Crystalline salts and polymorphs of a P2X3 antagonist
Provided are novel salts and polymorphs of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide, which are potentially useful for modulating a condition mediated by a P2X3 or P2X2/3 receptor. Also provided are pharmaceutical formulations and methods of administration and dosing of these salts and polymorphs to subjects in need thereof.
1. A crystalline citrate Form B of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide characterized by having X-ray powder diffraction peaks at 2θ values of approximately 11.3, 16.2 and 23.0 degrees.
2. The crystalline citrate Form B of claim 1 , further characterized by having an X-ray powder diffraction peak at 2θ value of approximately 5.7 degrees.
3. The crystalline citrate Form B of claim 2 , further characterized by having an X-ray powder diffraction peak at 2θ value of approximately 8.4 degrees.
4. The crystalline citrate Form B of claim 3 , further characterized by having an X-ray powder diffraction peak at 2θ value of approximately 18.8 degrees.
5. The crystalline citrate Form B of claim 4 , further characterized by having an X-ray powder diffraction peak at 2θ value of approximately 25.0 degrees.
6. A crystalline citrate Form B characterized by having X-ray powder diffraction peaks at 2θ values of approximately 5.7, 8.4, 11.3, 16.2, 18.8, 23.0 and 25.0 degrees.
7. The crystalline citrate Form B of claim 1 further characterized by having an X-ray powder diffraction pattern substantially as depicted in FIG. 6 .
8. A pharmaceutical composition comprising the crystalline citrate Form B of claim 1 and a pharmaceutically acceptable carrier.
9. A method of modulating a condition mediated by a P2X3 or P2X2/3 receptor, said method comprising administering an effective amount of the crystalline citrate Form B of claim 1 to a subject in need thereof.
10. The method of claim 9 , wherein the condition mediated by a P2X3 or P2X2/3 receptor is selected from cough, chronic cough and urge to cough.
11. A crystalline tartrate Form F of 5-(2,4-diamino-pyrimidin-5-yloxy)-4-isopropyl-2-methoxy-benzenesulfonamide characterized by having X-ray powder diffraction peaks at 2θ values of approximately 11.3, 18.7, and 22.7 degrees.
12. The crystalline tartrate Form F of claim 11 , further characterized by having X-ray powder diffraction peaks at 2θ values of approximately 12.1 and 17.7 degrees.
13. The crystalline tartrate Form F of claim 11 , further characterized by having an X-ray powder diffraction pattern substantially as depicted in FIG. 11 .
14. The crystalline tartrate Form F of claim 11 , further characterized by having a TGA thermogram showing weight losses of about 6.6 wt % from 27° C. to 100° C., a further weight loss of about 11.7 wt % between 180° C. and 240° C.
15. The crystalline tartrate Form F of claim 11 , further characterized by proton nuclear magnetic resonance (NMR) data showing a 2:1 Compound A to tartrate ratio.
16. The crystalline tartrate Form F of claim 11 , further characterized by having a TGA thermogram substantially as depicted in FIG. 12 .
17. A pharmaceutical composition comprising the crystalline tartrate Form F of claim 11 and a pharmaceutically acceptable carrier.
18. A method of modulating a condition mediated by a P2X3 or P2X2/3 receptor, said method comprising administering an effective amount of the crystalline tartrate Form F of claim 11 to a subject in need thereof.
19. The method of claim 18 , wherein the condition mediated by a P2X3 or P2X2/3 receptor is selected from cough, chronic cough and urge to cough.