Capsule formulation of pirfenidone and pharmaceutically acceptable excipients
View Patent ↗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.
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.