Extended release pellet formulation containing pramipexole or a pharmaceutically acceptable salt thereof

Abstract

An extended release pellet comprising an active ingredient selected from pramipexole and the pharmaceutically acceptable salts thereof, and at least one release-modifying excipient.

1 . An extended release pellet comprising pramipexole or a pharmaceutically acceptable salt thereof, and at least one release-modifying excipient.  
     
     
         2 . The extended release pellet according to  claim 1 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is embedded within a matrix formed by at least one release-modifying excipient.  
     
     
         3 . The extended release pellet according to  claim 1 , wherein at least one of the release-modifying excipients is a lipid, wax, or water-insoluble polymer.  
     
     
         4 . The extended release pellet according to  claim 1 , comprising a core and a coating, wherein at least one release-modifying excipient is incorporated in the coating.  
     
     
         5 . The extended release pellet according to  claim 4 , wherein the pramipexole or the pharmaceutically acceptable salt thereof is incorporated in the core.  
     
     
         6 . The extended release pellet according to  claim 4 , wherein the coating comprises at least a first layer and a second layer surrounding the first layer, wherein the first layer comprises the pramipexole or the pharmaceutically acceptable salt thereof, and wherein the second layer comprises at least one release-modifying excipient.  
     
     
         7 . The extended release pellet according to  claim 6 , wherein at least one release-modifying excipient is ethyl cellulose, cellulose acetate, polyvinylacetate, polyacrylate, polymethacrylate, or ammonio methacrylate copolymer.  
     
     
         8 . The extended release pellet according to  claim 7 , wherein the second layer further comprises at least one water-soluble excipient.  
     
     
         9 . The extended release pellet according to  claim 8 , wherein at least one water-soluble excipient is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, and polyethylene glycol.  
     
     
         10 . The extended release pellet according to  claim 7 , wherein the second layer further comprises an enteric coating polymer.  
     
     
         11 . The extended release pellet according to  claim 8 , wherein enteric coating polymer is methacrylic acid copolymers type A and B.  
     
     
         12 . The extended release pellet according to  claim 10 , wherein the second layer comprises from about 10 to about 85 wt.-% of the enteric coating polymer and from about 15 to about 75 wt.-% of the water-insoluble polymer.  
     
     
         13 . The extended release pellet according to  claim 6 , wherein the core comprises a saccharide.  
     
     
         14 . The extended release pellet according to  claim 13 , wherein the saccharide is saccharose, starch, cellulose, or a cellulose derivative.  
     
     
         15 . The extended release pellet according to  claim 14 , wherein the saccharide is microcrystalline cellulose.  
     
     
         16 . An extended release pellet comprising: 
 (1) an inert pellet core;    (2) a first layer comprising pramipexole or a pharmaceutically acceptable salt thereof; and    (3) a second layer provided on the first layer, the second layer being an extended release coating comprising: 
 (a) at least one water-insoluble polymer and optionally a pore former, the resulting pellet having a pH-independent in vitro release characteristic, or  
 (b) a mixture of a pH-dependent enteric-coating polymer and a pH-independently water swelling polymer,  
 wherein the extended release pellet has a close to zero order in vitro release characteristic at acidic pH values up to pH 6.8, an accelerated release above pH 6.8, and a more accelerated release above pH 7.3.  
   
     
     
         17 . The extended release pellet according to  claim 16 , wherein the first layer further comprises one or more wet binders and further excipients.  
     
     
         18 . The extended release pellet according to  claim 16 , wherein the inert pellet core comprises polysaccharides, cellulose, a cellulose derivative, starch, and/or waxes.  
     
     
         19 . The extended release pellet according to  claim 16 , wherein the inert pellet core comprises saccharose and/or microcrystalline cellulose.  
     
     
         20 . The extended release pellet according to  claim 16 , wherein the water-insoluble polymer is ethyl cellulose, cellulose acetate, polyvinylacetate, or polyacrylates and derivatives thereof.  
     
     
         21 . The extended release pellet according to  claim 16 , wherein the pH-dependent enteric-coating polymer is an anionic carboxylic acrylic polymer soluble above a pH value of 5.5.  
     
     
         22 . The extended release pellet according to  claim 21 , wherein the pH-dependent enteric-coating polymer is soluble above a pH value of 7.0.  
     
     
         23 . The extended release pellet according to  claim 21 , wherein the pH-dependent enteric-coating polymer is a partly methyl esterified methacrylic acid polymer.  
     
     
         24 . The extended release pellet according to  claim 16 , wherein the pH-independently water swelling polymer is a quaternary ammonium substituted acrylic polymer.  
     
     
         25 . The extended release pellet according to  claim 24 , wherein the quaternary ammonium substituted acrylic polymer has an ammonium substitution of about 5 to about 10 per cent by weight.  
     
     
         26 . The extended release pellet according to  claim 16 , wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.  
     
     
         27 . The extended release pellet according to  claim 21 , wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.  
     
     
         28 . The extended release pellet according to  claim 24 , wherein the pH-dependent enteric-coating polymer is present in an amount of 10 to 85% by weight of the coating and the pH-independently water swelling polymer is present in an amount of 15 to 75% by weight of the coating.  
     
     
         29 . The extended release pellet according to  claim 16 , comprising: 
 (1) an inert pellet core;    (2) a first layer comprising pramipexole or a pharmaceutically acceptable salt thereof; and    (3) a second layer provided on the first layer, the second layer being an extended release coating comprising a mixture of: 
 (i) a pH-dependent enteric-coating polymer,  
 (ii) a pH-independently water swelling polymer, and  
 (iii) a pore-forming component,  
 wherein the extended release pellet has a close to zero order in vitro release characteristic at acidic pH values up to pH 6.8, an accelerated release above pH 6.8, and a more accelerated release above pH 7.3.  
   
     
     
         30 . The extended release pellet according to  claim 29 , wherein the pore-forming component is hydroxypropyl cellulose, hydroxypropyl methyl cellulose, polyvinylpyrrolidone, or polyethylene glycol.  
     
     
         31 . An extended release pellet comprising pramipexole or a pharmaceutically acceptable salt thereof prepared by wet or melt extrusion or melt granulation using excipients achieving extended release without a further diffusion membrane.  
     
     
         32 . A method of manufacturing extended release pellets, the method comprising the steps of: 
 (1) providing an inert starter pellet core;    (2) applying a solution or dispersion of a first coating composition comprising pramipexole or a pharmaceutically acceptable salt thereof, at least a binder, and optionally excipient(s) onto the inert starter pellet core, wherein the pramipexole or a pharmaceutically acceptable salt thereof is used as unmilled material dissolved/dispersed in a solvent together with the binder(s) and optional excipient(s), and subsequently drying the first coated pellet;    (3) applying a solution or dispersion of a second coating composition as functional coating composition onto the first coated pellet obtained in step (2), wherein the coating composition comprises (a) at least one water-insoluble polymer and optionally a pore former or (b) a mixture of a pH-dependent enteric-coating polymer and a pH-independently water swelling polymer, and optional excipient(s), and a solvent, and subsequently drying the obtained extended release pellet.    
     
     
         33 . The method according to  claim 32 , further comprising performing manual screening after step (2) and/or step (3) in order to remove agglomerates.  
     
     
         34 . The method according to  claim 32 , wherein the applying the first coating composition of step (2) is done by spraying the solution or dispersion of the first coating composition onto the inert starter pellet core.  
     
     
         35 . The method according to  claim 32 , wherein the applying the second coating composition of step (3) is done by spraying the solution or dispersion of the second coating composition onto the first coated pellet.  
     
     
         36 . A capsule containing extended release pellets according to  claim 1 .  
     
     
         37 . A capsule containing extended release pellets according to  claim 16 .  
     
     
         38 . The capsule according to  claim 36 , wherein the capsule contains an amount of extended release pellets sufficient to provide an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof.  
     
     
         39 . The capsule according to  claim 37 , wherein the capsule contains an amount of extended release pellets sufficient to provide an effective daily dose of pramipexole or a pharmaceutically acceptable salt thereof.