Forms of rifaximin and uses thereof
View Patent ↗The present invention relates to Rifaximin polymorphic forms, to their use in medicinal preparations and to therapeutic methods using them.
1. A rifaximin polymorph Form ζ, wherein the polymorphic Form ζ exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
4.69, 7.63, 12.52, and 13.87;
4.69, 7.63 and 12.52;
4.69, 7.63 and 13.87;
4.69, 12.52 and 13.87; or
7.63, 12.52 and 13.87.
2. A rifaximin polymorph Form η, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
6.1, 7.3, and 7.5;
6.1, 7.3, and 7.9;
6.1, 7.3 and 8.8;
6.1, 7.3 and 12.7;
6.1, 7.5 and 7.9;
6.1, 7.5 and 8.8;
5.3, 6.1 and 7.3;
5.3, 6.1 and 7.5;
6.1, 7.3, 7.5, 7.9, 8.8 and 12.7;
5.3, 6.1, 7.3, 7.9, 8.8 and 12.7;
5.3, 6.1, 7.3, 7.5, 8.8, and 12.7; or
5.3, 6.1, 7.3, 7.5, 7.9, 8.8 and 12.7.
3. A rifaximin polymorph Form ι, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
5.49, 5.88, 7.86, 9.03, 12.66, and 13.89;
5.49, 5.88, 7.86, 9.03, and 12.66;
5.49, 5.88, 9.03, 12.66 and 13.89;
5.49, 7.86, 9.03, 12.66 and 13.89;
5.49, 5.88, 7.86, 9.03 and 13.89;
5.88, 7.86, 9.03, 12.66 and 13.89;
5.9, 7.9, and 9.0;
12.7, 13.9, and 14.9;
5.9, 7.9, and 12.7;
5.9, 9.0, and 12.7;
5.9, 13.9, and 14.9;
5.9, 7.9, and 14.9;
7.4, 20.0 and 20.9;
9.0, 12.7, and 14.9;
20.0, 20.9 and 23.4;
5.9, 7.9, 9.0, and 14.9;
5.9, 7.9, 9.0, and 12.7;
5.9, 7.4, 7.9 and 9.4;
7.4, 12.7, 13.9 and 23.4;
5.9, 13.9, 14.9, 20.0 and 20.9;
5.9, 7.9, 9.0, 12.7, 13.9, and 14.9;
5.9, 7.4, 7.9, 12.7, 13.9, 14.9, 20.0, 20.9 and 23.4; or
5.9, 7.4, 7.9, 9.0, 9.4, 12.7, 13.9, 14.9, 20.0, 20.9 and 23.4.
4. A rifaximin polymorph Form ι-dry, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
6.04, 7.90, 8.92, 9.49, 12.76, and 14.14;
6.04, 8.92, 9.49, 12.76 and 14.14;
6.04, 7.90, 9.49, 12.76 and 14.14;
6.04, 7.90, 8.92, 9.49 and 14.14;
6.04, 7.90, 8.92, 9.49 and 12.76;
6.04, 7.90, 8.92, 12.76 and 14.14; or
7.90, 8.92, 9.49, 12.76, and 14.14.
5. A rifaximin polymorph Form ι-dry′, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
6.16, 7.92, 8.89, 9.55, 12.80, and 14.25;
6.16, 8.89, 9.55, 12.80 and 14.25;
6.16, 7.92, 9.55, 12.80 and 14.25;
6.16, 7.92, 8.89, 12.80 and 14.25;
6.16, 7.92, 8.89, 9.55 and 14.25;
6.16, 7.92, 8.89, 9.55 and 12.80; or
7.92, 8.89, 9.55, 12.80 and 14.25.
6. A rifaximin polymorph Form B, wherein the polymorph exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2θ (+/−0.20 degree θ) comprising:
5.24, 6.84, 7.74, 8.71, 10.16, and 12.21;
5.24, 7.74, 8.71, 10.16 and 12.21;
5.24, 6.84, 8.71, 10.16 and 12.21;
5.24, 6.84, 7.74, 10.16 and 12.21;
5.24, 6.84, 7.74, 8.71 and 12.21;
5.24, 6.84, 7.74, 8.71 and 10.16;
6.84, 7.74, 8.71, 10.16 and 12.21; or
5.24, 6.84 and 7.74.
7. A pharmaceutical composition comprising the rifaximin polymorph Form ζ of claim 1 , rifaximin polymorph Form η of claim 2 , rifaximin polymorph Form ι of claim 3 , rifaximin polymorph Form ι-dry of claim 4 , rifaximin polymorph Form ι-dry′ of claim 5 , or rifaximin polymorph Form B of claim 6 , or mixtures thereof; and a pharmaceutically acceptable carrier.
8. The rifaximin polymorph Form ζ of claim 1 , containing less than 5% by weight total impurities.
9. The rifaximin polymorph Form η of claim 2 , containing less than 5% by weight total impurities.
10. The rifaximin polymorph Form ι of claim 3 , containing less than 5% by weight total impurities.
11. The rifaximin polymorph Form ι-dry of claim 4 , containing less than 5% by weight total impurities.
12. The rifaximin polymorph Form ι-dry′ of claim 5 , containing less than 5% by weight total impurities.
13. The rifaximin Form B of claim 6 , containing less than 5% by weight total impurities.
14. The rifaximin polymorph Form ζ of claim 1 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
15. The rifaximin polymorph Form η of claim 2 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
16. The rifaximin polymorph Form ζ claim 3 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
17. The rifaximin polymorph Form ι-dry of claim 4 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
18. The rifaximin polymorph Form ι-dry′ of claim 5 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.
19. The rifaximin polymorph Form B, of claim 6 , wherein the compound is at least 50% pure, or at least 75% pure, or at least 80% pure, or at least 90% pure, or at least 95% pure, or at least 98% pure.