Capsule formulation of pirfenidone and pharmaceutically acceptable excipients

• US 7,767,225 B2
• Filed: 04/17/2009
• Issued: 08/03/2010
• Est. Priority Date: 09/22/2005
• Status: Active Grant

• Current Assignee: Intermune Incorporated (Roche Holding AG)
• Original Assignee: Intermune Incorporated (Roche Holding AG)
• Inventors: Radhakrishnan, Ramachandran, Vladyka, Ronald, Sultzbaugh, Kenneth
• Primary Examiner(s): Sheikh; Humera N
• Application Number:
  US12/426,182
• Publication Number:
  US 20090191265A1
• Time in Patent Office: 473 Days
• Field of Search: None
• US Class Current: 424/452
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4418 having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
• CPC Class Codes: A61K 9/4841 Filling excipients; Inactive ingredients
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/4866 Organic macromolecular compounds
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 11/02 Nasal agents, e.g. decongestants
• CPC Class Codes: A61P 11/06 Antiasthmatics
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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 27/16 Otologicals
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• 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 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A capsule formulation of pirfenidone is provided that includes pharmaceutically acceptable excipients. In one embodiment, this capsule formulation is capable of sustaining desirable pharmacokinetic responses in a patient. Further provided are methods of treating fibrotic conditions and other cytokine-mediated disorders by administering pirfenidone capsules of such formulation to a patient in need.

Claims

1. A capsule comprising a pharmaceutical formulation of 5-methyl-1-phenyl-2-(1H)-pyridone, wherein said pharmaceutical formulation comprises 5-30% by weight of pharmaceutically acceptable excipients and 70-95% by weight of 5-methyl-1-phenyl-2-(1H)-pyridone, wherein said excipients comprise an effective amount of binder to increase the AUC of pirfenidone upon oral administration, as compared to a capsule comprising no excipients.

2. The capsule of claim 1, wherein said excipients further comprise one or more selected from the group consisting of disintegrators, fillers, and lubricants.

3. The capsule of claim 1, wherein said binders comprise one or more selected from the group consisting of microcrystalline cellulose, povidone, and a combination of povidone and microcrystalline cellulose.

4. The capsule of claim 2, wherein said disintegrator is 2-10% by weight of the capsule, said binder is 2-30% by weight of the capsule, said filler is 2-30% by weight of the capsule, and said lubricant is 0.3-0.8% by weight of the capsule.

5. The capsule of claim 3, wherein said binder comprises povidone.

6. The capsule of claim 5, wherein said povidone comprises at least about 1% by weight of the formulation.

7. The capsule of claim 1, comprising 100-400 mg 5-methyl-1-phenyl-2-(1H)-pyridone.

8. The capsule of claim 3, wherein said binder comprises microcrystalline cellulose.

9. The capsule of claim 1, wherein said formulation comprises a wet-granulated mixture comprising the 5-methyl-1-phenyl-2-(1H)-pyridone, said effective amount of binder to increase the AUC of pirfenidone upon oral administration, a filler, and a disintegrator.

10. The capsule of claim 6, wherein the povidone comprises about 1-4% by weight of the formulation.

11. A method for treating a fibrotic condition or inhibiting actions of cytokines, comprising administering the capsule of claim 1 to a patient suffering from said fibrotic condition or suffering from a disorder mediated by said cytokines.

12. The capsule of claim 1, wherein said effective amount of binder increases the AUC of pirfenidone upon oral administration at least 30%, as compared to a capsule comprising no excipients.

13. The capsule of claim 12, wherein said effective amount of binder increases the AUC of pirfenidone upon oral administration at least 40%, as compared to a capsule comprising no excipients.

14. The capsule of claim 13, wherein said effective amount of binder increases the AUC of pirfenidone upon oral administration at least 60%, as compared to a capsule comprising no excipients.

15. The capsule of claim 6, wherein said povidone comprises at least about 1.85% by weight of the formulation.

16. The capsule of claim 15, wherein the binder further comprises microcrystalline cellulose.

17. The capsule of claim 8, wherein the binder further comprises povidone.

18. The capsule of claim 10, wherein the binder further comprises microcrystalline cellulose.

19. The capsule of claim 18, wherein the total amount of binder is 2-30% by weight of the formulation.

20. The capsule of claim 2, wherein:

the pharmaceutically excipients comprise a lubricant, a filler, and a disintegrator, the binder comprises microcrystalline cellulose and povidone,

the povidone is included in an amount of 1-4% by weight of the formulation, the total amount of binder is 2-30% by weight of the formulation, and

the formulation comprises a wet-granulated mixture comprising the 5-methyl-1-phenyl-2-(1H)-pyridone, the binder, the filler, and the disintegrator.