Crystalline (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine

1. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 15.7±0.2 degrees 2θ, at 20.0±0.2 degrees 2θ and at 31.1±0.2 degrees 2θ.

2. The crystalline form of claim 1 , wherein the X-ray powder diffraction pattern further comprises a characteristic peak at 9.8±0.2 degrees 2θ and/or at 17.8±0.2 degrees 2θ.

3. The crystalline form of claim 1 , wherein the crystalline form has a melting endotherm at about 108-118° C. and/or at about 184-194° C.

4. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 1 .

5. The method of claim 4 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

6. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 8.4±0.2 degrees 2θ and at 23.2±0.2 degrees 2θ.

7. The crystalline form of claim 6 , wherein the X-ray powder diffraction pattern comprises characteristic peaks at 15.0±0.2 degrees 2θ and/or at 22.4±0.2 degrees 2θ.

8. The crystalline form of claim 6 , wherein the crystalline form has a melting endotherm at about 107-117° C. and/or at 120-126° C.

9. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 6 .

10. The method of claim 9 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

11. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 17.9±0.2 degrees 2θ and at 20.1±0.2 degrees 2θ.

12. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 11 .

13. The method of claim 12 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

14. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 8.1±0.2 degrees 2θ, at 19.1±0.2 degrees 2θ and at 20.3±0.2 degrees 2θ.

15. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 14 .

16. The method of claim 15 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

17. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 7.4±0.2 degrees 2θ, at 11.4±0.2 degrees 2θ, and at 13.1±0.2 degrees 2θ.

18. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 17 .

19. The method of claim 18 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

20. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 17.1±0.2 degrees 2θ and at 31.9±0.2 degrees 2θ.

21. The crystalline form of claim 20 , wherein the X-ray powder diffraction pattern comprises characteristic peaks at 10.9±0.2 degrees 2θ and/or at 14.6±0.2 degrees 2θ.

22. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 20 .

23. The method of claim 22 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

24. A crystalline form (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 8.6±0.2 degrees 2θ, at 14.0±0.2 degrees 2θ, at 18.8±0.2 degrees 2θ, and at 10.3±0.2 degrees 2θ.

25. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 24 .

26. The method of claim 25 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

27. A crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 9.5±0.2 degrees 2θ, at 14.3±0.2 degrees 2θ and at 18.2±0.2 degrees 2θ.

28. The crystalline form of claim 27 , wherein the X-ray powder diffraction pattern further comprises a characteristic peak at 25.4±0.2 degrees 2θ.

29. The crystalline form of claim 27 , wherein the crystalline form has a melting endotherm at about 110-120° C.

30. The crystalline form of claim 27 , wherein the crystalline form is an isolated and/or purified crystalline form.

31. The crystalline form of claim 28 , wherein the crystalline form is an isolated and/or purified crystalline form.

32. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the crystalline form of claim 27 .

33. The method of claim 32 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

34. The method of claim 32 , wherein the active ingredient comprises at least about 60% of the crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

35. The method of claim 33 , wherein the active ingredient comprises at least about 60% of the crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

36. The method of claim 32 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

37. The method of claim 33 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

38. A pharmaceutical composition comprising at least one pharmaceutically acceptable additive and/or adjuvant and an active ingredient that comprises a crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro-[cyclohexane-1,1′-pyrano-[3,4,b]indol]-4-amine having an X-ray powder diffraction pattern comprising characteristic peaks at 11.9±0.2 degrees 2θ, at 17.0±0.2 degrees 2θ, at 18.7±0.2 degrees 2θ, and at 30.8±0.2 degrees 2θ.

39. The pharmaceutical composition of crystalline form of claim 38 , wherein the crystalline form is an isolated and/or purified crystalline form.

40. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition according to claim 38 .

41. The method of claim 40 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

42. The method of claim 40 , wherein the active ingredient comprises at least about 60% of the crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

43. The method of claim 41 , wherein the active ingredient comprises at least about 60% of the crystalline form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

44. The method of claim 40 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

45. The method of claim 41 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

46. An amorphous form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyran-[3,4,b]indol]-4-amine.

47. The amorphous form of claim 46 , wherein the amorphous form is an isolated and/or purified amorphous form.

48. A method of treating chronic pain in a patient in need thereof, comprising orally administering to a patient who has been diagnosed with chronic pain a pharmaceutical composition comprising at least one pharmaceutically acceptable adjuvant or additive and an effective amount of active ingredient that comprises the amorphous form of claim 46 .

49. The method of claim 48 , wherein the pharmaceutical composition comprises 40±20 μg, 100±10 μg, 200±50 μg, 400±50 μg, or 600±50 μg of the active ingredient.

50. The method of claim 48 , wherein the active ingredient comprises at least about 50% of the amorphous form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

51. The method of claim 48 , wherein the active ingredient comprises at least about 60% of the amorphous form of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

52. The method of claim 48 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.

53. The method of claim 49 , wherein the active ingredient comprises at least about 80% relative to other isomers of (1r,4r)-6′-fluoro-N,N-dimethyl-4-phenyl-4′,9′-dihydro-3′H-spiro[cyclohexane-1,1′-pyrano[3,4,b]indol]-4-amine.