Pharmaceutical formulations comprising nitrocatechol derivatives and methods of making thereof

• US 9,132,094 B2
• Filed: 03/31/2010
• Issued: 09/15/2015
• Est. Priority Date: 04/01/2009
• Status: Active Grant

• Current Assignee: BIAL Portela & Ca, SA
• Original Assignee: BIAL Portela & Ca, SA
• Inventors: Cardoso de Vasconcelos, Tefilo, Jorge dos Santos Lima, Ricardo, Cerdeira de Campos Costa, Rui
• Primary Examiner(s): Soroush, Layla
• Application Number:
  US12/750,956
• Publication Number:
  US 20100256193A1
• Time in Patent Office: 1,994 Days
• Field of Search: 514/340
• US Class Current: 1/1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/4245 Oxadiazoles
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/1611 Inorganic compounds
• CPC Class Codes: A61K 9/1635 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/1652 Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin homeopathic globules A61K9/1623
• CPC Class Codes: A61K 9/4808 characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release capsules filled with granules or microparticles A61K9/16; filled with microcapsules or coated microparticles A61K9/50; with mixture of different granules, microcapsules, (coated) microparticles A61K9/5084
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 25/02 for peripheral neuropathies
• 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 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/10 Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/12 Antihypertensives

Abstract

The present disclosure relates to compositions and pharmaceutical formulations comprising at least one active pharmaceutical ingredient chosen from nitrocatechol derivatives of formula I as defined herein and salts, esters, hydrates, solvates and derivatives thereof and methods of making said compositions and pharmaceutical formulations.

Claims

1. A composition comprising at least one active pharmaceutical ingredient chosen from 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide, at least one phosphate derivative, and at least one polyvinylpyrrolidone derivative compound;

wherein said at least one active pharmaceutical ingredient is present in the composition in granular form and wherein the bulk density of the composition is greater than 0.2 g/mL.

2. The composition of claim 1, wherein the granules further comprise the at least one phosphate derivative and/or the at least one polyvinylpyrrolidone derivative compound.

3. The composition of claim 1, wherein the at least one phosphate derivative is chosen from calcium phosphate, dibasic anhydrous;

calcium phosphate, dibasic dihydrate; and

calcium phosphate tribasic.

4. The composition of claim 1, wherein the at least one phosphate derivative constitutes from 0.5 wt % to 99.5 wt % of the composition.

5. The composition of claim 1, wherein the at least one polyvinylpyrrolidone derivative compound is chosen from povidone or copovidone.

6. The composition of claim 1, wherein the at least one polyvinylpyrrolidone derivative compound constitutes from 0.1 wt % to 40 wt % of the composition.

7. The composition of claim 1 further comprising an additional active pharmaceutical ingredient.

32. The composition of claim 1, comprising at least one excipient selected from glycerinemonostearate, glycerylbehenate, glycerylpalmitostearate, hydrogenated castor oil, hydrogenated vegetable oil type 1, medium-chain triglycerides, calcium stearate, magnesium lauryl sulphate, magnesium stearate, sodium lauryl sulphate, sodium stearylfumarate, stearic acid and zinc stearate.

33. The composition according to claim 32, wherein the at least one excipient is chosen from calcium stearate.

34. The composition according to claim 32, wherein the at least one excipient is magnesium stearate.

35. The composition according to claim 1, wherein the at least one active pharmaceutical ingredient chosen from 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide is present in an amount ranging from about 0.02wt % to about 90wt %, relative to the weight of the composition.

8. A pharmaceutical formulation comprising a composition comprising at least one active pharmaceutical ingredient chosen from 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide, at least one phosphate derivative, and at least one polyvinylpyrrolidone derivative compound;

wherein said at least one active pharmaceutical ingredient is present in the composition in granular form and wherein the bulk density of the composition is greater than 0.2 g/mL.

9. The pharmaceutical formulation of claim 8, wherein the formulation is a dosage form chosen from tablets and capsules.

10. The pharmaceutical formulation of claim 9, wherein the formulation is a tablet exhibiting an apparent density of 0.5 g/mL to 1.5 g/mL.

17. The pharmaceutical formulation of claim 8, wherein the granules further comprise the at least one phosphate derivative and/or the at least one polyvinylpyrrolidone derivative compound.

18. The pharmaceutical formulation of claim 8, wherein the at least one phosphate derivative is chosen from calcium phosphate, dibasic anhydrous;

calcium phosphate dibasic dihydrate; and

calcium phosphate tribasic.

19. The pharmaceutical formulation of claim 18, wherein the at least one phosphate derivative is calcium phosphate dibasic dihydrate.

20. The pharmaceutical formulation of claim 8, wherein the at least one polyvinylpyrrolidone derivative compound is chosen from povidone or copovidone.

21. The pharmaceutical formulation of claim 20, wherein the at least one polyvinylpyrrolidone derivative compound is povidone.

22. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 2.5 mg or more.

23. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 5 mg or more.

24. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 10 mg or more.

25. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 20 mg or more.

26. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 40 mg or more.

27. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 50 mg or more.

28. The pharmaceutical formulation of claim 8, wherein said at least one active pharmaceutical ingredient is present in an amount of about 100 mg or more.

29. The pharmaceutical formulation of claim 8, further comprising L-DOPA, and a peripheral AADC inhibitor.

30. The pharmaceutical formulation of claim 8, wherein the at least one active pharmaceutical ingredient is present in an amount of about 1 mg or more.

31. The pharmaceutical formulation of claim 8, further comprising L-DOPA, and a peripheral AADC inhibitor.

36. The pharmaceutical formulation according to claim 8, wherein the at least one active pharmaceutical ingredient chosen from 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide is present in an amount ranging from about 0.02wt % to about 90wt %, relative to the weight of the composition.

11. A method of making a composition or pharmaceutical formulation comprising:

granulating at least one active pharmaceutical ingredient chosen from 2,5-dichloro-3-(5-(3,4-dihydroxy-5-nitrophenyl)-1,2,4-oxadiazol-3-yl)-4,6-dimethylpyridine 1-oxide to form granules;

mixing at least one phosphate derivative with the at least one active pharmaceutical ingredient before, during or after granulation; and

mixing at least one polyvinylpyrrolidone derivative compound with the at least one active pharmaceutical ingredient before, during or after granulation;

wherein said at least one active pharmaceutical ingredient is present in the composition in granular form and wherein the bulk density of the composition is greater than 0.2 g/mL.

12. The method of claim 11, wherein the at least one phosphate derivative is chosen from calcium phosphate, dibasic anhydrous;

calcium phosphate, dibasic dihydrate; and

calcium phosphate tribasic.

13. The method of claim 11, wherein the at least one polyvinylpyrrolidone derivative compound is chosen from povidone or copovidone.

14. The method of claim 11, wherein the granulating step is performed using a granulation liquid.

15. The method of claim 11, wherein when a pharmaceutical formulation is made, the method further comprises forming a pharmaceutical dosage form.

16. The method of claim 15, wherein the pharmaceutical dosage form is a tablet having an apparent density 0.5 g/mL to 1.5 g/mL.