Polymorphic mixture of rifaximin and its use for the preparation of solid formulations

Abstract

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler's diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3.

1 - 13 . (canceled) 
     
     
         14 . A method of treating a subject in need of Rifaximin treatment comprising:
 selecting a subject in need of Rifaximin treatment; and   administering to said subject a pharmaceutical composition comprising a therapeutically effective amount of a Rifaximin polymorphic mixture that comprises α and β Rifaximin polymorphs in a α/β relative ratio of 85/15±3 in an amount sufficient to treat said subject, wherein the Rifaximin polymorphic mixture is characterized by an X-Ray spectrum with characteristic 2theta values at about: 5.32, 5.78, 6.50, 7.24, 7.82, 8.80, 10.50, 11.02, 11.58, 13.08, 14.42, 17.32, 17.68, 18.58, 19.52, 21.04, 21.60, and 21.92.   
     
     
         15 . The method of  claim 14 , wherein the pharmaceutical composition is a solid pharmaceutical composition. 
     
     
         16 . The method of  claim 15 , wherein the pharmaceutical composition is a film coated tablet. 
     
     
         17 . The method of  claim 14 , wherein the pharmaceutical composition comprises 550 mg of the Rifaximin polymorphic mixture. 
     
     
         18 . The method of  claim 14 , wherein the pharmaceutical composition further comprises excipients. 
     
     
         19 . The method of  claim 18 , wherein the excipients comprise one or more of cellulose microcrystalline, sodium starch glycolate, glyceryl palmitostearate, hydrated silicon dioxide, and/or talc. 
     
     
         20 . The method of  claim 19 , wherein the pharmaceutical composition further comprises polyvinyl alcohol, polyethylene glycol, titanium dioxide, and/or red iron oxide. 
     
     
         21 . The method of  claim 20 , wherein the pharmaceutical composition has a hardness of 18.49±1.30 Kp, a thickness of about 5.48±0.06 mm, a friability of about 0.058%, and a disintegration in purified water at 37° C. of about 1′20″. 
     
     
         22 . The method of  claim 14 , wherein the Rifaximin polymorphic mixture is characterized by an X-Ray spectrum with characteristic 2theta and (relative intensity) values at about: 5.32 (11%), 5.78 (19%), 6.50 (27%), 7.24 (45%), 7.82 (61%), 8.80 (100%), 10.50 (59%), 11.02 (35%), 11.58 (32%), 13.08 (20%), 14.42 (26%), 17.32 (48%), 17.68 (93%), 18.58 (79%), 19.52 (61%), 21.04 (52%), 21.60 (30%), and 21.92 (46%). 
     
     
         23 . In a method of treating a subject with Rifaximin, the improvement comprising:
 carrying out said treating with a Rifaximin polymorphic mixture that comprises α and β Rifaximin polymorphs in a α/β relative ratio of 85/15±3, wherein the Rifaximin polymorphic mixture is characterized by an X-Ray spectrum with characteristic 2theta values at about: 5.32, 5.78, 6.50, 7.24, 7.82, 8.80, 10.50, 11.02, 11.58, 13.08, 14.42, 17.32, 17.68, 18.58, 19.52, 21.04, 21.60, and 21.92.   
     
     
         24 . The method of  claim 23 , wherein the Rifaximin is in a pharmaceutical composition. 
     
     
         25 . The method of  claim 24 , wherein the pharmaceutical composition is a film coated tablet. 
     
     
         26 . The method of  claim 23 , wherein the pharmaceutical composition comprises 550 mg of the Rifaximin polymorphic mixture. 
     
     
         27 . The method of  claim 23 , wherein the pharmaceutical composition further comprises excipients. 
     
     
         28 . The method of  claim 27 , wherein the excipients comprise cellulose microcrystalline, sodium starch glycolate, glyceryl palmitostearate, hydrated silicon dioxide, and/or talc. 
     
     
         29 . The method of  claim 28 , wherein the pharmaceutical composition further comprises polyvinyl alcohol, polyethylene glycol, titanium dioxide, and/or red iron oxide. 
     
     
         30 . The method of  claim 29 , wherein the pharmaceutical composition has a hardness of 18.49±1.30 Kp, a thickness of about 5.48±0.06 mm, a friability of about 0.058%, and a disintegration in purified water at 37° C. of about 1′20″. 
     
     
         31 . The method of  claim 23 , wherein the Rifaximin polymorphic mixture is characterized by an X-Ray spectrum with characteristic 2theta and (relative intensity) values at about: 5.32 (11%), 5.78 (19%), 6.50 (27%), 7.24 (45%), 7.82 (61%), 8.80 (100%), 10.50 (59%), 11.02 (35%), 11.58 (32%), 13.08 (20%), 14.42 (26%), 17.32 (48%), 17.68 (93%), 18.58 (79%), 19.52 (61%), 21.04 (52%), 21.60 (30%), and 21.92 (46%).