Polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations

  • US 8,193,196 B2
  • Filed: 02/27/2006
  • Issued: 06/05/2012
  • Est. Priority Date: 03/03/2005
  • Status: Active Grant
First Claim
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1. A process for the production of the rifaximin polymorphic forms δ

  • and ε

    , wherein;

    reacting a molar equivalent of rifamycin ο

    with an excess of 2-amino-4-methylpyridine in a first solvent mixture, comprising water and ethyl alcohol in volumetric ratios between 1;

    1 and 2;

    1, for between 2 and 8 hours at a temperature between 40°

    C. and 60°

    C., to obtain a first reaction mixture;

    treating the first reaction mixture at room temperature with a solution of ascorbic acid in a mixture of water, ethyl alcohol and concentrated aqueous hydrochloric acid to obtain a second reaction mixture;

    adding concentrated aqueous solution of hydrochloric acid to the second reaction mixture to bring the pH to 2.0 thereby obtaining a first suspension;

    filtering the first suspension to obtain a first solid;

    washing the first solid with the first solvent mixture to obtain raw rifaximin;

    dissolving the raw rifaximin in ethyl alcohol at a temperature between 45°

    C. and 65°

    C.;

    forming a precipitate by adding water and lowering the temperature of the mixture to between 50°

    C. and 0°

    C. while stirring for between 4 and 36 hours to obtain a second suspension;

    filtering the second suspension to obtain a second solid;

    washing the second solid with water and drying it under vacuum or under normal pressure, with or without a drying agent, at a temperature between room temperature and 105°

    C., for between 2 and 72 hours,wherein the rifaximin polymorphic form δ

    is free from other polymorphic forms of rifaximin and has x-ray powder diffraction pattern peaks at about 5.7°

    ±

    0.2, 10.8°

    ±

    0.2, 12.1°

    ±

    0.2, and 17.0°

    ±

    0.2 2-θ

    , andwherein the rifaximin polymorphic form ε

    is free from other polymorphic forms of rifaximin and has x-ray powder diffraction pattern peaks at about 8.2°

    ±

    0.2, 12.4°

    ±

    0.2, and 16.3°

    ±

    0.2 2-θ

    .

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