Adhesive mixture for transdermal delivery of highly plasticizing drugs

Abstract

Transdermal drug delivery patches and methods of their production are described. The patches can be made such that they accommodate highly plasticizing drugs such as selegiline and/or the use of protonated forms of various drugs.

1 . A method of producing a transdermal therapeutic adhesive formulation including at least one highly plasticizing drug comprising the steps of:
 providing between about 65% and about 97%, by weight, of an acrylic polymeric adhesive which includes between about 40% and about 90% of a C 4 -C 12  alkyl acrylate, between about 10% and about 40% by weight of a C 1 -C 3  alkyl acrylate hardening monomer; between about 1% and about 20% by weight of a functionalizing monomer which facilitates crosslinking; and a crosslinking agent;   mixing said acrylic polymeric adhesive with a highly plasticizing drug in an amount which is sufficient to provide between about 3% and about 35% of said drug by weight based on the weight of the mixture when said transdermal therapeutic adhesive formulation is dry;   and crosslinking said acrylic polymeric adhesive to form a matrix capable of controlling the release of said highly plasticizing drug.   
     
     
         2 . The method of  claim 1  wherein between about 3% and about 70% of said drug is mixed with said acrylic polymeric adhesive prior to the drying of said formulation, in order to provide said between about 3% and about 35% of said drug when said adhesive formulation is dry. 
     
     
         3 . The method of  claim 1  wherein crosslinking is accomplished in situ by drying the mixture. 
     
     
         4 . The method of  claim 1  wherein said C 4 -C 12  alkyl acrylate is selected from the group consisting of 2-ethylhexyl acrylate, butyl acrylate, n-decyl, n-nonyl, 2-ethyoctyl, isooctyl and dodecyl-acrylate. 
     
     
         5 . The method of  claim 1  wherein said C 4 -C 12  alkyl acrylate is provided in an amount of between about 60% and about 80% by weight based on the total weight of the acrylic polymeric adhesive. 
     
     
         6 . The method of  claim 1  wherein said C 1 -C 3  alkyl acrylate hardening monomer is selected from the group consisting of methyl acrylate, methyl methacrylate, ethylacrylate, ethyl methacrylate, hydroxyethyl acrylate and hydroxy propyl methacrylate. 
     
     
         7 . The method of  claim 1  wherein said C 1 -C 3  alkyl acrylate hardening monomer is provided in an amount of between about 15% and about 30% by weight based on the total weight of the acrylic polymeric adhesive. 
     
     
         8 . The method of  claim 1  wherein said functionalizing monomer which facilitates crosslinking is selected from the group consisting of acrylic acid, hydroxy ethylacrylate, methacrylic acid, and acrylamide. 
     
     
         9 . The method of  claim 1  wherein said functionalizing monomer which facilitates crosslinking is provided in an amount of between about 1% and about 10% by weight based on the total weight of the acrylic polymeric adhesive. 
     
     
         10 . The method of  claim 1  wherein said C 4 -C 12  alkyl acrylate is selected from the group consisting of 2-ethylhexyl acrylate, butyl acrylate, n-decyl, n-nonyl, 2 ethyoctyl, isooctyl and dodecyl-acrylate and is provided in an amount of between about 60% and about 80% by weight based on the total weight of the acrylic polymeric adhesive and wherein said C 1 -C 3  alkyl acrylate hardening monomer is selected from the group consisting of methyl acrylate, methyl methacrylate, ethylacrylate, ethyl methacrylate, hydroxyethyl acrylate and hydroxy propyl methacrylate and is provided in an amount of between about 15% and about 30% by weight based on the total weight of the acrylic polymeric adhesive. 
     
     
         11 . The method of  claim 10  wherein said highly plasticizing drug is selected from the group consisting of selegiline, fluoxetine, Des-methyl selegiline, tetracaine and chlorpheniramine. 
     
     
         12 . The method of  claim 11  wherein said highly plasticizing drug is provided in an amount of between about 3% and about 25% by weight of the therapeutic adhesive formulation. 
     
     
         13 . The method of  claim 12  wherein said highly plasticizing drug is provided in an amount of between about 3% and about 18% by weight of the therapeutic adhesive formulation. 
     
     
         14 . The method of  claim 1  wherein said crosslinking agent is selected from the group consisting of butyl titinate, polybutyl titinate, aluminum isopropoxide, aluminum zinc acetate, multivalent metals, methylol ureas and melamines. 
     
     
         15 . The method of  claim 1  wherein said crosslinking agent is provided in an amount of between about 0.005% and about 2% based on the total weight of the acrylic polymeric adhesive. 
     
     
         16 . A method of producing a therapeutic adhesive formulation for use in a transdermal patch comprising the steps of: selecting an acrylic polymeric adhesive which is suitable for use with highly plasticizing drugs based upon its content of between about 40% and about 90% of a C 4 -C 12  alkyl acrylate and between about 10% and about 40% by weight of a C 1 -C 3  alkyl acrylate hardening monomer; and mixing said acrylic polymeric adhesive with a highly plasticizing drug in an amount of between about 3% and about 65% by weight based on the weight of said mixture. 
     
     
         17 . The method of producing a therapeutic adhesive formulation for use in a transdermal patch of  claim 16  further comprising the step of: selecting an acrylic polymeric adhesive which is suitable for use with highly plasticizing drugs based upon its content of between about 40% and about 90% of a C 4 -C 12  alkyl acrylate and between about 10% and about 40% by weight of a C 1 -C 3  alkyl acrylate hardening monomer; between about 1% and about 20% by weight of a functionalizing monomer which facilitates crosslinking; and a crosslinking agent. 
     
     
         18 . The method of producing a therapeutic adhesive formulation for use in a transdermal patch of  claim 17  further comprising the step of: drying said mixture of said acrylic polymeric adhesive and said highly plasticizing drug to form a matrix capable of controlling the release of said highly plasticizing drug when placed in a transdermal patch and applied to the skin of a patient and which will not ooze, suffer from adhesive failure, fall off of a patient prematurely or be difficult to remove when necessary.