Modular transdermal delivery system and associated methods of manufacture and use

Abstract

A modular transdermal drug delivery system is provided, the system including: an upper module in which an outer backing layer is laminated to a pressure-sensitive adhesive layer that is covered by a removable release liner prior to assembly; and a lower module with a porous drug reservoir layer laminated to a skin-contact adhesive that affixes the system to the skin during drug delivery, where the skin-contact adhesive is, in one embodiment, an adhesive layer that is substantially co-extensive with the porous drug reservoir layer and, prior to use, protected with a second removable release liner. Methods of manufacture and use are also provided, as is an assembled transdermal drug delivery system fabricated by affixing the pressure-sensitive adhesive layer of the upper module to the porous drug reservoir layer of the lower module.

1 - 39 . (canceled) 
     
     
         40 . A method for making a transdermal drug delivery system, wherein the method comprises:
 providing an upper module comprising an outer backing layer, a pressure-sensitive adhesive layer laminated thereto, and a first removable release liner covering the pressure-sensitive adhesive layer;   selecting a lower module from at least two lower modules each comprising a porous drug reservoir layer for adhering to the pressure-sensitive adhesive layer of the upper module, and a skin-contact adhesive affixed to the drug reservoir layer, wherein the lower modules differ from each other in at least one aspect;   removing the first removable release liner to expose the pressure-sensitive adhesive layer of the upper module;   loading a pharmaceutical formulation into the porous drug reservoir layer of the selected lower module; and   affixing the upper module to the selected lower module by contacting the exposed pressure-sensitive layer of the upper module to the drug-loaded porous drug reservoir layer.   
     
     
         41 . A method for making a transdermal drug delivery system, wherein the method comprises:
 providing an upper module comprising an outer backing layer, a pressure-sensitive adhesive layer laminated thereto, and a first removable release liner covering the pressure-sensitive adhesive layer;   selecting a lower module from at least two lower modules each comprising a porous drug reservoir layer for adhering to the pressure-sensitive adhesive layer of the upper module upon assembly, a skin-contact adhesive affixed to the drug reservoir layer, and, contained within the porous drug reservoir layer, a pharmaceutical formulation comprising a pharmacologically active agent or precursor thereto, wherein the lower modules differ from each other in at least one aspect;   removing the first removable release liner to expose the pressure-sensitive adhesive layer of the upper module; and   affixing the upper module to the selected lower module by contacting the exposed pressure-sensitive layer of the upper module to the drug-loaded porous drug reservoir layer.   
     
     
         42 . A group of modular transdermal delivery system components that can be assembled to form a modular transdermal delivery system, the components comprising:
 an upper module comprising an outer backing layer, a pressure-sensitive adhesive layer laminated thereto, and a first removable release liner covering the pressure-sensitive adhesive layer; and   at least two lower modules each comprising a porous drug reservoir layer capable of adhering to the pressure-sensitive adhesive layer of the upper module and into which a pharmaceutical formulation can be loaded, and a skin-contact adhesive affixed to the drug reservoir layer,   wherein the lower modules differ from each other in at least one aspect, and further wherein the upper module can be assembled with any one of the lower modules to provide a laminated transdermal delivery system.   
     
     
         43 . The group of  claim 42 , wherein the at least one aspect includes module thickness. 
     
     
         44 . The group of  claim 42 , wherein the at least one aspect includes reservoir volume. 
     
     
         45 - 51 . (canceled) 
     
     
         52 . A group of modular transdermal delivery system components that can be assembled to form a modular transdermal delivery system, the components comprising:
 at least two upper modules each comprising an outer backing layer, a pressure-sensitive adhesive layer laminated thereto, and a first removable release liner covering the pressure-sensitive adhesive layer, where the upper modules differ from each other in at least one aspect; and   a lower module comprising a porous drug reservoir layer capable of adhering to the pressure-sensitive adhesive layer of an upper module and into which a pharmaceutical formulation can be loaded, and a skin-contact adhesive affixed to the drug reservoir layer,   wherein the lower module can be assembled with any one of the upper modules to provide a laminated transdermal delivery system.   
     
     
         53 - 58 . (canceled) 
     
     
         59 . The group of  claim 42 , wherein the skin-contact adhesive comprises a skin-contact adhesive layer that is laminated to the drug reservoir layer and serves as the basal surface of the system that adheres to a body surface during use. 
     
     
         60 . The group of  claim 42 , wherein the pharmaceutical formulation comprises a pharmacologically active agent. 
     
     
         61 . The group of  claim 60 , wherein the skin contact adhesive layer is comprised of a material selected to be permeable to the pharmacologically active agent. 
     
     
         62 . The group of  claim 60 , wherein the pressure-sensitive adhesive layer comprises a composition that exhibits low partitioning for the pharmacologically active agent. 
     
     
         63 . The group of  claim 60 , wherein the pressure-sensitive adhesive layer contains a permeation enhancer for the pharmacologically active agent. 
     
     
         64 . The group of  claim 42 , wherein the pharmaceutical formulation comprises a precursor to a pharmacologically active agent. 
     
     
         65 . The group of  claim 64 , wherein the pressure-sensitive adhesive layer contains an activator compound for converting the precursor to the pharmacologically active agent. 
     
     
         66 . The group of  claim 59 , wherein the basal surface of the system has an area in the range of about 5 cm 2  to about 100 cm 2 . 
     
     
         67 - 68 . (canceled) 
     
     
         69 . The group of  claim 42 , wherein the skin-contact adhesive comprises a peripheral ring underlying the drug reservoir layer. 
     
     
         70 - 71 . (canceled) 
     
     
         72 . The group of  claim 42 , wherein the at least two lower modules further comprise the pharmaceutical formulation. 
     
     
         73 . The group of  claim 52 , wherein the porous drug reservoir layer is loaded with the pharmaceutical formulation. 
     
     
         74 . The group of  claim 42 , wherein the porous drug reservoir layer has a porosity gradient such that porosity gradually decreases from an uppermost region of the reservoir layer to a lowermost region of the reservoir layer. 
     
     
         75 . The method of  claim 40 , wherein the pharmaceutical formulation comprises a pharmacologically active agent selected from: analgesic agents; anesthetic agents; antiarthritic agents; respiratory drugs; anticancer agents; anticholinergics; anticonvulsants; antidepressants; antidiabetic agents; antidiarrheals; antihelminthics; antihistamines; antihyperlipidemic agents; antihypertensive agents; anti-infective agents; anti-inflammatory agents; antimigraine preparations; antinauseants; antineoplastic agents; antiparkinsonism drugs; antipruritics; antipsychotics; antipyretics; antispasmodics; antitubercular agents; antiulcer agents; antiviral agents; anxiolytics; appetite suppressants; attention deficit disorder drugs; cardiovascular preparations; beta-blockers; antiarrhythmic agents; central nervous system stimulants; cough and cold preparations; diuretics; genetic materials; herbal remedies; hormonolytics; hypnotics; hypoglycemic agents; immunosuppressive agents; leukotriene inhibitors; mitotic inhibitors; muscle relaxants; narcotic antagonists; nicotine; nutritional agents; ophthalmic drugs; parasympatholytics; peptide drugs; psychostimulants; sedatives; steroids; sympathomimetics; tranquilizers; vasodilators; wound-healing agents; and combinations of any of the foregoing. 
     
     
         76 . The method of  claim 40 , wherein the pharmaceutical formulation comprises a cannabinoid. 
     
     
         77 . The method of  claim 76 , wherein the cannabinoid is selected from tetrahydrocannabinol (THC), dronabinol, cannabichromanone, cannabichromene (CBC), cannabichromenic acid, cannabichromevarin (CBCV), cannabichromevarinic acid, cannabicitran (CBT), cannabicoumaronone (CBCON), cannabicyclol (CBL), cannabicyclolic acid, cannabicyclovarin, cannabidiol (CBD), cannabidiol monomethyl ether, dimethyl heptylpentyl cannabidiol (DMHP-CBD), cannabidiolic acid, cannabidiorcol, cannabidivarin (CBV), cannabidivarinic acid, cannabielsoin (CBE), cannabielsoinic acid, cannabifuran, cannabigerol (CBG), cannabigerol monomethyl ether (CBGM), cannabigerolic acid, cannabigerolic acid monomethyl ether, cannabigerovarin (CBGV), cannabigerovarinic acid, cannabiglendol, cannabinodiol, cannabinodivarin, cannabinol (CBN), cannabinolic acid, cannabinol methyl ether, cannabiorcol, cannabiripsol, cannabitetrol, cannabitriol, 10-O-ethyl-cannabitriol, cannabivarichromene, cannabivarin, dehydrocannabifuran, 1,2-dihydroxyhexahydrocannabinol, 1,2-dihydroxyhexahydrocannabinol acetate, dimethylheptylpyran, isotetrahydrocannabivarin, levonantradol, nabilone, rimonabant, Δ 9 -tetrahydrocannabinolic acid, Δ 9 -tetrahydrocannabiorcol, Δ 9 -tetrahydrocannabiorcolic acid, Δ 9 -tetrahydrocannabivarin, Δ 9 -tetrahydrocannabivarinic acid, 8,11-dihydroxy-Δ 9 -tetrahydrocannabinol, 8,9-dihydroxy-Δ 6a,10a -tetrahydrocannabinol, Δ 8 -tetrahydrocannabinol, Δ 8 -isotetrahydrocannabinol, Δ 8 -tetrahydrocannabinolic acid, 10-oxo-Δ 6a,10a -tetrahydrocannabinol (OTHC), HU-210 (1,1-dimethylheptyl-11-hydroxy-Δ 8 -THC), HU-331 (3-hydroxy-2-[(1R)-6-isopropenyl-3-methyl-cyclohex-2-en-1-yl]-5-pentyl-1,4-benzoquinone), JWH-018 (1-pentyl-3-(1-naphthoyl)indole), JWH-073, AM-2201 (1-(5-fluoropentyl)-3-(1-naphthoyl)indole), and CP-55,940 (2-((1S,2S,5 S)-5-hydroxy-2-(3-hydroxypropyl) cyclohexyl)-5-(2-methyloctan-2-yl)phenol). 
     
     
         78 . The method of  claim 77 , wherein the pharmacologically active agent comprises cannabidiol. 
     
     
         79 . The method of  claim 77 , wherein the pharmaceutical formulation further includes a terpenoid. 
     
     
         80 . A transdermal drug delivery system prepared by the method of  claim 40 . 
     
     
         81 . A transdermal drug delivery system prepared by the method of  claim 41 . 
     
     
         82 . A transdermal drug delivery system prepared by the method of  claim 75 . 
     
     
         83 . A transdermal drug delivery system prepared by the method of  claim 76 . 
     
     
         84 . A transdermal drug delivery system prepared by the method of  claim 77 . 
     
     
         85 . A transdermal drug delivery system prepared by the method of  claim 78 . 
     
     
         86 . A transdermal drug delivery system prepared by the method of  claim 79 .