Crystalline freebase forms of a biphenyl compound

1. A pharmaceutical composition comprising a pharmaceutically acceptable propellant and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1; designated as Form III.

2. The composition of claim 1 , wherein the crystalline compound is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1, 11.4±0.1, 13.1±0.1, 16.1±0.1, 17.5±0.1, 18.2±0.1, 18.6±0.1, 19.3±0.1, 19.7±0.1, 19.9±0.1, 20.2±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1.

3. The composition of claim 1 , which further comprises an agent selected from β 2 adrenergic receptor agonists, steroidal anti-inflammatory agents, phosphodiesterase-4 inhibitors, and combinations thereof; wherein the crystalline form and the agent are formulated together or separately.

4. The composition of claim 3 , which comprises a β 2 adrenergic receptor agonist and a steroidal anti-inflammatory agent.

5. The composition of claim 1 , wherein the crystalline compound is in a suspension.

6. The composition of claim 1 , wherein the propellant is a hydrofluoroalkane.

7. The composition of claim 6 , wherein the hydrofluoroalkane is 1,1,1,2-tetrafluoroethane.

8. The composition of claim 6 , wherein the hydrofluoroalkane is 1,1,1,2,3,3,3-heptafluoro-n-propane.

9. The composition of claim 1 , wherein the composition further comprises a co-solvent selected from ethanol and pentane.

10. The composition of claim 1 , wherein the composition further comprises a surfactant selected from the sorbitan trioleate, oleic acid, lecithin, and glycerin.

11. The composition of claim 1 , comprising from about 0.01 to 5% by weight of the crystalline compound; from about 0 to 20% by weight ethanol; and from about 0 to 5% by weight surfactant; with the remainder being a hydrofluoroalkane propellant.

12. The composition of claim 1 , wherein the crystalline compound is micronized.

13. A pharmaceutical composition comprising 1,1,1,2-tetrafluoroethane and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-( 4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1; designated as Form III.

14. A pharmaceutical composition comprising 1,1,1,2,3,3,3- heptafluoro-n-propane and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl) piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1; designated as Form III.

15. The composition of claim 3 , which comprises a β 2 adrenergic receptor agonist.

16. The composition of claim 3 , which comprises a steroidal anti-inflammatory agent.

17. The composition of claim 3 , which comprises a phosphodiesterase-4inhibitor.