Tamper-resistant dosage form containing one or more particles

Abstract

The invention relates to a tamper-resistant pharmaceutical dosage form comprising one or more particles, wherein each of said one or more particles comprises a pharmacologically active ingredient and a physiologically acceptable polymer; has a breaking strength of at least 300 N; has a weight of at least 2 mg; and optionally, comprises a film-coating; wherein the total weight of the pharmaceutical dosage form is greater than the total weight of said one or more particles.

1 . A tamper-resistant pharmaceutical dosage form for oral administration, said pharmaceutical dosage form being a capsule comprising:
 (a) one or more prolonged release particles, wherein each of said one or more particles:
 (i) comprises a pharmacologically active ingredient selected from the group consisting of opioids; 
 (ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt.-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer; 
 (iii) has a breaking strength of at least 300 N; 
 (iv) has a weight of at least 100 mg; and 
 (v) optionally comprises a film-coating; and 
   (b) one or more additional particles having a weight of less than 2 mg;   wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b); and   wherein the pharmaceutical dosage form contains no aversive agent and contains no antagonist; and   wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.   
     
     
         2 . The pharmaceutical dosage form according to  claim 1 , wherein the total volume of the pharmaceutical dosage form is greater than the total volume of the one or more particles. 
     
     
         3 . The pharmaceutical dosage form according to  claim 1 , wherein the breaking strength of the pharmaceutical dosage form is below the breaking strength of the one or more particles. 
     
     
         4 . The pharmaceutical dosage form according  claim 1 , wherein the pharmacologically active ingredient is selected from the group consisting of oxycodone, oxymorphone, hydromorphone, hydrocodone, morphine, tapentadol, tramadol, buprenorphine, and the physiologically acceptable salts thereof, and combinations thereof. 
     
     
         5 . The pharmaceutical dosage form according to  claim 1 , wherein the content of the pharmacologically active ingredient is at least 1.0 wt.-%, based on the total weight of one of the one or more particles. 
     
     
         6 . The pharmaceutical dosage form according to  claim 1 , which has released at most 50% of the pharmacologically active ingredient after 60 min measured under in vitro conditions and in accordance with Ph. Eur. 
     
     
         7 . The pharmaceutical dosage form according to  claim 1 , wherein the pharmacologically active ingredient is embedded in a matrix material comprising the physiologically acceptable polymer. 
     
     
         8 . The pharmaceutical dosage form according to  claim 1 , wherein the total amount of the pharmacologically active ingredient that is contained in the pharmaceutical dosage form is contained in the one or more particles. 
     
     
         9 . The pharmaceutical dosage form according to  claim 1 , wherein the physiologically acceptable polymer is selected from the group consisting of polyalkylene oxides, non-ionic acrylates, anionic acrylates and cationic acrylates. 
     
     
         10 . The pharmaceutical dosage form according to  claim 1 , wherein the content of the physiologically acceptable polymer is at least 25 wt.-%, based on the total weight of one of the one or more particles. 
     
     
         11 . The pharmaceutical dosage form according to  claim 1 , which contains at least two particles that are identical or differ from one another. 
     
     
         12 . The pharmaceutical dosage form according to  claim 1 , wherein the one or more particles are of cylindrical shape. 
     
     
         13 . The pharmaceutical dosage form according to  claim 1 , wherein the one or more particles are melt-extruded. 
     
     
         14 . The pharmaceutical dosage form according to  claim 1 , wherein each of said one or more particles has a weight of at least 260 mg. 
     
     
         15 . The pharmaceutical dosage form according to  claim 1 , wherein each of said one or more particles has a weight of at least 300 mg. 
     
     
         16 . The pharmaceutical dosage form according to  claim 1 , which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form. 
     
     
         17 . A tamper-resistant pharmaceutical dosage form, said pharmaceutical dosage form being a capsule comprising:
 (a) one or more prolonged release particles, wherein each of said one or more particles:
 (i) comprises a first pharmacologically active ingredient selected from the group consisting of opioids; 
 (ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt.-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer; 
 (iii) has a breaking strength of at least 300 N; 
 (iv) has a weight of at least 100 mg; and 
 (v) optionally comprises a film-coating; and 
   (b) one or more additional particles having a weight of less than 2 mg;   wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b); and   wherein the pharmaceutical dosage form does not contain a second pharmacologically active ingredient; and   wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.   
     
     
         18 . The pharmaceutical dosage form according to  claim 17 , which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form. 
     
     
         19 . A tamper-resistant pharmaceutical dosage form for oral administration, said pharmaceutical dosage form being a capsule comprising:
 (a) one or more particles, wherein each of said one or more particles:
 (i) comprises a prolonged release pharmacologically active ingredient selected from the group consisting of opioids; 
 (ii) comprises a physiologically acceptable polymer selected from the group consisting of acrylic polymers and polyalkylene oxides, wherein the physiologically acceptable polymer has a weight average molecular weight of at least 200,000 g/mol, wherein the physiologically acceptable polymer is present in a content of at least 30 wt.-% relative to a total weight of the one or more particles, and wherein the pharmacologically active ingredient is embedded in a matrix comprising the physiologically acceptable polymer; 
 (iii) has a breaking strength of at least 300 N; 
 (iv) has a weight of at least 20 mg; and 
 (v) optionally comprises a film-coating; and 
   (b) one or more additional particles having a weight of less than 2 mg;   wherein the pharmaceutical dosage form has a total weight greater than a combined weight of the particles (a) and (b);   wherein the one or more particles number “n,” where n=1, 2, 3 or 4, and each of said n particles has a weight within the range of (250±150)/n mg; and   wherein the pharmaceutical dosage form contains no aversive agent and contains no antagonist; and   wherein the pharmaceutical composition can be chewed without significantly deteriorating tamper-resistance and without significantly altering drug release.   
     
     
         20 . The pharmaceutical dosage form according to  claim 19 , which under in vitro conditions in 600 mL 0.1 N HCl, using the basket method according to Ph. Eur. at 75 rpm, after 1 h, has released at most 60% of the pharmacologically active ingredient relative to the total amount of the pharmacologically active ingredients originally contained in the pharmaceutical dosage form. 
     
     
         21 . A method of treating pain in a patient in need of such treating, said method comprising administering to said patient a pharmaceutical dosage form according to  claim 1 .