Transdermal testosterone device and delivery

Abstract

Described are transdermal drug delivery systems for the transdermal administration of testosterone, comprising a polymer matrix and testosterone. Methods of making and using such systems also are described.

1 . A transdermal drug delivery system comprising a drug-containing layer defining an active surface area and comprising a polymer matrix comprising 2-25% by weight acrylic adhesive, 45-70% by weight silicone adhesive, about 2-25% by weight soluble polyvinylpyrrolidone (PVP), about 5-15% penetration enhancer, and about 0.1-10% by weight testosterone, all based on the total dry weight of the polymer matrix, wherein the system includes less than 0.3 mg/cm 2  testosterone, and achieves a testosterone flux that is at least 0.7 μg/cm 2 /hour, based on the active surface area. 
     
     
         2 . The transdermal drug delivery system of  claim 1 , wherein the system achieves a testosterone flux that is at least 0.89 μg/cm 2 /hour, based on the active surface area. 
     
     
         3 - 4 . (canceled) 
     
     
         5 . The transdermal drug delivery system of  claim 1 , wherein the penetration enhancer comprises oleyl alcohol. 
     
     
         6 . The transdermal drug delivery system of  claim 1 , wherein the composition further comprises an antioxidant selected from the group consisting of butylhydroxytoluene (BHT), butylhydroxyanisole (BHA), ascorbyl palmitate, alpha-tocopherol and its esters, citric acid and propyl gallate, and mixtures thereof. 
     
     
         7 . The transdermal drug delivery system of  claim 6 , wherein the antioxidant comprises BHT. 
     
     
         8 . The transdermal drug delivery system of  claim 1 , wherein the acrylic adhesive and silicone adhesive are present in a ratio of from about 1:2 to about 1:6, based on the total weight of the acrylic and silicone adhesives. 
     
     
         9 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of testosterone effective to deliver a therapeutically effective amount of testosterone over a period of time selected from the group consisting of at least 1 day, at least 2 days, at least 3 days, at least 4 days, at least 5 days, at least 6 days and at least 7 days. 
     
     
         10 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of testosterone effective to deliver an amount of testosterone of from about 100 to about 500 μg/day. 
     
     
         11 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of testosterone effective to deliver an amount of testosterone of from about 100 to about 450 μg/day. 
     
     
         12 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix comprises an amount of testosterone effective to deliver an amount of testosterone of from about 300 μg/day to about 500 μg/day. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix has a coat weight of greater than about 10 mg/cm 2 . 
     
     
         16 . The transdermal drug delivery system of  claim 1 , wherein the polymer matrix has a coat weight of about 12.5 mg/cm 2 . 
     
     
         17 . A transdermal drug delivery system comprising a polymer matrix comprising 2-25% by weight acrylic adhesive, 45-70% by weight silicone adhesive, about 2-25% by weight soluble PVP, about 5-15% penetration enhancer, and about 0.1-10% by weight testosterone, all based on the total dry weight of the polymer matrix, wherein the system has an active surface area of 14.0 cm 2  and is effective to deliver an amount of testosterone per day of from about 300 μg to about 500 μg. 
     
     
         18 . A method for administering testosterone, comprising applying to the skin or mucosa of a subject in need thereof a transdermal drug delivery system comprising a drug-containing layer defining an active surface area and comprising a polymer matrix comprising 2-25% by weight acrylic adhesive, 45-70% by weight silicone adhesive, about 2-25% by weight soluble PVP, about 5-15% penetration enhancer, and about 0.1-10% by weight testosterone, all based on the total dry weight of the polymer matrix, wherein the system includes less than 0.3 mg/cm 2  testosterone, and achieves an testosterone flux that is at least 0.7 μg/cm 2 /hour, based on the active surface area. 
     
     
         19 . The method of  claim 18 , wherein the system achieves a testosterone flux that is at least 0.89 μg/cm 2 /hour, based on the active surface area. 
     
     
         20 . The method of  claim 18 , wherein the system has an active surface area that is about 14.0 cm 2  and is effective to deliver an amount of testosterone per day of from about 300 μg to about 500 μg. 
     
     
         21 . A method of making a transdermal drug delivery system for administering testosterone, comprising forming a polymer matrix comprising about 0.1-10% by weight testosterone and a polymer blend comprising 2-25% by weight of an acrylic adhesive, 45-70% by weight of a silicone adhesive, about 5-15% by weight of a penetration enhancer, and about 2-25% by weight soluble PVP, all based on the total dry weight of the polymer matrix, and applying the polymer matrix to a support layer such that the system includes less than 0.3 mg/cm 2  testosterone. 
     
     
         22 . The method of  claim 21 , wherein the system has an active surface area that is about 14.0 cm 2 . 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 21 , wherein the polymer matrix further comprises about 0.01% by weight BHT, based on the total dry weight of the polymer matrix. 
     
     
         25 . The method of  claim 21 , wherein the polymer matrix is applied to the support layer at a coat weight of greater than about 10 mg/cm 2 . 
     
     
         26 . The method of  claim 21 , wherein the polymer matrix coat weight is about 12.5 cm 2 .