POLYMORPHOUS FORMS OF RIFAXIMIN, PROCESSES FOR THEIR PRODUCTION AND USE THEREOF IN THE MEDICINAL PREPARATIONS
Crystalline polymorphous forms of the rifaximin (INN) antibiotic named rifaximin δ and rifaximin ε useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization process 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 . Rifaximin in polymorphic form δ, wherein the rifaximin polymorphic form δ has x-ray powder diffraction pattern peaks at about 5.7°±0.2, 12.1°±0.2, and 17.0°±0.2 2-θ.
2 . The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises a peak at about 11.3°±0.2 2-θ.
3 . The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises peaks at about 7.1°±0.2 and 21.5°±0.2 2-θ.
4 . The rifaximin in polymorphic form δ of claim 1 , wherein the x-ray powder diffraction pattern further comprises peaks at about 6.7°±0.2 and 8.7°±0.2 2-θ.
5 . The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph has x-ray powder diffraction pattern peaks at about 5.7°±0.2, 6.7°±0.2, 7.1°±0.2, 8.0°±0.2, 8.7°±0.2, 10.4°±0.2, 11.3°±0.2, 12.1°±0.2, 17.0°±0.2, 17.3°±0.2, 17.5°±0.2, 18.5°±0.2, 18.8°±0.2, 19.1°±0.2, 21.0°±0.2 and 21.5°±0.2 2-θ.
6 . The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph δ has a water content of between 3% and 4.5%.
7 . The rifaximin in polymorphic form δ of claim 1 , wherein the polymorph δ has a water content of between 2.5% and 6%.
8 . Rifaximin in polymorphic form ε, wherein the rifaximin polymorphic form ε has x-ray powder diffraction pattern peaks at about 8.2°±0.2, 12.4°±0.2, and 16.3°±0.2 2-θ.
9 . A method of treating bacterial activity in the gastrointestinal tract of a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of rifaximin δ, thereby reducing the bacterial activity in the gastrointestinal tract, wherein the rifaximin polymorphic form δ has x-ray powder diffraction pattern peaks at about 5.7°±0.2, 12.1°±0.2, and 17.0°±0.2 2-θ.
10 . The method of claim 9 , wherein the bacterial activity causes infectious diarrhea.
11 . The method of claim 9 , wherein the bacteria are anaerobic bacteria.
12 . The method of claim 9 , wherein the pharmaceutical composition is administered orally.
13 . The method of claim 9 , wherein the bacteria are gastrointestinal bacteria.
14 . A method of treating bacterial activity in the gastrointestinal tract of a subject, comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of rifaximin ε, thereby reducing the bacterial activity in the gastrointestinal tract, wherein the rifaximin polymorphic form ε has x-ray powder diffraction pattern peaks at about 8.2°±0.2, 12.4°±0.2, and 16.3°±0.2 2-θ.
15 . The method of claim 14 , wherein the bacterial activity causes infectious diarrhea.
16 . The method of claim 14 , wherein the bacteria are anaerobic bacteria.
17 . The method of claim 14 , wherein the pharmaceutical composition is administered orally.
18 . The method of claim 14 , wherein the bacteria are gastrointestinal bacteria.