Tamper-resistant dosage form for oxidation-sensitive opioids

Abstract

Thermoformed pharmaceutical dosage form having a breaking strength of at least 300 N, comprising an opioid (A), a free physiologically acceptable acid (B) in an amount of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form, and a polyalkylene oxide (C) having a weight average molecular weight M w of at least 200,000 g/mol.

1 . A thermoformed pharmaceutical dosage form having a breaking strength of at least 300 N and comprising
 an opioid (A),   a free physiologically acceptable acid (B) in an amount of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form, and   a polyalkylene oxide (C) having a weight average molecular weight M w  of at least 200,000 g/mol.   
     
     
         2 . The pharmaceutical dosage form according to  claim 1 , wherein the acid (B) is a multicarboxylic acid. 
     
     
         3 . The pharmaceutical dosage form according to  claim 2 , wherein the multicarboxylic acid is selected from the group consisting of maleic acid, fumaric acid, glutaric acid, malonic acid and citric acid. 
     
     
         4 . The pharmaceutical dosage form according to  claim 1 , wherein the content of the acid (B) is within the range of from 0.005 to 2.5 wt.-%, based on the total weight of the pharmaceutical dosage form. 
     
     
         5 . The pharmaceutical dosage form according to  claim 1 , which comprises a polyalkylene glycol, wherein the relative weight ratio of the polyalkylene oxide to the polyalkylene glycol is within the range of 4.2±2:1. 
     
     
         6 . The pharmaceutical dosage form according to  claim 1 , which comprises an antioxidant. 
     
     
         7 . The pharmaceutical dosage form according to  claim 6 , wherein the antioxidant is α-tocopherol. 
     
     
         8 . The pharmaceutical dosage form according to  claim 6 , wherein the content of the antioxidant is within the range of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form. 
     
     
         9 . The pharmaceutical dosage form according to  claim 1 , wherein after storage for 4 weeks at 40° C. and 75% rel. humidity, the content of opioid (A) amounts to at least 98.0% of its original content before storage. 
     
     
         10 . The pharmaceutical dosage form according to  claim 1 , wherein the opioid (A) is embedded in a matrix comprising the polyalkylene oxide (C), said matrix controlling the release of the opioid from the pharmaceutical dosage form. 
     
     
         11 . The pharmaceutical dosage form according to  claim 1 , wherein the opioid (A) is selected from the group consisting of oxymorphone, oxycodone, hydromorphone, and the physiologically acceptable salts thereof. 
     
     
         12 . The pharmaceutical dosage form according to  claim 1 , wherein the relative weight ratio of the polyalkylene oxide (C) and the opioid (A) is at least 1:1. 
     
     
         13 . The pharmaceutical dosage form according to  claim 1 , which is adapted for administration once daily or twice daily. 
     
     
         14 . The pharmaceutical dosage form according to  claim 1 , which has a breaking strength of at least 500 N. 
     
     
         15 . A packaging containing the pharmaceutical dosage form of  claim 1  and an oxygen scavenger. 
     
     
         16 . The pharmaceutical dosage form according to  claim 7 , wherein the content of the antioxidant is within the range of from 0.001 to 5.0 wt.-%, based on the total weight of the pharmaceutical dosage form.