IP Library › Granted Patent US 10,179,779
Granted Patent B2
US 10,179,779 · App. 14/442,860 · Granted Jan 15, 2019

Polymorph forms

Inventors: Toyoharu Numata (Aichi, JP); Hideyuki Aoyama (Aichi, JP); Kaori Muraji (Aichi, JP)
Assignee: RaQualia Pharma Inc.
C07D413/14C07B2200/13
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Quick Facts
Patent No.
US 10,179,779
App. No.
14/442,860
Granted
Jan 15, 2019
Kind
B2
Abstract

The present invention relates to novel crystal forms of 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid. More particularly, the invention relates to polymorph forms of Polymorph Form I, Polymorph Form II, Polymorph Form III, Polymorph Form IV, Polymorph Form V, and Polymorph Form VI, and to processes for the preparation of, compositions containing and to uses of, such polymorph forms.

Claims (18)

1. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kalpha radiation which includes main peaks at 2-theta 5.5, 10.1, 10.9, 13.9, 15.7, 18.5, 18.9, 20.8, 21.8 and 23.6(°), wherein each peak has a margin of error of +/−0.2(°).

2. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , which is further characterized by an infrared (IR) spectrum (diffuse reflection) which shows absorption bands at 4376-4370, 3525-3519, 3462, 2946-2940, 2127, 1713, 1624, 1537, 1508, 1441, 1368, 1287, 1157, 1121, 1103, 1063, 1034, 1013, 916, 870, 816, 781, 746, 733, 654, 619, 590 and 556 cm −1 , wherein each peak has a margin of error of +/−2 cm −1 .

3. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , which is further characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at 170° C., wherein the temperature has a margin of error of +/−1° C.

4. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form IV, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kalpha radiation which includes main peaks at 2-theta 5.6, 9.8, 10.2, 11.3, 13.6, 13.8, 15.7, 17.0, 18.7, 19.3, 21.3 and 22.8(°), wherein each peak has a margin of error of +/−0.2(°).

5. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form V, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kalpha radiation which includes main peaks at 2-theta 5.2, 10.0, 10.3, 11.6, 15.5, 17.7, 18.6, 19.2, 20.5, 21.7, 22.4 and 24.3(°), wherein each peak has a margin of error of +/−0.2(°).

6. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form V according to claim 5 , which is further characterized by an infrared (IR) spectrum (diffuse reflection) which shows absorption bands at 4381-4375, 4130, 2853, 2760, 1701, 1630, 1618, 1541, 1387, 1281, 1186, 1171, 1157, 1123, 1103, 1069, 1032, 1013, 991, 962, 917, 787, 748, 731, 660, and 650 cm −1 , wherein each peak has a margin of error of +/−2 cm −1 .

7. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form V according to claim 5 , which is further characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at 169° C., wherein the temperature has a margin of error of +/−1° C.

8. 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form VI, which is characterized by a powder X-ray diffraction pattern (PXRD) obtained by irradiation with Cu-Kalpha radiation which includes main peaks at 2-theta 10.3, 10.6, 11.4, 12.6, 18.8, 19.2, 19.5, 20.2, 21.2 and 21.7(°), wherein each peak has a margin of error of +/−0.2(°).

9. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form VI according to claim 8 , which is further characterized by an infrared (IR) spectrum (diffuse reflection) which shows absorption bands at 4378-4372, 3944, 3467-3461, 3306, 2959, 2884, 2835, 1711, 1537, 970, 920, 883, and 785 cm −1 , wherein each peak has a margin of error of +/−2 cm −1 .

10. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form VI according to claim 8 , which is further characterized by differential scanning calorimetry (DSC) in which it exhibits an endothermic event at 170° C., wherein the temperature has a margin of error of +/−1° C.

11. A pharmaceutical composition comprising the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , and at least one pharmaceutically acceptable excipient.

12. A process for preparing the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , comprising a step of exposing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I to a relative humidity condition in the range of 60 to 100% at room temperature or higher.

13. A process for preparing the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , comprising a step of exposing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I to 3 to 5% (v/v) water in alcohol.

14. A process for preparing the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form IV according to claim 4 , comprising a step of placing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III in an atmosphere of 90 to 115° C.

15. A process for preparing the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form V according to claim 5 , comprising a step of exposing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I under a condition to form Polymorph Form V without forming any other crystalline forms in a mixture of water and an organic solvent.

16. A process for preparing the 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form VI according to claim 8 , comprising a step of exposing 4-{[4-({[4-(2,2,2-trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form I under a condition to form Polymorph Form VI without forming any other crystalline forms in a mixture of water and an organic solvent.

17. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 1 , wherein the Form III has a purity of at least 90% by weight.

18. The 4-{[4-({[4-(2,2,2-Trifluoroethoxy)-1,2-benzisoxazol-3-yl]oxy}methyl)piperidin-1-yl]methyl}-tetrahydro-2H-pyran-4-carboxylic acid Polymorph Form III according to claim 2 , wherein the Form III has a purity of at least 90% by weight.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 14, 2015
From: NUMATA, TOYOHARU; AOYAMA, HIDEYUKI; MURAJI, KAORI
To: RAQUALIA PHARMA INC.
Reel/Frame 035642/0743 →
Continuity (2)
Provisional Application 61729174 · Nov 21, 2012
Related Publication 20150322055A1 · Nov 12, 2015
Cited By (2)
US 12,605,394 US 12,667,578