Niraparib compositions
The present invention relates to compositions comprising the compound niraparib, in particular certain solid forms of niraparib.
1. A composition comprising 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 is characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees, and is further characterized by at least two 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, and
wherein substantially free of Form II and Form III means the composition comprises 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 monohydrate is characterized by an X-ray powder diffraction (XRPD) 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 monohydrate is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
2. The composition 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 pattern substantially in accordance with FIG. 1 .
3. The composition of claim 1 , wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) 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 composition of claim 1 , wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) 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 composition of claim 1 , wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) 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 composition of claim 1 , wherein the crystalline Form I is characterized by a scanning differential calorimetry pattern substantially as shown in FIG. 2 .
7. The composition of claim 1 , wherein the crystalline Form I is characterized by a Raman spectroscopy pattern substantially as shown in FIG. 3 .
8. The composition 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 composition of claim 1 , wherein the crystalline Form I is characterized by an infrared spectroscopy pattern substantially as shown in FIG. 4 .
10. The composition of claim 1 , wherein the presence of Form III is characterized by at least one diffraction angle selected from a group consisting of 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
11. The composition of claim 1 , wherein substantially free of Form II and Form III means less than about 4% (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.
12. The composition of claim 1 , wherein substantially free of Form II and Form III means less than about 3% (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.
13. The composition of claim 1 , wherein substantially free of Form II and Form III means less than about 2% (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.
14. The composition of claim 1 , wherein substantially free of Form II and Form III means less than about 1% (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.
15. A method of making 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, 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, wherein
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) comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees, and is further characterized by at least two 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;
Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate is characterized by an X-ray powder diffraction (XRPD) 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 monohydrate is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
16. The composition of claim 1 , prepared by 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.
17. The composition of claim 16 , wherein the water:organic solvent ratio is about 10:1 (v/v), about 50:1 (v/v), about 100:1 (v/v), about 200:1 (v/v), about 300:1 (v/v), or about 400:1 (v/v).
18. The composition of claim 16 , wherein the organic solvent is acetone, methyl ethyl ketone, acetonitrile, methyl tert-butyl ether, dioxane, dimethyl sulfoxide, or any combination thereof.
19. The composition of claim 16 , wherein the organic solvent is 2-propanol, acetic acid, formic acid, or any combination thereof.
20. The composition of claim 1 , wherein the composition is a pharmaceutical composition.
21. A pharmaceutical composition comprising the composition of claim 1 , and at least one pharmaceutically acceptable excipient.
22. The pharmaceutical composition of claim 21 , wherein the composition is in an oral dosage form.
23. The pharmaceutical composition of claim 22 , wherein the oral dosage form is a tablet or capsule.
24. An article of manufacture comprising multiple unit doses of the pharmaceutical composition of claim 23 in a sealed container with written instructions for use.
25. The article of manufacture of claim 24 , further comprising an induction seal, desiccant, or any combination thereof.
26. The pharmaceutical composition of claim 21 wherein the composition is in unit dose form.
27. A composition comprising crystalline Form II of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate, non-stoichiometric hydrate substantially free of crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate, wherein the crystalline Form II is characterized by an X-ray powder diffraction (XRPD) 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
wherein 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) comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees, and is further characterized by at least two 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.
28. The composition of claim 27 , wherein the crystalline Form II is substantially characterized by an X-ray powder diffraction pattern substantially in accordance with FIG. 9 for Form II.
29. A composition comprising crystalline Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate substantially free of crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate, wherein the crystalline Form III is substantially characterized by an X-ray powder diffraction (XRPD) comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees; and
wherein 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) comprising diffraction angles at 2θ values of 9.5±0.2, 24.9±0.2, and 26.0±0.2 degrees, and is further characterized by at least two 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.
30. The composition of claim 29 , wherein the crystalline Form III is substantially characterized by an X-ray powder diffraction pattern substantially in accordance with FIG. 9 for Form III.