Polymorphs of rucaparib camsylate and methods of making same
Novel polymorphs of rucaparib camsylate include Form alpha having XRPD peaks at diffraction angles (2θ) of 6.14±0.2, 12.41±0.2, 15.34±0.2, 15.95±0.2, 16.36±0.2, 16.51±0.2 and 19.67±0.2, Form beta having XRPD peaks at diffraction angles (2θ) of 6.86±0.2, 9.58±0.2, 12.75±0.2, 14.56±0.2, 15.05±0.2, 20.76±0.2 and 22.45±0.2, and Form gamma having XRPD peaks at diffraction angles (2θ) of 9.5±0.2, 12.73±0.2, 14.77±0.2, 15.16±0.2, 20.62±0.2, 22.33±0.2, 22.63±0.2 and 27.29±0.2. Methods are disclosed for the preparation of such polymorphic forms and pharmaceutical compositions containing such polymorphic forms. A method is disclosed for preparing a highly pure Form B of rucaparib camsylate. Pharmaceutical compositions containing highly pure Form B prepared by the method are disclosed.
1. A crystalline Form beta of rucaparib camsylate having an XRPD pattern comprising peaks at diffraction angles (2θ) of 9.58±0.2, 12.75±0.2, 14.56±0.2, 15.05±0.2, 20.76±0.2 and 22.45±0.2.
2. The crystalline Form beta of rucaparib camsylate of claim 1 comprising XRPD peaks at diffraction angles (2θ) of 6.86±0.2, 9.58±0.2, 12.75±0.2, 14.56±0.2, 15.05±0.2, 15.41±0.2, 15.99±0.2, 20.76±0.2, 22.45±0.2 and 27.44±0.2.
3. The crystalline Form beta of rucaparib camsylate of claim 1 comprising XRPD peaks at diffraction angles (2θ) of 6.86±0.2, 9.58±0.2, 11.08±0.2, 12.75±0.2, 14.56±0.2, 15.05±0.2, 15.41±0.2, 15.99±0.2, 19.35±0.2, 19.59±0.2, 20.76±0.2, 22.11±0.2, 22.45±0.2, 23.80±0.2, and 27.44±0.2.
4. The crystalline Form beta of rucaparib camsylate of claim 1 characterized by an XRPD pattern substantially as shown in FIG. 3 .
5. The crystalline form Beta of rucaparib camsylate of claim 1 characterized by a DSC pattern substantially as shown in FIG. 4 .
6. A method of preparing the crystalline Form beta of rucaparib camsylate of claim 1 comprising the steps of a) reacting rucaparib free base with DL-10-camphorsulfonic acid in a solvent; and b) isolating the crystalline Form beta of rucaparib camsylate.
7. A pharmaceutical composition comprising the crystalline Form beta of rucaparib camsylate of claim 1 and one or more pharmaceutically acceptable excipients.
8. A crystalline Form gamma of rucaparib camsylate having an XRPD pattern comprising peaks at diffraction angles (2θ) of 9.5±0.2, 12.73±0.2, 14.77±0.2, 15.16±0.2, 20.62±0.2, 22.33±0.2, 22.63±0.2 and 27.29±0.2.
9. The crystalline Form gamma of rucaparib camsylate of claim 8 comprising XRPD peaks at diffraction angles (2θ) of 9.5±0.2, 12.73±0.2, 14.77±0.2, 15.16±0.2, 20.62±0.2, 20.95±0.2, 22.11±0.2, 22.33±0.2, 22.63±0.2, 23.57±0.2 and 27.29±0.2.
10. The crystalline Form gamma of rucaparib camsylate of claim 8 comprising XRPD peaks at diffraction angles (2θ) of 6.95±0.2, 9.5±0.2, 12.73±0.2, 14.77±0.2, 15.16±0.2, 20.62±0.2, 20.95±0.2, 21.45±0.2, 22.11±0.2, 22.33±0.2, 22.63±0.2, 23.57±0.2, 23.93±0.2, 26.71±0.2, and 27.29±0.2.
11. The crystalline Form gamma of rucaparib camsylate of claim 8 characterized by an XRPD pattern substantially as shown in FIG. 8 .
12. The crystalline Form gamma of rucaparib camsylate of claim 8 characterized by a DSC pattern substantially as shown in FIG. 9 .
13. The crystalline Form gamma of rucaparib camsylate of claim 8 characterized by a thermogravimetric analysis (TGA) as illustrated by FIG. 10 .
14. A method of preparing the crystalline Form gamma of rucaparib camsylate of claim 8 comprising the steps of a) combining rucaparib free base with a solvent to achieve a clear solution, b) reacting the clear solution with aq. S-camphorsulfonic acid; and c) isolating the crystalline form gamma rucaparib camsylate.
15. The method of claim 14 wherein the solvent is methanol.
16. A pharmaceutical composition comprising the crystalline Form gamma of rucaparib camsylate of claim 8 and one or more pharmaceutically acceptable excipients.