Solid forms of a toll-like receptor modulator
The present invention provides crystalline forms, solvates and hydrates of 4-amino-2-butoxy-8-(3-(pyrrolidin-1-ylmethyl)benzyl)-7,8-dihydropteridin-6(5H)-one, and methods of making.
1. A crystalline form of Compound I having the structure:
characterized by an X-ray powder diffraction (XRPD) pattern comprising three or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
2. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 5.3, 9.8 and 15.6 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
3. The crystalline form of claim 1 , characterized by an XRPD pattern comprising peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 and 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
4. The crystalline form of claim 1 , characterized by the XRPD pattern substantially in accordance with that of FIG. 20 .
5. The crystalline form of claim 1 , characterized by a differential scanning calorimetry (DSC) endotherm at about 141° C. or about 173° C.
6. The crystalline form of claim 1 , characterized by
an XRPD pattern comprising peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 and 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation; and
a DSC endotherm at about 173° C.
7. A method of preparing a crystalline form of claim 1 , comprising:
forming a mixture comprising a crystalline Form I of Compound I characterized by an XRPD pattern comprising three or more peaks at 5.8, 11.4, 11.6, 17.7, 20.1, 20.9, 22.3, 23.9, 26.0 or 26.8 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation, water and trifluoroethanol, under conditions suitable to prepare the crystalline form of claim 1 .
8. The method of claim 7 , wherein the ratio of trifluoroethanol to water is from about 10:1 to about 1:1 (volume/volume).
9. The method of claim 7 , wherein the ratio of trifluoroethanol to water is about 5:1 (volume/volume).
10. A pharmaceutical composition comprising a therapeutically effective amount of a crystalline form of Compound I of claim 1 , and a pharmaceutically acceptable carrier or excipient.
11. The pharmaceutical composition of claim 10 , further comprising at least one additional therapeutic agent.
12. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising four or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
13. The crystalline form of claim 1 , characterized by an X-ray powder diffraction (XRPD) pattern comprising five or more peaks at 5.3, 9.8, 13.1, 15.6, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
14. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising one or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
15. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising two or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
16. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising three or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
17. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising four or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.
18. The crystalline form of claim 2 , characterized by an XRPD pattern further comprising five or more peaks at 13.1, 17.0, 19.6, 20.0, 20.7, 21.9 or 24.9 degrees 2θ (±0.2 degrees 2θ), wherein the XRPD is made using CuK α1 radiation.