Sodium bicarbonate in situ conversion driven transdermal delivery of amine drug

Abstract

Compositions, devices, and methods for transdermal administration of active agents provided in their salt form instead of neutral form are provided.

It is claimed: 
     
         1 . A transdermal delivery system, comprising:
 a drug reservoir comprising an amine salt form of donepezil and an amphoteric inorganic base compound selected from sodium bicarbonate and potassium bicarbonate, wherein the pKa of the amphoteric inorganic base compound is lower than that of the amine salt form of the active agent.   
     
     
         2 . The transdermal delivery system of  claim 1 , wherein the amphoteric inorganic base compound is sodium bicarbonate. 
     
     
         3 . The transdermal delivery system of  claim 1 , wherein the amine salt form of donezpezil is present in the drug reservoir in an amount between about 5-35% w/w. 
     
     
         4 . The transdermal delivery system of  claim 1 , wherein the sodium bicarbonate is present in the drug reservoir in an amount between about 0.5-35% w/w. 
     
     
         5 . The transdermal delivery system of  claim 1 , wherein the amine salt form of donezpezil is donepezil HCl, and wherein the drug reservoir comprises a molar amount of donepezil HCl and a less than equimolar amount of sodium bicarbonate. 
     
     
         6 . The transdermal delivery system of  claim 1 , wherein the drug reservoir further comprises a salt form solubilizer selected from the group consisting of water, alcohols, glycerol, propylene glycol, ethylene glycol, dimethyl sulfoxide, and N-methylpyrrolidone. 
     
     
         7 . The transdermal delivery system of  claim 6 , wherein the salt form solubilizer is present in the drug reservoir in an amount of up to 15% w/w. 
     
     
         8 . The transdermal delivery system of  claim 1 , wherein the drug reservoir further comprises a neutral form solubilizer selected from the group consisting of a fatty acid ester, a dicarboxylic acid ester, a glycerol ester, a lactate, and a fatty alcohol. 
     
     
         9 . The transdermal delivery system of  claim 1 , wherein the drug reservoir further comprises a neutral form solubilizer selected from the group consisting of sorbitan monolaurate, lauryl lactate, and triethyl citrate. 
     
     
         10 . The transdermal delivery system of  claim 9 , wherein the neutral form solubilizer is present in the drug reservoir in an amount of up to 20% w/w. 
     
     
         11 . The transdermal delivery system of  claim 1 , wherein the drug reservoir further comprises an additive selected from the group consisting of crospovidone and colloidal silicone dioxide. 
     
     
         12 . The transdermal delivery system of  claim 11 , wherein the additive is present in the drug reservoir in an amount of up to 25% w/w. 
     
     
         13 . The composition of  claim 1 , wherein the drug reservoir further comprises an acrylate polymer or copolymer adhesive agent. 
     
     
         14 . The transdermal delivery system of  claim 13 , wherein the adhesive agent comprises up to 65% w/w of the drug reservoir. 
     
     
         15 . The transdermal delivery system of  claim 1 , further comprising a backing layer. 
     
     
         16 . The transdermal delivery system of  claim 15 , wherein the backing layer is an occlusive polymer film. 
     
     
         17 . The transdermal delivery system of  claim 15 , further comprising a contact adhesive layer comprised of an acrylate polymer or copolymer. 
     
     
         18 . The transdermal delivery system of  claim 17 , further comprising a nonwoven tie layer between the drug reservoir and the contact adhesive layer. 
     
     
         19 . The transdermal delivery system of  claim 17 , further comprising a rate-controlling membrane between the drug reservoir and the contact adhesive layer. 
     
     
         20 . A method for treating Alzheimer's disease, comprising: providing a transdermal delivery system according to  claim 1  to a patient in need thereof. 
     
     
         21 . The method of  claim 20 , further comprising administering or instructing to administer to the skin of the patient the composition. 
     
     
         22 . The method of  claim 21 , wherein said administering achieves a therapeutically effective blood concentration of donepezil.