Dermal Delivery Device

Abstract

A transdermal drug delivery device is disclosed. Over an extended wear period, the device causes cumulative moderate irritation plus significant irritation of less than 5% and/or achieves a meaningful degree of detachment over a seven day period of less than 20%.

1 . A transdermal drug delivery patch that comprises:
 (a) a polymer matrix active ingredient (AI) layer having a skin-contacting surface and a non-skin contacting surface, the AI layer comprising an AI, a pressure sensitive adhesive (PSA), and a volatile component that is at least partly solubilized in the PSA of the AI layer;   (b) a release liner in direct contact with the skin-contacting surface of the AI layer, the perimeter of which extends beyond the perimeter of the AI layer in all directions;   (c) an overlay adjacent to the non-skin contacting surface of the AI layer, the perimeter of which extends beyond the perimeter of the AI layer in all directions; the overlay comprising: (i) a PSA layer; and (ii) an overlay covering; and   (d) an internal backing layer between the non-skin contacting surface of the AI layer and the PSA layer of the overlay;   wherein:   the volatile component is one or more volatile organic solvents having a vapor pressure above 0.1 mm mercury (Hg) at 20° C.;   the PSA of the AI layer is a polyacrylate PSA;   the PSA layer of the overlay is a polyisobutylene (PIB) PSA, a silicone PSA, a styrene copolymer PSA, or an isoprene rubber PSA;   the release liner and the PSA layer of the overlay are in direct contact with and adhered to each other around the perimeter of the AI layer to form a PSA seal between the overlay and the release liner;   the solubility of the volatile component in the PSA of the PSA layer of the overlay is less than the solubility of the volatile component in the PSA of the AI layer such that the PSA seal between the overlay and the release liner reduces or prevents loss of the volatile component from the AI layer;   during wear, moisture from the skin permeates the overlay;   the internal backing layer is impermeable or substantially impermeable to the components of the AI layer; and   adhesion of the layers is achieved without heat sealing.   
     
     
         2 . The patch of  claim 1 , wherein the AI layer comprises a humectant. 
     
     
         3 . The patch of  claim 2 , wherein the humectant is polyvinyl pyrrolidone (PVP) or a PVP copolymer. 
     
     
         4 . The patch of  claim 1 , wherein the volatile component is one or more of a sulfoxide, an alcohol, a fatty acid or an alkyl ester thereof, a polyol, an amide, a terpene, an alkane, or an organic acid. 
     
     
         5 . The patch of  claim 1 , wherein the volatile component is one or more of DMSO, decyl methyl sulfoxide, ethanol, propanol, hexanol, benzyl alcohol, lactic acid, valeric acid, isovaleric acid, isopropyl butyrate, ethyl acetate, butyl acetate, butanediol, ethylene glycol, dimethylacetamide, diethyl toluamide, dimethylformamide, pyrrolidone, methylpyrrolidone, limonene, pinene, terpinone, mentone, eucalyptus, menthol, hexane, heptane, or citric acid. 
     
     
         6 . The patch of  claim 1 , wherein the volatile component is one or more of dimethyl sulfoxide (DMSO) or a C 8 -C 20  saturated or unsaturated fatty acid or an ester or alcohol thereof. 
     
     
         7 . The patch of  claim 1 , in which the overlay additionally comprises an intermediate layer between the PSA layer and the overlay covering, said intermediate layer being permeable to moisture but impermeable to the PSA in the PSA layer. 
     
     
         8 . The patch of  claim 7 , in which the PSA layer in the overlay comprises a polyisobutylene (PIB) PSA and a humectant, and the intermediate layer in the overlay is a polyacrylate PSA, and the overlay covering is non-tacky, flexible and moisture permeable. 
     
     
         9 . The patch of  claim 8  in which the volatile component of the AI layer is one or more of DMSO or a C 8 -C 20  saturated or unsaturated fatty acid or an ester or alcohol thereof. 
     
     
         10 . The patch of  claim 1  in which the overlay covering is a foam or a woven or nonwoven fabric that allows water vapor permeation through it at a rate that is greater than the transepidermal water loss. 
     
     
         11 . The patch of  claim 1  in which the AI is a progestin, an estrogen, or both a progestin and an estrogen. 
     
     
         12 . The patch of  claim 11 , wherein the volatile component is one or more skin permeation enhancers. 
     
     
         13 . The patch of  claim 12 , wherein:
 the skin permeation enhancer comprises one or both of DMSO or ethyl lactate;   the AI layer comprises PVP or a PVP co-polymer,   the PSA layer of the overlay is a PIB PSA;   the overlay comprises an intermediate PSA layer that is a polyacrylate PSA; and   the overlay covering is non-tacky, flexible, and moisture permeable and comprises a foam or a woven or nonwoven fabric.   
     
     
         14 . The patch of  claim 13  wherein:
 the AI is levonorgestrel or a combination of levonorgestrel and ethinyl estradiol; 
 the polyacrylate PSA of the AI layer is a copolymer having a 2-ethylhexyl acrylate monomer and a vinyl acetate co-monomer; 
 the skin permeation enhancer further comprises one or both of lauryl lactate or capric acid; and 
 the PIB PSA of the overlay comprises a low to medium molecular weight and a high molecular weight PIB, a plasticizer, and a hydrocolloid. 
 
     
     
         15 . A method of delivering a drug to a patient in need thereof that comprises applying to the skin of the patient a transdermal drug delivery patch of  claim 1 , wherein the AI layer comprises an effective amount of the drug. 
     
     
         16 . A process for making a non-heat sealed transdermal drug delivery device, said device comprising:
 (a) a polymer matrix active ingredient (AI) layer having a skin-contacting surface and a non-skin contacting surface; the AI layer comprising an AI, a first pressure sensitive adhesive (PSA), and at least one volatile component which is at least partly solubilized in the first PSA;   (b) a release liner in direct contact with the skin-contacting surface of the AI layer, the perimeter of which extends beyond the perimeter of the AI layer in all directions;   (c) an overlay adjacent to the non-skin contacting surface of the AI layer, the perimeter of which extends beyond the perimeter of the AI layer in all directions; the overlay comprising: (i) a second PSA layer; and (ii) an overlay covering; and   (d) an internal backing layer between the AI layer and the overlay;   wherein the release liner and the PSA layer of the overlay are in direct contact with and adhered to each other around the perimeter of the AI layer to form a PSA seal between the overlay and the release liner, and the solubility of the volatile component in the second PSA is less than the solubility of the volatile component in the first PSA such that the PSA seal between the overlay and the release liner reduces or prevents loss of the at least one volatile component from the AI layer;   said process comprising:   determining the solubility of the one or more volatile components in the first PSA relative to its solubility in the second PSA and selecting a first PSA in which the solubility of the one or more volatile components is greater than it is in the second PSA; and thereafter making the device by: (1) fabricating an internal backing/AI layer/release liner laminate by applying the AI layer to one of the release liner or to the internal backing layer, drying the AI layer, and then applying the other of the internal backing layer or the release liner to the AI layer and then (2) fabricating the drug delivery device by laminating the overlay onto the internal backing layer side of the internal backing/AI layer/release liner laminate.   
     
     
         17 . The process of  claim 16 , wherein the first PSA is a polyacrylate PSA. 
     
     
         18 . The process of  claim 17 , wherein the second PSA is a polyisobutylene (PIB) PSA, a silicone PSA, a styrene copolymer PSA, or an isoprene rubber PSA. 
     
     
         19 . The process of  claim 16 , wherein the volatile component is one or more of a sulfoxide, an alcohol, a fatty acid or an alkyl ester thereof, a polyol, an amide, a terpene, an alkane, or an organic acid. 
     
     
         20 . The process of  claim 16 , wherein the volatile component is one or more of DMSO, decyl methyl sulfoxide, ethanol, propanol, hexanol, benzyl alcohol, lactic acid, valeric acid, isovaleric acid, isopropyl butyrate, ethyl acetate, butyl acetate, butanediol, ethylene glycol, dimethylacetamide, diethyl toluamide, dimethylformamide, pyrrolidone, methylpyrrolidone, limonene, pinene, terpinone, mentone, eucalyptus, menthol, hexane, heptane, or citric acid.