Extended Release Tablet Formulation Containing Pramipexole or a Pharmaceutically Acceptable Salt Thereof

Abstract

An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch.

We claim: 
     
         1 . An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch, and wherein the formulation does not contain pregelatinized starch. 
     
     
         2 . The extended release tablet formulation according to  claim 1 , wherein the matrix comprises at least two water swelling polymers other than pregelatinized starch, and wherein at least one of the at least two polymers is an anionic polymer. 
     
     
         3 . The extended release tablet formulation according to  claim 1 , wherein the at least one water swelling polymer other than pregelatinized starch is an anionic polymer. 
     
     
         4 . The extended release tablet formulation according to  claim 2  or  3 , wherein the anionic polymer is selected from the group consisting of optionally crosslinked acrylic acid polymers, methacrylic acid polymers, alginates, and carboxymethyl cellulose. 
     
     
         5 . The extended release tablet formulation according to  claim 2  or  3 , wherein the anionic polymer is an optionally crosslinked acrylic acid polymer, and wherein the content of the optionally crosslinked acrylic acid polymer in the matrix is from about 0.25 wt.-% to about 25 wt.-%. 
     
     
         6 . The extended release tablet formulation according to  claim 5 , wherein the anionic polymer is an optionally crosslinked acrylic acid polymer, and wherein the content of the optionally crosslinked acrylic acid polymer in the matrix is from about 0.5 wt.-% to about 15 wt.-%. 
     
     
         7 . The extended release tablet formulation according to  claim 6 , wherein the anionic polymer is an optionally crosslinked acrylic acid polymer, and wherein the content of the optionally crosslinked acrylic acid polymer in the matrix is from about 1 wt.-% to about 10 wt.-%. 
     
     
         8 . An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch and optionally excipients, the resulting tablet providing a pH-independent in vitro release rate in the range from pH 1 to 7.5, and wherein the formulation does not contain pregelatinized starch. 
     
     
         9 . The extended release formulation of  claim 8 , whereby the at least one water swelling polymer is an anionic polymer. 
     
     
         10 . An extended release tablet formulation according to  claim 1 ,  8  or  9 , wherein the contained amount of pramipexole or pharmaceutically acceptable salt thereof is sufficient to provide a daily dose administered at one time. 
     
     
         11 . A method of manufacturing an extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch, and wherein the formulation does not contain pregelatinized starch, by a direct compression process comprising the steps of:
 (1) producing an active ingredient trituration wherein the active ingredient is pramipexole or a pharmaceutically acceptable salt thereof by preblending it with a portion of water swelling polymer(s) and/or excipient(s) in a mixer, wherein pramipexole or the pharmaceutically acceptable salt thereof is milled prior to use;   (2) premixing the active ingredient trituration of step (1), the main portion of the water swelling polymer(s) and/or excipients in a mixer to obtain a pre-mixture;   (3) optionally dry screening the pre-mixture through a screen in order to segregate cohesive particles and to improve content uniformity;   (4) mixing the pre-mixture of step (2) or (3) in a mixer, optionally by adding remaining excipients to the mixture and continuing mixing; and   (5) tabletting the final mixture by compressing it on a suitable tablet press to produce matrix tablets.   
     
     
         12 . The method according to  claim 11 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1). 
     
     
         13 . A method of manufacturing an extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch, and wherein the formulation does not contain pregelatinized starch, by a wet granulation process comprising the steps of:
 (1) producing an active ingredient trituration wherein the active ingredient is pramipexole or a pharmaceutically acceptable salt thereof by blending it with a portion of the excipients in a mixer, wherein pramipexole or the pharmaceutically acceptable salt thereof is milled prior to use;   (2) granulating the active ingredient trituration of step (1) by adding the granulation liquid;   (3) drying the granules of step (2) in a fluidized bed dryer or a drying oven;   (4) mixing the dried granules of step (3) with the water swelling polymer(s) and/or excipients in a mixer to obtain the final mixture; and   (5) tabletting the final mixture of step (4) by compressing it on a suitable tablet press to produce matrix tablets.   
     
     
         14 . The method according to  claim 13 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1). 
     
     
         15 . The method according to  claim 13 , wherein the granulation liquid of step (2) is water. 
     
     
         16 . A method of manufacturing an extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch, and wherein the formulation does not contain pregelatinized starch, by a dry granulation process comprising the steps of:
 (1) mixing the active ingredient pramipexole or a pharmaceutically acceptable salt thereof with either a portion of the fillers or all the excipients in a mixer, wherein pramipexole or the pharmaceutically acceptable salt thereof is milled prior to use;   (2) compaction of the mixture of step (1) on a suitable roller compactor;   (3) reducing the ribbons obtained during step (1) to small granules by suitable milling or sieving steps;   (4) optionally mixing the granules of step (3) with the remaining excipients in a mixer to obtain the final mixture; and   (5) tabletting the granules of step (3) or the final mixture of step (4) by compressing it on a suitable tablet press to produce matrix tablets.   
     
     
         17 . The method according to  claim 16 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1).