Solid forms of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide

1. A crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, having at least one peak within a 2θ value range selected from 6.0 to 6.4, 10.8 to 11.2, 16.9 to 17.3, 19.2 to 19.6, 20.9 to 21.3, 22.4 to 22.8, 26.5 to 26.9 and 27.3 to 27.7 degrees in an X-ray powder diffraction pattern obtained using Cu K alpha radiation.

2. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 8.2 to 8.6 degrees.

3. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 10.8 to 11.2 degrees.

4. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 14.6 to 15.0 degrees.

5. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 15.9 to 16.3 degrees.

6. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 16.9 to 17.3 degrees.

7. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 18.4 to 18.8 degrees.

8. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 19.2 to 19.6 degrees.

9. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 20.9 to 21.3 degrees.

10. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 22.4 to 22.8 degrees.

11. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 23.2 to 23.6 degrees.

12. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 23.7 to 24.1 degrees.

13. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 24.7 to 25.1 degrees.

14. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 25.3 to 25.7 degrees.

15. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 26.5 to 26.9 degrees.

16. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 27.3 to 27.7 degrees.

17. A pharmaceutical composition comprising the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide according to claim 1 , and a pharmaceutically acceptable adjuvant or carrier.

18. A process for preparing the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide according to claim 1 , wherein said process comprises the steps of alternatively heating and cooling a slurry of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and acetonitrile.

19. A crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, having a monoclinic crystal system, a P2 1 space grouping, and the following unit cell dimensions:

a=11.8011(7) Å α=90°

b=5.9819(3) Å β=105.110(4)°

c=14.7974(8) Å γ=90°.

20. A method of treating a CFTR mediated disease in a patient comprising the step of administering to said patient a crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide or a pharmaceutical composition comprising a crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide according to claim 1 or 19 .

21. The method according to claim 20 , wherein said disease is cystic fibrosis.

22. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide has a peak within a 2θ value range of 6.0 to 6.4 degrees.

23. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 7.4 to 7.8 degrees.

24. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 12.1 to 12.5 degrees.

25. The crystal form of claim 1 , wherein the crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide further has a peak within a 2θ value range of 17.8 to 18.2 degrees.

26. A crystal form of N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, having an X-ray powder diffraction pattern, obtained using Cu K alpha radiation, substantially similar to FIG. 7 .