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

• US 20060198887A1
• Filed: 08/12/2005
• Published: 09/07/2006
• Est. Priority Date: 08/13/2004
• Status: Active Grant

• 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, Eisenreich, Wolfram
• Granted Patent: US 7,695,734 B2
• Time in Patent Office: Days
• US Class Current: 424/468
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• CPC Class Codes: A61K 9/14 Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51
• CPC Class Codes: A61K 9/2027 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/2031 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
• CPC Class Codes: A61K 9/2054 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2059 Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
• CPC Class Codes: A61K 9/2846 Poly(meth)acrylates
• CPC Class Codes: A61K 9/2866 Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
• CPC Class Codes: A61K 9/2886 having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer of the type active core-drug layer-inactive layer A61K9/209
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

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.

Claims

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.

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 2, wherein the anionic polymer is selected from the group consisting of optionally crosslinked acrylic acid polymers, methacrylic acid polymers, alginates, and carboxymethyl cellulose.

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 0.25 wt.-% to about 25 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 0.5 wt.-% to about 15 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 1 wt.-% to about 10 wt.-%.

7. The extended release tablet formulation according to claim 2, wherein at least one of the at least two polymers is a substantially neutral polymer other than pregelatinized starch.

8. The extended release tablet formulation according to claim 7, wherein the substantially neutral polymer is hydroxypropyl cellulose or hydroxypropyl methyl cellulose.

9. The extended release tablet formulation according to claim 8, wherein the substantially neutral polymer is hydroxypropyl methyl cellulose.

10. The extended release tablet formulation according to claim 9, wherein the content of hydroxypropyl methyl cellulose in the matrix is from about 10 wt.-% to about 75 wt.-%.

11. The extended release tablet formulation according to claim 10, wherein the content of hydroxypropyl methyl cellulose in the matrix is from about 25 wt.-% to about 65 wt.-%.

12. The extended release tablet formulation according to claim 7, 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 neutral water swelling polymer(s); and

(d) to 100 wt.-% of further excipients.

13. The extended release tablet formulation of claim 7, consisting of pramipexole dihydrochloride monohydrate, hypromellose 2208, corn starch, Carbomer 941, colloidal silicon dioxide, and magnesium stearate.

14. An extended release tablet formulation comprising pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising:

(a) at least one water swelling polymer other than pregelatinized starch 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 one 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.

15. An extended release tablet formulation according to claim 14, wherein the matrix comprises at least one water swelling polymer other than pregelatinized starch, 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.

16. An extended release tablet formulation, wherein the contained amount of pramipexole or pharmaceutically acceptable salt thereof is sufficient to provide a daily dose administered at one time.

17. A method of manufacturing the extended release tablet formulation 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.

18. The method according to claim 17, wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1).

19. A method of manufacturing the extended release tablet formulation 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.

20. The method according to claim 19, wherein the pramipexole or the pharmaceutically acceptable salt thereof is peg-milled prior to use in step (1).

21. The method according to claim 19, wherein the granulation liquid of step (2) is water.

22. A method of manufacturing the extended release tablet formulation 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.

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).