Crystalline forms of selinexor and process for their preparation
The present disclosure relates to solid state forms of Selinexor, processes for preparation thereof and pharmaceutical compositions thereof.
1. A crystalline form of Selinexor designated as Form T8, characterized by data selected from one or more of the following:
a. an X-ray powder diffraction pattern having peaks at 6.0, 13.4, 17.6, 19.6, and 24.9 degrees 2-theta±0.2 degrees 2-theta;
b. an XRPD pattern as depicted in FIG. 8 ;
c. a solid state 13 C-NMR spectrum having characteristic peaks at 107.5, 126.0, 132.2, 141.5, 151.7 and 157.9 ppm±0.2 ppm;
d. a solid state 13 C-NMR spectrum having the following chemical shift absolute differences from a reference peak at 154.1 ppm±2 ppm of 46.6, 28.1, 21.9, 12.6, 2.4 and 3.8 ppm±0.1 ppm;
e. a solid state 13 C-NMR spectrum as depicted in FIG. 18 or 19 or 20 ; and
f. a combination of any two or more of the above.
2. The crystalline Form T8 of Selinexor according to claim 1 , characterized by an XRPD pattern having peaks at 6.0, 13.4, 17.6, 19.6, and 24.9 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 15.3, 20.8, 23.3, 26.4 and 29.6 degrees two theta±0.2 degrees two theta.
3. A crystalline form of Selinexor designated as Form T1, characterized by data selected from one or more of the following:
a. an XRPD pattern having peaks 10.2, 16.9, 21.1, 21.5, 22.7, and 26.7 degrees 2-theta±0.2 degrees 2-theta;
b. an XRPD pattern as depicted in FIG. 1 ; and
c. a combination of (a) and (b).
4. The crystalline Form T1 of Selinexor according to claim 3 , characterized by an XRPD pattern having peaks at 10.2, 16.9, 21.1, 21.5, 22.7, and 26.7 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.8, 19.2, 19.7, 23.5 and 24.3 degrees two theta±0.2 degrees two theta.
5. A crystalline form of Selinexor designated as Form T6, characterized by data selected from one or more of the following:
a. an XRPD pattern having peaks at 13.0, 13.7, 20.1, 23.2, 23.9 and 27.7 degrees 2-theta±0.2 degrees 2-theta;
b. an XRPD pattern as depicted in FIG. 6 ; and
c. a combination of (a) and (b).
6. The crystalline Form T6 of Selinexor according to claim 5 , characterized by an XRPD pattern having peaks at 13.0, 13.7, 20.1, 23.2, 23.9 and 27.7 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 5.4, 10.9, 21.2, 26.2 and 27.1 degrees two theta±0.2 degrees two theta.
7. A crystalline form of Selinexor designated as Form T7, characterized by data selected from one or more of the following:
a. an XRPD pattern having peaks 15.1, 15.5, 21.6, 24.0 and 26.4 degrees 2-theta±0.2 degrees 2-theta;
b. an XRPD pattern as depicted in FIG. 7 ; and
c. a combination of (a) and (b).
8. The crystalline Form T7 of Selinexor according to claim 7 , characterized by an XRPD pattern having peaks at 15.1, 15.5, 21.6, 24.0 and 26.4 degrees 2-theta±0.2 degrees 2-theta, and also having one, two, three, four or five additional peaks selected from 16.2, 18.3, 23.3, 30.4 and 34.3 degrees two theta±0.2 degrees two theta.
9. A pharmaceutical composition comprising a crystalline form according to claim 1 , optionally further comprising at least one pharmaceutically acceptable excipient.
10. A process for preparing the pharmaceutical formulation according to claim 9 , comprising combining the crystalline form with at least one pharmaceutically acceptable excipient.
11. A method of treating a cancer that is treatable by the selective inhibition of nuclear export, comprising administering a therapeutically effective amount of the crystalline form according to claim 1 to a subject suffering from cancer, otherwise in need of the treatment.
12. A pharmaceutical composition comprising a crystalline form according to claim 3 , optionally further comprising at least one pharmaceutically acceptable excipient.
13. A pharmaceutical composition comprising a crystalline form according to claim 5 , optionally further comprising at least one pharmaceutically acceptable excipient.
14. A pharmaceutical composition comprising a crystalline form according to claim 7 , optionally further comprising at least one pharmaceutically acceptable excipient.
15. A process for preparing the pharmaceutical formulation according to claim 12 , comprising combining the crystalline form with at least one pharmaceutically acceptable excipient.
16. A process for preparing the pharmaceutical formulation according to claim 13 , comprising combining the crystalline form with at least one pharmaceutically acceptable excipient.
17. A process for preparing the pharmaceutical formulation according to claim 14 , comprising combining the crystalline form with at least one pharmaceutically acceptable excipient.
18. A method of treating a cancer that is treatable by the selective inhibition of nuclear export, comprising administering a therapeutically effective amount of the crystalline form according to claim 3 to a subject suffering from cancer, otherwise in need of the treatment.
19. A method of treating a cancer that is treatable by the selective inhibition of nuclear export, comprising administering a therapeutically effective amount of the crystalline form according to claim 5 to a subject suffering from cancer, otherwise in need of the treatment.
20. A method of treating a cancer that is treatable by the selective inhibition of nuclear export, comprising administering a therapeutically effective amount of the crystalline form according to claim 7 to a subject suffering from cancer, otherwise in need of the treatment.