Crystals

1. A hydrate of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate

wherein the hydrate exhibits an XRPD pattern comprising at least five 2-theta (°) values selected from the group consisting of 8.8, 9.5, 11.1, 15.2, 15.5, 16.4, 20.2, 20.6, 23.6, 24.0, 24.9, and 27.2, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

2. A hydrate of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate

wherein the hydrate exhibits at least one of an XRPD pattern comprising at least five 2-theta (°) values selected from the group consisting of 4.7, 5.4, 5.6, 8.8, 9.5, 9.9, 10.8, 11.1, 13.1, 14.0, 14.9, 15.2, 15.5, 16.4, 16.5, 17.6, 17.7, 18.8, 19.1, 19.3, 19.5, 19.8, 20.0, 20.2, 20.6, 20.9, 21.2, 21.7, 21.9, 22.4, 22.7, 22.8, 23.2, 23.3, 23.6, 24.0, 24.9, 25.5, 25.8, 26.3, 26.5, 27.0, 27.2, and 27.4, wherein the XRPD is measured using an incident beam of Cu Kα radiation, or an XRPD pattern comprising at least five d-spacing (Å) values selected from the group consisting of 18.7, 16.5, 15.9, 10.0, 9.3, 9.0, 8.2, 8.0, 6.8, 6.3, 5.9, 5.8, 5.7, 5.4, 5.0, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, and 3.3.

3. The hydrate of claim 2 , wherein the hydrate exhibits an XRPD pattern comprising at least twelve d-spacing (Å) values selected from the group consisting of 18.7, 16.5, 15.9, 10.0, 9.3, 9.0, 8.2, 8.0, 6.8, 6.3, 5.9, 5.8, 5.7, 5.4, 5.0, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, and 3.3.

4. The hydrate of claim 2 , wherein the hydrate exhibits at least one of an XRPD pattern comprising 2-theta (°) values of 8.8±0.2, 9.5±0.2, 11.1±0.2, 15.2±0.2, 15.5±0.2, 16.4±0.2, 20.2±0.2, 20.6±0.2, 23.6±0.2, 24.0±0.2, 24.9±0.2, and 27.2±0.2, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å, or an XRPD pattern comprising d-spacing (Å) values of 10.0, 9.3, 8.0, 5.8, 5.7, 5.4, 4.4, 4.3, 3.8, 3.7, 3.6, and 3.3.

5. The hydrate of claim 1 , wherein the hydrate exhibits an XRPD substantially as shown in FIG. 24, 45, 46, 48, 50, 51, 54 , or 57 , wherein the XRPD is measured using radiation of wavelength 1.54059 Å.

6. The hydrate of claim 1 , wherein the hydrate exhibits 14% water by Karl Fischer analysis.

7. A non-solvate non-hydrate crystalline form of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate

wherein the non-solvate non-hydrate crystalline form exhibits an XRPD pattern comprising at least five 2-theta (°) values selected from the group consisting of 6.6, 11.0, 12.6, 14.5, 14.6, 18.0, 19.7, 20.1, 21.0, 21.6, 22.0, 22.4, 23.8, 24.5, 24.8, and 27.4, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

8. A non-solvate non-hydrate crystalline form of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate

wherein the non-solvate non-hydrate crystalline form exhibits at least one of an XRPD pattern comprising at least five 2-theta (°) values selected from the group consisting of 6.6, 11.0, 11.1, 12.6, 14.5, 14.6, 15.3, 16.4, 17.1, 18.0, 19.7, 20.1, 21.0, 21.4, 21.6, 22.0, 22.4, 22.8, 23.8, 24.5, 24.8, 25.8, 27.4, and 29.0, wherein the XRPD is measured using an incident beam of Cu Kα radiation, or an XRPD pattern comprising at least five d-spacing (Å) values selected from the group consisting of 13.3, 8.1, 7.9, 7.0, 6.1, 5.8, 5.4, 5.2, 4.9, 4.5, 4.4, 4.2, 4.1, 4.0, 3.9, 3.7, 3.6, 3.5, 3.3, and 3.1.

9. The non-solvate non-hydrate crystalline form of claim 8 , wherein the non-solvate non-hydrate crystalline form exhibits an XRPD pattern comprising at least sixteen d-spacing (Å) values selected from the group consisting of 13.3, 8.1, 7.9, 7.0, 6.1, 5.8, 5.4, 5.2, 4.9, 4.5, 4.4, 4.2, 4.1, 4.0, 3.9, 3.7, 3.6, 3.5, 3.3, and 3.1.

10. The non-solvate non-hydrate crystalline form of claim 8 , wherein the non-solvate non-hydrate crystalline form exhibits at least one of an XRPD pattern comprising 2-theta (°) values of 6.6±0.2, 11.0±0.2, 12.6±0.2, 14.5±0.2, 14.6±0.2, 18.0±0.2, 19.7±0.2, 20.1±0.2, 21.0±0.2, 21.6±0.2, 22.0±0.2, 22.4±0.2, 23.8±0.2, 24.5±0.2, 24.8±0.2, and 27.4±0.2, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å, or an XRPD pattern comprising d-spacing (Å) values of 13.3, 8.1, 7.0, 6.1, 4.9, 4.5, 4.4, 4.2, 4.1, 4.0, 3.7, 3.6, and 3.3.

11. The non-solvate non-hydrate crystalline form of claim 7 , wherein the non-solvate non-hydrate crystalline form exhibits an XRPD substantially as shown in FIG. 21, 41, 42, 43, 49, 53 , or 55 , wherein the XRPD is measured using radiation of wavelength 1.54059 Å.

12. A pharmaceutical composition comprising the hydrate of claim 4 .

13. A pharmaceutical composition comprising the non-solvate non-hydrate crystalline form of claim 10 .

14. A process for preparing a pharmaceutical composition comprising a mono- or di-anion of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, wherein the process comprises admixing the hydrate of claim 4 and a pharmaceutically acceptable liquid.

15. A process for preparing a pharmaceutical composition comprising a mono- or di-anion of 2-{[3,5-bis(trifluoromethyl)phenyl]carbamoyl}-4-chlorophenyl dihydrogen phosphate, wherein the process comprises admixing the non-solvate non-hydrate crystalline form of claim 10 and a pharmaceutically acceptable liquid.

16. A method of treating or controlling edema in a human in need thereof, wherein the method comprises administering the hydrate of claim 4 to the human.

17. A method of treating or controlling edema in a human in need thereof, wherein the method comprises administering the non-solvate non-hydrate crystalline form of claim 10 to the human.

18. The process of claim 14 , wherein the pharmaceutically acceptable liquid is an aqueous solution comprising a base.

19. The process of claim 18 , wherein the base is an amine and/or a salt thereof.

20. The process of claim 14 , wherein the pharmaceutical composition is for injection.

21. The process of claim 15 , wherein the pharmaceutically acceptable liquid is an aqueous solution comprising a base.

22. The process of claim 14 , wherein the process comprises admixing the hydrate and a base prior to admixture with the pharmaceutically acceptable liquid.

23. The process of claim 19 , wherein the base is tris(hydroxymethyl)aminomethane and/or a salt thereof, meglumine, and/or diethanolamine.

24. The process of claim 22 , wherein the base is an amine and/or a salt thereof.

25. The process of claim 24 , wherein the base is tris(hydroxymethyl)aminomethane and/or a salt thereof, meglumine, and/or diethanolamine.

26. The hydrate of claim 2 , wherein the hydrate exhibits an XRPD pattern comprising at least ten 2-theta (°) values selected from the group consisting of 4.73±0.20, 5.36±0.20, 5.55±0.20, 8.82±0.20, 9.49±0.20, 9.85±0.20, 10.77±0.20, 11.12±0.20, 13.05±0.20, 13.99±0.20, 14.91±0.20, 15.23±0.20, 15.53±0.20, 16.35±0.20, 16.53±0.20, 17.59±0.20, 17.70±0.20, 18.78±0.20, 19.07±0.20, 19.30±0.20, 19.47±0.20, 19.75±0.20, 19.99±0.20, 20.20±0.20, 20.62±0.20, 20.91±0.20, 21.16±0.20, 21.65±0.20, 21.89±0.20, 22.39±0.20, 22.68±0.20, 22.83±0.20, 23.17±0.20, 23.31±0.20, 23.63±0.20, 23.95±0.20, 24.89±0.20, 25.54±0.20, 25.83±0.20, 26.32±0.20, 26.52±0.20, 27.00±0.20, 27.16±0.20, and 27.42±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

27. The hydrate of claim 2 , wherein the hydrate exhibits an XRPD pattern comprising 2-theta (°) values of 4.73±0.20, 5.36±0.20, 5.55±0.20, 8.82±0.20, 9.49±0.20, 9.85±0.20, 10.77±0.20, 11.12±0.20, 13.05±0.20, 13.99±0.20, 14.91±0.20, 15.23±0.20, 15.53±0.20, 16.35±0.20, 16.53±0.20, 17.59±0.20, 17.70±0.20, 18.78±0.20, 19.07±0.20, 19.30±0.20, 19.47±0.20, 19.75±0.20, 19.99±0.20, 20.20±0.20, 20.62±0.20, 20.91±0.20, 21.16±0.20, 21.65±0.20, 21.89±0.20, 22.39±0.20, 22.68±0.20, 22.83±0.20, 23.17±0.20, 23.31±0.20, 23.63±0.20, 23.95±0.20, 24.89±0.20, 25.54±0.20, 25.83±0.20, 26.32±0.20, 26.52±0.20, 27.00±0.20, 27.16±0.20, and 27.42±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

28. The hydrate of claim 1 , wherein the hydrate exhibits an XRPD substantially as shown in FIG. 24 , wherein the XRPD is measured using radiation of wavelength 1.54059 Å.

29. The non-solvate non-hydrate crystalline form of claim 8 , wherein the non-solvate non-hydrate crystalline form exhibits an XRPD pattern comprising at least ten 2-theta (°) values selected from the group consisting of 6.64±0.20, 10.95±0.20, 11.13±0.20, 12.55±0.20, 14.48±0.20, 14.61±0.20, 15.28±0.20, 16.35±0.20, 17.09±0.20, 17.99±0.20, 19.74±0.20, 20.07±0.20, 20.97±0.20, 21.36±0.20, 21.63±0.20, 22.02±0.20, 22.40±0.20, 22.77±0.20, 23.80±0.20, 24.50±0.20, 24.78±0.20, 25.76±0.20, 27.42±0.20, and 29.01±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.

30. The non-solvate non-hydrate crystalline form of claim 8 , wherein the non-solvate non-hydrate crystalline form exhibits an XRPD pattern comprising 2-theta (°) values of 6.64±0.20, 10.95±0.20, 11.13±0.20, 12.55±0.20, 14.48±0.20, 14.61±0.20, 15.28±0.20, 16.35±0.20, 17.09±0.20, 17.99±0.20, 19.74±0.20, 20.07±0.20, 20.97±0.20, 21.36±0.20, 21.63±0.20, 22.02±0.20, 22.40±0.20, 22.77±0.20, 23.80±0.20, 24.50±0.20, 24.78±0.20, 25.76±0.20, 27.42±0.20, and 29.01±0.20, wherein the XRPD is measured using an incident beam of Cu Kα radiation of wavelength 1.54059 Å.