Novel Polymorphs of Azabicyclohexane
The invention provides polymorphic crystalline forms of acid addition salts of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane designated as polymorph form A, polymorph form B and polymorph form C, where polymorph form A is more thermodynamically stable than the other forms, methods for preparing and using such polymorph forms and pharmaceutical compositions containing such polymorph forms.
1 . A polymorph of an acid addition salt of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in crystalline form substantially free of other geometric, optical and polymorphic isomers thereof.
2 . The acid addition salt of claim 1 wherein said salt is a hydrochloride salt.
3 . The polymorph form A of an acid addition salt of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in crystalline form substantially free of other geometric, optical and polymorphic isomers thereof.
4 . The polymorph form A of claim 3 wherein said acid addition salt is a hydrochloride salt.
5 . The polymorph form A of claim 4 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at one or more of and at about the following °2θ (degree) values:
17.14;
19.62;
21.96;
24.52; and
26.74.
6 . The polymorph form A of claim 4 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at all of and at about the following °2θ (degree) values:
17.14;
19.62;
21.96;
24.52; and
26.74.
7 . The polymorph form A of claim 4 wherein the Raman spectrum of said polymorph is characterized by peaks at one or more of and at about the following wavenumbers (cm −1 ):
762;
836;
921;
959:
1393;
1597;
2890;
2982; and
3064.
8 . The polymorph form A of claim 4 wherein the Raman spectrum of said polymorph is characterized by peaks at all of and at about the following wavenumbers (cm −1 ):
762;
836;
921;
959;
1393;
1597;
2890;
2982; and
3064.
9 . The polymorph form B of an acid addition salt of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in crystalline form substantially free of other geometric, optical and polymorphic isomers thereof.
10 . The polymorph form B of claim 9 wherein said acid addition salt is a hydrochloride salt.
11 . The polymorph form B of claim 10 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at one or more of and at about the following °2θ (degree) values:
15.58;
17.52;
21.35;
23.04;
25.43; and
30.72.
12 . The polymorph form B of claim 10 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at all of and at about the following °2θ (degree) values:
15.58;
17.52;
21.35;
23.04;
25.43;
and 30.72.
13 . The polymorph form B of claim 10 wherein the Raman spectrum of said polymorph is characterized by peaks at one or more of and at about the following wavenumbers (cm −1 ):
1245;
1380;
2963;
2993;
3027; and
3066.
14 . The polymorph form B of claim 10 wherein the Raman spectrum of said polymorph is characterized by peaks at all of and at about the following wavenumbers (cm −1 ):
1245;
1380;
2963;
2993;
3027; and
3066.
15 . The polymorph form C of an acid addition salt of (+)-1-(3,4-dichlorophenyl)-3-azabicyclo[3.1.0]hexane in crystalline form substantially free of other geometric, optical and polymorphic isomers thereof.
16 . The polymorph form C of claim 15 wherein said acid addition salt is a hydrochloride salt.
17 . The polymorph form C of claim 16 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at one or more of and at about the following °2θ (degree) values:
13.34;
17.64;
20.07;
21.32;
22.97;
24.86;
26.32; and
27.90.
18 . The polymorph form C of claim 16 wherein the X-ray powder diffraction pattern of said polymorph, as measured at crystal sizes of from about 10 to 40 microns, is characterized by peaks at all of and at about the following °2θ (degree) values:
13.34;
17.64;
20.07;
21.32;
22.97;
24.86;
26.32; and
27.90.
19 . The polymorph form C of claim 16 wherein the Raman spectrum of said polymorph is characterized by peaks at one or more of and at about the following wavenumbers (cm −1 ):
1059;
1094;
1266;
1343;
1595;
2966;
2900; and
3070.
20 . The polymorph form C of claim 16 wherein the Raman spectrum of said polymorph is characterized by peaks at all of and at about the following wavenumbers (cm −1 ):
1059;
1094;
1266;
1343;
1595;
2966;
2900; and
3070.
21 - 65 . (canceled)