WO2016063289A2 - Pharmaceutical tablet compositions comprising rifaximin - Google Patents
Pharmaceutical tablet compositions comprising rifaximin Download PDFInfo
- Publication number
- WO2016063289A2 WO2016063289A2 PCT/IN2015/000312 IN2015000312W WO2016063289A2 WO 2016063289 A2 WO2016063289 A2 WO 2016063289A2 IN 2015000312 W IN2015000312 W IN 2015000312W WO 2016063289 A2 WO2016063289 A2 WO 2016063289A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- rifaximin
- composition
- prepared
- powder diffraction
- ray powder
- Prior art date
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- This invention relates to pharmaceutical tablet compositions comprising Rifaximin and novel polymorph thereof. More particularly, the invention relates to pharmaceutical tablet compositions comprising novel polymorph of Rifaximin.
- [1,1 1, 13]trienimino)benzofuro[4,5-e]pyrido[ 1 ,2-a]-benzimidazole- 1 , 15(2H)-dione, 25- acetate ⁇ represented by formula I, is a semisynthetic rifamycin-based non-systemic antibiotic, disclosed and claimed in IT 1 154655. It is marketed in the US as XifaxanTM by Salix Pharmaceuticals.
- Rifaximin is useful for the treatment of travellers' diarrhoea in adults and in children 12- years or more of age caused by E. coli bacteria. Rifaximin has also been evaluated for the treatment of irritable bowel syndrome, diverticular disease, hepatic encephalopathy, pyogenic skin infections, and as an antibacterial prophylactic prior to colon surgery.
- Rifaximin is a pyrido-imidazo derivative of 4-deoxy-4'- methylpyrido[r,2': l,2]imidazo[5,4-c]rifamycin SV (Rifamycin SV). Unlike other Rifamycin SV derivatives, rifaximin exerts broad spectrum activity and has a specific mode of action which results in low gastrointestinal absorption.
- GB 2079270 discloses imidazo-rifamycin derivatives having antibacterial activity, prepared from 3-halorifamycin S.
- U.S. Pat. No. 4,341 ,785 and EP 0161534 describe the processes for preparation of pyrido-imidazo rifamycin starting from rifamycin O.
- solvent systems comprising methylene chloride, chloroform, methanol, ethanol, isopropanol and water as an anti-solvent without disclosing the polymorphic form of the obtained Rifaximin.
- Rifaximin exhibits variety of polymorphism when subjected to differential conditions. It is very well established that the polymorphism in rifaximin is not only dependent on solvent, but also depends on other conditions such as moisture content, time and temperature at which both the crystallization and the drying are carried out.
- EP1698630 reported two more polymorphic forms 6- and ⁇ -forms which are crystalline and there is a significant degree of overlap with the other reported forms.
- U.S. Pat. No. 7,709,634 reported an amorphous form of rifaximin having two PXRD peaks at 2 ⁇ values 7.2° and 15.0°.
- US8633234 describes another amorphous form and its preparation.
- US8569326 and US 8067429 describes Rifaximin polymorph Form ⁇ (Zeta), Rifaximin polymorph Form ⁇ (Eta); Rifaximin polymorph Form I (Iota); Rifaximin mesylate form; Pharmaceutical compositions comprising the above forms in association with pharmaceutical excipients.
- US8513275 describes polymorph Form kappa, a Rifaximin polymorph Form theta, a Rifaximi piperazine cocrystal 1 or a Rifaximi piperazine cocrystal 2.
- US'275 further reports process for producing the polymorphic forms and pharmaceutical compositions comprising the polymorphic forms.
- US8227482 reports Rifaximin polymorph Form Mu or a salt, or hydrate form thereof; polymorph Form Pi, or a salt, or hydrate form thereof; polymorph Form Omicron, or a salt, or hydrate form thereof.
- US'482 further discloses a method of producing Rifaximin Form Eta and a method of treating a bowel related disorder using the above forms.
- US2014/001 1828 discloses another amorphous form of Rifaximin that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2 ⁇ (+/-0.20 degree ⁇ ) at 7.3 (approximate halo maximum), 11.3-17.8 (amorphous halo range), and 15.8 (approximate halo maximum) degrees 2- ⁇ .
- Rifaximin exhibits innumerable polymorphic forms under differential conditions that include solvent, moisture, temperature, time and drying conditions. It is also evident that Rifaximin exhibits polyamorphism as the molecule takes on several different amorphous modifications as reported in the literature.
- Rifaximin is poorly water soluble and minimally absorbed drug. Formulation scientists always look for suitable polymorphic form which is more stable in formulation and bioavailable. Since Rifaximin is sensitive to external conditions and thus exhibits innumerable polymorphic forms under differential conditions, the bioavailability of the same also varies with polymorphic modification.
- compositions comprising Rifaximin that is consistently stable during its shelf-life so as to minimize the fluctuation in bioavailability of the drug upon administration.
- the object of the present invention is to provide Rifaximin compositions, wherein the polymorphic form is consistently stable during its shelf-life so as to minimize the fluctuation in bioavailability of the drug upon administration.
- the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2 ⁇ , at least two or more of about 8.80; about 9.38; about 9.44; about 14.85; about 15.14; about 15.16; about 15.66; about 15.76; about 15.93; about 16.06; about 20.55; about 21.21 ; about 21.
- composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2 ⁇ 7.2°.
- novel polymorphic form characterized as above remains stable in the formulation during its shelf-life.
- the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2 ⁇ , at least two or more of about 9.38; about 9.44; about 15.16; about 15.66; about 15.93; about 21. 94; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.67; about 34.35; about 34.45 and about 34.58 ⁇ 0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2 ⁇ 7.2°.
- the novel polymorphic form characterized as above remains stable in the formulation during its shelf-life.
- compositions provided according to the invention are prepared by the methods known in the art viz., dry granulation and wet granulation.
- the invention provides dissolution profile of the compositions according to the invention that matches with the profile of marketed drug.
- Fig 1 depicts the XRD of the formulation 1 containing Rifaximin 200mg (after 3 months) prepared by wet granulation
- Fig 2 depicts the XRD of the formulation 3 containing Rifaximin 550mg (after 3months) prepared by wet granulation
- Fig 3 depicts the XRD of the formulation 4 containing Rifaximin 550mg (after 3months) prepared by wet granulation
- any of the words “including,” “includes,” “comprising,” and “comprises” mean “including without limitation” and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it.
- Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
- the term "about” when used with regard to x-ray powder diffraction pattern peak positions that invariably denotes to the inherent variability of the peaks of Rifaximin in the composition depending on various factors, for example, the process used to produce such formulation such as wet and dry granulation methods, compression forces, the age of the amorphous Rifaximin that has been used in the composition and the calibration of the equipment used.
- the variability of the instrument in measuring the peaks may be considered about ⁇ 0.2 degrees 2- ⁇ .
- the variability as disclosed herein is in consistent with the USP definition for peak position error. Therefore, a skilled person in the pertinent art would understand as such the use of "about” in the context of the disclosure and appreciate the same.
- the invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the formulation is characterized by X-ray powder diffraction having peaks, in terms of 2 ⁇ , at least two or more of about 8.80; about 9.38; about 9.44; about 14.85; about 15.16; about 15.66; about 15.93; about 16.06; about 20.55; about 21.21 ; about 21.
- composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2 ⁇ 7.2°,
- the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2 ⁇ , at least two or more of about 9.33; about 9.44; about 15.16; about 15.66; about 15.93; about 21. 94; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.67; about 34.35; about 34.45 and about 34.58 ⁇ 0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2 ⁇ 7.2°.
- the novel polymorphic form characterized as above remains stable in the formulation during its shelf-life.
- the original amorphous form incorporated into the formulation according to the invention is converted into another polymorphic form, which remains stable in the formulation during its shelf-life, as per the XRD data provided.
- the tablet compositions according to the invention are subjected to accelerated degradation studies (40°C/75% RH) before subjecting to X-ray powder diffraction.
- the compositions provided according to the invention is prepared by the methods known in the art viz., dry granulation and wet granulation.
- the invention provides dissolution profile of the compositions according to the invention that matches with the profile of marketed drug.
- step (a) Granulating the mixture of step (a) with the solution of step (b) in RMG; Drying at 60 P C in rapid drier & Sizing through 20mesh;
- step (c) Passing Extragranular material like sodium starch glycolate, colloidal silicon dioxide , Purified talc through # 40mesh and blending with step (c); and e) Lubricating the blend with Glycerol palmito sterate (40mesh) and compressed with tablet presser.
- step (b) Blending the mixture of step (a) with Colloidal silicon dioxide and Glycerol palmito sterate passed through 40mesh;
- step (c) lubricating the blend of step (c) with Glycerol palmito sterate, Purified Talc through # 40mesh followed by compressed with tablet presser.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Abstract
Disclosed herein is pharmaceutical tablet composition comprising Rifaximin and process for preparation thereof.
Description
"PHARMACEUTICAL TABLET COMPOSITIONS COMPRISING RIFAXIMIN
Technical filed:
This invention relates to pharmaceutical tablet compositions comprising Rifaximin and novel polymorph thereof. More particularly, the invention relates to pharmaceutical tablet compositions comprising novel polymorph of Rifaximin.
Background and prior art:
Rifaximin, chemically known as
{(2S,16Z,18E,20S,21 S,22R,23R,24R,25S,26S,27S,28E)-5,6,21,23,25-pentahydroxy-27- methoxy-2,4, 1 1,16,20,22,24,26-octamethyl-2,7-(epoxypentadeca-
[1,1 1, 13]trienimino)benzofuro[4,5-e]pyrido[ 1 ,2-a]-benzimidazole- 1 , 15(2H)-dione, 25- acetate} represented by formula I, is a semisynthetic rifamycin-based non-systemic antibiotic, disclosed and claimed in IT 1 154655. It is marketed in the US as Xifaxan™ by Salix Pharmaceuticals.
Rifaximin is useful for the treatment of travellers' diarrhoea in adults and in children 12- years or more of age caused by E. coli bacteria. Rifaximin has also been evaluated for the treatment of irritable bowel syndrome, diverticular disease, hepatic encephalopathy, pyogenic skin infections, and as an antibacterial prophylactic prior to colon surgery.
Structurally Rifaximin is a pyrido-imidazo derivative of 4-deoxy-4'- methylpyrido[r,2': l,2]imidazo[5,4-c]rifamycin SV (Rifamycin SV). Unlike other Rifamycin SV derivatives, rifaximin exerts broad spectrum activity and has a specific mode of action which results in low gastrointestinal absorption.
GB 2079270 discloses imidazo-rifamycin derivatives having antibacterial activity, prepared from 3-halorifamycin S. U.S. Pat. No. 4,341 ,785 and EP 0161534 describe the processes for preparation of pyrido-imidazo rifamycin starting from rifamycin O. These patents describe a method for the purification of rifaximin using solvent systems comprising methylene chloride, chloroform, methanol, ethanol, isopropanol and water as an anti-solvent without disclosing the polymorphic form of the obtained Rifaximin.
Rifaximin exhibits variety of polymorphism when subjected to differential conditions. It is very well established that the polymorphism in rifaximin is not only dependent on solvent, but also depends on other conditions such as moisture content, time and temperature at which both the crystallization and the drying are carried out.
Consequently, there is ample literature available on various crystalline polymorphic forms and amorphous forms of Rifaximin. All these polymorphous forms of rifaximin have been characterized using powder X-ray diffraction.
U.S. Patents. Nos. 7,045,620; US7612199; US7902206; US7906542; US8158644; US8158781 and US 8404704 describe three polymorphic forms of rifaximin named as α-, β-, and γ-form and pharmaceutical compositions comprising the same. These forms are characterised by the different water contents and different 2Θ values in powder X-ray diffractogram (PXRD) analysis. According to these patents, the formation of the α, β and γ forms depends on the presence of water within the crystallization solvent, on the temperature at which the product is crystallized and on the amount of water present in the product at the end of the drying phase.
EP1698630 reported two more polymorphic forms 6- and ε-forms which are crystalline and there is a significant degree of overlap with the other reported forms. U.S. Pat. No. 7,709,634 reported an amorphous form of rifaximin having two PXRD peaks at 2Θ values 7.2° and 15.0°. US8633234 describes another amorphous form and its preparation.
US 8,759,513 reports yet another amorphous form with a sharp peak at angle 2Θ =7.2°. US8569326 and US 8067429 describes Rifaximin polymorph Form ζ (Zeta), Rifaximin polymorph Form η (Eta); Rifaximin polymorph Form I (Iota); Rifaximin mesylate form; Pharmaceutical compositions comprising the above forms in association with pharmaceutical excipients.
US8513275 describes polymorph Form kappa, a Rifaximin polymorph Form theta, a Rifaximi piperazine cocrystal 1 or a Rifaximi piperazine cocrystal 2. US'275 further reports process for producing the polymorphic forms and pharmaceutical compositions comprising the polymorphic forms.
US8227482 reports Rifaximin polymorph Form Mu or a salt, or hydrate form thereof; polymorph Form Pi, or a salt, or hydrate form thereof; polymorph Form Omicron, or a salt, or hydrate form thereof. US'482 further discloses a method of producing Rifaximin Form Eta and a method of treating a bowel related disorder using the above forms.
US2014/001 1828 discloses another amorphous form of Rifaximin that exhibits an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2Θ (+/-0.20 degree Θ) at 7.3 (approximate halo maximum), 11.3-17.8 (amorphous halo range), and 15.8 (approximate halo maximum) degrees 2-Θ.
In the light of the foregoing, it is evident that Rifaximin exhibits innumerable polymorphic forms under differential conditions that include solvent, moisture, temperature, time and drying conditions. It is also evident that Rifaximin exhibits polyamorphism as the molecule takes on several different amorphous modifications as reported in the literature.
Rifaximin is poorly water soluble and minimally absorbed drug. Formulation scientists always look for suitable polymorphic form which is more stable in formulation and bioavailable. Since Rifaximin is sensitive to external conditions and thus exhibits innumerable polymorphic forms under differential conditions, the bioavailability of the same also varies with polymorphic modification.
In the light of above, there remains a need in the art to provide compositions comprising Rifaximin that is consistently stable during its shelf-life so as to minimize the fluctuation in bioavailability of the drug upon administration.
Accordingly, the object of the present invention is to provide Rifaximin compositions, wherein the polymorphic form is consistently stable during its shelf-life so as to minimize the fluctuation in bioavailability of the drug upon administration.
Summary of the invention:
In line with the above objective, the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the
composition is characterized by X-ray powder diffraction having peaks, in terms of 2Θ, at least two or more of about 8.80; about 9.38; about 9.44; about 14.85; about 15.14; about 15.16; about 15.66; about 15.76; about 15.93; about 16.06; about 20.55; about 21.21 ; about 21. 94; about 23.41 ; about 24.48; about 25.18; about 25.22; about 25.33; about 25.25; about 28.55; about 28.59; about 28.60; about 28.67; about 31.49; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2Θ 7.2°. The novel polymorphic form characterized as above remains stable in the formulation during its shelf-life.
According to a preferred aspect, the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2Θ, at least two or more of about 9.38; about 9.44; about 15.16; about 15.66; about 15.93; about 21. 94; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.67; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2Θ 7.2°. The novel polymorphic form characterized as above remains stable in the formulation during its shelf-life. According to a preferred aspect, the invention provides compositions comprising Rifaximin, prepared by using amorphous form characterized by XRD having a sharp peak at angle 2Θ =1.2°, as reported in US 8,759,513.
The compositions provided according to the invention are prepared by the methods known in the art viz., dry granulation and wet granulation.
In another aspect, the invention provides dissolution profile of the compositions according to the invention that matches with the profile of marketed drug.
Description of drawings:
Fig 1 depicts the XRD of the formulation 1 containing Rifaximin 200mg (after 3 months) prepared by wet granulation
Fig 2 depicts the XRD of the formulation 3 containing Rifaximin 550mg (after 3months) prepared by wet granulation
Fig 3 depicts the XRD of the formulation 4 containing Rifaximin 550mg (after 3months) prepared by wet granulation
Detailed description:
The invention will now be described in detail in connection with certain preferred and optional embodiments, so that various aspects thereof may be more fully understood and appreciated. As used herein, the following terms and phrases shall have the meaning set forth below.
Unless specified otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. To describe the invention, certain terms are defined herein specifically as follows.
Unless stated to the contrary, any of the words "including," "includes," "comprising," and "comprises" mean "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth in the appended claims.
As referred herein below throughout the specification, the term "about" when used with regard to x-ray powder diffraction pattern peak positions that invariably denotes to the inherent variability of the peaks of Rifaximin in the composition depending on various factors, for example, the process used to produce such formulation such as wet and dry granulation methods, compression forces, the age of the amorphous Rifaximin that has been used in the composition and the calibration of the equipment used. In the current context, the variability of the instrument in measuring the peaks may be considered about
±0.2 degrees 2-Θ. The variability as disclosed herein is in consistent with the USP definition for peak position error. Therefore, a skilled person in the pertinent art would understand as such the use of "about" in the context of the disclosure and appreciate the same.
Accordingly, the invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the formulation is characterized by X-ray powder diffraction having peaks, in terms of 2Θ, at least two or more of about 8.80; about 9.38; about 9.44; about 14.85; about 15.16; about 15.66; about 15.93; about 16.06; about 20.55; about 21.21 ; about 21. 94; about 23.41 ; about 24.48; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.60; about 28.67; about 31.59; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2Θ 7.2°,
According to a preferred aspect, the present invention provides pharmaceutical tablet compositions comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2Θ, at least two or more of about 9.33; about 9.44; about 15.16; about 15.66; about 15.93; about 21. 94; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.67; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 2Θ 7.2°. The novel polymorphic form characterized as above remains stable in the formulation during its shelf-life.
According to a preferred embodiment, the invention provides pharmaceutical tablet compositions comprising Rifaximin, prepared by using Rifaximin amorphous form characterized by XRD having a sharp peak at angle 20 =7.2°, reported in US 8,759,513. The original amorphous form incorporated into the formulation according to the invention is converted into another polymorphic form, which remains stable in the formulation during its shelf-life, as per the XRD data provided. The tablet compositions according to the invention are subjected to accelerated degradation studies (40°C/75% RH) before subjecting to X-ray powder diffraction.
The compositions provided according to the invention is prepared by the methods known in the art viz., dry granulation and wet granulation.
In another aspect, the invention provides dissolution profile of the compositions according to the invention that matches with the profile of marketed drug.
The following examples, which include preferred embodiments, will serve to illustrate the practice of this invention, it being understood that the particulars shown are by way of example and for purpose of illustrative discussion of preferred embodiments of the invention.
Examples:
Example 1
Approach Wet granulation Wet
granulation
Procedure for preparation of formulation 1
a) Dispensing and sifting Rifaximin, Avicel 101 , sodium starch glycolate through #40 sieve followed by dry mixing for 15mins;
b) Separately dissolving HPMC and Disodium edetate in hot water and added Disodium edetate solution to HPMC solution;
c) Granulating the mixture of step (a) with the solution of step (b) in RMG; Drying at 60PC in rapid drier & Sizing through 20mesh;
d) Passing Extragranular material like sodium starch glycolate, colloidal silicon dioxide , Purified talc through # 40mesh and blending with step (c); and e) Lubricating the blend with Glycerol palmito sterate (40mesh) and compressed with tablet presser.
Example 2
Rifaximin 200 mg tablet prepared by dry granulation
tablet)
Approach Dry granulation
Procedure:
a) Dispensing and sifting Rifaximin, Avicel 102, Disodium edeate, sodium starch glycolate through #40 sieve and mixing thoroughly;
b) Blending the mixture of step (a) with Colloidal silicon dioxide and Glycerol palmito sterate passed through 40mesh;
c) dry Granulating to prepare Sluggs with 16mm faced followed by deslugging using Milling by 2.5mm screen & Sizing the granules through # 18mesh; and
d) lubricating the blend of step (c) with Glycerol palmito sterate, Purified Talc through # 40mesh followed by compressed with tablet presser.
Example 3
Rifaximin 550 mg tablet prepared by wet granulation
Total tablets weight (Coated 1045.5mg tablet)
Example 4
Rifaximin 550 mg tablet prepared by wet granulation
Comparative dissolution profile of the instant formulations vis-a-vis marketed formulation (Xifaxan)
Media: pH 6.8 Phosphate buffer + 0.8% SLS
Instant
Time(min)
Xifaxan Formulation
0 0 0
5 54.7 47.2
10 65.3 77.9
15 72.7 86.2
30 84.1 97.2
45 91.3 98.8
60 93.3 101.0
90 96.2 102.3
120 97.4 103.1
Claims
1. A stable pharmaceutical tablet composition comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 2Θ, at least two or more of about 8.80; about 9.38; about 9.44; about 14.85; about 15.16; about 15.66; about 15.93; about 16.06; about 20.55; about 21.21 ; about 21. 94; about 23.41 ; about 24.48; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.60; about 28.67; about 31.59; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 20 7.2°.
2. A stable pharmaceutical tablet composition comprising Rifaximin, wherein, the Rifaximin polymorphic form in the composition is characterized by X-ray powder diffraction having peaks, in terms of 20, at least two or more of about 9.33; about 9.44; about 15.16; about 15.66; about 15.93; about 21. 94; about 25.18; about 25.22; about 25.25; about 25.33; about 28.55; about 28.59; about 28.67; about 34.35; about 34.45 and about 34.58 ±0.2 and wherein, the composition is prepared by using amorphous Rifaximin characterized by X-ray powder diffraction comprising a sharp peak at angle 20 7.2°.
3. The stable tablet composition according to claims 1 or 2, wherein the composition is prepared by a method selected from wet granulation and dry granulation.
4. The stable tablet composition according to claims 1 or 2, wherein the Rifaximin in the composition is provided in strength selected from 200mg or 550mg.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN3379MU2014 | 2014-10-22 | ||
| IN3379/MUM/2014 | 2014-10-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2016063289A2 true WO2016063289A2 (en) | 2016-04-28 |
| WO2016063289A3 WO2016063289A3 (en) | 2016-07-14 |
Family
ID=55761708
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/IN2015/000312 WO2016063289A2 (en) | 2014-10-22 | 2015-08-04 | Pharmaceutical tablet compositions comprising rifaximin |
Country Status (1)
| Country | Link |
|---|---|
| WO (1) | WO2016063289A2 (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9938298B2 (en) | 2014-05-12 | 2018-04-10 | Alfa Wassermann S.P.A. | Solvated crystal form of rifaximin, production, compositions and uses thereof |
| KR20190062458A (en) * | 2016-09-30 | 2019-06-05 | 샐릭스 파마슈티컬스 인코포레이티드 | Solid dispersion form of rifaximin |
| WO2020128583A1 (en) * | 2018-12-19 | 2020-06-25 | Friulchem S.P.A. | Process for the manufacture of a tablet of rifaximin and tablet of rifaximin |
| US10703763B2 (en) | 2005-03-03 | 2020-07-07 | Alfasigma S.P.A. | Polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR101667534B1 (en) * | 2006-09-22 | 2016-10-19 | 씨아이피엘에이 엘티디. | Rifaximin |
| IT1398550B1 (en) * | 2010-03-05 | 2013-03-01 | Alfa Wassermann Spa | RIFAXIMINA COMPREHENSIVE FORMULATIONS USEFUL TO OBTAIN A PROLONGED EFFECT IN TIME |
| WO2012035544A2 (en) * | 2010-09-13 | 2012-03-22 | Sequent Scientific Ltd. | A novel polymorphic form of rifaximin and process for its preparation |
| IT1403847B1 (en) * | 2010-09-22 | 2013-11-08 | Alfa Wassermann Spa | PHARMACEUTICAL COMPOSITIONS INCLUDING RIFAXIMINA AND THEIR USE. |
-
2015
- 2015-08-04 WO PCT/IN2015/000312 patent/WO2016063289A2/en active Application Filing
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10703763B2 (en) | 2005-03-03 | 2020-07-07 | Alfasigma S.P.A. | Polymorphous forms of rifaximin, processes for their production and use thereof in the medicinal preparations |
| US9938298B2 (en) | 2014-05-12 | 2018-04-10 | Alfa Wassermann S.P.A. | Solvated crystal form of rifaximin, production, compositions and uses thereof |
| US10428086B2 (en) | 2014-05-12 | 2019-10-01 | Alfasigma S.P.A. | Solvated crystal form of rifaximin, production, compositions and uses thereof |
| KR20190062458A (en) * | 2016-09-30 | 2019-06-05 | 샐릭스 파마슈티컬스 인코포레이티드 | Solid dispersion form of rifaximin |
| KR102494049B1 (en) | 2016-09-30 | 2023-01-31 | 샐릭스 파마슈티컬스 인코포레이티드 | Solid Dispersion Forms of Rifaximin |
| US11660292B2 (en) | 2016-09-30 | 2023-05-30 | Salix Pharmaceuticals, Inc. | Solid dispersion forms of rifaximin |
| WO2020128583A1 (en) * | 2018-12-19 | 2020-06-25 | Friulchem S.P.A. | Process for the manufacture of a tablet of rifaximin and tablet of rifaximin |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2016063289A3 (en) | 2016-07-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7346353B2 (en) | rifaximin | |
| AU2011222432B2 (en) | Rifaximin powder, process for preparing the same and controlled release compositions containing said rifaximin useful for obtaining a long-lasting effect. | |
| WO2016063289A2 (en) | Pharmaceutical tablet compositions comprising rifaximin | |
| DK161080B (en) | CRYSTALLIC HYDRATE OF ORAL USED CEPHALOSPORIN AND PREPARATION | |
| JP6577143B2 (en) | Dosage form composition comprising an inhibitor of breton tyrosine kinase | |
| AU2013285085B2 (en) | Pharmaceutical compositions comprising rifaximin and amino acids, preparation method and use thereof | |
| TWI831848B (en) | Pharmaceutical composition for oral administration comprising aminopyrimidine derivative or its salt | |
| KR102362719B1 (en) | New solvated crystal form of rifaximin, production, compositions and uses thereof | |
| BR122020022453B1 (en) | USE OF POLYMORPHIC MIXTURES OF RIFAXIMIN IN THE PREPARATION OF SOLID FORMULATIONS AND PROCESS FOR PREPARING A FILM COATED TABLET | |
| CN117412749A (en) | Tolebutinib salt and crystal form thereof, preparation method, pharmaceutical composition and application thereof | |
| WO2017144109A1 (en) | Dasatinib formulation | |
| EP3255048A1 (en) | Non-crystalline form of palbociclib | |
| CN109153677B (en) | Hydrochloride crystal form of PLX3397 and preparation method and application thereof | |
| CN108602774B (en) | Novel crystal form of aripiprazole | |
| CN112334470A (en) | Crystalline salts of 5-methyl- (6S) -tetrahydrofolic acid and amino acid ethyl ester | |
| WO2021229480A1 (en) | Polymorph of rifaximin, process for the preparation thereof and pharmaceutical composition containing rifaximin | |
| WO2016097025A1 (en) | Pharmaceutical composition comprising amorphous lenalidomide | |
| CN116744931A (en) | Pharmaceutical composition of multi-target protein kinase inhibitor and application thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 15852354 Country of ref document: EP Kind code of ref document: A2 |
|
| NENP | Non-entry into the national phase in: |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 15852354 Country of ref document: EP Kind code of ref document: A2 |