EP2705042A1 - Solvate de diméthylformamide rifaximine - Google Patents

Solvate de diméthylformamide rifaximine

Info

Publication number
EP2705042A1
EP2705042A1 EP12721936.8A EP12721936A EP2705042A1 EP 2705042 A1 EP2705042 A1 EP 2705042A1 EP 12721936 A EP12721936 A EP 12721936A EP 2705042 A1 EP2705042 A1 EP 2705042A1
Authority
EP
European Patent Office
Prior art keywords
rifaximin
solvate
hours
process according
dmf solvate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP12721936.8A
Other languages
German (de)
English (en)
Inventor
Jagdev Singh Jaryal
Munish Kapoor
Swargam Sathyanarayana
Rajesh Kumar Thaper
Mohan Prasad
Sudershan Kumar Arora
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Ranbaxy Laboratories Ltd
Original Assignee
Ranbaxy Laboratories Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ranbaxy Laboratories Ltd filed Critical Ranbaxy Laboratories Ltd
Publication of EP2705042A1 publication Critical patent/EP2705042A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/22—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system

Definitions

  • the present invention provides a new polymorphic form of rifaximin designated as DMF solvate and the process for its preparation. It also provides a pharmaceutical composition comprising the same and its use for the treatment of bowel related disorders.
  • Rifaximin is a semi-synthetic, nonsystemic antibiotic which was disclosed in U.S. Patent No. 4,341,785. It is marketed in the United States under the trade name Xifaxan® for the treatment of Travelers' diarrhea and Hepatic Encephalopathy.
  • Rifaximin is designated as (2S,16Z,18E,20S,21S,22R,23R,24R,25S,26S,27S, 28E)5,6,21,23,25- pentahydroxy-27-methoxy-2,4, 11 , 16,20,22,24,26-octamethyl-2,7(epoxypenta-deca- [ 1 , 11 , 13]trienimino)benzofuro[4,5-e]pyrido[ 1 ,2-a]-benzimidazole-l,15(2H)dione,25- acetate and is represented by the structural formula as shown below:
  • Polymorphism is a property exhibited by several compounds and compound complexes, including pharmaceutical compounds, whether by way of crystal forms or solvates. Different crystalline forms or polymorphs of the same pharmaceutical compounds can have different solubility characteristics, and this, in turn, affects bioavailability.
  • the discovery of new polymorphic forms and solvates of a pharmaceutically useful compound provides opportunities to design the performance characteristics of a pharmaceutical product for formulation according to the need. But there is no real way to predict if a compound actually exhibits polymorphism, and if it did what kind of crystal structures it will exhibit. It requires diligent experimentation and analysis.
  • WO 2009/108730 mentions Form ⁇ -l to be an ethanolate/trihydrate of rifaximin but does not provide any example/experimental evidence to support it.
  • the literature does not provide any specific reference related to the solvated forms of rifaximin.
  • the present invention provides ⁇ , ⁇ -dimethylformamide solvate of rifaximin which is free flowing, stable, easily reproducible and suitable to develop formulations.
  • the present invention provides a new polymorphic form of rifaximin designated as
  • DMF solvate and the process for its preparation. It also provides a pharmaceutical composition comprising the same and its use for the treatment of bowel related disorders.
  • the first aspect of the present invention provides DMF solvate of the rifaximin.
  • the second aspect of the present invention provides DMF solvate of the rifaximin characterized by d-spacing (A) values selected from 17.79, 12.31, 11.82, 10.54, 6.74, 5.91, 4.70, 4.22, 4.16, 4.06, 3.98 or 3.53.
  • A d-spacing
  • the third aspect of the present invention provides a process for the preparation of DMF solvate of the rifaximin, the steps comprising of:
  • the fourth aspect of the present invention provides substantially pure DMF solvate of the rifaximin having a purity greater than 99%, when measured by HPLC area percentage.
  • the present invention provides a pharmaceutical composition comprising DMF solvate of the rifaximin with one or more pharmaceutically acceptable carriers and/or excipients.
  • the present invention provides a method for treating, preventing or alleviating bowel related disorders in humans comprising administering to said patient a therapeutically effective amount of DMF solvate of the rifaximin or a pharmaceutical composition comprising the same.
  • Figure 1 X-Ray Diffraction (XRD) pattern of DMF solvate of rifaximin
  • Ambient temperature refers to temperature ranging from about 15°C to about 30°C.
  • substantially pure refers to the DMF solvate of the rifaximin having purity greater than 99%.
  • the first aspect of the present invention provides DMF solvate of the rifaximin.
  • DMF solvate of the rifaximin having characteristics d-spacing (A) values selected from 17.79, 12.31, 1 1.82, 10.54, 6.74, 5.91, 4.70, 4.22, 4.16, 4.06, 3.98 or 3.53.
  • DMF solvate of rifaximin may be characterized by d-spacing (A) values at about 17.79, 14.91, 13.41, 12.31, 11.82, 10.54, 10.13, 8.83, 8.28, 7.86, 7.18, 6.74, 6.42, 6.16, 5.91, 5.71, 5.65, 5.26, 5.10, 4.98, 4.70, 4.50, 4.32, 4.22, 4.16, 4.06, 3.98, 3.83, 3.66, 3.53, 3.39, 3.18, 3.04, 2.95, 2.78 and the corresponding 2-theta values at about 4.97, 5.93, 6.59, 7.18, 7.48, 8.39, 8.73, 10.02, 10.69, 1 1.26, 12.32, 13.14, 13.79, 14.38, 15.00, 15.51, 15.67, 16.85, 17.39, 17.83, 18.90, 19.71, 20.56, 21.04, 21.34, 21.89, 22.32, 23.24, 24.29, 25.22, 26.32, 28.05, 29,39, 30
  • DMF solvate of the rifaximin can also be characterized by (i) XRD having substantially the same pattern as depicted in Figure 1, (ii) DSC having substantially the same pattern as depicted in Figure 2, (iii) TGA having substantially the same pattern as depicted in Figure 3.
  • the DSC shows two characteristic endotherm peaks.
  • the first endothermal peak is in the range from about 45.60°C to about 71.59°C and the second endothermal peak is from about 110.15°C to about 1 11.82°C.
  • the DMF solvate of the rifaximin has water content from about 0% to about 5%, when measured by Karl-Fischer analysis. Preferably, water content can be in between 1% to 3%.
  • the rifaximin, used herein, for the preparation of DMF solvate can be obtained by any of the methods known in literature such as those described in U.S. Patent Nos.
  • the mixture of rifaximin in ⁇ , ⁇ -dimethylformamide solvent may be heated at a temperature of about 45°C to about 60°C followed by optional stirring of the mixture, if required for complete dissolution of the mixture.
  • the reaction mixture obtained may be cooled to ambient temperature, preferably to about 20°C to 30°C, followed by stirring.
  • the stirring of the cooled mixture can be carried out for long hours, for about 30 hours, preferably for about 12 hours to about 24 hours for complete precipitation of the solid.
  • the solid thus formed can be isolated by conventional means known to a person of ordinary skill in the art including, for example, decantation, filtration or centrifugation.
  • the isolated solid, designated as DMF solvate of the rifaximin can be washed with solvent if desired, followed by drying, wherein the drying can be carried out by any drying means known to a person of ordinary skill in the art including, for example, under reduced pressure, vacuum tray drying, air drying and/or combinations thereof.
  • DMF solvate of rifaximin can be dried for a certain period of time, for example, for about 8 hours to 15 hours under reduced pressure at a temperature range of from about 45°C to about 75°C.
  • the drying time can be changed accordingly depending on drying temperature, preferably, drying is done at 45°C to 50°C.
  • the isolated crystalline solid refers to substantially pure DMF solvate of the rifaximin.
  • the DMF solvate of the rifaximin can be formulated into pharmaceutical compositions with excipients or carriers.
  • the various dosage forms which include, but are not limited to, coated or uncoated tablets, hard or soft gelatin capsules, sugar coated pills, lozenges, wafer sheets, pellets, or powders in a sealed packet.
  • the DMF solvate of the rifaximin can also be formulated as a topical composition.
  • the pharmaceutical composition comprises an amount of DMF solvate of rif-iximin effective to treat, prevent or alleviate the desired indication, i.e., bowel related disorders in an animal, such as a human.
  • DMF solvate of the rifaximin as a medicament for treatment, prevention, alleviating bowel related disorders, preferably Travelers' diarrhea and Hepatic encephalopathy.
  • the packaging of the DMF solvate of the rifaximin can be done in self sealing polybags under vacuum after nitrogen flushing, or under nitrogen atmosphere, optionally including a desiccant to improve stability of the material.
  • preferred embodiments are described by way of examples to illustrate the process. However, these are not intended in any way to limit the scope of the claims. Several variants of these examples would be evident to persons ordinarily skilled in the art.
  • the DMF solvate of the rifaximin obtained by the present invention has an HPLC purity greater than 99.1% as measured by area percentage.
  • HPLC high performance liquid chromatography
  • the XRD pattern was recorded using a PANalytical XPert PRO.
  • the TGA and DSC patterns were recorded using TA instruments-Q500 and Mettler DSC 821 e Perkin Elmer, respectively.

Landscapes

  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

Abstract

La présente invention concerne une nouvelle forme polymorphe de rifaximine connue sous le nom de solvate DMF et son procédé de préparation. L'invention concerne également une composition pharmaceutique la comprenant ainsi que son utilisation pour le traitement de troubles intestinaux.
EP12721936.8A 2011-05-02 2012-05-02 Solvate de diméthylformamide rifaximine Withdrawn EP2705042A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN1289DE2011 2011-05-02
PCT/IB2012/052200 WO2012150561A1 (fr) 2011-05-02 2012-05-02 Solvate de diméthylformamide rifaximine

Publications (1)

Publication Number Publication Date
EP2705042A1 true EP2705042A1 (fr) 2014-03-12

Family

ID=46124584

Family Applications (1)

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EP12721936.8A Withdrawn EP2705042A1 (fr) 2011-05-02 2012-05-02 Solvate de diméthylformamide rifaximine

Country Status (4)

Country Link
EP (1) EP2705042A1 (fr)
AU (1) AU2012251385A1 (fr)
CA (1) CA2834829A1 (fr)
WO (1) WO2012150561A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI1698630T1 (sl) 2005-03-03 2015-01-30 Alfa Wassermann S.P.A. Nove polimorfne oblike rifaksimina, postopki za njihovo pripravo in njihova uporaba v medicinskih pripravkih
US9018684B2 (en) 2009-11-23 2015-04-28 California Institute Of Technology Chemical sensing and/or measuring devices and methods
IT1398550B1 (it) 2010-03-05 2013-03-01 Alfa Wassermann Spa Formulazioni comprendenti rifaximina utili per ottenere un effetto prolungato nel tempo
CA2876737A1 (fr) 2012-06-13 2013-12-19 Apotex Pharmachem Inc. Formes polymorphes de rifaximine
ITBO20120368A1 (it) 2012-07-06 2014-01-07 Alfa Wassermann Spa Composizioni comprendenti rifaximina e amminoacidi, cristalli di rifaximina derivanti da tali composizioni e loro uso.
MX2015014307A (es) 2013-04-12 2015-12-08 Alfa Wassermann Spa Administracion de farmacos antiinflamatorios no esteroidales y composiciones, metodos y sistemas relacionados.
ES2621557T3 (es) 2014-03-31 2017-07-04 Euticals S.P.A. Mezcla polimórfica de rifaximina y su uso para la preparación de formulaciones sólidas
PL3546464T3 (pl) 2014-05-12 2020-11-02 Alfasigma S.P.A. Sposób wytwarzania i zastosowanie postaci krystalicznej Tau rifaksyminy solwatowanej z DEGME

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1154655B (it) 1980-05-22 1987-01-21 Alfa Farmaceutici Spa Derivati imidazo-rifamicinici metodi per la loro preparazione e loro uso come sostanza ad azione antibatterica
IT1199374B (it) 1984-05-15 1988-12-30 Alfa Farmaceutici Spa Processo per la preparazione di pirido-imidazo-rifamicine
US7902206B2 (en) 2003-11-07 2011-03-08 Alfa Wassermann, S.P.A. Polymorphic forms α, β and γ of rifaximin
ITMI20032144A1 (it) 2003-11-07 2005-05-08 Alfa Wassermann Spa Forme polimorfe di rifaximina, processi per ottenerle e
SI1698630T1 (sl) 2005-03-03 2015-01-30 Alfa Wassermann S.P.A. Nove polimorfne oblike rifaksimina, postopki za njihovo pripravo in njihova uporaba v medicinskih pripravkih
KR101667534B1 (ko) 2006-09-22 2016-10-19 씨아이피엘에이 엘티디. 리팍시민
US7709634B2 (en) 2007-09-20 2010-05-04 Apotex Pharmachem Inc. Amorphous form of rifaximin and processes for its preparation
BRPI0908864A2 (pt) * 2008-02-25 2018-09-18 Salix Pharmaceuticals Ltd formas da rifaximina e usos das mesmas
US8486956B2 (en) * 2008-02-25 2013-07-16 Salix Pharmaceuticals, Ltd Forms of rifaximin and uses thereof
MX2012013945A (es) * 2010-06-03 2013-05-06 Salix Pharmaceuticals Ltd Nuevas formas de rifaximina y usos de las mismas.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2012150561A1 *

Also Published As

Publication number Publication date
WO2012150561A1 (fr) 2012-11-08
AU2012251385A1 (en) 2013-11-21
CA2834829A1 (fr) 2012-11-08

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