic solvent, a donepezil salt, an alkaline salt, and donepezil base generated in situ by reaction of the donepezil salt and the alkaline salt.
2 . The system of claim 1 , further comprising an adhesive in the drug reservoir.
3 . The system of claim 2 , wherein the adhesive is comprised of an acrylate adhesive.
4 . The system of claim 2 , wherein the adhesive is comprised of a copolymer of acrylic acid/vinyl acetate.
5 . The system of claim 1 , wherein the alkaline salt is selected from the group consisting of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, trisodium phosphate, disodium hydrogen phosphate, sodium oxylate, sodium succinate, sodium citrate, and sodium salicylate.
6 . The system of claim 1 , the hydrophilic solvent is selected from the group consisting of polyethylene glycol, propylene glycol, glycerin, acetonitrile, 1-propanol, N,N-dimethylformamide and dimethyl sulfoxide.
7 . The system of claim 6 , wherein the hydrophilic solvent in present in the drug reservoir in an amount between about 5-15 wt %.
8 . The system of claim 1 , wherein the drug reservoir layer additionally comprises a solvent selected from the group consisting of sorbitan monolaurate, triethyl citrate and lauryl lactate.
9 . The system of claim 1 , wherein the donepezil salt is donepezil HCl present in the drug reservoir in an amount between about 5-25 wt %.
10 . A method for delivering donepezil base to a subject, comprising:
providing a transdermal delivery system according to claim 1 , and
administering or instructing to administer the transdermal delivery system to the skin of a subject.