POLYMORPHIC MIXTURE OF RIFAXIMIN AND ITS USE FOR THE PREPARATION OF SOLID FORMULATIONS

• US 20200002357A1
• Filed: 09/12/2019
• Published: 01/02/2020
• Est. Priority Date: 03/31/2014
• Status: Active Grant

• Current Assignee: Curia IP Holdings LLC
• Original Assignee: Euticals SpA
• Inventors: Grisenti, Paride, Argese, Maria, Pengo, Daniele, Grilli, Maria Donata, Fumagalli, Emanuela, Motta, Giuseppe
• Granted Patent: US 10,961,257 B2
• Time in Patent Office: Days
• 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 9/2095 Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing mechanical aspects A61J3/00
• CPC Class Codes: A61K 9/28 Dragees; Coated pills or tablets , e.g. with film or compression coating A61K9/2072 takes precedence, e.g. partially coated tablets A61K9/2072, coated multilayer tablets A61K9/2086, tablets with drug-coated core A61K9/209
• CPC Class Codes: A61K 9/2893 Tablet coating processes mechanical aspects A61J3/06
• CPC Class Codes: A61P 1/12 Antidiarrhoeals
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 498/22 in which the condensed system contains four or more hetero rings

Abstract

A Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3 and a process for its preparation. The polymorphic mixture of Rifaximin is for use as a medicament, in particular in the treatment of traveler'"'"'s diarrhea and hepatic encephalopathy. A pharmaceutical composition comprises the polymorphic mixture of Rifaximin as active ingredient, in particular, a solid formulation, more in particular, a film coated tablet. A polymorphic form of crude wet rifaximin and of purified wet rifaximin their use are used as intermediates in a process for the preparation of Rifaximin polymorphic mixture of α/β form in a relative ratio of 85/15±3.

Claims

1-13. -13. (canceled)

14. A Rifaximin polymorphic mixture of α

/β

form in a relative ratio of 85/15±

3, characterized by an X-Ray spectrum with characteristic 2theta values at;

5.32, 5.78, 6.50, 7.24, 7.82, 8.80, 10.50, 11.02, 11.58, 13.08, 14.42, 17.32, 17.68, 18.58, 19.52, 21.04, 21.60, and 21.92.

15. A pharmaceutical composition comprising the polymorphic mixture of Rifaximin of claim 14, and a vehicle, excipient, or formulative ingredient.

16. The pharmaceutical composition of claim 15, wherein the pharmaceutical composition is a solid pharmaceutical composition.

17. The pharmaceutical composition of claim 16, wherein the pharmaceutical composition is a film coated tablet.

18. The pharmaceutical composition of claim 15, wherein the pharmaceutical composition comprises 550 mg of Rifaximin α

/β

polymorphic mixture of 85/15±

3.

19. The pharmaceutical composition of claim 15, wherein the pharmaceutical composition further comprises excipients.

20. The pharmaceutical composition of claim 19, wherein the excipients comprise cellulose microcrystalline, sodium starch glycolate, glyceryl palmitostearate, hydrated silicon dioxide, and talc.

21. The pharmaceutical composition of claim 20, wherein the pharmaceutical composition further comprises polyvinyl alcohol, polyethylene glycol, titanium dioxide, and red iron oxide.

22. The pharmaceutical composition of claim 21, wherein the pharmaceutical composition has a hardness of 18.49±

1.30 Kp, a thickness of about 5.48±

0.06 mm, a friability of about 0.058%, and a disintegration in purified water at 37°

C. of about 1′

20″

.

23. A tablet, comprising the Rifaximin polymorphic mixture of claim 14 and a film coating.

24. A Rifaximin polymorphic mixture of α

/β

form in a relative ratio of 85/15±

3, characterized by an X-Ray spectrum with characteristic 2Θ

values at 5.32, 5.78, 6.50, 7.24, 7.82, 8.80, 10.50, 11.02, 11.58, 13.08, 14.42, 17.32, 17.68, 18.58, 19.52, 21.04, 21.60, and 21.92, wherein said rifaximin polymorphic mixture is produced by drying wet Rifaximin at atmospheric pressure, at a temperature between 38 and 42°

C. to reach a final water content of 6±

2%.