Abuse-Resistant Formulations

Abstract

This disclosure relates to a sustained-release oral dosage form for once-a-day administration comprising a matrix containing a viscosity modifier and coated granules containing hydromorphone. The dosage form can have a release profile such that 16 hours following administration, less than about 85 percent of the hydromorphone is released. In addition, the dosage form may have alcohol and/or crush resistance.

1 . A method of making a stable dosage form, comprising:
 granulating an amount of hydromorphone or a salt thereof, a first viscosity modifier and a first strong film former in the presence of a solvent consisting of an organic solvent to form a granule;   coating the granule with a coating comprising a second strong film former to form a coated granulate;   compressing the granulate in a matrix, wherein the matrix comprises a second viscosity modifier.   
     
     
         2 . The method according to  claim 1 , wherein the first viscosity modifier is selected from sodium alginate, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, crosslinked polyacrylic acid, gelatin, pectins, gums, polyethylene oxides, Konjac flour, carrageenan, xanthan gum, or mixtures thereof. 
     
     
         3 . The method according to  claim 1 , wherein the second viscosity modifier is selected from sodium alginate, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, crosslinked polyacrylic acid, gelatin, pectins, gums, polyethylene oxides, Konjac flour, carrageenan, xanthan gum, or mixtures thereof. 
     
     
         4 . The method according to  claim 1 , wherein the first viscosity modifier is hydroxypropylmethylcellulose. 
     
     
         5 . The method according to  claim 1 , wherein the second viscosity modifier is hydroxypropylmethylcellulose. 
     
     
         6 . The method according to  claim 1 , wherein the first strong film former is selected from natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylate and shellac. 
     
     
         7 . The method according to  claim 1 , wherein the second strong film former is selected from natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylate and shellac. 
     
     
         8 . The method according to  claim 1 , wherein the first strong film former comprises ethylcellulose. 
     
     
         9 . The method according to  claim 1 , wherein the second strong film former comprises ethylcellulose. 
     
     
         10 . The method according to  claim 1 , wherein the second viscosity modifier is in an amount of from 30 to 60 percent by weight of the dosage form. 
     
     
         11 . The method according to  claim 1 , wherein the first viscosity modifier and the second viscosity modifier are the same. 
     
     
         12 . The method according to  claim 1 , wherein the first viscosity modifier and the second viscosity modifier are gelling polymers. 
     
     
         13 . A tablet made according to the method of  claim 1 . 
     
     
         14 . A stable sustained release tablet comprising:
 a. a granule comprising an amount of hydromorphone or a salt thereof, a first viscosity modifier, a first strong film former and no exogenous water;   b. a coating substantially surrounding the granule to form a coated granule, wherein the coating comprises a second strong film former; and   c. a matrix comprising a second viscosity modifier, wherein the coated granule is compressed in the matrix.   
     
     
         15 . The tablet according to  claim 14 , wherein the first viscosity modifier is selected from sodium alginate, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, crosslinked polyacrylic acid, gelatin, pectins, gums, polyethylene oxides, Konjac flour, carrageenan, xanthan gum, or mixtures thereof. 
     
     
         16 . The tablet according to  claim 14 , wherein the second viscosity modifier is selected from sodium alginate, hydroxypropylmethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyvinylpyrrolidone, crosslinked polyacrylic acid, gelatin, pectins, gums, polyethylene oxides, Konjac flour, carrageenan, xanthan gum, or mixtures thereof. 
     
     
         17 . The tablet according to  claim 14 , wherein the first viscosity modifier is hydroxypropylmethylcellulose. 
     
     
         18 . The tablet according to  claim 14 , wherein the second viscosity modifier is hydroxypropylmethylcellulose. 
     
     
         19 . The tablet according to  claim 14 , wherein the first strong film former is selected from natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylate and shellac. 
     
     
         20 . The tablet according to  claim 14 , wherein the second strong film former is selected from natural and synthetic starches, natural and synthetic celluloses, acrylics, vinylics, resins, methacrylate and shellac. 
     
     
         21 . The tablet according to  claim 14 , wherein the first strong film former comprises ethylcellulose. 
     
     
         22 . The tablet according to  claim 14 , wherein the second strong film former comprises ethylcellulose. 
     
     
         23 . The tablet according to  claim 14 , wherein the second viscosity modifier is in an amount of from 30 to 60 percent by weight of the dosage form. 
     
     
         24 . The tablet according to  claim 14 , wherein the first viscosity modifier and the second viscosity modifier are the same. 
     
     
         25 . The tablet according to  claim 14 , wherein the first viscosity modifier and the second viscosity modifier are gelling polymers. 
     
     
         26 . The tablet according to  claim 14 , wherein the matrix does not contain a fat/wax. 
     
     
         27 . The tablet according to  claim 13 , wherein the percent of hydromorphone released after 2 hours in a solution of 0.1N HCl and 40% alcohol is no more than 10 percentage points greater than the percent of hydromorphone released in a solution of 0.1N HCl in the absence of alcohol. 
     
     
         28 . The tablet according to  claim 14 , wherein the percent of hydromorphone released after 2 hours in a solution of 0.1N HCl and 40% alcohol is no more than 10 percentage points greater than the percent of hydromorphone released in a solution of 0.1N HCl in the absence of alcohol.