Pharmaceutical compositions comprising polymorphic forms alpha, beta, and gamma of rifaximin

Abstract

Crystalline polymorphous forms of rifaximin (INN), referred to as rifaximin α and rifaximin β, and a poorly crystalline form referred to as rifaximin γ, useful in the production of medicaments 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 fixed temperature and for a fixed period of time, followed by a drying under controlled conditions until reaching a precise water content in the end product, are the object of the invention.

1 - 3 . (canceled) 
     
     
         4 . A pharmaceutical composition comprising a polymorph rifaximin preparation and pharmaceutically acceptable carrier, the polymorph rifaximin preparation having X-ray powder diffraction pattern peaks at about:
 7.4°±0.2, 7.9°±0.2, and 6.6°±0.2, or   7.4°±0.2, 8.8°±0.2, and 6.6°±0.2, or   7.4°±0.2, 10.5°±0.2, and 6.6°±0.2, or   7.4°±0.2, 11.1°±0.2, and 6.6°±0.2, or   7.4°±0.2, 6.6°±0.2, and 12.9°±0.2, or   7.4°±0.2, 11.8°±0.2, and 17.6°±0.2, or   7.4°±0.2, 11.8°±0.2, and 19.7°±0.2, or   7.4°±0.2, 11.8°±0.2, and 21.4°±0.2, or   7.4°±0.2, 11.8°±0.2, and 22.1°±0.2, or   7.4°±0.2, 11.1°±0.2, and 12.9°±0.2, or   7.4°±0.2, 11.1°±0.2 and 19.7°±0.2, or   7.4°±0.2, 12.9°±0.2 and 19.7°±0.2, or   11.1°±0.2, 11.8°±0.2, and 19.7°±0.2, or   11.1°±0.2, 19.7°±0.2, and 21.4°±0.2, or   11.1°±0.2, 19.7°±0.2, and 22.1°±0.2, or   11.8°±0.2, 12.9°±0.2, and 19.7°±0.2, or   11.8°±0.2, 19.9°±0.2, and 22.1°±0.2, 2θ; and   a halo peak.   
     
     
         5 . The pharmaceutical composition of  claim 4 , further comprising an excipient. 
     
     
         6 . The pharmaceutical composition of  claim 5 , 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. 
     
     
         7 . The pharmaceutical composition of  claim 5 , 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 gelatin capsules, sugar-coated pills, lozenges, wafer sheets, pellets, and powders in sealed packet. 
     
     
         8 . The medicinal preparation of  claim 5 , wherein the composition comprises one or more of white petrolatum, white wax, lanoline and derivative thereof, stearylic alcohol, propylene glycol, sodium lauryl sulfate, ethers of fatty polyoxyethylene alcohols, esters of fatty polyoxyethylene acids, sorbitan monostearate, glyceryl monostearate, propylene glycol monostearate, polyethylene glycols, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, colloidal aluminum and magnesium silicate and sodium alginate. 
     
     
         9 . The pharmaceutical composition of  claim 4 , comprising rifaximin predominantly in polymorphic form α. 
     
     
         10 . A method for treating gastrointestinal infections, the method comprising administering to a subject in need an effective amount of the pharmaceutical composition of  claim 4 . 
     
     
         11 . A pharmaceutical composition comprising a polymorph rifaximin preparation and pharmaceutically acceptable carrier, the polymorph rifaximin preparation having X-ray powder diffraction pattern peaks at about:
 5.4°±0.2, 6.4°±0.2, and 7.0°±0.2, or   5.4°±0.2, 6.4°±0.2, and 7.8°±0.2; or   5.4°±0.2, 6.4°±0.2, and 9.0°±0.2; or   5.4°±0.2, 6.4°±0.2, and 10.4°±0.2; or   5.4°±0.2, 6.4°±0.2, and 13.1°±0.2, or   5.4°±0.2, 7.0°±0.2, and 14.4°±0.2; or   5.4°±0.2 10.4°±0.2, and 18.3°±0.2; or   5.4°±0.2 10.4°±0.2, and 20.9°±0.2; or   5.4°±0.2 10.4°±0.2, and 17.1°±0.2, or   6.4°±0.2 7.0°±0.2, and 10.4°±0.2; or   6.4°±0.2 7.8°±0.2, and 10.4°±0.2; or   6.4°±0.2 9.0°±0.2, and 10.4°±0.2; or   6.4°±0.2 10.4°±0.2, and 14.4°±0.2; or   10.4°±0.2 13.1°±0.2, and 14.4°±0.2; or   10.4°±0.2 17.1°±0.2, and 17.9°±0.2; or   10.4°±0.2 17.9°±0.2, and 18.3°±0.2; or   10.4°±0.2 17.9°±0.2, and 20.9°±0.2; or   10.4°±0.2 18.3°±0.2, and 20.9°±0.2; or   14.4°±0.2 17.1°±0.2, and 18.3°±0.2; or   17.1°±0.2 18.3°±0.2, and 20.9°±0.2; or   14.4°±0.2 17.1°±0.2, and 20.9°±0.2, 2θ; and   a halo peak.   
     
     
         12 . The pharmaceutical composition of  claim 11 , further comprising an excipient. 
     
     
         13 . The pharmaceutical composition of  claim 12 , 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. 
     
     
         14 . 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 gelatin capsules, sugar-coated pills, lozenges, wafer sheets, pellets, and powders in sealed packet. 
     
     
         15 . The pharmaceutical composition of  claim 12 , wherein the composition comprises one or more of white petrolatum, white wax, lanoline and derivative thereof, stearylic alcohol, propylene glycol, sodium lauryl sulfate, ethers of fatty polyoxyethylene alcohols, esters of fatty polyoxyethylene acids, sorbitan monostearate, glyceryl monostearate, propylene glycol monostearate, polyethylene glycols, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, colloidal aluminum and magnesium silicate and sodium alginate. 
     
     
         16 . The pharmaceutical composition of  claim 11  comprising rifaximin predominately in polymorphic form β. 
     
     
         17 . A method for treating gastrointestinal infections, the method comprising administering to a subject in need an effective amount of the pharmaceutical composition of  claim 12 . 
     
     
         18 . A pharmaceutical composition comprising a polymorph rifaximin preparation and pharmaceutically acceptable carrier, the polymorph rifaximin preparation having X-ray powder diffraction pattern peaks at about:
 5.0°±0.2, 7.1°±0.2, and 8.4°±0.2, 2θ; and   a halo peak.   
     
     
         19 . The pharmaceutical composition of  claim 18 , further comprising an excipient. 
     
     
         20 . The pharmaceutical composition of  claim 19 , 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. 
     
     
         21 . The pharmaceutical composition of  claim 19 , 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 gelatin capsules, sugar-coated pills, lozenges, wafer sheets, pellets, and powders in sealed packet. 
     
     
         22 . The pharmaceutical composition of  claim 19 , wherein the composition comprises one or more of white petrolatum, white wax, lanoline and derivative thereof, stearylic alcohol, propylene glycol, sodium lauryl sulfate, ethers of fatty polyoxyethylene alcohols, esters of fatty polyoxyethylene acids, sorbitan monostearate, glyceryl monostearate, propylene glycol monostearate, polyethylene glycols, methylcellulose, hydroxypropylmethylcellulose, sodium carboxymethylcellulose, colloidal aluminum and magnesium silicate and sodium alginate. 
     
     
         23 . A method for treating gastrointestinal infections in subject, the method comprising administering to a subject in need an effective amount of the pharmaceutical composition of  claim 18 .