Polymorphic forms α, β and γ of rifaximin
View Patent ↗Crystalline polymorphous forms of rifaximin (INN) antibiotic named rifaximin α and rifaximin β, and a poorly crystalline form named rifaximin γ, useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization carried out by hot-dissolving the raw rifaximin in ethyl alcohol and by causing the crystallization of the product by addition of water at a determinate temperature and for a determinate period of time, followed by a drying carried out under controlled conditions until reaching a settled water content in the end product, are the object of the invention.
1. A polymorph rifaximin preparation comprising a polymorph rifaximin in form α, β and/or γ wherein the polymorph rifaximin in form a has x-ray powder diffraction pattern peaks at about:
7.4°, 7.9°, and 11.8°; or
7.4°, 8.8°, and 11.8°; or
7.4°, 10.5°, and 11.8°; or
7.4°, 11.1°, and 11.8°; or
7.4°, 11.8°, and 12.9°; or
7.4°, 11.8°, and 17.6°; or
7.4°, 11.8°, and 19.7°; or
7.4°, 11.8°, and 21.4°; or
7.4°, 11.8°, and 22.1°, or
7.4°,11.1°, and 12.9°; or
7.4°, 11.1°, and 19.7°; or
7.4°, 12.9°, and 19.7°; or
11.1°, 11.8°, and 19.7°; or
11.1°, 19.7°, and 21.4°; or
11.1°, 19.7°, and 22.1°, or
11.8°, 12.9°, and 19.7°; or
11.8°, 19.9°, and 22.1°, 2θ.
the polymorph rifaximin in form β has x-ray powder diffraction pattern peaks at about:
5.4°, 6.4°, and 7.0°, or
5.4°, 6.4°, and 7.8°; or
5.4°, 6.4°, and 9.0°; or
5.4°, 6.4°, and 10.4°; or
5.4°, 6.4°, and 13.1°, or
5.4°, 7.0°, and 14.4°; or
5.4° 10.4°, and 18.3°; or
5.4° 10.4°, and 20.9°; or
5.4° 10.4°, and 17.1°, or
6.4° 7.0°, and 10.4°; or
6.4° 7.8°, and 10.4°; or
6.4° 9.0°, and 10.4°; or
6.4° 10.4°, and 14.4°; or
10.4° 13.1°, and 14.4°; or
10.4° 17.1°, and 17.9°; or
10.4° 17.9°, and 18.3°; or
10.4° 17.9°, and 20.9°; or
10.4° 18.3°, and 20.9°; or
14.4° 17.1°, and 18.3°; or
17.1° 18.3°, and 20.9°; or
14.4° 17.1°, and 20.9°, 2θ;
and the polymorph rifaximin in form γ as x-ray powder diffraction pattern peaks at about:
5.0°, 7.1°, and 8.4° 2θ.
2. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form α and β.
3. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form α and γ.
4. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form β and γ.
5. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form a free from other polymorphic forms of rifaximin.
6. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form β free from other polymorphic forms of rifaximin.
7. The polymorph rifaximin preparation of claim 1 , wherein the preparation comprises rifaximin polymorph in form γ free from other polymorphic forms of rifaximin.
8. A pharmaceutical composition comprising the rifaximin preparation of claim 1 and a pharmaceutically acceptable excipient or carrier.
9. The pharmaceutical composition of claim 8 , wherein the rifaximin preparation comprises rifaximin polymorph in form a free from other polymorphic forms of rifaximin.
10. The pharmaceutical composition of claim 8 , wherein the rifaximin preparation comprises rifaximin polymorph in form β free from other polymorphic forms of rifaximin.
11. The pharmaceutical composition of claim 8 , wherein the rifaximin preparation comprises rifaximin polymorph in form γ free from other polymorphic forms of rifaximin.
12. The pharmaceutical composition of claim 8 , wherein the excipient is selected from the group consisting of a diluting agent, a binding agent, a lubricating agent, a disintegrating agent, a coloring agent, a flavoring agent, and a sweetening agent.
13. The pharmaceutical composition of claim 12 , wherein the composition is for oral use and is in a form selected from the group consisting of coated or uncoated tablets, hard or soft gelatine capsules, sugar-coated pills, lozenges, wafer sheets, pellets, and powders in sealed packet.
14. The pharmaceutical composition of claim 13 , wherein the composition comprises colloidal silicon dioxide.
15. The pharmaceutical composition of claim 14 , wherein the composition comprises cellulose.
16. The pharmaceutical composition of claim 14 , wherein the composition comprises microcrystalline cellulose.
17. The pharmaceutical composition of claim 14 , wherein the composition comprises sodium starch glycolate.
18. The pharmaceutical composition of claim 12 wherein the composition is for topical use and is in a form selected from the group consisting of ointments, pomades, creams, gels and lotions.
19. The pharmaceutical composition of claim 10 , wherein the composition comprises hydroxypropyl methylcellulose.
20. The pharmaceutical composition of claim 10 , wherein the composition comprises colloidal silicon dioxide.
21. The pharmaceutical composition of claim 10 , wherein the composition comprises propylene glycol.