Dosage units of 3-(6-(1-(2,2-difluorobenzo[D] [1,3] dioxol-5-yl) cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid

1. A dosage unit comprising 25 to 400 mg of substantially crystalline and salt free 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid characterized by one or more peaks at 15.2 to 15.6 degrees, 16.1 to 16.5 degrees, and 14.3 to 14.7 degrees in an X-ray powder diffraction obtained using Cu K alpha radiation.

2. The dosage unit of claim 1 , wherein the amount of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is 100 to 300 mg.

3. The dosage unit of claim 1 , wherein the amount of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is 200 mg.

4. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is characterized by one or more peaks at about 15.4, 16.3, and 14.5 degrees.

5. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 14.6 to 15.0 degrees.

6. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 14.8 degrees.

7. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 17.6 to 18.0 degrees.

8. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 17.8 degrees.

9. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 16.4 to 16.8 degrees.

10. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 16.6 degrees.

11. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 7.6 to 8.0 degrees.

12. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 7.8 degrees.

13. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 25.8 to 26.2 degrees.

14. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 26.0 degrees.

15. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 21.4 to 21.8 degrees.

16. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 21.6 degrees.

17. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 23.1 to 23.5 degrees.

18. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is further characterized by a peak at 23.3 degrees.

19. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid has a monoclinic crystal system, a P2 1 /n space group, and the following unit cell dimensions:

a=4.9626 (7) Å α=90°

b=12.2994 (18) Å β=93.938 (9)°

c=33.075 (4) Å γ=90°.

20. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is characterized by a diffraction pattern substantially similar to that of FIG. 1 .

21. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid is characterized by a diffraction pattern substantially similar to that of FIG. 2 .

22. The dosage unit of claim 1 , wherein the dosage unit is a solid oral dosage unit.

23. The dosage unit of claim 1 , wherein the dosage unit is in the form of a capsule.

24. The dosage unit of claim 1 , wherein the dosage unit comprises more than one capsule.

25. The dosage unit of claim 1 , wherein the dosage unit comprises 4 capsules of 50 mg of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid each.

26. The dosage unit of claim 1 , further comprising a filler.

27. The dosage unit of claim 26 , wherein the filler is lactose and microcrystalline cellulose.

28. The dosage unit of claim 26 , wherein the amount of filler is 40 to 80 percent by weight.

29. The dosage unit of claim 26 , wherein the amount of filler is 60 percent by weight.

30. The dosage unit of claim 1 , further comprising a disintegrant.

31. The dosage unit of claim 30 , wherein the disintegrant is sodium starch glycolate.

32. The dosage unit of claim 30 , wherein the amount of disintegrant is 1 to 20 percent by weight.

33. The dosage unit of claim 30 , wherein the amount of disintegrant is 10 percent by weight.

34. The dosage unit of claim 1 further comprising a surfactant.

35. The dosage unit of claim 34 , wherein the surfactant is an anionic, cationic, or nonionic surfactant.

36. The dosage unit of claim 34 , wherein the surfactant is sodium lauryl sulfate.

37. The dosage unit of claim 34 , wherein the amount of surfactant is 0.5 to 15 percent by weight.

38. The dosage unit of claim 34 , wherein the amount of surfactant is 5 percent by weight.

39. The dosage unit of claim 1 , further comprising a glidant or viscosity agent.

40. The dosage unit of claim 39 , wherein the glidant is colloidal silicon dioxide.

41. The dosage unit of claim 39 , wherein the amount of glidant or viscosity agent is 0.05 to 2 percent by weight.

42. The dosage unit of claim 39 , wherein the amount of glidant or viscosity agent is 0.5 percent by weight.

43. The dosage unit of claim 1 , further comprising a lubricant.

44. The dosage unit of claim 43 , wherein the lubricant is magnesium stearate.

45. The dosage unit of claim 43 , wherein the amount of lubricant is 0.05 to 2 percent by weight.

46. The dosage unit of claim 43 , wherein the amount of lubricant is 0.5 percent by weight.

47. The dosage unit of claim 1 , wherein the dosage unit comprises a capsule comprising 50 mg of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid, 40 to 44 percent by weight lactose, 15 to 20 percent by weight microcrystalline cellulose, 10 percent by weight sodium starch glycolate, 5 to 6 percent by weight sodium lauryl sulfate, 0.5 to 0.6 percent by weight colloidal silicon dioxide, and 0.5 percent by weight magnesium stearate.

48. The dosage unit of claim 1 , wherein the dosage unit comprises a capsule comprising 25 mg of 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid.

49. The dosage unit of claim 48 , wherein the dosage unit further comprises 40 or 44 percent by weight lactose, 15 to 20 percent by weight microcrystalline cellulose, 10 percent by weight sodium starch glycolate, 5 to 6 percent by weight sodium lauryl sulfate, 0.5 to 0.6 percent by weight colloidal silicon dioxide, and 0.5 percent by weight magnesium stearate.

50. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid has a particle size of 0.1 microns to 50 microns.

51. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid has a particle size of 1.0 microns to 5 microns.

52. The dosage unit of claim 1 , wherein the 3-(6-(1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)-3-methylpyridin-2-yl)benzoic acid has a particle size D50 of 2.0 microns.

53. A method of treating cystic fibrosis in a subject comprising administering to a subject in need thereof wherein the subject has a defective gene that causes a deletion of phenylalanine at position 508 of the cystic fibrosis transmembrane conductance regulator amino acid sequence an effective amount of the dosage unit of claim 1 .

54. The method of claim 53 , wherein the method comprises administering an additional therapeutic agent.

55. The method of claim 54 , wherein the additional therapeutic agent is selected from the group consisting of mucolytic agent, bronchodialator, an anti-biotic, an anti-infective agent, an anti-inflammatory agent, a CFTR modulator other than a compound of the present invention, and a nutritional agent.

56. The method of claim 53 , wherein the dosage unit is administered to the subject once a week.

57. The method of claim 53 , wherein the dosage unit is administered to the subject once a day.

58. A pharmaceutical pack or kit comprising the dosage unit of claim 1 and instructions for use thereof.