Transdermal nicotine salt delivery system

Abstract

A transdermal nicotine salt delivery system to an individual. The system has a high nicotine salt loading to effect therapeutic flux rate. Acrylate polymeric drug reservoir with the high nicotine salt dissolved therein provides desirable adhesive characteristics and effective transdermal therapeutic properties.

1 - 31 . (canceled) 
     
     
         32 . A transdermal nicotine salt delivery device, comprising:
 a drug reservoir comprising (i) an acrylate polymer with at least about 10 wt % polar functional monomer and (ii) a nicotine salt dissolved in the drug reservoir in an amount of at least about 10 wt %, wherein the acrylate polymer constitutes about 50 wt % to about 90 wt % of the drug reservoir.   
     
     
         33 . The device of  claim 32 , wherein the drug reservoir has a glass transition temperature (T g ) of less than −10° C. whereas the acrylate polymer has a T g  of −15° C. or higher and a creep compliance of 6×10 −5  cm 2 /dyn to 2×10 −6  cm 2 /dyn. 
     
     
         34 . The device of  claim 32 , wherein the acrylate polymer includes (i) about 40 to about 50 wt % of soft monomer, each soft monomer having a homopolymer T g  of −80 to −20° C., (ii) about 40 wt % to about 60 wt % of nonfunctional hard modifying monomer,
 each hard modifying monomer having a homopolymer T g  of 0 to 250° C., and (iii) up to about 30 wt % of functional monomer. 
 
     
     
         35 . The device of  claim 32 , wherein the acrylate polymer comprises a soft monomer selected from the group consisting of butyl, hexyl, 2-ethylhexyl, octyl, and dodecyl acrylates and isomers thereof. 
     
     
         36 . The device of  claim 32 , wherein the acrylate polymer includes about 40 wt % to about 50 wt % of soft monomer having a homopolymer T g  of less than −20° C. 
     
     
         37 . The device of  claim 32 , wherein the acrylate polymer has a T g  of 0 to −20° C. if without nicotine salt and without permeation enhancer, and the drug reservoir having the dissolved nicotine salt has a T g  of −10 to −20° C., a creep compliance of 1×10 −4  cm 2 /dyn to 6×10 −4  cm 2 /dyn, and a storage modulus of 1×10 5  dyn/cm 2  to 8×10 5  dyn/cm 2 . 
     
     
         38 . The device of  claim 32 , wherein the acrylate polymer has a T g  of 0 to −20° C. and a storage modulus of 8×10 5  dyn/cm 2  or above if without the nicotine salt and without any permeation enhancer, and the drug reservoir with the nicotine salt has a T g  of −10 to −20° C., a creep compliance of 1×10 −4  cm 2 /dyn to 6×10 −4  cm 2 /dyn, and a storage modulus of 1×10 5  dyn/cm 2  to 8×10 5  dyn/cm 2 . 
     
     
         39 . The device of  claim 32 , wherein the acrylate polymer comprises between about 50 wt % to about 60 wt % vinyl acetate, between about 10 wt % to about 20 wt % hydroxyethyl acrylate, and between about 20 wt % to about 40 wt % 2-ethylhexyl acrylate. 
     
     
         40 . The device of  claim 32 , wherein the acrylate polymer comprises between about 55 wt % to about 65 wt % butyl acrylate, between about 5 wt % to about 15 wt % t-octyl acrylamide, between about 20 wt % to about 30 wt % hydroxyethyl or hydroxypropyl acrylate, and between about 5 wt % to about 10 wt % acid monomer. 
     
     
         41 . The device of  claim 32 , wherein the nicotine salt is a salt of an acid having a pKa lower than 2. 
     
     
         42 . The device of  claim 32 , wherein the nicotine salt is a salt of an acid having at least one pKa higher than 2 and a melting point higher than 50° C. 
     
     
         43 . The device of  claim 32 , wherein the device can deliver between about 5 mg to about 30 mg of nicotine salt per day. 
     
     
         44 . The device of  claim 32 , wherein the nicotine salt dissolved in the drug reservoir is in an amount selected from between about 15 wt % to about 30 wt %. 
     
     
         45 . The device of  claim 32 , wherein the nicotine salt dissolved in the drug reservoir is in an amount selected from between about 20 wt % to about 30 wt %. 
     
     
         46 . The device of  claim 32 , wherein the acrylate polymer has a creep compliance of 7×10 −5  cm 2 /dyn or below. 
     
     
         47 . The device of  claim 32 , wherein the acrylate polymer has an elastic modulus of 8×10 5  dyn/cm 2  or above. 
     
     
         48 . The device of  claim 32 , wherein the drug reservoir further comprises one or more permeation enhancers. 
     
     
         49 . A method of smoking cessation therapy, comprising:
 administering a transdermal nicotine salt delivery device to a subject in need thereof, the device comprising:   a drug reservoir comprising (i) an acrylate polymer with at least about 10 wt % polar functional monomer and (ii) a nicotine salt dissolved in the drug reservoir in an amount of at least about 10 wt %, wherein the acrylate polymer constitutes between about 50 wt % to about 90 wt % of the drug reservoir.   
     
     
         50 . A method of smoking cessation therapy, comprising:
 administering a transdermal nicotine salt delivery device to a subject in need thereof, the device comprising:   (i) a backing; and   (ii) a drug reservoir comprising an acrylate polymer and dissolved nicotine salt of at least about 10 wt %,   wherein the acrylate polymer comprises no more than about 60 wt % soft monomer, at least about 40 wt % hard monomer, and between about 10 wt % to about 35 wt % polar functional monomer, and   wherein the acrylate polymer has a glass transition temperature (T g ) of −15° C. or higher and a creep compliance of 6×10 −5  cm 2 /dyn to 2×10 −6  cm 2 /dyn before the nicotine salt is dissolved therein, whereas after dissolution of the nicotine salt, the acrylate polymer exhibits a T g  of −10° C. or lower, a creep compliance of less than 1×10 −3  cm 2 /dyn, and a storage modulus of 1×10 5  dyn/cm 2  to 8×10 5  dyn/cm 2 .   
     
     
         51 . The method of  claim 50 , wherein the drug reservoir further comprises at least one permeation enhancer.