Niraparib Compositions
The present invention relates to compositions comprising the compound niraparib, in particular certain solid forms of niraparib.
1 . A composition consisting of crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate monohydrate substantially free of 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,
wherein substantially free of Form III means the composition consists of less than about 6% (w/w) total weight for Form III compared to the combined total weight of Form I and Form III; 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) 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 as shown in FIG. 1 .
3 .- 5 . (canceled)
6 . 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.
7 .- 8 . (canceled)
9 . 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.
10 . The composition of claim 1 , wherein the crystalline Form I is characterized by an X-ray powder diffraction (XRPD) comprising at least four X-ray 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.
11 . The composition of claim 1 , A wherein the crystalline Form I is characterized by a scanning differential calorimetry pattern substantially as shown in FIG. 2 .
12 . (canceled)
13 . The composition of claim 1 , wherein the crystalline Form I is characterized by a Raman spectroscopy pattern substantially as shown in FIG. 3 .
14 . (canceled)
15 . 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 .
16 . (canceled)
17 . The composition of claim 1 , wherein the crystalline Form I is characterized by an infrared spectroscopy pattern substantially as shown in FIG. 4 .
18 .- 40 . (canceled)
41 . A method of making crystalline Form I of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide substantially free of Form III of 2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide tosylate anhydrate, comprising dissolving a composition comprising 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; 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) comprising diffraction angles at 2θ values of 17.8±0.2, 19.0±0.2, and 22.8±0.2 degrees.
42 .- 47 . (canceled)
48 . The composition of claim 1 , prepared by dissolving a composition comprising 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.
49 . The composition of claim 48 , 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).
50 .- 51 . (canceled)
52 . The composition of claim 48 , wherein the organic solvent is acetone, methyl ethyl ketone, acetonitrile, methyl tert-butyl ether, dioxane, dimethyl sulfoxide, or any combination thereof.
53 . The composition of claim 48 , wherein the organic solvent is 2-propanol, acetic acid, formic acid, or any combination thereof.
54 . (canceled)
55 . The composition of claim 1 , wherein the composition is a pharmaceutical composition.
56 . A pharmaceutical composition comprising the composition of claim 1 , and at least one pharmaceutically acceptable excipient.
57 . The pharmaceutical composition of claim 56 , wherein the composition is in an oral dosage form.
58 . The pharmaceutical composition of claim 57 , wherein the oral dosage form is a tablet or capsule.
59 . An article of manufacture comprising multiple unit doses of the pharmaceutical composition of claim 58 in a sealed container with written instructions for use.
60 . The article of manufacture of claim 59 , further comprising an induction seal, desiccant, or any combination thereof.
61 . The pharmaceutical composition of claim 56 wherein the composition is in unit dose form.