Polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations

Abstract

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.

What is claimed is: 
     
         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 5 has a water content of between 3% and 4.5%. 
     
     
         7 . The rifaximin in polymorphic form δ of  claim 1 , wherein the polymorph 5 has a water content of between 2.5% and 6%. 
     
     
         8 . Rifaximin in polymorphic form ε, wherein the rifaximin polymorphic form c 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.