Compositions and methods to effect the release profile in the transdermal administration of active agents

Abstract

Compositions and methods for the transdermal delivery of active agents up to a period of seven days or more at substantially a zero-order release rate comprising a pharmaceutically acceptable adhesive matrix and a polymeric plastic material that provides a release rate regulating effect on the active agents.

What is claimed is:  
     
         1 . A transdermal delivery system for delivery of a therapeutically effective amount of an active agent comprising: 
 (a) a pharmaceutically acceptable pressure-sensitive adhesive matrix carrier composition,    (b) one or more polymeric plastic materials which are substantially insoluble in water in an amount up to 30%, said amount being sufficient to provide a substantially zero-order drug release profile in excess of 72 hours,    (c) one or more active agents,    (d) a crystallization inhibitor capable of absorbing and holding water, and    (e) optionally, one or more solvents, co-solvents and permeation enhancers.    
     
     
         2 . The transdermal system according to  claim 1 , wherein the one or more insoluble polymeric materials are selected from the group consisting of celluloses, cellulose derivatives, polycarbonates, polystyrenes, alkylacrylates, polyvinyl chloride, polyurethanes and polyacrylonitrile.  
     
     
         3 . The transdermal system according to  claim 2 , wherein the cellulose derivatives are cellulose esters and cellulose ethers.  
     
     
         4 . The transdermal system according to  claim 3 , wherein the cellulose ethers are ethyl cellulose polymers.  
     
     
         5 . The transdermal system according to  claim 3 , wherein the cellulose esters are selected from the group consisting of cellulose acetate, cellulose acetate butyrate, cellulose acetate phthalate and cellulose acetate propionate.  
     
     
         6 . The transdermal system according to  claim 1 , wherein the solvents and co-solvents are polyhydric alcohols.  
     
     
         7 . The transdermal system according to  claim 1 , wherein the pressure-sensitive adhesive matrix carrier is a blend of a polyacrylate adhesive and a polysiloxane adhesive.  
     
     
         8 . The transdermal system according to  claim 1 , wherein the crystallization inhibitor is polyvinylpyrrolidone.  
     
     
         9 . The transdermal system according to  claim 1 , wherein the one or more active agents are selected from the group consisting of steroidal and hormonal agents, analgesics and anti-migraine agents, anesthetics, anti-inflammatory and corticoid agents, central nervous system stimulants and agents, cardioactive agents, anti-Parkinson's and anti-Alzheimer's agents, anti-psychotic agents, anti-anxiety agents, anti-depressants, anxiolytic agents, sedatives, hypnotics, anti-microbial agents, and anti-cancer agents.  
     
     
         10 . The transdermal system according to  claim 9 , wherein the steroidal and hormonal agents are selected from the group consisting of ethinyl estradiol, progesterone, norethindrone, norethindrone acetate, norethisterone, methyltestosterone, testosterone, and mixtures thereof.  
     
     
         11 . The transdermal system according to  claim 10 , wherein the estradiol is 17 β-estradiol.  
     
     
         12 . The transdermal system according to  claim 1 , comprising about 10%-40% polyacrylate adhesive, about 30%-60% polysiloxane adhesive, about 2%-10% dipropylene glycol, about 1%-10% oleyl alcohol, about 5%-20% ethyl cellulose, about 5%-15% polyvinylpyrrolidone and about 1%-5% 17 β-estradiol by weight based on the dry weight of the total composition.  
     
     
         13 . The transdermal system according to  claim 1 , comprising about 3%-25% polyacrylate adhesive, about 30%-70% polysiloxane adhesive, about 5%-15% dipropylene glycol, about 1%-10% oleyl alcohol, about 5%-15% polyvinylpyrrolidone, about 1%-15% ethyl cellulose, about 0%-15% cellulose acetate butyrate, about 0%-15% cellulose acetate propionate, about 0.1%-5% 17 β-estradiol, and about 1%-7% norethindrone acetate by weight based on the dry weight of the total composition.  
     
     
         14 . A method of prolonged transdermal administration of a therapeutically effective amount of one or more active agents to a subject comprising the steps of:: 
 (a) providing the transdermal system of  claim 1 , and    (b) topically applying the transdermal system to administer the one or more active agents.