Niraparib solid state form
The present disclosure relates to a stabilized anhydrous p-toluenesulfonic acid salt of niraparib, Form A. The present disclosure is also related to processes for the preparation of the stabilized anhydrous p-toluenesulfonic acid salt of niraparib. Further, the present disclosure also relates to pharmaceutical compositions comprising the stabilized anhydrous p-toluenesulfonic acid salt of niraparib and methods for treating disease using the stabilized anhydrous p-toluenesulfonic acid salt of niraparib.
1. Stabilized anhydrous p-toluenesulfonic acid salt of niraparib prepared under anhydrous conditions.
2. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 1 wherein the preparation under anhydrous conditions comprises:
a. adding a solution of anhydrous p-toluene sulfonic acid in an anhydrous polar organic solvent to an anhydrous solution of niraparib in an anhydrous polar organic solvent at an elevated temperature under a dry atmosphere;
b. stirring the resultant mixture of solutions at a reduced temperature overnight to precipitate anhydrous p-toluenesulfonic acid salt of niraparib under a dry atmosphere;
c. isolating the precipitated anhydrous p-toluenesulfonic acid salt of niraparib; and
d. placing the precipitated anhydrous p-toluenesulfonic acid salt of niraparib in a sealed vial, with desiccant, and optionally with or without sealing the vial in a foil bag.
3. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein for the anhydrous solution of niraparib in an anhydrous polar organic solvent the anhydrous polar organic solvent is selected from DMSO, DMF, NMP, and mixtures thereof.
4. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein for the anhydrous solution of p-toluene sulfonic acid in an anhydrous polar organic solvent the polar organic solvent is selected from IPAC, IPA, ACE, MeCN, THF, CPME, EtOAc, and mixtures thereof.
5. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein for the anhydrous solution of p-toluene sulfonic acid in an anhydrous polar organic solvent the p-toluene sulfonic acid is prepared by azeotropic distillation to remove water.
6. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein the elevated temperature is at about 70° C.
7. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein the reduced temperature is at about 5° C.
8. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 2 wherein the dry atmosphere is under nitrogen.
9. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 1 that is Form A.
10. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 9 wherein an onset of a thermal event is at about 227° C., as measured by differential scanning calorimetry.
11. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 10 wherein the thermal event is at about 229° C., as measured by differential scanning calorimetry.
12. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 9 which has single crystal parameters
a=9.8 ű1.5%
b=11.2 ű1.5%
c=11.7 ű1.5%
α=87±3°, β=72°±+3°, γ=84°±3°.
13. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 9 which has a cell volume of about 1216 Å 3 ±3%.
14. The stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 9 , characterized by having at least 2 or more X-ray powder diffraction peaks selected from about 17.9, 17.6, 19.3, and 23.1° 2Θ degrees±0.2° 2θ.
15. A pharmaceutical composition comprising a pharmaceutically effective amount of the stabilized anhydrous p-toluenesulfonic acid salt of niraparib of claim 1 and a pharmaceutically acceptable excipient.
16. A process for the preparation of the stabilized anhydrous p-toluenesulfonic acid salt of niraparib according to claim 1 comprising,
a. adding a solution of anhydrous p-toluene sulfonic acid in an anhydrous polar organic solvent to an anhydrous solution of niraparib in an anhydrous polar organic solvent at an elevated temperature under a dry atmosphere;
b. stirring the resultant mixture of solutions at a reduced temperature overnight to precipitate anhydrous p-toluenesulfonic acid salt of niraparib under a dry atmosphere;
c. isolating the precipitated anhydrous p-toluenesulfonic acid salt of niraparib; and
d. placing the precipitated anhydrous p-toluenesulfonic acid salt of niraparib in a sealed vial, with desiccant, and optionally with or without sealing the vial in a foil bag.