Crystal modifications of elobixibat
The present invention relates to crystal modifications of N-{(2R)-2-[({[3,3-dibutyl-7-(methyl-thio)-1,1-dioxido-5-phenyl-2,3,4,5-tetrahydro-1,5-benzothiazepin-8-yl]oxy}acetyl)amino]-2-phenylethanolyl}glycine (elobixibat), more specifically crystal modifications I, IV, MeOH-1, EtOH-1, 1-PrOH-1 and 2-PrOH-1. The invention also relates to a process for the preparation of these crystal modifications and to a pharmaceutical composition comprising crystal modification IV.
1. Crystal modification EtOH-1 of elobixibat, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 18.9±0.2.
2. Crystal modification EtOH-1 of elobixibat according to claim 1 , having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 18.9±0.2 and one or more of peaks: 10.1±0.2, 14.5±0.2, 18.4±0.2, 19.1±0.2, 20.7±0.2, 10.4±0.2, 13.1±0.2, and 11.1±0.2.
3. Crystal modification EtOH-1 of elobixibat according to claim 1 , having an XRPD pattern, obtained with CuKα1-radiation, as shown in FIG. 2 .
4. Crystal modification MeOH-1 of elobixibat, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.2±0.2 and 18.9±0.2.
5. Crystal modification MeOH-1 of elobixibat according to claim 4 , having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.2±0.2 and 18.9±0.2 and one or more of peaks: 10.1±0.2, 14.6±0.2, 18.6±0.2, 19.1±0.2, 22.2±0.2, 24.7±0.2, 12.3±0.2, 13.3±0.2, and 16.1±0.2.
6. Crystal modification MeOH-1 of elobixibat according to claim 4 , having an XRPD pattern, obtained with CuKα1-radiation, as shown in FIG. 8 .
7. Crystal modification 1-PrOH-1 of elobixibat, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 19.0±0.2.
8. Crystal modification 1-PrOH-1 of elobixibat according to claim 7 , having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 19.0±0.2 and one or more of peaks: 10.0±0.2, 14.4±0.2, 18.3±0.2, 18.8±0.2, 20.5±0.2, 10.3±0.2, 13.0±0.2, and 11.0±0.2.
9. Crystal modification 1-PrOH-1 of elobixibat according to claim 7 , having an XRPD pattern, obtained with CuKα1-radiation, as shown in FIG. 9 .
10. Crystal modification 2-PrOH-1 of elobixibat, having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 19.0±0.2.
11. Crystal modification 2-PrOH-1 of elobixibat according to claim 10 , having an XRPD pattern, obtained with CuKα1-radiation, with peaks at °2θ positions 6.1±0.2 and 19.0±0.2 and one or more of peaks: 10.0±0.2, 14.4±0.2, 18.3±0.2, 18.8±0.2, 20.5±0.2, 10.3±0.2, 12.9±0.2, and 11.0±0.2.
12. Crystal modification 2-PrOH-1 of elobixibat according to claim 10 , having an XRPD pattern, obtained with CuKα1-radiation, as shown in FIG. 10 .