Compositions and methods for controlling drug loss and delivery in transdermal drug delivery systems

Abstract

A transdermal delivery system is provided 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 and/or adhesive coating that is applied to either the transdermal system's backing or release liner. The transdermal delivery device is manufactured to optimize drug loading while providing desirable adhesion to skin or mucosa as well as providing modulation of the drug delivery and profile.

1 - 43 . (canceled) 
     
     
         44 . A transdermal drug delivery system comprising:
 a backing layer;   a carrier composition layer comprising a therapeutically effective amount of an estrogen selected from the group consisting of conjugated estrogenic hormones, equilenin, equilin, esterified estrogens, 17β-estradiol, estradiol benzoate, 17β-estradiol valerate, estradiol 17β-cypionate, estriol, estrone, estropipate, 17β-ethinyl estradiol and mestranol; and   a non-drug containing layer comprising a silicone adhesive polymer, wherein the carrier composition layer has a first surface and a second surface, the first being affixed to a surface of the backing layer and the second surface being affixed to surface of the non-drug containing layer.   
     
     
         45 . The transdermal drug delivery system of  claim 44 , wherein the estrogen is equilenin, equilin, 17β-estradiol, estradiol benzoate, 17β-estradiol valerate, estradiol 17β-cypionate, estriol, estrone, estropipate, 17β-ethinyl estradiol and mestranol. 
     
     
         46 . The transdermal drug delivery system of  claim 44 , wherein the estrogen is estradiol. 
     
     
         47 . The transdermal drug delivery system of  claim 44 , wherein the carrier composition layer comprises a blend of at least one silicone polymer and at least one acrylic polymer. 
     
     
         48 . The transdermal drug delivery system of  claim 47 , wherein the carrier composition layer further comprises polyvinylpyrrolidone (PVP). 
     
     
         49 . The transdermal drug delivery system of  claim 44 , wherein the carrier composition layer further comprises a permeation enhancer. 
     
     
         50 . The transdermal drug delivery system of  claim 49 , wherein the permeation enhancer comprises oleyl alcohol. 
     
     
         51 . The transdermal drug delivery system of  claim 48 , wherein the carrier composition layer comprises a blend of at least one silicone polymer, at least one acrylic polymer, PVP, and oleyl alcohol. 
     
     
         52 . The transdermal drug delivery system of  claim 51 , wherein the carrier composition layer further comprises one or more pharmaceutically acceptable additives. 
     
     
         53 . The transdermal drug delivery system of  claim 52 , wherein the one or more pharmaceutically acceptable additives are selected from the group consisting of tackifying agents, binders, rheological agents, diluents, stabilizers, fillers, clays, buffering agents, biocides, humectants, anti-irritants, antioxidants, preservatives, plasticizing agents, cross-linking agents, flavoring agents, colorants, and pigments. 
     
     
         54 . The transdermal drug delivery system of  claim 47 , wherein the carrier composition layer comprises a blend of at least two acrylic polymers, one having functional groups and one having substantially no functional groups. 
     
     
         55 . The transdermal drug delivery system of  claim 54 , wherein the functional groups of the acrylic polymer having functional groups are one or more selected from the group consisting of carboxyl groups and hydroxyl groups. 
     
     
         56 . The transdermal drug delivery system of  claim 44 , wherein the silicone adhesive polymer of the non-drug containing layer is a polydiorganosiloxane cross-linked with a resin. 
     
     
         57 . The transdermal drug delivery system of  claim 44 , wherein the silicone adhesive polymer of the non-drug containing layer is produced through a condensation reaction of a silanol endblocked polydimethylsiloxane with a silicate resin having medium to high tack. 
     
     
         58 . The transdermal drug delivery system of  claim 44 , wherein the silicone adhesive polymer of the non-drug containing layer is selected from the group consisting of a Dow Corning BIO-PSA® -4501, -4503, -4602, and -4603. 
     
     
         59 . The transdermal drug delivery system of  claim 44 , wherein the non-drug containing layer has a coat weight of about 2.5 mg/cm 2  to 15 mg/cm 2 . 
     
     
         60 . The transdermal drug delivery system of  claim 44 , further comprising a release liner. 
     
     
         61 . A method of making the transdermal drug delivery system of  claim 44 , comprising combining (i) a pre-formed carrier composition layer affixed to a backing layer with (ii) a pre-formed non-drug containing layer. 
     
     
         62 . The method of  claim 61 , wherein said (i) a pre-formed carrier composition layer and (ii) pre-formed non-drug containing layer are formed separately, and then combined. 
     
     
         63 . The method of  claim 61 , wherein said (i) a pre-formed carrier composition layer and (ii) pre-formed non-drug containing layer are formed concomittently, and then combined in an in-line process. 
     
     
         64 . The method of  claim 61 , wherein the pre-formed non-drug containing layer is affixed to a release liner. 
     
     
         65 . The method of  claim 61 , wherein the non-drug containing layer has a coat weight of about 2.5 mg/cm 2  to 15 mg/cm 2 .