Processes for the production of polymorphic forms of rifaximin

Abstract

Crystalline polymorphous forms of rifaximin (INN) antibiotic named rifaximin α and rifaximin β, and a poorly crystalline form named rifaximin γ, useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization 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.

1 . A process for the production of rifaximin in polymorphic form α, comprising:
 dissolving rifaximin in an alcoholic solvent at a temperature between approximately 45° C. and approximately 65° C.; 
 precipitating the rifaximin by adding water to the alcoholic solvent to form a suspension and by lowering the temperature of the suspension to between approximately 0° C. and approximately 50° C.; and 
 drying the rifaximin for a period of time between approximately 2 and approximately 72 hours to form rifaximin in polymorphic form α. 
 
     
     
         2 . A process for the production of rifaximin in polymorphic form β, comprising:
 dissolving rifaximin in an alcoholic solvent at a temperature between approximately 45° C. and approximately 65° C.; 
 precipitating the rifaximin by adding water to the alcoholic solvent to form a suspension and by lowering the temperature of the suspension to between approximately 0° C. and approximately 50° C.; and 
 drying the rifaximin for a period of time between approximately 2 and approximately 72 hours to form rifaximin in polymorphic form β. 
 
     
     
         3 . A process for the production of rifaximin in polymorphic form γ, comprising:
 dissolving rifaximin in an alcoholic solvent at a temperature between approximately 45° C. and approximately 65° C.; 
 precipitating the rifaximin by adding water to the alcoholic solvent to form a suspension and by lowering the temperature of the suspension to between approximately 0° C. and approximately 50° C.; and 
 drying the rifaximin for a period of time between approximately 2 and approximately 72 hours to form rifaximin in polymorphic form γ.