Patent NZ-598883-A (NZ)
Title: Crystalline forms of a parp inhibitor compound
Inventor: KRESS MICHAEL
IPC: A61K31/407
Filed: 2010-08-25
Abstract: Disclosed are crystalline forms of 4,5,6,7-tetrahydro-11-methoxy-2-[(4-methyl-1-piperazinyl)methyl]-1H-cyclopenta[a]pyrollo[3,4-c]carbazole-1,3(2H)-dione (Compound I), wherein the crystalline form of Compound I is characterized by (a) an X-ray powder diffraction pattern comprising at least the following peaks: 4.32, 6.07 and 8.55 ± 0.2 degrees 2-theta, and one or more of the following peaks: 12.07 and 15.37 ± 0.2 degrees 2-theta (form A0); (b) an X-ray powder diffraction pattern comprising at least the following peaks: 7.16, 7.89 and 16.54 ± 0.2 degrees 2-theta, and one or more of the following peaks: 10.77 and 21.20 ± 0.2 degrees 2-theta (form B0); (c) an X-ray powder diffraction pattern comprising at least the following peaks: 8.36, 17.39 and 24.59 ± 0.2 degrees 2-theta, and one or more of the following peaks 8.71 and 16.69 ± 0.2 degrees 2-theta (form HC0); (d) a compound of formula I characterized by an X-ray powder diffraction pattern comprising at least the following peaks: 7.60, 8.99, 15.16, 17.99 and 25.00 ± 0.2 degrees 2-theta (form HD0); (e) an X-ray powder diffraction pattern comprising at least the following peaks: 8.56, 14.64, 16.07, 22.24 and 23.02 ± 0.2 degrees 2-theta, and one or more of the following peaks: 9.80, 10.62, 11.04, 12.68, 17.18, 17.23, 19.75, 23.31, 27.06 and 27.85 ± 0.2 degrees 2-theta (form S20); (f) a compound of formula I characterised by an X-ray powder diffraction pattern comprising at least the following peaks: 6.70, 8.67 and 16.80 ± 0.2 degrees 2-theta, and one or more of the following peaks: 7.61, 10.29, 11.57, 13.36, 15.02, 16.85, 17.33 and 25.20 ± 0.2 degrees 2-theta (form S30); (g) a compound of formula I characterised by an X-ray powder diffraction pattern comprising at least the following peaks: 8.42, 8.60 and 13.92 ± 0.2 degrees 2-theta, and one or more of the following peaks: 7.95, 17.20, 21.07, 21.30 and 24.46 ± 0.2 degrees 2-theta (form S40); (h) a compound of formula I characterised by an X-ray powder diffraction pattern comprising at least the following peaks: 8.68, 11.10 and 23.31 ± 0.2 degrees 2-theta, and one or more of the following peaks: 8.36, 15.42, 16.21, 16.94, 17.25, 17.39 and 26.27 ± 0.2 degrees 2-theta (form S60); (i) a compound of formula I characterised by an X-ray powder diffraction pattern comprising at least the following peaks: 8.34, 8.67 and 24.57 ± 0.2 degrees 2-theta, and one or more of the following peaks 16.68 and 17.33 ± 0.2 degrees 2-theta (form S90); (j) a compound of formula I characterised by an X-ray powder diffraction pattern comprising at least the following peaks: 7.63, 7.67 and 24.46 ± 0.2 degrees 2-theta, and one or more of the following peaks: 8.63, 9.00, 14.78, 17.13, 17.39, 17.99 and 18.15 ± 0.2 degrees 2-theta (form S120), and a mixtures thereof. Further disclosed is a process for preparing anhydrous crystalline form A0 of Compound I as defined above, the process comprising the steps of: a. dissolving a non-crystalline form of Compound I in a solvent such as tetrahydrofuran; b. filtering the resulting solution; c. partially distilling the solvent while adding an anti-solvent such as heptane to precipitate Compound I; d. further distilling the resulting slurry while adding additional anti-solvent to reduce the volume of the solvent used in step (a); e. heating the slurry to achieve complete conversion to Form A0; f. cooling; g. collecting the product via filtration; and h. drying. Further disclosed is a pharmaceutical composition comprising a crystalline form of Compound I as defined above or a mixture thereof.