Thermoformed, tamper-resistant pharmaceutical dosage form containing zinc

Abstract

A thermoformed, tamper-resistant pharmaceutical dosage form comprises: a) a pharmacologically active ingredient; b) a polyalkylene oxide having a weight average molecular weight of more than 200,000 g/mol; and c) a zinc component, wherein the content of said zinc component is at least 1 ppm, relative to the total weight of the pharmaceutical dosage form. When the pharmacologically active ingredient is effective against pain, the pharmaceutical dosage form may be used in a method of treating pain. When the pharmacologically active ingredient has abuse potential, the pharmaceutical dosage form may be used in a method of reducing the incidence of the abuse of said pharmacologically active ingredient.

1 . A thermoformed, tamper-resistant pharmaceutical dosage form comprising:
 a) a pharmacologically active ingredient;   b) a polyalkylene oxide having a weight average molecular weight of more than 200,000 g/mol; and   c) a zinc component, wherein the content of said zinc component is at least 1 ppm, relative to the total weight of the pharmaceutical dosage form.   
     
     
         2 . The pharmaceutical dosage form according to  claim 1 , which comprises a polyalkylene oxide composition comprising the polyalkylene oxide and the zinc component, and/or wherein the content of said zinc component is in the range of from 0.01 to 1 mol-% based on the zinc atom content per mol of alkylene oxide units contained in the polyalkylene oxide. 
     
     
         3 . The pharmaceutical dosage form according to  claim 2 , wherein the polyalkylene oxide is obtainable by polymerizing alkylene oxide in presence of the zinc component. 
     
     
         4 . The pharmaceutical dosage form according to  claim 2 , wherein an aqueous dispersion of the pure polyalkylene oxide composition in pure water at 25° C. and at a concentration of 1 wt.-% has a pH value of at most 7.7. 
     
     
         5 . The pharmaceutical dosage form according to  claim 2 , wherein the content of said zinc component is at least 10 ppm relative to the total weight of the polyalkylene oxide composition. 
     
     
         6 . The pharmaceutical dosage form according to  claim 1 , which has a breaking strength of at least 300 N. 
     
     
         7 . The pharmaceutical dosage form according to  claim 1 , wherein the content of the zinc component is at most 10,000 ppm, relative to the total weight of the pharmaceutical dosage form. 
     
     
         8 . The pharmaceutical dosage form according to  claim 1 , wherein the pharmacologically active ingredient is an opioid. 
     
     
         9 . The pharmaceutical dosage form according to  claim 1 , wherein the pharmacologically active ingredient is embedded in a controlled-release matrix comprising the polyalkylene oxide and the zinc component. 
     
     
         10 . The pharmaceutical dosage form according to  claim 1 , which is monolithic or multiparticulate. 
     
     
         11 . The pharmaceutical dosage form according to  claim 1 , which is melt-extruded. 
     
     
         12 . The pharmaceutical dosage form according to  claim 1 , which is adapted for administration once daily, twice daily or thrice daily. 
     
     
         13 . A process for the manufacture of a pharmaceutical dosage form according to  claim 1  comprising the steps of:
 (a) mixing the pharmacologically active ingredient, the polyalkylene oxide composition, and optionally present excipients to obtain a mixture; and 
 (b) press-forming the mixture obtained in step (a) with preceding, simultaneous, or subsequent exposure to heat. 
 
     
     
         14 . The process according to  claim 13 , wherein step (b) is performed by means of an extruder. 
     
     
         15 . A pharmaceutical dosage form obtainable by the process of  claim 13 . 
     
     
         16 . A method of treating pain in a patient in need thereof, said method comprising administering to said patient a pharmaceutical dosage form according to  claim 1 , said pharmaceutical dosage form comprising a pharmacologically active ingredient effective to treat pain. 
     
     
         17 . A method of reducing the incidence of drug abuse of a pharmacologically active ingredient with abuse potential, said method comprising providing said pharmacologically active ingredient in the form of a pharmaceutical dosage form according to  claim 1 .