Forms of rifaximin and uses thereof

Abstract

Embodiments relate to Rifaximin polymorphic, salt, and hydrate forms, methods of producing polymorphic forms and to their use in medicinal preparations and to therapeutic methods using them.

What is claimed is: 
     
         1 . A form of rifaximin selected from one or more of Form Mu, Form Pi, Form Xi, Form Omicron, Form Xi or a salt, or hydrate form thereof. 
     
     
         2 . The Form Mu of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two or more of about 4.72, about 4.79, about 7.84, about 8.11, about 8.36, about 8.55, about 8.70, about 9.60, and about 12.54. 
     
     
         3 . The Form Mu of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two more of about 4.72, about 4.79, about 6.29, about 6.94, about 7.44, about 7.84, about 8.11, about 8.36, about 8.55, about 8.70, about 8.88, about 9.60, about 10.15, about 10.32, about 10.88, about 11.02, about 11.20, about 12.09, about 12.54, about 12.79, about 12.96, about 13.42, about 13.63, about 13.86, about 14.54, about 14.90, about 15.25, about 15.50, about 16.00, about 16.30, about 16.62, about 16.78, about 16.97, about 17.27, about 17.47, about 17.57, about 17.84, about 18.20, about 18.57, about 18.97, about 19.42, about 19.88, about 20.78, about 21.76, about 22.18, about 22.52, about 22.83, about 23.27, about 23.70, about 24.17, about 24.47, about 24.67, about 25.26, about 25.81, about 26.53, about 26.98, about 27.55, about 28.23, about 28.50, about 28.87, and about 29.15. 
     
     
         4 . The Form Mu of  claim 1 , comprising an X-ray powder diffraction substantially similar to one or more of  FIGS. 1-3 . 
     
     
         5 . The Form Mu of  claim 1 , comprising an X-ray powder diffraction substantially similar to one or more of  FIGS. 1-8  and one or more of Tables 1-9. 
     
     
         6 . The Form Pi of  claim 1 , comprising an X-ray powder diffraction substantially similar to one or more of FIGS.  9  and  12 - 14 . 
     
     
         7 . The Form Pi of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at about 6.91 and about 7.16. 
     
     
         8 . The Form Pi of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at about 7.05 and about 7.29. 
     
     
         9 . The Form Pi of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two or more of about 7.05, about 7.29, and about 9.33. 
     
     
         10 . The Form Pi of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at about 6.91-7.05 and about 7.16-7.29. 
     
     
         11 . The Form Pi of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at about 6.91-7.05, about 7.16-7.29, and about 9.15-9.33. 
     
     
         12 . The Form Omicron of  claim 1 , comprising an X-ray powder diffraction substantially similar to  FIG. 11 . 
     
     
         13 . The Form Omicron of  claim 1 , comprising an X-ray powder diffraction comprising the peaks in  FIG. 11 . 
     
     
         14 . The Form Omicron of  claim 1 , comprising and XRPD substantially similar to one or more of  FIGS. 32 ,  34 , and  37 . 
     
     
         15 . The Form Omicron of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two or more of about 5.87, about 6.99, and about 8.31. 
     
     
         16 . The Form Omicron of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two or more of about 5.87, about 6.99, about 8.31, about 9.13, about 13.27, about 13.69, and about 17.67. 
     
     
         17 . The Form Omicron of  claim 1 , having an X-ray powder diffraction comprising peaks, in terms of 2θ, at two or more of about 5.87, about 6.99, about 7.77, about 8.31, about 8.47, about 9.13, about 9.58, about 9.74, about 10.86, about 12.35, about 13.27, about 13.69, about 14.01, about 14.44, about 14.79, about 15.19, about 15.33, about 15.68, about 15.94, about 16.04, about 16.31, about 16.66, about 17.00, about 17.35, about 17.67, about 18.08, about 19.04, about 19.24, about 19.52, about 19.85, about 20.17, about 20.42, about 20.76, about 21.07, about 21.28, about 21.61, about 21.83, about 22.14, about 22.36, about 22.65, about 22.93, about 23.20, about 23.46, about 23.71, about 24.15, about 24.35, about 24.67, about 25.07, about 25.40, about 25.80, about 26.22, about 26.54, about 26.76, about 27.17, about 27.78, about 28.69, about 28.88, about 29.21, about 29.46, about 23.71, about 24.15, about 24.35, about 24.67, about 25.07, about 25.40, about 25.80, about 26.22, about 26.54, about 26.76, about 27.17, about 27.78, about 28.69, about 28.88, about 29.21, and about 29.46. 
     
     
         18 . A Form of rifaximin according to  claim 1 , wherein the rifaximin Form contains less than 5% by weight impurities. 
     
     
         19 . A Form of rifaximin according to  claim 1 , wherein one or more of the rifaximin forms is at least 50% pure, at least 75% pure, at least 80% pure, at least 90% pure, at least 95% pure, or at least 98% pure. 
     
     
         20 . A Form of rifaximin according to  claim 1 , wherein one or more of the rifaximin forms are formulated as coated or uncoated tablets, hard or soft gelatin capsules, sugar-coated pills, lozenges, wafer sheets, pellets, or powders in sealed packet. 
     
     
         21 . A pharmaceutical composition comprising one or more forms of rifaximin according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         22 . A method of treating, preventing, or alleviating a bowel related disorder, comprising administering to a subject in need thereof and effective amount of one or more forms of rifaximin according to  claim 1 , comprising one or more steps as disclosed herein. 
     
     
         23 . A method of producing one or more of forms of rifaximin according to  claim 1 , comprising one or more steps as disclosed herein. 
     
     
         24 . A method of producing rifaximin Form Eta, comprising:
 dissolving a Form of rifaximin to form a first mixture;   cooling the first mixture to a seeding temperature;   adding a slurry of rifaximin Form Zeta to form a second mixture;   cooling the second mixture to sub-ambient temperature; and   filtering the second mixture to obtain Form Eta, which is optionally washed and dried.   
     
     
         25 . The method of  claim 24 , wherein the Form of rifaximin comprises a solid form. 
     
     
         26 . The method of  claim 24 , wherein the Form of rifaximin is selected from Form Mu, Form Pi, Form Alpha, Form Beta, Form Xi, Form Nu, Form Theta, Form Gamma, Form Omicron, Form Zeta, or a salt, or mixtures thereof. 
     
     
         27 . The method of  claim 24 , wherein the Form of rifaximin is Form Zeta. 
     
     
         28 . The method of  claim 24 , wherein the first mixture comprises ethanol. 
     
     
         29 . The method of  claim 28 , wherein the water content of the first mixture is higher than approximately 3 wt %. 
     
     
         30 . The method of  claim 29 , wherein the water content of the first mixture ranges from about 3 wt % to about 10 wt %.