Niraparib compositions
The present invention relates to compositions comprising the compound niraparib, in particular certain solid forms of niraparib.
1. A crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate substantially free of Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate,
wherein the crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees; and
wherein substantially free of Form II and Form III means less than about 6% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II, and Form III; and
wherein Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 9.7±0.3, 12.8±0.3, 17.9±0.3, 19.7±0.3, and 21.8±0.3 degrees; and
Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
2. The crystalline Form I of claim 1 , wherein the crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 1 .
3. The crystalline Form I of claim 1 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
4. The crystalline Form I of claim 1 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three diffraction angles selected from a group consisting of 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
5. The crystalline Form I of claim 1 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least four diffraction angles selected from a group consisting of 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
6. The crystalline Form I of claim 1 , wherein the crystalline Form I is characterized by a scanning differential calorimetry pattern substantially as shown in FIG. 2 .
7. The crystalline Form I of claim 1 , wherein the crystalline Form I is characterized by a Raman spectroscopy pattern substantially as shown in FIG. 3 .
8. The crystalline Form I of claim 1 , wherein the crystalline Form I is characterized by a dynamic water vapor sorption pattern substantially as shown in FIG. 5 .
9. The crystalline Form I of claim 1 , wherein the crystalline Form I is characterized by an infrared spectroscopy pattern substantially as shown in FIG. 4 .
10. The crystalline Form I of claim 1 , wherein the crystalline Form I is prepared by a method comprising dissolving a composition comprising Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate or Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, or a mixture thereof, in a solvent having a water:organic solvent ratio of about 10:1 to about 400:1 (v/v), and crystallizing the crystalline Form I.
11. A method of treating a patient diagnosed with ovarian cancer, fallopian tube cancer, epithelial ovarian cancer, recurrent ovarian cancer, prostate cancer, colon cancer, or rectal cancer comprising:
administering to the patient a pharmaceutically acceptable dose of a crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate substantially free of Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate and Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate;
wherein the crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees; and
wherein substantially free of Form II and Form III means less than about 6% (w/w) combined total weight for Form II and Form III compared to the combined total weight of Form I, Form II, and Form III; and
wherein Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 9.7±0.3, 12.8±0.3, 17.9±0.3, 19.7±0.3, and 21.8±0.3 degrees; and
Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate is characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
12. The method of claim 11 , wherein the crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) pattern substantially in accordance with FIG. 1 .
13. The method of claim 11 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising diffraction angles at 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
14. The method of claim 11 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three diffraction angles selected from a group consisting of 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
15. The method of claim 11 , wherein the crystalline Form I is further characterized by an X-ray powder diffraction (XRPD) pattern comprising at least four diffraction angles selected from a group consisting of 2θ values of 12.4±0.2, 13.2±0.2, 17.4±0.2, 18.4±0.2, 21.0±0.2, 25.6±0.2, and 26.9±0.2 degrees.
16. The method of claim 11 , wherein the crystalline Form I is characterized by a scanning differential calorimetry pattern substantially as shown in FIG. 2 .
17. The method of claim 11 , wherein the crystalline Form I is characterized by a Raman spectroscopy pattern substantially as shown in FIG. 3 .
18. The method of claim 11 , wherein the crystalline Form I is characterized by a dynamic water vapor sorption pattern substantially as shown in FIG. 5 .
19. The method of claim 11 , wherein the crystalline Form I is characterized by an infrared spectroscopy pattern substantially as shown in FIG. 4 .
20. The method of claim 11 , wherein the crystalline Form I is prepared by a method comprising dissolving a composition comprising Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate or Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, or a mixture thereof, in a solvent having a water:organic solvent ratio of about 10:1 to about 400:1 (v/v), and crystallizing the crystalline Form I.