Modified Release Formulation

• US 20110150994A1
• Filed: 02/28/2011
• Published: 06/23/2011
• Est. Priority Date: 02/10/2006
• Status: Abandoned Application

• 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
• Application Number:
  US13/036,928
• Publication Number:
  US 20110150994A1
• Time in Patent Office: Days
• US Class Current: 424/465
• CPC Class Codes: A61K 31/428 condensed with carbocyclic rings
• 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 9/2054 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: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: A61P 25/24 Antidepressants

Abstract

The invention is directed to the use of an extended release tablet formulation for pramipexole.

Claims

1. An extended release formulation comprising pramipexole or a pharmaceutically acceptable salt thereof having a reduced side effect profile when administered to a patient in terms of at least one condition selected from sleepiness and/or hallucinations and/or dizziness and/or headache and/or dyskinesia and/or obstipation and/or periphere oedema and/or nausea when compared to an immediate release formulation comprising pramipexole or a pharmaceutically acceptable salt thereof when the immediate release formulation is administered to the patient as often as needed to provide the same average blood plasma concentration of pramipexole in said patient as is achieved during the release period of the extended release formulation when the extended release formulation is administered once in the same period.

13. A formulation according to claim 1 wherein the extended release formulation comprises pramipexole or a pharmaceutically acceptable salt thereof in a matrix comprising at least one water swelling polymer other than pregelatinized starch.

14. A formulation according to claim 13, 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.

15. A formulation according to claim 14, wherein the anionic polymer is selected from the group consisting of optionally crosslinked acrylic acid polymers, methacrylic acid polymers, alginates and carboxymethylcellulose.

16. A formulation according to claim 15, 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.-%.

17. A formulation according to claim 13, comprising a substantially neutral polymer other than pregelatinized starch.

18. A formulation according to claim 17, wherein the substantially neutral polymer is selected from hydroxypropyl cellulose and hydroxypropylmethyl cellulose.

19. A formulation according to claim 18, wherein the substantially neutral polymer is hydroxypropyl methylcellulose, and wherein the content of hydroxypropyl methylcellulose in the matrix is from about 10 wt.-% to about 75 wt.-%.

20. A formulation according to claim 13, wherein the matrix comprises about:

(a) pramipexole or a salt thereof 0.05 to 5 wt.-%;

(b) anionic water swelling polymer(s) 0.25 to 25 wt.-%;

(c) neutral water swelling polymer(s) 10 to 75 wt.-%; and

(d) further excipients ad 100 wt.-%.

21. A formulation according to claim 13, characterised in that the formulation is a 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 pH-independent release characteristic in the range from pH 4.5 to 7.5.

23. A formulation according to claim 1, characterised in that the immediate release formulation is a tablet which comprises as inactive ingredients mannitol, corn starch, colloidal silicon dioxide, povidone, and magnesium stearate and as active ingredient pramipexole dihydrochloride monohydrate in an amount of either 0.125 mg or 0.25 mg or 0.5 mg or 1.0 mg or 1.5 mg or more.

24. A formulation according to claim 1, characterised in that the extended release formulation is in the form of a tablet.

25. A formulation according to claim 1, characterised in that the extended release formulation is in the form of a tablet having a non-functional coating.

2. A method for treating a disease in a patient that is responsive to dopaminergic treatment, comprising administering to a patient having said disease an extended release formulation comprising pramipexole or pramipexoledichloride monohydrate or another pharmaceutically acceptable salt of pramipexole and said formulation having an at least partially pH-dependant release profile.

3. A method according to claim 2, wherein the pH-dependent release profile shows a faster release characteristic in the range of pH<

4.5 and a slower and pH-independent release characteristic in the range from pH 4.5 to 7.5.

4. A method according to claim 2 wherein the formulation shows a reduced side effect profile when administered to a patient in terms of at least one condition selected from sleepiness and/or hallucinations and/or dizziness and/or headache and/or dyskinesia and/or obstipation and/or periphere oedema and/or nausea in comparison to an immediate release formulation comprising pramipexole or a pharmaceutically acceptable salt thereof when the immediate release formulation is administered to the patient as often as needed to provide the same average blood plasma concentration of pramipexole in said patient as is achieved during the release period of the extended release formulation when the extended release formulation is administered once in the same period.

5. A method according to claim 2 wherein the disease treated is idiopathic Parkinson'"'"'s disease.

6. A method according to claim 2 wherein the disease treated is idiopathic Parkinson'"'"'s disease with non-motor symptoms.

7. A method according to claim 2 wherein the disease treated is idiopathic Parkinson'"'"'s disease and the treatment is in addition to another anti-Parkinson baseline treatment.

8. A method according to claim 2 wherein the patient has depressive symptoms.

9. A method according to claim 2 wherein the disease treated is idiopathic Parkinson'"'"'s disease with motor symptoms.

10. A method according to claim 2 wherein the disease treated is idiopathic RLS.

11. A method according to claim 2 wherein the disease treated is Fibromyalgia.

12. A method according to claim 2 wherein the disease treated is Bipolar Disorder.

22. A method according to claim 2, characterised in that the extended release formulation is administered once daily.

26. A method for treating a disease in a patient that is responsive to dopaminergic treatment, comprising administering to a patient having said disease an extended release formulation comprising pramipexole or pramipexoledichloride monohydrate or another pharmaceutically acceptable salt of pramipexole and said formulation having an at least partially pH-independent in vitro release profile.

27. A method according to claim 26, characterised in that the release profile is pH independent over a pH range of pH 1 to 7.5.

28. A method according to claim 26, characterised in that the formulation comprises at least one water swelling polymer.

29. A method according to claim 28, characterised in that the water swelling polymer is a substantially neutral polymer.

30. A method according to claim 28, characterised in that the water swelling polymer is selected from the group consisting of alkylcelluloses;

hydroxyalkylcelluloses;

hydroxyalkyl alkylcelluloses;

carboxyalkylcellulose esters;

other natural, semi-synthetic, or synthetic di-, oligo- and polysaccharides;

methacrylate copolymers;

polyvinylalcohol;

polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone with vinyl acetate;

combinations of polyvinylalcohol and polyvinylpyrrolidone; and

polyalkylene oxides.

31. A method according to claim 28, characterised in that the formulation further comprises at least one additive selected from the group consisting of diluents or fillers, glidants, binding agents, granulating agents, anti-caking agents, lubricants, flavors, dyes, preservatives, and coating agents, provided that it does not comprise an ionic or anionic water swelling polymer in an amount that substantially impacts the pH release profile.

32. A method according to claim 26, wherein the formulation shows a reduced side effect profile when administered to a patient in terms of at least one condition selected from sleepiness and/or hallucinations and/or dizziness and/or headache and/or dyskinesia and/or obstipation and/or periphere oedema and/or nausea in comparison to an immediate release formulation comprising pramipexole or a pharmaceutically acceptable salt thereof when the immediate release formulation is administered to the patient as often as needed to provide the same average blood plasma concentration of pramipexole in said patient as is achieved during the release period of the extended release formulation when the extended release formulation is administered once in the same period.

33. A method according to claim 26 wherein the disease treated is idiopathic Parkinson'"'"'s disease.

34. A method according to claim 26 wherein the disease treated is idiopathic Parkinson'"'"'s disease with non-motor symptoms.

35. A method according to claim 26 wherein the disease treated is idiopathic Parkinson'"'"'s disease and the treatment is in addition to another anti-Parkinson baseline treatment.

36. A method according to claim 26 wherein the patient has depressive symptoms.

37. A method according to claim 26 wherein the disease treated is idiopathic Parkinson'"'"'s disease with motor symptoms.

38. A method according to claim 26 wherein the disease treated is idiopathic RLS.

39. A method according to claim 26 wherein the disease treated is Fibromyalgia.

40. A method according to claim 26 wherein the disease treated is Bipolar Disorder.