Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate
View Patent ↗Crystalline Forms I and II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate and compositions, methods of manufacture and therapeutic uses thereof are described.
1. A crystalline Form II 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 21.16 and 21.38±0.20 degrees when measured against an internal silicon standard; and
ii) at least four peaks selected from a group of peaks consisting of: 4.48, 9.00, 13.58, 15.62, 16.48, 19.02, 19.44, 22.46, and 25.00+0.20 degrees when measured against an internal silicon standard.
2. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern, wherein at least six peaks are selected from the group of peaks.
3. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern, wherein at least eight peaks are selected from the group of peaks.
4. The crystalline Form II of claim 1 , characterized by an x-ray powder diffraction pattern, wherein all of the peaks are selected from the group of peaks.
5. A pharmaceutical composition comprising the crystalline Form II of claim 1 .
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.
7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.
8. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.
9. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.
10. A pharmaceutical composition comprising the crystalline Form II of claim 2 .
11. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.
12. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.
13. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.
14. The pharmaceutical composition of claim 10 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.
15. A pharmaceutical composition comprising the crystalline Form II of claim 3 .
16. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.
17. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.
18. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.
19. The pharmaceutical composition of claim 15 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.
20. A pharmaceutical composition comprising the crystalline Form II of claim 4 .
21. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Alzheimer's disease.
22. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is for the treatment of cognitive loss in a subject suffering from Schizophrenia.
23. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Alzheimer's disease.
24. The pharmaceutical composition of claim 20 , wherein the pharmaceutical composition is for the improvement of cognition in a subject suffering from Schizophrenia.
25. A method of improving cognition in a patient suffering from Schizophrenia, comprising administering to the patient a crystalline Form II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate.
26. The method of claim 25 , wherein the crystalline Form II 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 21.16 and 21.38±0.20 degrees when measured against an internal silicon standard; and
ii) at least four peaks selected from a group of peaks consisting of: 4.48, 9.00, 13.58, 15.62, 16.48, 19.02, 19.44, 22.46, and 25.00±0.20 degrees when measured against an internal silicon standard.
27. The method of claim 26 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.
28. The method of claim 26 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.
29. The method of claim 26 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.
30. The method of claim 25 , wherein the method further treats cognitive loss in the patient.
31. The method of claim 30 , wherein the patient is over age 60.
32. The method of claim 30 , wherein the patient further suffers from age-related memory loss.
33. A method of improving cognition in a patient suffering from Alzheimer's Disease, comprising administering to the patient a pharmaceutical composition comprising a crystalline Form II of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate.
34. The method of claim 33 , wherein the crystalline Form II 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 21.16 and 21.38±0.20 degrees when measured against an internal silicon standard; and
ii) at least four peaks selected from a group of peaks consisting of: 4.48, 9.00, 13.58, 15.62, 16.48, 19.02, 19.44, 22.46, and 25.00±0.20 degrees when measured against an internal silicon standard.
35. The method of claim 34 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with at least six peaks selected from the group of peaks.
36. The method of claim 34 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with at least eight peaks selected from the group of peaks.
37. The method of claim 34 , wherein the crystalline Form II is characterized by an x-ray powder diffraction pattern with all of the peaks selected from the group of peaks.
38. The method of claim 33 , wherein the method further treats cognitive loss in the patient.
39. The method of claim 38 , wherein the patient is over age 60.
40. The method of claim 38 , wherein the patient further suffers from age-related memory loss.
41. A method for preparing a pharmaceutical composition, the method comprising combining the crystalline Form II of claim 1 with an excipient or pharmaceutically acceptable carrier.
42. The method according to claim 41 , the method comprising combining the crystalline Form II of claim 1 with a liquid.
43. A method for preparing a pharmaceutical composition, the method comprising filling a capsule with a composition comprising the crystalline Form II of claim 1 .
44. A method for preparing the crystalline Form II of claim 1 , the method comprising:
a) adding (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride to acetonitrile or an aqueous acetonitrile to create a composition that is 10-20 wt. % of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride;
b) optionally adding water to the composition to make the water content 6-10%;
c) optionally cooling the solution at below 10° C.;
d) allowing crystals to form; and
e) isolating crystalline (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate.