Delayed release pharmaceutical composition containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol

Abstract

A pharmaceutical formulation for delayed release of the active ingredient 3-(3-dimethylamino-1-ethyl-2-methylpropyl)phenol or a pharmaceutically acceptable salt thereof in a matrix containing between 1 and 80 wt. % of at least one pharmaceutically acceptable hydrophilic or hydrophobic polymer as a matrix forming agent and exhibiting in vivo the following release rate: 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours; 5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour; 10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours; 15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours; 30 to 97% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 6 hours; more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours; more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.

1 . A slow-release pharmaceutical formulation containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a matrix, wherein the matrix contains 1 to 80% by weight of one or more pharmaceutically acceptable hydrophilic or hydrophobic polymers as matrix forming agents and has the following release rate in vitro, measured by the Ph. Eur. Paddle Method at 75 rpm in a buffer (to Ph. Eur.) at a pH of 6.8 at 37° C. and detected using a UV spectrometer: 
 3 to 35% by weight (based on 100% by weight active ingredient) 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 0.5 hours,    5 to 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 1 hour,    10 to 75% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 2 hours,    15 to 82% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 3 hours,    30 to 97% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 6 hours,    more than 50% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 12 hours,    more than 70% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 18 hours, and    more than 80% by weight 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol released after 24 hours.    
     
     
         2 . A pharmaceutical composition according to  claim 1 , wherein the matrix forming agents comprise cellulose ethers, cellulose esters or a mixture thereof having a viscosity of 10,000 to 150,000 mPa·s in a 2% by weight solution at 20° C.  
     
     
         3 . A pharmaceutical composition according to  claim 1 , wherein the matrix forming agents comprise cellulose ethers, cellulose esters or a mixture thereof having a viscosity of 50,000 to 150,000 mPa·s in a 2% by weight solution at 20° C.  
     
     
         4 . A pharmaceutical composition according to  claim 1 , wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses (HPMC), hydroxyethyl celluloses, hydroxypropyl celluloses (HPC), methyl celluloses, ethyl celluloses and carboxymethyl celluloses.  
     
     
         5 . A pharmaceutical composition according to  claim 1 , wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses, hydroxyethyl celluloses, hydroxypropyl celluloses and hydroxypropyl celluloses.  
     
     
         6 . A pharmaceutical composition according to  claim 1 , wherein said composition contains from 0.5 to 85% by weight active ingredient and from 8 to 40% by weight matrix forming agents.  
     
     
         7 . A pharmaceutical composition according to  claim 1 , wherein said composition comprises from 3 to 70% by weight active ingredient and from 10 to 35% by weight matrix forming agents.  
     
     
         8 . A pharmaceutical composition according to  claim 7 , wherein said composition comprises from 8 to 66% by weight active ingredient and from 10 to 30% by weight matrix forming agents.  
     
     
         9 . A pharmaceutical composition according to  claim 1 , wherein a peak plasma level of the active ingredient is obtained in vivo 2 to 10 hours after administration of the composition.  
     
     
         10 . A pharmaceutical composition according to  claim 9 , wherein the peak plasma level of the active ingredient is obtained in vivo 3.5 to 6 hours after administration of the composition.  
     
     
         11 . A pharmaceutical formulation according to  claim 1 , wherein the active ingredient comprises (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof.  
     
     
         12 . A pharmaceutical formulation according to  claim 1 , wherein the active ingredient comprises (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof.  
     
     
         13 . A tablet for twice daily oral administration of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, said tablet containing a pharmaceutical formulation according to  claim 1 .  
     
     
         14 . A slow-release pharmaceutical formulation containing 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof as active ingredient in a matrix, wherein the matrix contains 1 to 80% by weight of one or more pharmaceutically acceptable hydrophilic or hydrophobic polymers as matrix forming agents and comprises cellulose ethers cellulose esters or a mixture thereof having a viscosity of 3,000 to 150,000 mPa·s in a 2% by weight aqueous solution at 20° C.  
     
     
         15 . A pharmaceutical composition according to  claim 14 , wherein the matrix forming agents comprise cellulose ethers, cellulose esters or a mixture thereof having a viscosity of 10,000 to 150,000 mPa·s in a 2% by weight solution at 20° C.  
     
     
         16 . A pharmaceutical composition according to  claim 14 , wherein the matrix forming agents comprise cellulose ethers, cellulose esters or a mixture thereof having a viscosity of 50,000 to 150,000 mPa·s in a 2% by weight solution at 20° C.  
     
     
         17 . A pharmaceutical composition according to  claim 14 , wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses (HPMC), hydroxyethyl celluloses, hydroxypropyl celluloses (HPC), methyl celluloses, ethyl celluloses and carboxymethyl celluloses.  
     
     
         18 . A pharmaceutical composition according to  claim 14 , wherein the matrix forming agent comprises at least one substance selected from the group consisting of hydroxypropylmethyl celluloses, hydroxyethyl celluloses, hydroxypropyl celluloses and hydroxypropyl celluloses.  
     
     
         19 . A pharmaceutical composition according to  claim 14 , wherein said composition contains from 0.5 to 85% by weight active ingredient and from 8 to 40% by weight matrix forming agents.  
     
     
         20 . A pharmaceutical composition according to  claim 14 , wherein said composition comprises from 3 to 70% by weight active ingredient and from 10 to 35% by weight matrix forming agents.  
     
     
         21 . A pharmaceutical composition according to  claim 20 , wherein said composition comprises from 8 to 66% by weight active ingredient and from 10 to 30% by weight matrix forming agents.  
     
     
         22 . A pharmaceutical composition according to  claim 14 , wherein a peak plasma level of the active ingredient is obtained in vivo 2 to 10 hours after administration of the composition.  
     
     
         23 . A pharmaceutical composition according to  claim 22 , wherein the peak plasma level of the active ingredient is obtained in vivo 3.5 to 6 hours after administration of the composition.  
     
     
         24 . A pharmaceutical formulation according to  claim 14 , wherein the active ingredient comprises (+)-(1S,2S)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof.  
     
     
         25 . A pharmaceutical formulation according to  claim 14 , wherein the active ingredient comprises (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol or a pharmaceutically acceptable salt thereof.  
     
     
         26 . A tablet for twice daily oral administration of 3-(3-dimethylamino-1-ethyl-2-methyl-propyl)phenol, said tablet containing a pharmaceutical formulation according to  claim 14.