Tamper-resistant dosage form comprising pharmacologically active compound and anionic polymer

Abstract

The invention relates to a pharmaceutical dosage form having a breaking strength of at least 300 N and comprising a pharmacologically active compound, an anionic polymer bearing carboxylic groups, wherein the content of the anionic polymer is 20 wt.-%, based on the total weight of the pharmaceutical dosage form, and a nonionic surfactant.

1 . A pharmaceutical dosage form having a breaking strength of at least 300 N and comprising
 a pharmacologically active compound,   an anionic polymer bearing carboxylic groups, wherein the content of the anionic polymer is ≧20 wt.-%, based on the total weight of the pharmaceutical dosage form, and   a nonionic surfactant.   
     
     
         2 . The pharmaceutical dosage form according to  claim 1 , wherein the anionic polymer is obtainable by polymerization of a monomer composition comprising an ethylenically unsaturated monomer selected from ethylenically unsaturated carboxylic acids, ethylenically unsaturated carboxylic acid anhydrides, ethylenically unsaturated sulfonic acids, and mixtures thereof. 
     
     
         3 . The pharmaceutical dosage form according to  claim 1 , wherein the anionic polymer is derived from an ethylenically unsaturated monomer selected from (alk)acrylic acids, (alk)acrylic anhydrides, alkyl (alk)acrylates, or a combination thereof. 
     
     
         4 . The pharmaceutical dosage form according to  claim 2 , wherein the monomer composition further comprises at least one cross-linking agent selected from the group consisting of allyl sucrose, allyl pentaerythritol, divinyl glycol, divinyl polyethylene glycol and (meth)acrylic acid esters of diols. 
     
     
         5 . The pharmaceutical dosage form according to  claim 1 , which either does not contain any polyalkylene oxide having an average molecular weight of at least 200,000 g/mol, or wherein the total content of polyalkylene oxide(s) having an average molecular weight of at least 200,000 g/mol is ≦35 wt.-%, based on the total weight of the pharmaceutical dosage form. 
     
     
         6 . The pharmaceutical dosage form according to  claim 1 , wherein the pharmacologically active compound is an opioid. 
     
     
         7 . The pharmaceutical dosage form according to  claim 1 , wherein the nonionic surfactant
 (i) in pure water at a concentration of 25 wt.-% forms an aqueous dispersion having a viscosity η 1  at a temperature of 20° C. and a viscosity η 2  at a temperature of more than 20° C., where η 2 >η 1 ; and/or   (ii) has an HLB value of at least 20, and/or   (iii) has a surface tension in 0.1% aqueous solution at 30° C. of at least 35 dynes/cm; and/or   (iv) has a viscosity of at most 4000 mPa·s, measured at 70° C. using a model LVF or LVT Brookfield viscosimeter.   
     
     
         8 . The pharmaceutical dosage form according to  claim 1 , wherein the nonionic surfactant is a synthetic copolymer of ethylene oxide and propylene oxide. 
     
     
         9 . The pharmaceutical dosage form according to  claim 1 , wherein the nonionic surfactant is selected from block copolymers according to general formula (I-a) 
       
         
           
           
               
               
           
         
         wherein a and c are each independently an integer of from 5 to 300, and b is an integer of from 10 to 100; 
         and/or block copolymers according to general formula (I-b) 
       
       
         
           
           
               
               
           
         
         wherein e, f, g and h are each independently an integer of from 1 to 150, and i, j, k and l are each independently an integer of from 2 to 50. 
       
     
     
         10 . The pharmaceutical dosage form according to  claim 1 , wherein the content of the nonionic surfactant is at least 10 wt.-%, based on the total weight of the pharmaceutical dosage form. 
     
     
         11 . The pharmaceutical dosage form according to  claim 1 , wherein the pharmacologically active compound is embedded in a prolonged release matrix comprising the anionic polymer and the optionally present nonionic surfactant. 
     
     
         12 . The pharmaceutical dosage form according to  claim 1 , which is configured for administration once daily or twice daily. 
     
     
         13 . The pharmaceutical dosage form according to  claim 1 , which is thermoformed. 
     
     
         14 . The pharmaceutical dosage form according to  claim 1 , which is tamper-resistant. 
     
     
         15 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient a dosage form according to  claim 6 .