Extended Release Abuse Deterrent Liquid Fill Dosage Form

Abstract

The present disclosure relates to an oral, extended release, abuse deterrent dosage form containing a controlled release agent, a second agent and/or polyethylene glycol, and at least one active pharmaceutical ingredient susceptible to abuse. The dosage form is stable at high temperatures and abuse deterrent to oral and parenteral administration via dose dumping, extraction, and purification. The present disclosure also relates to processes of preparing the dosage form.

We claim: 
     
         1 . An extended release, abuse deterrent capsule comprising:
 (a) an active substance susceptible to abuse;   (b) a controlled release agent that has a melting temperature less than or equal to about 70° C.; and   (c) a second agent that has a melting temperature greater than or equal to about 100° C., or   (d) a polyethylene glycol having an average molecular weight between about 3000 Daltons and about 4000 Daltons.   
     
     
         2 . The capsule of  claim 1  comprising an active substance susceptible to abuse; a controlled release agent that has a melting temperature less than or equal to about 70° C.; and a second agent that has a melting temperature greater than or equal to about 100° C. 
     
     
         3 . The capsule of  claim 1  comprising an active substance susceptible to abuse; a controlled release agent that has a melting temperature less than or equal to about 70° C.; and a polyethylene glycol having an average molecular weight between about 3000 Daltons and about 4000 Daltons. 
     
     
         4 . The capsule of  claim 1 , wherein the controlled release agent is selected from the group consisting of glyceryl behenate, behenoyl polyoxylglycerides, glycerol monostearate, glycerol esters of sat. C8-C18 fatty acids, glycerol esters of sat. C12-C18 fatty acids, lauroyl polyoxylglycerides/PEG-32 glyceryl laurate, stearoyl polyoxylglyceride, PEG-32 glyceryl stearate, saturated polyglycolized glycerides, glycerol disterate/glyceryl palmitostearate, and hard fats. 
     
     
         5 . The capsule of  claim 1 , wherein the second agent is selected from the group consisting of hydroxypropyl methylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, cellulose ethers, cellulose esters and acrylic resins. 
     
     
         6 . The capsule of  claim 1 , wherein the controlled release agent is stearoyl polyoxylglyceride. 
     
     
         7 . The capsule of  claim 1 , wherein the second agent is polyvinylpyrrolidone. 
     
     
         8 . The capsule of  claim 1 , wherein the controlled release agent is from about 15 wt % to about 70 wt % of the capsule. 
     
     
         9 . The capsule of  claim 1 , wherein the second agent is from about 5 wt % to about 20 wt % of the capsule. 
     
     
         10 . The capsule of  claim 1 , wherein the polyethylene glycol is from about 10 wt % to about 40 wt % of the capsule. 
     
     
         11 . The capsule of  claim 1 , wherein the active substance is hydrocodone. 
     
     
         12 . The capsule of  claim 1 , wherein the active substance is oxycodone HCl. 
     
     
         13 . The capsule of  claim 1 , wherein the active substance is oxymorphone HCl. 
     
     
         14 . The capsule of  claim 1 , wherein the active substance is hydromorphone HCl. 
     
     
         15 . The capsule of  claim 1 , further comprising a dye. 
     
     
         16 . The capsule of  claim 15 , wherein the dye comprises FD&C Blue #1, FD&C Yellow #6, and FD&C Red #40. 
     
     
         17 . The capsule of  claim 15 , wherein the dye reduces abuse via extracting and injecting. 
     
     
         18 . The capsule of  claim 1 , wherein the capsule comprises at least about 2.5 wt % of the active substance. 
     
     
         19 . The capsule of  claim 1 , wherein the capsule is prepared by filling a capsule body with a heated homogenized suspension comprising the active substance, the controlled release agent, the second agent or the polyethylene glycol. 
     
     
         20 . The capsule of  claim 1 , wherein the capsule comprises about 10 mg, about 20 mg, about 40 mg, or about 80 mg of the active substance, and exhibits an extended release of the active substance. 
     
     
         21 . The capsule of  claim 1 , wherein the contents of the capsule are solid at 40° C./75% relative humidity. 
     
     
         22 . A process for the production of an extended release, abuse deterrent capsule comprising at least one active substance susceptible to abuse comprising:
 (a) preparing a homogenized suspension of:
 (i) the at least one active substance susceptible to abuse; 
 (ii) a controlled release agent that has a melting temperature less than or equal to about 100° C.; and 
 (iii) a second agent that has a melting temperature greater than or equal to about 100° C.; or 
 (iv) a polyethylene glycol having an average molecular weight between about 3000 Daltons and about 4000 Daltons; and 
   (b) dispensing the homogenized suspension into a capsule body to produce the capsule.   
     
     
         23 . The process of  claim 22 , wherein the controlled release agent is stearoyl polyoxylglyceride. 
     
     
         24 . The process of  claim 22 , wherein the second agent is polyvinylpyrrolidone. 
     
     
         25 . The process of  claim 22 , wherein the active substance is hydrocodone. 
     
     
         26 . The process of  claim 22 , wherein the active substance is oxycodone HCl. 
     
     
         27 . The process of  claim 22 , wherein the active substance is oxymorphone HCl. 
     
     
         28 . The process of  claim 22 , wherein the active substance is hydromorphone HCl. 
     
     
         29 . The process of  claim 22 , wherein the capsule is formed by joining a capsule body with a capsule cap. 
     
     
         30 . A method of treating pain comprising administering to a subject in need thereof a therapeutically effective amount of the capsule of  claim 1 .