Transdermal drug delivery device including an occlusive backing

Abstract

A transdermal drug delivery system for the topical application of one or more active agents contained in one or more polymeric and/or adhesive carrier layers, proximate to a non-drug containing polymeric backing layer which can control the delivery rate and profile of the transdermal drug delivery system by adjusting the moisture vapor transmission rate of the polymeric backing layer.

1 . A transdermal drug delivery system comprising: 
 (a) a pressure sensitive adhesive    (b) a therapeutically effective amount at least one drug for transdermal drug delivery, and    (c) an occlusive backing layer, wherein said backing being formed from at least one layer and having a high moisture vapor transmission rate.    
   
   
       2 . The transdermal drug delivery system according to  claim 1 , wherein the drug is selected from the group consisting of amphetamine, d-amphetamine, l-amphetamine, d,l-amphetamine, methaphetamine, prilocalne, benzocaine, butacaine, butamben, butanilicaine, corticaine, lidocaine, memantine, pilocarpine, cyclobenzaprine, paroxetine, fluoxetine, duloxetine, imipramine, decipramine, doxeprin, nortriptylene, protriptylene, bupropion, azelastine, chlorphenamine, bisoprolol, pheniramine, alprazolam, captopril, clonidine, clonazepam, enalapril, ramipril, haloperidol, ketoprofen, loratadine, methimazole, methylphenidate, methyl testosterone, nicotine, nitroglycerin, pramipexole, ropinirole, hydromorphone, scopolamine, testosterone, estradiol, methamphetamine, frovatriptan and phentermine.  
   
   
       3 . The transdermal drug delivery system according to  claim 1 , wherein the drug includes clonidine.  
   
   
       4 . The transdermal drug delivery system according to  claim 1 , wherein the drug is present in said transdermal drug delivery system from about 0.1% to about 50% by weight.  
   
   
       5 . The transdermal drug delivery system according to  claim 1 , wherein the drug is present in said transdermal drug delivery system from about 0.3% to 30% by weight.  
   
   
       6 . The transdermal drug delivery system according to  claim 1 , wherein the drug is present in said transdermal drug delivery system from about 0.5% to about 15% by weight.  
   
   
       7 . The transdermal drug delivery system according to  claim 1 , wherein the drug is present in said transdermal drug delivery system from about 1% to about 10% by weight.  
   
   
       8 . The transdermal drug delivery system according to  claim 1 , wherein the backing layer has a thickness of from about 0.2 mm to about 3 mm.  
   
   
       9 . The transdermal drug delivery system according to  claim 1 , wherein said backing layer has a moisture vapor transmission rate of from about 0.5 to about 1500 g/m 2 /24 hrs.  
   
   
       10 . The transdermal drug delivery system according to  claim 1 , wherein said backing layer has a moisture vapor transmission rate of from about 0.5 to about 1000 g/m 2 /24 hrs.  
   
   
       11 . The transdermal drug delivery system according to  claim 1 , wherein said backing layer has a moisture vapor transmission rate of from about 1.5 to about 500 g/m 2 /24 hrs.  
   
   
       12 . The transdermal drug delivery system according to  claim 1 , wherein said backing layer has a moisture vapor transmission rate of from 10 to about 100 g/m 2 /24 hrs.  
   
   
       13 . The transdermal drug delivery system according to  claim 1 , wherein said backing layer is formed of a plurality of layers.  
   
   
       14 . The transdermal drug delivery system according to  claim 13 , wherein a first layer of said backing layer is formed from a material selected from the group consisting of acrylonitrile, cellulose acetate, polycarbonate, ethylene vinyl acetate, ethylene methyl acrylate, polyester, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl alcohol, ethylene vinyl alcohol, polyamides, polyvinylidene chloride and polyvinyl chloride.  
   
   
       15 . The transdermal drug delivery system according to  claim 13 , wherein said backing layer further comprises a second layer having a greater water vapor transmission rate than said first layer.  
   
   
       16 . The transdermal drug delivery system according to  claim 15 , wherein said second layer is formed from cellulose acetate, nylon, polycarbonate, acrylonitrile, polystyrene, polyurethane and polyvinyl alcohol, or copolymers or multipolymers of these plastics with additional monomers.  
   
   
       17 . The transdermal drug delivery system according to  claim 15 , wherein said second layer is formed from polyurethane.  
   
   
       18 . The transdermal drug delivery system according to  claim 1 , wherein the pressure sensitive adhesive is a rubber based adhesive which is present in an amount from 5% to 97% by weight of said transdermal drug delivery system.  
   
   
       19 . The transdermal drug delivery system according to  claim 18 , wherein said pressure sensitive adhesive includes a rubber adhesive selected from the group consisting of natural and synthetic polyisoprene, polybutylene, polyisobutylene, styrene based polymers, styrene block copolymers, butadiene based polymers, styrene/butadiene polymers, styrene-isoprene-styrene block copolymers, hydrocarbon polymers, halogen-containing polymers and polysiloxanes.  
   
   
       20 . The transdermal drug delivery system according to  claim 18 , wherein said rubber adhesive includes polyisobutylene.  
   
   
       21 . The transdermal drug delivery system according to  claim 1 , wherein said pressure sensitive adhesive includes a polysiloxane polymer.  
   
   
       22 . The transdermal drug delivery system according to  claim 1 , wherein said pressure sensitive adhesive includes at least one acrylic-based polymer.  
   
   
       23 . The transdermal drug delivery system according to  claim 22 , wherein said acrylic-based polymer includes at least 50% by weight of an acrylate or alkyl acrylate monomer, from 0 to 20% of a functional monomer copolymerizable with the acrylate or alkyl acrylate monomer, and from 0 to 40% of other monomers.  
   
   
       24 . The transdermal drug delivery composition according to  claim 22 , wherein said pressure sensitive adhesive is a blend of at least one acrylic-based polymer and at least one second polymer selected from the group consisting of silicone-based polymers, rubbers, gums, polyisobutylenes, polyvinylethers, polyurethanes, styrene block copolymers, styrene/butadiene polymers, polyether block amide copolymers, ethylene/vinyl acetate copolymers, vinyl acetate based adhesives, and bioadhesives.  
   
   
       25 . The transdermal drug delivery composition according to  claim 24 , wherein said at least one second polymer includes a silicone-based polymer.  
   
   
       26 . The transdermal drug delivery composition according to  claim 22 , wherein the acrylic-based polymer which is present from about 2% to about 95% of the total dry weight of the of the composition.  
   
   
       27 . The transdermal drug delivery composition according to  claim 1 , wherein said pressure sensitive adhesive includes: (i) a first acrylic-based polymer having a first functionality and a first solubility parameter; and (ii) a second acrylic-based polymer having a second functionality and solubility parameter, wherein the first and second functionalities differ in the amount and type of functional groups, to provide an acrylic-based polymer combination having a net functionality proportional to the ratio of the first and second acrylic based polymers used, and are present in proportions to provide a net solubility parameter.  
   
   
       28 . A transdermal drug delivery system comprising: 
 (a) a pressure sensitive adhesive comprising (i) a pressure sensitive adhesive present in an amount from 5% to 97% by weight of said transdermal drug delivery system,    (b) 0.1% to about 50% by weight of at least one drug for transdermal drug delivery, and    (c) an occlusive backing layer, wherein said backing being formed from at least one layer and having a moisture vapor transmission rate of from about 0.5 to about 1500 g/m 2 /24 hrs.    
   
   
       29 . The transdermal drug delivery system according to  claim 28 , wherein the drug is selected from the group consisting of amphetamine, d-amphetamine, l-amphetamine, d,l-amphetamine, methaphetamine, prilocalne, benzocaine, butacaine, butamben, butanilicaine, corticaine, lidocaine, memantine, pilocarpine, cyclobenzaprine, paroxetine, fluoxetine, duloxetine, imipramine, decipramine, doxeprin, nortriptylene, protriptylene, bupropion, azelastine, chlorphenamine, bisoprolol, pheniramine, alprazolam, captopril, clonidine, clonazepam, enalapril, ramipril, haloperidol, ketoprofen, loratadine, methimazole, methylphenidate, methyl testosterone, nicotine, nitroglycerin, pramipexole, ropinirole, hydromorphone, scopolamine, testosterone, estradiol, methamphetamine, frovatriptan, and phentermine.  
   
   
       30 . The transdermal drug delivery system according to  claim 28 , wherein the drug includes clonidine.  
   
   
       31 . The transdermal drug delivery system according to  claim 28 , wherein the drug is present in said transdermal drug delivery system from about 1% to about 10% by weight.  
   
   
       32 . The transdermal drug delivery system according to  claim 28 , wherein the backing layer has a thickness of from about 0.2 mm to about 3 mm.  
   
   
       33 . The transdermal drug delivery system according to  claim 28 , wherein said backing layer has a moisture vapor transmission rate of from about 0.5 to about 1000 g/m 2 /24 hrs.  
   
   
       34 . The transdermal drug delivery system according to  claim 28 , wherein said backing layer has a moisture vapor transmission rate of from about 1.5 to about 500 g/m 2 /24 hrs.  
   
   
       35 . The transdermal drug delivery system according to  claim 28 , wherein said backing layer has a moisture vapor transmission rate of from 10 to about 100 g/m 2 /24 hrs.  
   
   
       36 . The transdermal drug delivery system according to  claim 28 , wherein said backing layer is formed of a plurality of layers.  
   
   
       37 . The transdermal drug delivery system according to  claim 36 , wherein a first layer of said backing layer is formed from a material selected from the group consisting of acrylonitrile, cellulose acetate, polycarbonate, ethylene vinyl acetate, ethylene methyl acrylate, polyester, polyethylene, polypropylene, polystyrene, polyurethane, polyvinyl alcohol, ethylene vinyl alcohol, polyamides, polyvinylidene chloride and polyvinyl chloride.  
   
   
       38 . The transdermal drug delivery system according to  claim 36 , wherein said backing layer further comprises a second layer having a greater water vapor transmission rate than said first layer.  
   
   
       39 . The transdermal drug delivery system according to  claim 38 , wherein said second layer is formed from cellulose acetate, nylon, polycarbonate, acrylonitrile, polystyrene, polyurethane and polyvinyl alcohol, or copolymers or multipolymers of these plastics with additional monomers.  
   
   
       40 . The transdermal drug delivery system according to  claim 39 , wherein said second layer is formed from polyurethane.  
   
   
       41 . The transdermal drug delivery system according to  claim 28 , wherein the pressure sensitive adhesive is a rubber based adhesive which is present in an amount from 5% to 97% by weight of said transdermal drug delivery system.  
   
   
       42 . The transdermal drug delivery system according to  claim 41 , wherein said pressure sensitive adhesive includes a rubber adhesive selected from the group consisting of natural and synthetic polyisoprene, polybutylene, polyisobutylene, styrene based polymers, styrene block copolymers, butadiene based polymers, styrene/butadiene polymers, styrene-isoprene-styrene block copolymers, hydrocarbon polymers, halogen-containing polymers and polysiloxanes.  
   
   
       43 . The transdermal drug delivery system according to  claim 41 , wherein said rubber adhesive includes polyisobutylene.  
   
   
       44 . The transdermal drug delivery system according to  claim 28 , wherein said pressure sensitive adhesive includes a polysiloxane polymer.  
   
   
       45 . The transdermal drug delivery system according to  claim 28 , wherein said pressure sensitive adhesive includes at least one acrylic-based polymer.  
   
   
       46 . The transdermal drug delivery system according to  claim 45 , wherein said acrylic-based polymer includes at least 50% by weight of an acrylate or alkyl acrylate monomer, from 0 to 20% of a functional monomer copolymerizable with the acrylate or alkyl acrylate monomer, and from 0 to 40% of other monomers.  
   
   
       47 . The transdermal drug delivery composition according to  claim 45 , wherein said pressure sensitive adhesive is a blend of at least one acrylic-based polymer and at least one second polymer selected from the group consisting of silicone-based polymers, rubbers, gums, polyisobutylenes, polyvinylethers, polyurethanes, styrene block copolymers, styrene/butadiene polymers, polyether block amide copolymers, ethylene/vinyl acetate copolymers, vinyl acetate based adhesives, and bioadhesives.  
   
   
       48 . The transdermal drug delivery composition according to  claim 47 , wherein said at least one second polymer includes a silicone-based polymer.  
   
   
       49 . The transdermal drug delivery composition according to  claim 45 , wherein the acrylic-based polymer which is present from about 2% to about 95% of the total dry weight of the of the composition.  
   
   
       50 . The transdermal drug delivery composition according to  claim 28 , wherein said pressure sensitive adhesive includes: (i) a first acrylic-based polymer having a first functionality and a first solubility parameter; and (ii) a second acrylic-based polymer having a second functionality and solubility parameter, wherein the first and second functionalities differ in the amount and type of functional groups, to provide an acrylic-based polymer combination having a net functionality proportional to the ratio of the first and second acrylic based polymers used, and are present in proportions to provide a net solubility parameter.  
   
   
       51 . A method for transdermally delivering a drug to a user in need thereof comprising administering the transdermal drug delivery device according to  claim 1  to said user.  
   
   
       52 . A method for transdermally delivering a drug to a user in need thereof comprising administering the transdermal drug delivery device according to  claim 28  to said user.  
   
   
       53 . A method of producing the transdermal drug delivery composition according to  claim 1 , comprising the steps of: 
 thoroughly and uniformly mixing together in a vessel appropriate amounts of the drug(s), polymer(s), adhesive(s), solvent(s), co-solvent(s), enhancer(s), additive(s) and/or excipient(s) to form said adhesive coating layer;    casting said adhesive coating layer onto a backing film having a high moisture vapor transmission rate and exposing said cast adhesive layer to elevated temperatures to remove the volatile processing solvents; and    applying a release liner to the surface opposite the backing film to form the transdermal drug delivery composition.