Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate

1. A method for preparing crystalline Form I of crystalline Form I of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate, the method comprising:

a) heating 10-30% by weight of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride in acetonitrile or an aqueous acetonitrile to between 60° C. and the boiling point of the solution;

b) optionally adding water to the mixture to fully dissolve the (R)-7-chloro-N(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride;

c) cooling the solution until crystals are just visible;

d) if the water content is greater than 3% volume/volume when crystals are just visible, adding acetonitrile to the mixture so that the water content is less than 3% volume/volume;

e) cooling the resulting mixture to below 15° C.; and

f) isolating crystalline (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate;

wherein the crystalline Form I of crystalline Form I of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate is characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at:

i) one or both of 17.48 and 20.58 ±0.20 degrees when measured against an internal silicon standard; and

ii) at least four peaks selected from a group of peaks consisting of: 4.50, 9.04, 14.60, 15.14, 15.80, 16.60, 18.16, 18.44, 19.48, 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard.

2. The method of claim 1 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.

3. The method of claim 1 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.

4. The method of claim 1 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.

5. The method of claim 1 , wherein the water added in step a) does not bring the water content of the mixture above 30% volume/volume, wherein (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride is present at 15-25% by weight in step a), wherein the method further comprises adding Form I (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate to the mixture after crystals are just visible, or wherein step c) comprises cooling the solution to below 55° C.

6. The method of claim 5 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.

7. The method of claim 5 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.

8. The method of claim 5 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.

9. A method for preparing a pharmaceutical composition, the method comprising: combining:

a) crystalline Form I of crystalline Form I of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate, characterized by an x-ray powder diffraction pattern having peaks expressed as 2Θ at:

i) one or both of 17.48 and 20.58±0.20 degrees when measured against an internal silicon standard; and

ii) at least four peaks selected from a group of peaks consisting of: 4.50, 9.04, 14.60, 15.14, 15.80, 16.60, 18.16, 18.44, 19.48, 21.74 and 25.46±0.20 degrees when measured against an internal silicon standard; and

b) an excipient or pharmaceutically acceptable carrier.

10. The method of claim 9 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.

11. The method of claim 9 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.

12. The method of claim 9 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.

13. The method of claim 9 , wherein the method further comprises combining the prepared pharmaceutical composition with a liquid.

14. The method of claim 13 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.

15. The method of claim 13 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.

16. The method of claim 13 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.

17. The method of claim 9 , wherein the method further comprises filling a capsule with the prepared pharmaceutical composition.

18. The method of claim 17 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.

19. The method of claim 17 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.

20. The method of claim 17 , wherein the crystalline Form I is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.