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

• US 8,715,728 B2
• Filed: 12/03/2009
• Issued: 05/06/2014
• Est. Priority Date: 08/13/2004
• Status: Expired due to Fees

• Current Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Original Assignee: Boehringer Ingelheim International GmbH (C.H. Boehringer Sohn AG & Co. KG)
• Inventors: Friedl, Thomas, Brickl, Rolf-Stefan
• Primary Examiner(s): Sasan, Aradhana
• Application Number:
  US12/630,271
• Publication Number:
  US 20100086589A1
• Time in Patent Office: 1,615 Days
• Field of Search: 424/468, 424/461, 424/462, 424/490, 424/494, 424/497, 514/367, 427/2.21
• US Class Current: 424/468
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs

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.

Claims

1. An extended release pellet formulation comprising:

an inert pellet core;

a first layer being an active ingredient layer comprising pramipexole or a pharmaceutically acceptable salt thereof and one or more wet binders and at least one further excipient; and

a second layer provided on the first layer, the second layer being an extended release coating comprising a mixture of 10 to 85% by weight of a pH-dependent enteric-coating polymer, which is an anionic polymer, and 15 to 75% by weight of a pH-independent water swelling polymer, which is a quaternary ammonium substituted acrylic polymer, and optionally additionally containing a pore-forming component,

the resulting pellet having 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.

2. The extended release pellet formulation of claim 1, wherein the inert pellet core comprises a polysaccharide, cellulose, a cellulose derivative, a starch or a wax.

3. The extended release pellet formulation of claim 1, wherein the inert pellet core comprises saccharose and/or microcrystalline cellulose.

4. The extended release pellet formulation of claim 1, wherein the inert pellet core comprises microcrystalline cellulose.

5. The extended release pellet formulation according to claim 1, wherein the pH-dependent enteric-coating anionic polymer is a carboxylic acrylic polymer.

6. The extended release pellet formulation according to claim 5, wherein the carboxylic acrylic polymer is a partly methyl esterified methacrylic acid polymer, soluble above a pH value of 5.5.

7. The extended release pellet formulation according to claim 6, wherein the partly methyl esterified methacrylic acid polymer is soluble above a pH value of 7.0.

8. The extended release pellet formulation according to claim 1, wherein the quaternary ammonium substituted acrylic polymer has an ammonium substitution of about 5 to about 10 percent by weight.

9. The extended release pellet formulation according to claim 1, wherein the second layer contains a pore-forming component.

10. The extended release pellet formulation according to claim 9, wherein the amount of the pore-forming component is 1% to 25% by weight of the polymer mixture in the second layer.

11. The extended release pellet formulation according to claim 9, wherein the pore-forming component comprises at least one component selected from hydroxypropylcellulose, hydroxypropyl methylcellulose, polyvinylpyrrolidone and polyethylene glycol.

12. A capsule containing the extended release pellets of the formulation according to claim 1.

13. A capsule according to claim 12, wherein the amount of pramipexole or a pharmaceutically acceptable salt thereof contained in the extended release pellets in the capsule, is sufficient to provide a daily dose of pramipexole or a pharmaceutically acceptable salt thereof when administered at one time.

14. A method of manufacturing the extended release pellet formulation according to claim 1, comprising the steps of:

first, providing an inert starter pellet core;

second, 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 to obtain an active ingredient pellet;

third, applying a solution or dispersion of a second coating composition comprising a mixture of the pH-dependent enteric-coating polymer and the pH-independent water swelling polymer, and optionally a pore-forming component as functional coating composition onto the active ingredient pellet obtained in the second step; and

optionally performing a manual screening after the second and/or third process step to remove agglomerates.

15. The method of manufacturing the extended release pellet formulation according to claim 14, wherein:

the second step of applying a solution or dispersion of a first coating composition is conducted by spraying the solution or dispersion of the coating composition onto the inert starter pellet core, wherein the pramexipole or a pharmaceutically acceptable salt thereof is used as unmilled material, dissolved/dispersed in a solvent together with the binder and optional excipient(s) and sprayed onto the inert starter pellet core and subsequently dried to obtain an active ingredient pellet; and

the third step of applying a solution or dispersion of a second coating composition is conducted by spraying the second coating composition solution/dispersion and a solvent onto the active ingredient pellet and subsequently drying the obtained extended release pellet.

16. A method for the treatment of Parkinson'"'"'s disease and complications or disorders associated therewith which comprises administering to a patient the extended release pellet formulation according to claim 1.