Solid state forms of Relugolix
The present disclosure provides solid state forms of Relugolix, crystalline forms of Relugolix, pharmaceutical compositions thereof, and pharmaceutical formulations thereof. Methods for producing these forms of Relugolix, pharmaceutical compositions, and pharmaceutical formulations are also provided.
1. A method comprising:
dissolving Relugolix Form F in a first solvent to form a solution, wherein the Relugolix Form F is characterized by data including at least one of:
an X-ray powder diffraction pattern substantially as depicted in FIG. 1 or in FIG. 7 ;
an X-ray powder diffraction pattern having peaks at 6.9, 7.5, 9.5, 13.9 and 18.1 degrees 2-theta±0.2 degrees 2-theta; an
FT-IR spectrum having peaks at 1720, 1680, 1626, 1595, 1528, 1460, 1412, 1313, 1237 and 1095 cm −1 ±4 cm −1 ; or
an FT-IR spectrum substantially as depicted in at least one of FIG. 6 a or FIG. 6 b;
contacting the solution with a second solvent to form a suspension;
cooling the suspension; and
recovering Relugolix Form B having a formula of 1-{4-[1-(2,6-difluorobenzyl)-5-dimethylaminomethyl-3-(6-methoxypyridazin-3-yl)-2,4-dioxo-1,2,3,4-tetrahydrothieno[2,3-d]pyrimidin-6-yl]phenyl}-3-methoxyurea).
2. The method of claim 1 , wherein the first solvent is dimethyl sulfoxide.
3. The method of claim 1 , wherein dissolving the Relugolix Form F in the first solvent occurs at a temperature from about 30° C. to about 50° C.
4. The method of claim 1 , wherein dissolving the Relugolix Form F in the first solvent occurs at a temperature from about 35° C. to about 45° C.
5. The method of claim 1 , wherein the second solvent is ethanol.
6. The method of claim 1 , wherein contacting the solution with the second solvent to form the suspension occurs at a temperature from about 30° C. to about 50° C.
7. The method of claim 1 , wherein contacting the solution with the second solvent to form the suspension occurs at a temperature from about 35° C. to about 45° C.
8. The method of claim 1 , wherein contacting the solution with the second solvent to form the suspension occurs for a period of time from about 30 minutes to about 90 minutes.
9. The method of claim 1 , wherein contacting the solution with the second solvent to form the suspension occurs for a period of time from about 45 minutes to about 75 minutes.
10. The method of claim 1 , wherein contacting the solution with the second solvent to form the suspension occurs with stirring.
11. The method of claim 1 , wherein cooling the suspension cools the suspension to a temperature from about 15° C. to about 50° C.
12. The method of claim 1 , wherein cooling the suspension cools the suspension to a temperature from about 20° C. to about 45° C.
13. The method of claim 1 , wherein cooling the suspension occurs for a period of time from about 30 minutes to about 90 minutes.
14. The method of claim 1 , wherein cooling the suspension occurs for a period of time from about 45 minutes to about 75 minutes.
15. The method of claim 1 , further comprising stirring the suspension for a period of time from about 8 hours to about 20 hours after cooling the suspension.
16. The method of claim 1 , wherein recovering the Relugolix Form B occurs by filtration.
17. The method of claim 16 , wherein the filtration is vacuum filtration.