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

• US 9,550,767 B2
• Filed: 01/20/2016
• Issued: 01/24/2017
• Est. Priority Date: 05/17/2010
• Status: Expired due to Fees

• Current Assignee: Forum Pharmaceuticals Inc.
• Original Assignee: Forum Pharmaceuticals Inc.
• Inventors: Oliver-Shaffer, Patricia, Shapiro, Gideon, Chesworth, Richard, Kishida, Muneki, Ishige, Takayuki
• Primary Examiner(s): REESE, HEIDI L
• Application Number:
  US15/002,163
• Publication Number:
  US 20160137638A1
• Time in Patent Office: 370 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 9/4833 Encapsulating processes; Filling of capsules mechanical aspects A61J3/07
• CPC Class Codes: A61K 9/4841 Filling excipients; Inactive ingredients
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/14 for treating abnormal movements, e.g. chorea, dyskinesia
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 453/02 containing not further condensed quinuclidine ring systems
• CPC Class Codes: C30B 29/54 Organic compounds
• CPC Class Codes: C30B 7/08 by cooling of the solution

Abstract

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.

Claims

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.