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

• US 9,271,968 B2
• Filed: 04/25/2014
• Issued: 03/01/2016
• Est. Priority Date: 03/03/2005
• Status: Active Grant

• Current Assignee: Alfasigma S.p.A.
• Original Assignee: ALFA Wassermann BV (Alfasigma S.p.A.)
• Inventors: Viscomi, Giuseppe Claudio, Campana, Manuela, Confortini, Donatella, Barbanti, Maria, Braga, Dario
• Primary Examiner(s): Kifle, Bruck
• Application Number:
  US14/262,612
• Publication Number:
  US 20150073007A1
• Time in Patent Office: 676 Days
• Field of Search: 514/254.11
• US Class Current: 1/1
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• 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 the rifaximin (INN) antibiotic named rifaximin δ and rifaximin ε useful in the production of medicinal preparations containing rifaximin for oral and topical use and obtained by means of a crystallization process 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. A pharmaceutical composition comprising a therapeutically effective amount of rifaximin together with excipients, wherein the rifaximin has a X-ray powder diffraction pattern peaks at about 5.7°

±

0.2, 6.7°

±

0.2 and 8.0°

±

0.2.

2. The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern further comprises a peak at about 7.1°

±

0.2, 2θ

.

3. The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern further comprises peaks at about 10.4°

±

0.2, 2θ

.

4. The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern further comprises peaks at about 11.3°

±

0.2, 2θ

.

5. The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern further comprises peaks at about 7.1°

±

0.2 and 10.8°

±

0.2, 2θ

.

6. The pharmaceutical composition of claim 1, wherein the X-ray powder diffraction pattern further comprises peaks at about 12.1±

0.2, 2θ

.

7. The pharmaceutical composition according to claim 1 wherein the X-ray powder diffractogram further comprises peaks at 7.1°

±

0.2, 8.7°

±

0.2, and 10.4°

±

0.2, 2θ

.

8. The pharmaceutical composition of claim 1, wherein the rifaximin has an X-ray powder diffraction pattern peaks at about 5.7°

±

0.2, 6.7°

±

0.2, 7.1°

±

0.2, 8.0°

±

0.2, 8.7°

±

0.2, 10.4°

±

0.2, 11.3°

±

0.2, 12.1°

±

0.2, 17.0°

±

0.2, 17.3°

±

0.2, 17.5°

±

0.2, 18.5°

±

0.2, 18.8°

±

0.2, 19.1°

±

0.2, 21.0°

±

0.2 and 21.5°

±

0.2, 2θ

.

9. The pharmaceutical composition of claim 1, wherein the composition has a water content of between 2.5% and 6.0%.

10. The pharmaceutical composition according to claim 1 wherein the excipients are selected from the group consisting of diluting agents, binding agents, lubricating agents, disintegrating agents, coloring agents and flavoring agents.

11. The pharmaceutical composition according to claim 1, wherein the composition is in a solid form selected from granules, tablets capsules, and powders in sealed packets.

15. The pharmaceutical composition of claim 11, wherein the X-ray powder diffraction pattern further comprises peaks at about 17.5 °

±

0.2 and 21.5°

±

0.2, 2θ

.

16. The pharmaceutical composition according to claim 11 wherein the X-ray powder diffraction pattern peaks comprises peaks at about 5.7°

±

0.2, 6.7°

±

0.2, 7.1°

±

0.2, 8.0°

±

0.2, 8.7°

±

0.2, 10.4°

±

0.2, 11.3°

±

0.2, 12.1°

±

0.2, 17.0°

±

0.2, 17.3°

±

0.2, 17.5°

±

0.2, 18.5°

±

0.2, 18.8°

±

0.2, 19.1°

±

0.2, 21.0°

±

0.2 and 21.5°

±

0.2, 2θ

.

12. A pharmaceutical composition comprising a therapeutically effective amount of rifaximin together with excipients wherein the rifaximin has X-ray powder diffraction pattern peaks at about 7.3°

±

0.2, 8.2°

±

0.2 and 10.3°

±

0.2, 2θ

.

13. The pharmaceutical composition of claim 12, wherein the X-ray powder diffraction pattern further comprises peaks at 7.0°

±

0.2 and 11.1 °

±

0.2, 2θ

.

14. The pharmaceutical composition of claim 12, wherein the X-ray powder diffraction pattern further comprises peaks at about 12.4°

±

0.2, 8.7°

±

0.2 and 11.7°

±

0.2,2θ

.

17. The pharmaceutical composition according to claim 12, wherein the excipients are selected from the group consisting of diluting agents, binding agents, lubricating agents, disintegrating agents, coloring agents and flavoring agents.

18. The pharmaceutical composition according to claim 12, wherein the composition is in a solid form, selected from granules, tablets capsules, and powders in sealed packets.