Use of polyols to obtain stable polymorphous forms of rifaxmin

Abstract

Polyols stabilize polymorphous form of rifaximin, in particular the β form. When polyols having at least two hydroxy groups are added to rifaximin powder, polymorph β is stable and remains stable in time independently from the environment humidity. In this invention a method to prepare formulations constituted by pure and stable polymorphous forms able to give a pharmaceutical product is described.

1 .- 15 . (canceled) 
     
     
         16 . A pharmaceutical composition comprising rifaximin and excipients, wherein the rifaximin has an X-ray diffraction spectra characterized by peaks at the values of the diffraction angles at about:
 7.7 °±0.2, 8.9°±0.2, 10.4°±0.2 and 17.7°±0.2, 2 θ; or   8.9°±0.2, 10.4°±0.2, 17.7°±0.2 and 18.2°, ±0.2, 2 θ or   7.7°±0.2, 8.9°±0.2, 10.4°±0.2, 17.7°±0.2 and 18.2°±0.2, 2 θ.   
     
     
         17 . The pharmaceutical composition of  claim 16 , wherein the X-ray diffraction spectra further comprises a peak at a diffraction angle of about 7.4°±0.2, 2θ. 
     
     
         18 . The pharmaceutical composition of  claim 17  wherein the rifaximin comprises polymorphous form α. 
     
     
         19 . The pharmaceutical composition of  claim 16 , wherein the rifaximin has a water content less than 4.5%. 
     
     
         20 . A pharmaceutical composition comprising rifaximin and excipients, wherein the rifaximin has an X-ray diffraction spectra comprises peaks at diffraction angles of about 5.3°±0.2, 6.7°±0.2, 7.7°±0.2, 8.9°±0.2, 10.4°±0.2, and 12.3°±0.2, 2θ. 
     
     
         21 . The pharmaceutical composition of  claim 20 , wherein the X-ray diffraction spectra further comprises a peak at diffraction angle of about 7.4°±0.2, 2θ. 
     
     
         22 . The pharmaceutical composition of  claim 16 , wherein the excipients comprise one or more polyols having general formula H—[O—CH 2 —CH 2 ] n —OH, wherein n is between 2 and 16. 
     
     
         23 . The pharmaceutical composition of  claim 22 , wherein n is between 2 and 14. 
     
     
         24 . The pharmaceutical composition of  claim 23 , wherein the one or more polyols are at a concentration having a range between 5%(w/w) and 50% (w/w). 
     
     
         25 . The pharmaceutical composition of  claim 23  wherein the one or more polyols comprise 1,2,3-propanetriol and/or 1,2-propanediol. 
     
     
         26 . The pharmaceutical composition of  claim 23 , wherein the one or more polyols comprise polyols having two to seven carbon atoms and two to seven hydroxyl groups. 
     
     
         27 . The pharmaceutical composition of  claim 23 , wherein the excipient comprise fructose, dextrose, sucrose, starch, cellulose and/or derivatives thereof, maltodextrin and/or dextrin. 
     
     
         28 . The pharmaceutical composition of  claim 16 , wherein the rifaximin is comprised in form of granules or gastroresistant granules. 
     
     
         29 . The pharmaceutical composition according to  claim 28  wherein the gastroresistant granules comprise diluents in an amount from 1% (w/w) to 20% (w/w). 
     
     
         30 . The pharmaceutical composition of  claim 29 , wherein the composition is in solid form in thermo-welded bags or in tablets form. 
     
     
         31 . The pharmaceutical composition of  claim 30 , wherein the composition is in form of a tablet and wherein the rifaximin granules comprise extra granule excipients selected from the group consisting of diluents, ligands, lubricants, disintegrants, dyes, flavors and sweeteners. 
     
     
         32 . The pharmaceutical composition of  claim 30 , wherein the tablet is coated with coating excipients. 
     
     
         33 . The pharmaceutical composition of  claim 32 , wherein the coating excipients comprise a plasticizer selected from 1,2,3-propanetriol and 1,2-propanediol.