Pyridine or N,N-dimethyl acetamide solvated solid state forms of solvated idelalisib, their use and preparation
The invention relates to a crystalline pyridine or N,N-dimethylacetamide solvated solid-state form of idelalisib (IDB). The invention is also directed to the preparation of the aforesaid solvated solid-state forms of IDB. Furthermore, the invention is directed to the use of the aforesaid solvated solid-state forms of IDB.
1. A compound which is a crystalline pyridine or N,N-dimethyl acetamide solvate of idelalisib.
2. The compound of claim 1 which is the pyridine solvate of idelalisib.
3. The compound of claim 1 which is the N,N-dimethylacetamide solvate of idelalisib.
4. The compound of claim 2 having at least 3 or more X-ray powder diffraction peaks selected from about 6.82, 9.98, 18.99, 19.64, 20.16, and 20.72 2Θ measured by CuKa radiation.
5. The compound of claim 3 having one or two X-ray powder diffraction peaks selected from about 6.88 or 10.20 2Θ measured by CuKa radiation.
6. The compound of claim 5 further comprising at least one pair of X-ray powder diffraction peaks at either about 19.39 and 19.60, 20.35 and 20.53, or 21.04 and 21.28° 2Θ measured by CuKa radiation.
7. The compound of claim 2 having one to three DSC peaks at 126.1° C., 133.8° C. and 255.9° C.
8. The compound of claim 3 having a DSC peak at 119.0° C.
9. The compound of claim 2 having a thermal gravimetric curve having about a 10.1% weight loss in the range of about 114.4° C. to 145.5° C.
10. The compound of claim 2 having a thermal gravimetric curve having about a 4.8% weight loss in the range of about 145.5° C. to about 185.4° C.
11. The compound of claim 3 having a thermal gravimetric curve having about a 16.7% weight loss in the range of about 109.1° C. to 120.5° C.
12. A process for the preparation of solid-state pyridine solvate form of idelalisib, comprising:
(a) dissolving idelalisib in pyridine to form a pyridine solution of idelalisib; and
(b) evaporating slowly the pyridine solution of idelalisib to yield the solid-state pyridine solvate form of idelalisib.
13. A process for the preparation of solid-state pyridine solvate form of idelalisib, comprising:
(a) dissolving idelalisib in pyridine at about 50-60° C. to form a pyridine solution of idelalisib; and
(b) cooling the solution to yield the solid-state pyridine solvate form of idelalisib.
14. The process of claim 13 wherein the dissolving is conducted at about 60° C.
15. The process of claim 13 wherein the cooling is conducted to about −10° C.
16. A process for the preparation of solid-state N,N-dimethylacetamide solvate form of idelalisib, comprising:
(a) dissolving idelalisib in N,N-dimethylacetamide to form a N,N-dimethylacetamide solution of idelalisib; and
(b) evaporating N,N-dimethylacetamide to yield the solid-state N,N-dimethylacetamide solvate form of idelalisib.
17. A process for the preparation of solid-state N,N-dimethylacetamide solvate form of idelalisib, comprising:
(a) dissolving idelalisib in N,N-dimethylacetamide to form a N,N-dimethylacetamide solution of idelalisib;
(b) adding water to the N,N-dimethylacetamide solution of idelalisib; and
(c) stirring the N,N-dimethylacetamide solution of idelalisib with added water with cooling to about 5° C. to yield the solid-state N,N-dimethylacetamide solvate form of idelalisib.
18. A process for the preparation of solid-state amorphous form of idelalisib, comprising:
(a) adding water to a 0.4M N,N-dimethylacetamide solution of idelalisib in a 3:1 v:v respectively;
(b) vacuum filtering the resultant mixture of step (a) to yield solid-state amorphous form of idelalisib;
(c) rinsing the solid-state amorphous form of idelalisib with water;
(d) rinsing the solid-state amorphous form of idelalisib with methanol at about 0° C.; and
(e) drying the solid-state amorphous form of idelalisib under vacuum.
19. The process of claim 18 wherein the drying is conducted at about 25° C.