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 . A transdermal drug-containing dosage unit which comprises: 
 a) a backing layer substantially impervious to the drug to be delivered transdermally;    b) a first polymeric adhesive matrix, in at least partial contact with the backing layer, having dispersed therein the drug and having a first initial rate of delivery of the drug;    c) a second polymeric adhesive matrix, in at least partial contact with said first polymeric adhesive matrix, having dispersed therein the drug and having a second initial rate of delivery of the drug, wherein said second initial rate of delivery is different from said first initial rate of delivery; and    d) a release liner in at least partial contact with the second polymeric adhesive matrix.    
     
     
         2 . The transdermal drug-containing dosage unit of  claim 1 , wherein said first polymeric adhesive matrix delivers said drug more slowly than said second polymeric adhesive matrix.  
     
     
         3 . The transdermal drug-containing dosage unit of  claim 1 , wherein said second polymeric adhesive matrix delivers said drug more slowly than said first polymeric adhesive matrix.  
     
     
         4 . The transdermal drug-containing dosage unit of  claim 1 , wherein one of said first and second adhesive matrices has an initial delivery rate of a given amount of said drug that is at least about 10% faster than that of the other of said adhesive matrices.  
     
     
         5 . The transdermal drug-containing dosage unit of  claim 1 , wherein either said first or said second polymeric adhesive matrix comprises an acrylic adhesive.  
     
     
         6 . The transdermal drug-containing dosage unit of  claim 1 , wherein said first adhesive matrix comprises an acrylic adhesive and said second adhesive matrix comprises a silicone adhesive.  
     
     
         7 . The transdermal drug-containing dosage unit of  claim 1 , wherein said first adhesive matrix comprises an acrylic adhesive and said second adhesive matrix comprises a polyisobutylene adhesive.  
     
     
         8 . The transdermal drug-containing dosage unit of  claim 6 , wherein said silicone adhesive comprises a standard silicone adhesive or an amine compatible silicone adhesive.  
     
     
         9 . The transdermal drug-containing dosage unit of  claim 7 , wherein said polyisobutylene adhesive comprises a mixture of a high molecular weight polyisobutylene having a molecular weight of at least 1,000,000 and a low molecular weight polyisobutylene having a molecular weight of at least about 100 but less than 1,000,000.  
     
     
         10 . The transdermal drug-containing dosage unit of  claim 9 , wherein said high molecular weight polyisobutylene comprises between about 20% and 80% by weight of the total polyisobutylene and said low molecular weight polyisobutylene comprises between about 20% and 80% by weight of the total polyisobutylene.  
     
     
         11 . The transdermal drug-containing dosage unit of  claim 6  or  7 , wherein said acrylic adhesive comprises polymers of acrylic acid, methacrylic acid, N-butyl acrylate, n-butyl methacrylate, hexyl acrylate, 2-ethylbutyl acrylate, isooctyl acrylate, 2-ethylhexyl acrylate, 2-ethylhexyl methacrylate, decyl acrylate, decylmethacrylate, dodecyl acrylate, dodecyl methacrylate, tridecyl acrylate, or tridecyl methacrylate.  
     
     
         12 . The transdermal drug-containing dosage unit of  claim 6  or  7 , wherein said acrylic adhesive comprises a crosslinked carboxyl functional acrylic adhesive, non-crosslinked carboxyl functional acrylic adhesive, a crosslinked hydroxyl functional adhesive, a non-crosslinked hydroxyl functional adhesive, a grafted adhesive or a non-functional adhesive.  
     
     
         13 . The transdermal drug-containing dosage unit of  claim 1 , which further comprises at least one additional drug-containing polymeric adhesive matrix in between said first and second polymeric adhesive matrices.  
     
     
         14 . A transdermal drug-containing dosage unit which comprises: 
 a) a backing layer substantially impervious to the drug to be delivered transdermally;    b) a first polymeric adhesive matrix, in at least partial contact with the backing layer, having dispersed therein the drug and having a first initial rate of delivery of the drug;    c) a second polymeric adhesive matrix, in at least partial contact with the first adhesive matrix, having dispersed therein the drug and having a second initial rate of delivery of the drug;    d) a third polymeric adhesive matrix, in at least partial contact with the second adhesive matrix, having dispersed therein the drug and having a third initial rate of delivery of the drug; and    e) a release liner in at least partial contact with the third polymeric adhesive matrix;    wherein said initial rates of delivery of at least two of said matrices are different from one another.    
     
     
         15 . The transdermal drug-containing dosage unit of  claim 14 , which further comprises at least one additional drug-containing polymeric adhesive matrix in between said first and second polymeric adhesive matrices.  
     
     
         16 . The transdermal drug-containing dosage unit of  claim 14 , wherein each of said first, second and third initial rates of delivery is different from said other initial rates of delivery.  
     
     
         17 . The transdermal drug-containing dosage unit of  claim 14 , wherein either said first and third adhesive matrices or said second adhesive matrix comprises an acrylic adhesive.  
     
     
         18 . The transdermal drug-containing dosage unit of  claim 17 , wherein said matrix or matrices which does (do) not comprise an acrylic adhesive comprise(s) a silicone adhesive or a polyisobutylene adhesive.  
     
     
         19 . The transdermal drug-containing dosage unit of  claim 16 , wherein one matrix comprises an acrylic adhesive, one matrix comprises a polyisobutylene adhesive and one matrix comprises a silicone adhesive.  
     
     
         20 . The transdermal drug-containing dosage unit of  claim 1 ,  13  or  14 , wherein said drug comprises a cardiovascular drug, an androgenic steroid, an estrogen, a progestational agent, a drug which acts on the central nervous system, a nutritional agent, an anti-inflammatory agent, an antihistamine, a miotic, a dermatological agent, an anti-spasmodic, an anti-depressant, an anti-cancer drug, an anti-diabetic, an anti-estrogen, an anti-psychotic, an anti-infective agent, an anti-allergenic, an anti-pyretic, an anti-migraine agent or a tranquilizer.  
     
     
         21 . The transdermal drug-containing dosage unit of  claim 1  or  14 , wherein said drug comprises an estrogen or a combination of an estrogen and a progestin.  
     
     
         22 . The transdermal drug-containing dosage unit of  claim 21 , wherein said estrogen comprises estradiol or mono- or di-esters thereof which are transdermally absorbable.  
     
     
         23 . The transdermal drug-containing dosage unit of  claim 21 , wherein said progestin comprises norethindrone acetate or levonorgestrel.  
     
     
         24 . A transdermal drug-containing dosage unit which comprises: 
 a) a backing layer substantially impervious to the drug to be delivered transdermally;    b) a first polymeric adhesive matrix, in at least partial contact with the backing layer;    c) a second polymeric adhesive matrix, in at least partial contact with said first polymeric adhesive matrix; and    d) a release liner in at least partial contact with the second polymeric adhesive matrix,    wherein a drug to be delivered transdermally is initially suspended or dispersed within at least one of said first and second adhesive matrices and wherein if said drug is suspended or dispersed within both of said first and second adhesive matrices, said drug is initially delivered from said first adhesive matrix at a rate which is different from the initial rate of delivery of said second adhesive matrix.    
     
     
         25 . The transdermal drug-containing dosage unit of  claim 1 ,  13  or  14  which comprises from about 0.05% to about 40% w/w of drug.  
     
     
         26 . The transdermal drug-containing dosage unit of  claim 25 , which comprises from about 0.1% to about 4.0% w/w of drug.  
     
     
         27 . The transdermal drug-containing dosage unit of  claim 21 , which comprises from about 0.1% to about 4.0% of said estrogen.  
     
     
         28 . The transdermal drug-containing dosage unit of  claim 27 , which further comprises from about 0.1% to about 20% of a progestin.  
     
     
         29 . A method for administering a drug transdermally to an individual in need of such administration, comprising applying to skin of the individual a transdermal dosage unit comprising: 
 a) a backing layer substantially impervious to the drug to be delivered transdermally;    b) a first polymeric adhesive matrix, in at least partial contact with the backing layer, having dispersed therein the drug and having a first initial rate of delivery of the drug; and    c) a second polymeric adhesive matrix, in at least partial contact with said first polymeric adhesive matrix, having dispersed therein the drug and having a second initial rate of delivery of the drug, wherein said second rate of delivery is different from said first rate of delivery.    
     
     
         30 . The method of  claim 27 , wherein the dosage unit further comprises at least one additional drug-containing polymeric adhesive matrix in between said first and second polymeric adhesive matrices.  
     
     
         31 . A method for administering a drug transdermally to an individual in need of such administration, comprising applying to skin of the individual a transdermal dosage unit comprising: 
 a) a backing layer substantially impervious to the drug to be delivered transdermally;    b) a first polymeric adhesive matrix, in at least partial contact with the backing layer, having dispersed therein the drug and having a first initial rate of delivery of the drug;    c) a second polymeric adhesive matrix, in at least partial contact with the first adhesive matrix, having dispersed therein the drug and having a second initial rate of delivery of the drug; and    d) a third polymeric adhesive matrix, in at least partial contact with the second adhesive matrix, having dispersed therein the drug and having a third initial rate of delivery of the drug.    
     
     
         32 . The method of  claim 31 , wherein at least two of said initial rates of delivery are different from one another.  
     
     
         33 . The method of  claim 31 , wherein each of said initial rates of delivery is different from the others.