Crystalline composition of tildacerfont and methods of use and preparation thereof
Described herein are crystalline composition comprising a Corticotropin-releasing hormone receptor 1 (CRF1) antagonist, such as Compound 1: methods of making such crystalline composition, pharmaceutical compositions and medicaments comprising such crystalline composition, and methods of using such crystalline composition in the treatment of conditions, diseases, or disorders that would benefit from modulation of CRF.
1. A crystalline composition comprising:
Compound 1:
at T=150° K. of: a=34.003(4) Å, b=6.5843(13) Åc=21.062(5) Å; β=108.703(12)°, V=4466.5(15) Å 3 and a monoclinic C2/c space group.
2. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by an X-ray powder diffraction pattern comprising peaks at 10.84±0.2° 2-θ, 15.96±0.2° 2-θ, 23.44±0.2° 2-θ, and 24.80±0.2° 2-θ, and as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å.
3. The crystalline composition of claim 2 , wherein the X-ray powder diffraction pattern further comprising at least one peak selected from 5.44±0.2° 2-θ, 20.78±0.2° 2-θ, 22.74±0.2° 2-θ, 23.04±0.2° 2-θ, 26.80±0.2° 2-θ, and 28.86±0.2° 2-θ, and as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å.
4. The crystalline composition of claim 3 , wherein the X-ray powder diffraction pattern further comprising at least five peaks selected from 8.82±0.2° 2-θ, 11.70±0.2° 2-θ, 14.60±0.2° 2-θ, 15.56±0.2° 2-θ, 16.70±0.2° 2-θ, 18.82±0.2° 2-θ, 19.18±0.2° 2-θ, 20.02±0.2° 2-θ, 20.50±0.2° 2-θ, 21.72±0.2° 2-θ, 25.52±0.2° 2-θ, 25.92±0.2° 2-θ, 26.94±0.2° 2-θ, and 28.00±0.2° 2-θ, and as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å.
5. The crystalline composition of claim 3 , wherein the X ray powder diffraction pattern further comprises a peak at 5.44±0.2° 2-θ.
6. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 160° C. to 170° C.
7. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset of about 164° C. and a peak of about 166° C.
8. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by a melting point of about 166° C.
9. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by a thermogravimetric analysis (TGA) thermogram comprising a loss in mass of about 11% over a temperature range of about 25° C. to about 200° C.
10. The crystalline composition of claim 1 , wherein the crystalline composition is characterized by:
(a) an X-ray powder diffraction pattern comprising peaks at 10.84±0.2° 2-θ, 15.96±0.2° 2-θ, 23.44±0.2° 2-θ, and 24.80±0.2° 2-θ, and as measured by X-ray powder diffraction using an X-ray wavelength of 0.71073 Å;
(b) a differential scanning calorimetry (DSC) thermogram comprising an endotherm in the range of about 160° C. to 170° C.;
(c) a differential scanning calorimetry (DSC) thermogram comprising an endotherm with an onset of about 164° C. and a peak of about 166° C.;
(d) a thermogravimetric analysis (TGA) thermogram comprising a loss in mass of about 11% over a temperature range of about 25° C. to about 200° C.; or
(e) combinations thereof.
11. A pharmaceutical composition comprising a crystalline composition comprising
Compound 1:
at T=150° K. of: a=34.003(4) Å, b=6.5843(13) Åc=21.062(5) Å; β=108.703(12)°, V=4466.5(15) Å 3 and a monoclinic C2/c space group.
12. The pharmaceutical composition of claim 11 , wherein the pharmaceutical composition comprises between about 1 mg and about 500 mg of the crystalline composition comprising Compound I and oxalic acid.