Polymeric Adhesive Matrix with Salified Carboxylic Groups for Transdermal Use

Abstract

Polymeric matrices for the controlled release of medicaments for the topical transdermal use comprising copolymers of acrylic and/or methacrylic acid or esters thereof having a Tg lower than 0.degree. C., whose free carboxy groups are salified with compatible organic or inorganic bases. The matrices of the invention allow to prepare therapeutical systems for the controlled-release of active principles through the transdermal route, thus solving stability, solubility and/or bioavailability problems of the active ingredient within the matrix.

1 . A polymeric matrix for the controlled release of medicaments for the topical transdermal use comprising copolymers of acrylic or methacrylic acid and/or esters thereof having a Tg lower than 0° C.,
 wherein the free carboxy groups are salified with stoichiometric amounts of compatible organic bases, the organic bases comprising at least one of ammonia, ammonium methyl-acrylate copolymers, ethylenediamine, and lysine. 
 
     
     
         2 . A matrix as claimed in  claim 1  wherein the copolymers are selected from poly(2-ethyl-hexyl acrylate-co-acrylic acid), poly(2-hydroxy ethylacrylate-co-acrylic acid-co-methyl acrylates), poly(2-ethyl-hexyl acrylate-co-acrylic acid-co-methyl acrylates), poly(2-ethyl-hexyl acrylate-co-acrylic acid-co-butyl acrylate-co-vinyl acetate). 
     
     
         3 . A matrix as claimed in  claim 1  wherein the acrylic or methacrylic copolymers have a percentage of free carboxy groups ranging from 0.1 to 15%. 
     
     
         4 . A matrix as claimed in  claim 3  wherein the acrylic or methacrylic copolymers have a percentage of free carboxy groups ranging from 1 to 10%. 
     
     
         5 . A matrix as claimed in  claim 1  comprising 0.1 to 20% by weight of water. 
     
     
         6 . A matrix as claimed in  claim 5  comprising 1 to 5% by weight of water. 
     
     
         7 . A matrix as claimed in  claim 1  as adhesive layer in a transdermal patch. 
     
     
         8 . A process for the preparation of the matrices of  claim 1  which comprises the treatment of a copolymer having a Tg lower than 0° C. and free carboxylic groups suspended in an organic solvent with an aqueous solution of organic bases in stoichiometric amounts in respect of the carboxylic groups, followed by addition of the active ingredient and any other excipients. 
     
     
         9 . A matrix as claimed in  claim 1 , further comprising a medicament selected from the group consisting of non-steroidal anti-inflammatory agents, corticosteroids, local anesthetics, alpha-adrenergic agonists, analgesics, antimigraine drugs, anti-allergics, antihistaminics, antimicrobials, antiemetics, anticholinergics, bronchodilators, antivirals, myorelaxants, cholinergic agents, central nervous system stimulators, cardioactive agents, beta-adrenergic agonists, hormones, anxiolytics, antidepressants, antipsychotics, opioid antagonists, and coronary dilators. 
     
     
         10 . A matrix as claimed in  claim 10 , wherein the non-steroidal anti-inflammatory is selected from the group consisting of diclofenac, fenoprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, ketorolac, naproxen, oxametacine, oxyphenbutazone, piroxicam, suprofen, and celecoxib. 
     
     
         11 . A polymeric matrix for the controlled release of a medicament for topical or transdermal use, the matrix comprising:
 copolymers of at least one of acrylic acid, methacrylic acid, and esters thereof, the copolymers having a Tg lower than 0° C.; and   stoichiometric amounts of compatible organic bases sufficient to salify the free carboxy groups of the copolymers, the organic bases comprising at least one of ammonia, ammonium methyl-acrylate copolymers, ethylenediamine, and lysine.   
     
     
         12 . A matrix as claimed in  claim 11  wherein the copolymers are selected from poly(2-ethyl-hexyl acrylate-co-acrylic acid), poly(2-hydroxy ethylacrylate-co-acrylic acid-co-methyl acrylates), poly(2-ethyl-hexyl acrylate-co-acrylic acid-co-methyl acrylates), poly(2-ethyl-hexyl acrylate-co-acrylic acid-co-butyl acrylate-co-vinyl acetate). 
     
     
         13 . A matrix as claimed in  claim 11  wherein the acrylic or methacrylic copolymers have a percentage of free carboxy groups ranging from 0.1 to 15%. 
     
     
         14 . A matrix as claimed in  claim 13  wherein the acrylic or methacrylic copolymers have a percentage of free carboxy groups ranging from 1 to 10%. 
     
     
         15 . A matrix as claimed in  claim 11  comprising 0.1 to 20% by weight of water. 
     
     
         16 . A matrix as claimed in  claim 15  comprising 1 to 5% by weight of water. 
     
     
         17 . An adhesive layer in a transdermal patch comprising the matrix as claimed in  claim 11 . 
     
     
         18 . A process for the preparation of the matrices of  claim 11  which comprises the treatment of a copolymer having a Tg lower than 0° C. and free carboxylic groups suspended in an organic solvent with an aqueous solution of organic bases in stoichiometric amounts in respect of the carboxylic groups, followed by addition of the active ingredient and any other excipients. 
     
     
         19 . A matrix as claimed in  claim 18 , further comprising a medicament selected from the group consisting of non-steroidal anti-inflammatory agents, corticosteroids, local anesthetics, alpha-adrenergic agonists, analgesics, antimigraine drugs, anti-allergics, antihistaminics, antimicrobials, antiemetics, anticholinergics, bronchodilators, antivirals, myorelaxants, cholinergic agents, central nervous system stimulators, cardioactive agents, beta-adrenergic agonists, hormones, anxiolytics, antidepressants, antipsychotics, opioid antagonists, and coronary dilators. 
     
     
         20 . A matrix as claimed in  claim 19 , wherein the non-steroidal anti-inflammatory is selected from the group consisting of diclofenac, fenoprofen, flurbiprofen, ibuprofen, ibuproxam, indoprofen, ketoprofen, ketorolac, naproxen, oxametacine, oxyphenbutazone, piroxicam, suprofen, and celecoxib.