Polymorphic forms α, β, and γ of rifaximin

• US 7,612,199 B2
• Filed: 06/04/2009
• Issued: 11/03/2009
• Est. Priority Date: 11/07/2003
• Status: Active Grant

• Current Assignee: Alfasigma S.p.A.
• Original Assignee: ALFA Wassermann BV (Alfasigma S.p.A.)
• Inventors: Cannata, Vicenzo, Viscomi, Guiseppe Glaudio, Righi, Paolo, Braga, Dario, Confortini, Donatella, Rosini, Goffredo, Campana, Manuela
• Primary Examiner(s): Kifle; Bruck
• Application Number:
  US12/478,638
• Publication Number:
  US 20090234114A1
• Time in Patent Office: 152 Days
• Field of Search: 540/456
• US Class Current: 540/456
• CPC Class Codes: C07B 2200/13 Crystalline forms, e.g. polymorphs
• CPC Class Codes: C07D 491/22 in which the condensed system contains four or more hetero rings
• CPC Class Codes: C07D 498/22 in which the condensed system contains four or more hetero rings

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.

Claims

1. Rifaximin in polymorphic form α

, wherein the rifaximin has x-ray powder diffraction pattern peaks at about 7.4°

;

19.7°

;

21.0° and

22.1°

2-θ and

wherein the rifaximin has a water content of less than 4.5%.

2. The compound of claim 1, wherein the rifaximin has a water content of between 2.0-3.0%.

3. The compound of claim 1, wherein the rifaximin has a water content of 2.5%.

4. Rifaximin in polymorphic form β

, wherein the rifaximin has x-ray powder diffraction pattern peaks at about 5.4°

;

9.0°

; and

20.9°

2θ and

wherein the rifaximin has a water content of greater than 5%.

5. The compound of claim 4, wherein the rifaximin has a water content of between 5.0-6.0%.

6. Rifaximin in polymorphic form γ

, wherein the rifaximin has x-ray powder diffraction pattern peaks at about 5.0°

, 7.1°

, and 8.4°

2-θ and

wherein the rifaximin has a water content of from between 0% to 2%.

7. The compound of claim 6, wherein the rifaximin has a water content of 1.5%.