Transdermal systems containing multilayer adhesive matrices to modify drug delivery

Abstract

A transdermal drug-containing dosage unit comprises: a backing layer substantially impervious to the drug to be delivered transdermally; a first polymeric adhesive matrix, in contact with the backing layer, having dispersed therein the drug and having a first delivery profile of the drug; a second polymeric adhesive matrix, in contact with said first polymeric adhesive matrix, having dispersed therein the drug and having a second delivery profile of the drug, wherein said second delivery profile is different from said first delivery profile; and a release liner in contact with the second polymeric adhesive matrix. The first polymeric adhesive matrix can release the drug more quickly or more slowly than the second polymeric adhesive matrix. Through the selection of the two matrices, the delivery profile of the drug through the skin can be selectively modified and controlled.

1 - 47 . (canceled) 
     
     
         48 . A method of providing hormone replacement therapy to a post-menopausal woman comprising:
 contacting the skin of the post-menopausal woman with a transdermal drug-containing dosage unit which comprises a laminate comprising:   a) a backing layer substantially impervious to a drug to be delivered transdermally;   b) a first polymeric adhesive matrix, in contact with the backing layer, having dispersed therein a therapeutically effective amount of the drug and having a first initial rate of delivery of the drug;   c) a second polymeric adhesive matrix, in contact with the first adhesive matrix, having dispersed therein a therapeutically effective amount of the drug and having a second initial rate of delivery of the drug;   d) a third polymeric adhesive matrix in contact with the second adhesive matrix, having dispersed therein a therapeutically effective amount of the drug and having a third initial rate of delivery of the drug; and   e) a release liner at least in partial contact with the third polymeric adhesive matrix; wherein the initial rates of delivery of at least two of the matrices are different from one another and the first, second, and third polymeric adhesive matrices each comprise a different polymeric adhesive; and   
       wherein the drug comprises an estrogen or a combination of an estrogen and a progestin. 
     
     
         49 . The method of  claim 48 , wherein the estrogen comprises estradiol or mono- or di-esters thereof which are transdermally absorbable. 
     
     
         50 . The method of  claim 49 , wherein the estradiol or mono- or di-esters thereof is selected from the group consisting of estradiol-3,17-diacetate; estradiol-17-acetate; estradiol-3,17-valerate; estradiol-3-valerate; estradiol-17-valerate; 3-mono-17-mono- and 3,17-dipilivate esters; 3-mono-, 17-mono-, and 3,17-dipropionate esters; ethanol estradiol; estrone; and other estrogenic steroids; and combinations thereof. 
     
     
         51 . The method of  claim 48 , wherein the transdermal drug-containing dosage unit comprises about 0.1% to about 4.0% w/w of estrogen. 
     
     
         52 . The method of  claim 48 , wherein the progestin comprises norethindrone acetate or levonorgestrel. 
     
     
         53 . The method of  claim 48 , wherein the progestin is selected from the group consisting of progesterone, medroxyprogesterone acetate, ethynodiol diacetate, and combinations thereof. 
     
     
         54 . The method of  claim 48 , wherein the transdermal drug-containing dosage unit comprises about 0.1% to about 20% w/w of the progestin. 
     
     
         55 . The method of  claim 48 , wherein one matrix comprises an acrylic adhesive, one matrix comprises a polyisobutylene adhesive and one matrix comprises a silicon adhesive