Crystalline form of (R)-7-chloro-N-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide hydrochloride monohydrate
First Claim
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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.
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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.
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Citations
20 Claims
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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:
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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.; andf) 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; andii) 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.- View Dependent Claims (2, 3, 4, 5, 6, 7, 8)
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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; andii) 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; andb) an excipient or pharmaceutically acceptable carrier. - View Dependent Claims (10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20)
- combining;
Specification