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, the matrix comprising at least two water swelling polymers, wherein one of the polymers is pregelatinized starch, and wherein another one of the polymers is an anionic polymer.

1 . An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising:
 (a) pregelatinized starch; and   (b) an anionic polymer.   
   
   
       2 . The extended release tablet formulation according to  claim 1 , wherein the anionic polymer is selected from the group consisting of optionally crosslinked acrylic acid polymers, methacrylic acid polymers, alginates, and carboxymethyl cellulose. 
   
   
       3 . The extended release tablet formulation according to  claim 2 , 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.-%. 
   
   
       4 . The extended release tablet formulation according to  claim 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 0.5 wt.-% to about 15 wt.-%. 
   
   
       5 . The extended release tablet formulation according to  claim 4 , 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. -% . 
   
   
       6 . The extended release tablet formulation according to  claim 1 , further comprising a water swelling polymer which is not pregelatinized starch or an anionic polymer. 
   
   
       7 . The extended release tablet formulation according to  claim 6 , wherein the water swelling polymer which is not pregelatinized starch or an anionic polymer is hydroxypropyl cellulose or hydroxypropyl methyl cellulose. 
   
   
       8 . The extended release tablet formulation according to  claim 7 , wherein the water swelling polymer which is not pregelatinized starch or an anionic polymer is hydroxypropyl methyl cellulose. 
   
   
       9 . The extended release tablet formulation according to  claim 8 , wherein the content of hydroxypropyl methyl cellulose in the matrix is from about 10 wt.-% to about 75 wt.-%. 
   
   
       10 . The extended release tablet formulation according to  claim 9 , wherein the content of hydroxypropyl methyl cellulose in the matrix is from about 25 wt.-% to about 65 wt.-%. 
   
   
       11 . The extended release tablet formulation according to  claim 1 , wherein the matrix comprises about:
 (a) 0.05 to 5 wt.-% of pramipexole or a salt thereof,   (b) 0.25 to 25 wt.-% of anionic water swelling polymer(s);   (c) 10 to 75 wt.-% of water swelling polymer(s) other than (b); and   (d) to 100 wt.-% of further excipients.   
   
   
       12 . An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising:
 (a) at least pregelatinized starch as water swelling polymer and optionally excipients, the resulting tablet providing a pH-independent in vitro release characteristic in the range from pH 1 to 7.5, or   (b) at least pregelatinized starch as water swelling polymer, a water swelling anionic polymer, and optionally excipients, the resulting tablet providing a pH-dependent release characteristic with a faster release characteristic in the range of pH<4.5, and a slower and further on pH-independent release characteristic in the range from pH 4.5 to 7.5.   
   
   
       13 . The extended release tablet formulation according to  claim 6 , wherein the water swelling polymer which is not pregelatinized starch or an anionic polymer is hydroxypropyl methyl cellulose, hydroxypropyl cellulose, carboxymethyl cellulose sodium, or sodium alginate. 
   
   
       14 . The extended release tablet formulation according to  claim 12 , wherein the matrix comprises hydroxypropyl methyl cellulose and excipients, wherein the amount of hydroxypropyl methyl cellulose ranges from 10 to 75% by weight and the amount of excipients ranges from 25 to 90% by weight. 
   
   
       15 . The extended release tablet formulation according to  claim 12 , wherein the matrix comprises hydroxypropyl methyl cellulose and excipients, wherein the amount of hydroxypropyl methyl cellulose ranges from 25 to 65% by weight and the amount of excipients ranges from 35 to 75% by weight. 
   
   
       16 . The extended release tablet formulation according to  claim 1 , wherein the anionic polymer is an acrylic acid polymerisate. 
   
   
       17 . The extended release tablet formulation according to  claim 16 , wherein the acrylic acid polymerisate is present in the range of 0.25 to 25% by weight. 
   
   
       18 . The extended release tablet formulation according to  claim 17 , wherein the acrylic acid polymerisate is present in the range of 0.5 to 15% by weight. 
   
   
       19 . The extended release tablet formulation according to  claim 18 , wherein the acrylic acid polymerisate is present in the range of 1 to 10% by weight. 
   
   
       20 . A method of manufacturing the extended release tablet formulation of  claim 1  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.   
   
   
       21 . The method according to  claim 20 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1). 
   
   
       22 . A method of manufacturing the extended release tablet formulation of  claim 1  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;   (5) tabletting the final mixture of step (4) by compressing it on a suitable tablet press to produce matrix tablets.   
   
   
       23 . The method according to  claim 22 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1). 
   
   
       24 . The method according to  claim 22 , wherein the granulation liquid of step (2) is water. 
   
   
       25 . A method of manufacturing the extended release tablet formulation of  claim 1  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.   
   
   
       26 . The method according to  claim 25 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1).