FORM 2
THE PATENTS ACT 1970
(39 of 1970)
AND
The Patents Rules, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13)
1. TITLE OF THE INVENTION:
"PHARMACEUTICAL COMPOSITION"
2. APPLICANT:
(a) NAME: CIPLA LTD.
(b)NATIONALITY: Indian Company incorporated under the Companies Act, 1956
(c) ADDRESS: 289, Bellasis Road, Mumbai Central, Mumbai - 400 008, Maharashtra, India.
3. PREAMBLE TO THE DESCRIPTION:
The following specification particularly describes the invention and the manner in which it is to be formed.

FIELD OF INVENTION:
The present invention relates to a hot-melt extruded pharmaceutical composition comprising an antibacterial drug. The invention also relates to processes for the preparation of the said pharmaceutical compositions and its use for the treatment and/or prevention of colonic diseases.
BACKGROUND AND PRIOR ART:
One of the major obstacles to the development of highly potent pharmaceutical formulations is the poor water solubility of many drugs. Approximately 40% of potential drugs that are identified by pharmaceutical companies are poorly soluble in water, which greatly hinders their clinical use. Low water solubility limits the bioavailability and absorption of these agents.
Rifaximin is a semisynthetic antibiotic belonging to the rifamycin class of antimicrobial drugs exhibiting in vitro activity against Gram-positive, Gram-negative and anaerobic bacteria. Rifaximin acts by inhibiting bacterial ribonucleic acid (RNA) synthesis. Rifaximin is chemically named as[(2S,6Z,1,£,20S215,22R23R24R25S,26S27S28E) 5,6,21,23,25-pentahydroxy-27-methoxy-2,4,11,16,20,22,24,26-octamethyl-2,7 (epoxypentadeca-[1,11,I3]trienimino)benzofuro [4,5-e]pyrido[l,2-a]-benzimida-zole l,15(2/H-dione,25-acetate]. Rifaximin has the following chemical formula.

Rifaximin has been indicated for the treatment of traveler's diarrhea caused by noninvasive strains of Escherichia coli, a micro-organism which is not able to penetrate into GI mucosa and therefore remains in contact with gastrointestinal fluids. Rifaximin is highly effective in preventing and treating traveler's diarrhea, with fewer side effects and a low risk of developing antibiotic resistance.

Rifaximin is also approved for the treatment of pathologies whose etiology is in part or totally due to intestinal acute and chronic infections sustained by Gram-positive and Gram-negative bacteria, with diarrhea syndromes, altered intestinal microbial flora, summer diarrhea-like episodes, traveler's diarrhea and enterocolitis, pre- and post- surgery prophylaxis of the infective complications in gastro intestinal surgery; and hyperammonaemia therapy as a coadjutant.
Rifaximin is a poorly water-soluble and minimally absorbed (<0.4%) drug with in vitro activity against enteric Gram-negative bacteria including enteric pathogens. [Gerard L. et al.,faximin, a non-absorbable rifamycin antibiotic for use in nonsystemic gastrointestinal infections. Expert Review of Anti-infective therapy, 3(2), 201-211, (2005)].
It has also been reported that Rifaximin is characterized by negligible systemic absorption, due to its chemical and physical characteristics [Descombe J. J. et at, Pharmacokinetic study of Rifaximin after oral administration in healthy volunteers. International Journal of Clinical Pharmacology Research, 14 (2), 51-56, (1994)].
Hence, in addition to poor water solubility, Rifaximin has no systemic absorption which possesses a challenge to formulate suitable formulations of Rifaximin.
Rifaximin is currently available as tablets, granules for oral suspension and ointment and is marketed in Europe and U.S.A. and in many other countries. Tablets, for example are currently marketed that have strength of 200 mg for traveler's diarrhea under the brand name Xifaxan®.
Moreover, the approved dosage for rifaximin is 200 mg three times a day.
WO2007/047253 discloses methods of increasing the aqueous solubility of an antifungal azole using hydroxybutenyl cyclodextrins.
WO2010/067072 discloses complexes of rifaximin and process for preparing such complexes.

EP0858804 discloses use of oral rifaximin compositions in the treatment of diarrhea from cryptosporidiosis. The rifaximin formulations disclosed are in the dosage form of tablet, capsule, sugar coated tablet, granules or syrup for oral administration.
US5352679 discloses use of rifaximin in formulations for treatment of gastric dyspepsia caused by Helicobacter pylori bacteria. The rifaximin formulations disclosed are in the dosage form of tablet, capsule, sugar coated tablet, granules or syrup for oral administration.
Several strategies and formulations have been employed to overcome these limitations of solubility and poor systemic absorption. Although, existing strategies such as complexing drugs with cyclodextrins, conjugation of drugs to dendrimers, salt formation of ionizable drugs and use of co-solvents have been shown to improve drug solubility, solubilization methods that can improve thebioavailability of drugs significantly are stiff highfy desirable.
Another approach to improve the solubility of the drug is to use the amorphous form of the drug which inturn helps to enhance the absorption. The amorphous state is thermodynamically metastable, and therefore is expected that amorphous compounds will assume a stable crystalline conformation with time, as well as in response to perturbations such as elevations in temperature and exposure to moisture. Thus, recrystallization of amorphous solid dispersion formulations on storage is a common problem.
Hence, there still exists a need to develop and formulate a suitable formulation of rifaximin with improved stability and which alleviates the problems in the prior art.
OBJECT OF THE INVENTION:
The object of the present invention is to provide a. pharmaceutical composition of rifaximin having improved solubility.

Another more object of the present invention is to provide a process for preparing the pharmaceutical composition comprising rifaximin.
Yet another object of the present invention is to provide a method for treatment and/or prevention of colonic diseases which method comprises administering a pharmaceutical composition comprising rifaximin.
A still further object of the present invention is to provide a pharmaceutical composition of rifaximin having improved stability.
SUMMARY OF THE INVENTION:
According to one aspect of the present invention there is provided a pharmaceutical composition comprising rifaximin and a polymer optionally with one or more pharmaceutically acceptable excipients.
According to one more aspect of the present invention there is provided a process for preparing a pharmaceutical composition of rifaximin and a polymer optionally with one or more pharmaceutically acceptable excipients.
According to a further aspect of the present invention there is provided a method of treatment and/or prevention of colonic diseases using a pharmaceutical composition comprising rifaximin and a polymer optionally with one or more pharmaceutically acceptable excipients.
DETAILED DESCRIPTN F THE INVENTION:
Rifaximin is a poorly water-soluble drug exhibiting minimal absorption. Rifaximin is also characterized by negligible systemic absorption, due to its chemical and physical characteristics.

Using amorphous drug to formulate the dosage forms is highly desirable however; a drawback with amorphous drugs is that they tend to convert back to stable crystalline forms.
The inventors of the present invention have found that, the solubility and stability of rifaximin was greatfy improved when rifaximin was formulated using hot melt technology.
Further, the inventors of the present invention have observed that, use of amorphous form of rifaximin leads to a significant reduction in the dose required as compared to rifaximin.
The present invention thus provides a pharmaceutical composition comprising rifaximin and a polymer optionally with one or more pharmaceutically acceptable excipients using hot melt technology.
The term "Rifaximin" is used in broad sense to include not only "Rifaximin" per se but also their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, pharmaceutically acceptable hydrates, pharmaceutically acceptable enantiomers, pharmaceutically acceptable derivatives, pharmaceutically acceptable polymorphs, pharmaceutically acceptable prodrugs, pharmaceutically acceptable complexes etc.
The term "extrudates" as used herein refers to solid product solutions, solid dispersions and glass solutions of rifaximin with one or more polymers and optionally pharmaceutically acceptable excipients.
The term "pharrnaceutically acceptable" mentioned throughout the specification would be applied to a carrier, diluent or excipient which is compatible with the actives as employed.
Rifaximin can be present in crystalline or amorphous form or a combination thereof. The form of rifaximin does not substantially change during hot-melt extrusion.

According to one embodiment, of the present invention there is provided a hot melt extruded pharmaceutical formulation comprising rifaximin and at least one pharmaceutically acceptable water soluble and/or insoluble polymer or combination thereof and optionally one or more pharmaceutically acceptable excipients.
Water soluble polymers which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, homopolymers and co-polymers of N-vinyl lactams, especially homopolymers and co-polymers of N- vinyl pyrrolidone e.g. polyvinylpyrrolidone (PVP), co-polymers of PVP and vinyl acetate, co-polymers of N-vinyl pyrrolidone and vinyl acetate (Copovidone) or vinyl propionate, dextrins such as grades of maltodextrin, cellulose esters and cellulose ethers, high molecular polyalkylene oxides such as polyethylene oxide and polypropylene oxide and co-polymers of ethylene oxide, propylene oxide and mixtures thereof.
Water insoluble polymers which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, acrylic copolymers e.g. Eudragit EIOO or Eudragit EPO; Eudragit L30D-55, Eudragit FS30D, Eudragit RL30D, Eudragit RS30D, Eudragit NE30D, Acryl-Eze (Colorcon Co.); polyvinylacetate, for example, Kollicoat SR 30D (BASF Co.); cellulose derivatives such as ethylcellulose, cellulose acetate e.g. Surelease (Colorcon Co.), Aquacoat ECD and Aquacoat CPD (FMC Co.) and mixtures thereof.
One or more optional pharmaceutically acceptable excipients may include, but are not limited to, plasticizers, disintegrating agents, lubricants, glidants, diluents, binders, chelating agents.
Plasticizers reduce the viscosity of the polymer melt and thereby allow for lower processing temperature and extruder torque during hot melt extrusion. They further decrease the glass transition temperature of the polymer.
Plasticizers which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, polysorbates such as sorbitan monolaurate (Span 20), sorbitan monopalmitate, sorbitan monostearate, sorbitan monoisostearate;

citrate ester type plasticizers like triethyl citrate, citrate phthalate; propylene glycol; glycerin; polyethylene glycol (low & high molecular weight); triacetin; dibutyl sebacate, tributyl sebacate; dibutyltartrate, dibutyl phthalate, glycerol palmitosterate and mixtures thereof.
The process of hot melt extrusion is carried out in the conventional extruders as known to a person skilled in the art.
Typically, the melt-extrusion process comprises the steps of preparing a homogeneous melt of one or more drugs, the polymer and the excipients, and cooling the melt until it solidifies.
Melting usually involves heating above the softening point of the polymer. The preparation of the melt can take place in a variety of ways. The mixing of the components can take place before, during or after the formation of the melt.
Usually, the melt temperature is in the range of about 50° C to about 200° C.
Suitable extruders include single screw extruders, intermeshing screw extruders or else multiscrew extruders, preferably twin screw extruders, which can be co - rotating or counter - rotating and, optionally, be equipped with kneading disks.
The extrudates can be in the form of beads, granulates, tube, strand or cylinder and this can be further processed into any desired shape.
In an alternative process, the present invention may further be allowed to form granules which may be compressed to form tablets, or the granules may be filled into capsules, sachets, pellets in capsules or in a similar dosage form.
This process involves heating the polymer(s) to soften it, without melting it, and mixing the active ingredient(s) with polymer(s), to form granules.

The process can be carried out in the same type of extrusion apparatus as the hot melt extrusion process, except that the product is not extruded through the extrusion nozzle of the apparatus.
In one embodiment of the present invention, the process for preparing the pharmaceutical composition comprises forming a powder blend, transferring the blend through a heated barrel of the extruder, whereby the powder blend melts and molten solution product is collected on a conveyor whereby it is allowed to cool and form an extrudate.
Alternatively, the extrudate is cut into pieces after solidification and can be further processed into suitable dosage forms.
The rifaximin compositions of the present invention can be administered to a subject via any conventional means including, but not limited to, orally, rectally, ocularly, parenterally (e.g., intravenous, intramuscular, or subcutaneous), intracisternally, intravaginally, intraperitoneally, locally (e.g., powders, ointments or drops), or as a buccal or nasal spray.
Moreover, the extrudates/granules of rifaximin according to the present invention may be formulated into any suitable dosage form, including but not limited to liquid dispersions, gels, aerosols, ointments, creams, controlled release formulations, lyophilized formulations, tablets, capsules, immediate release formulations, delayed release formulations, extended release formulations, pulsatile release formulations, and mixed immediate release and controlled release formulations.
The rifaximin compositions may be formulated for parenteral injection (e.g., intravenous, intramuscular, or subcutaneous), oral administration in solid, liquid, or aerosol form, foams (vaginal, rectal), vaginal, rectal, ocular, local (powders, ointments or drops), buccal, intracistemal, intraperitoneal, or topical administration, and the like.
Solid dosage forms according to the present invention are preferably in the form of tablets which may be coated and pellets in capsules but also other conventional dosages such as

powders, pellets, capsules, suspensions, solutions, dry syrup, emulsions and sachets may be provided.
Liquid dosage forms according to the present invention for oral administration include pharmaceuticall acceptable emulsions, solutions, suspensions, syrups, and elixirs.
In one embodiment of the present invention, the pharmaceutical compositions are provided in the form of tablets.
The extrudates/granules so obtained according to the present invention may then be admixed with other suitable pharmaceutically acceptable excipients. The present invention may comprise one or more of pharmaceutically acceptable excipients.
Suitable disintegrating agents which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, croscarmellose sodium, crospovidone, sodium starch glycolate, corn starch, potato starch, maize starch and modified starches, calcium silicates, low substituted hydroxy- propylcellulose and mixtures thereof.
Suitable lubricants and glidants which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, stearic acid and its derivatives or esters like sodium stearate, magnesium stearate and calcium stearate and the corresponding esters such as sodium stearyl fumarate; talc and colloidal silicon dioxide respectively and mixtures thereof.
Suitable diluents or bulking agents which may be used in the pharmaceutical composition of the present invention, include, but are not limited to, saccharides, including monosaccharides, disaccharides, polysaccharides and sugar alcohols such as arabinose, lactose, dextrose, sucrose, fructose, maltose, mannitol, erythritol, sorbitol, xylitol, lactitol, and other bulking agents such as powdered cellulose, microcrystalline cellulose, purified sugar and derivatives thereof. The composition may incorporate one or more of the above bulking agents.

Suitable binders may include, one or more of, but not limited to methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, hypromellose, polyvinylpyrrolidone, gelatin, gum arable, polyvinyl alcohol, pullulan, starch, pregelatinized starch, agar, tragacanth, sodium alginate, propylene glycol, alginate and other cellulose derivatives and equivalents thereof.
Suitable chelating agents include, one or more of, but not limited to ethylenediaminetetraacetic acid (EDTA), disodium EDTA and derivatives thereof, citric acid and derivatives thereof, niacinamide and derivatives thereof, and sodium desoxycholate and derivatives thereof.
The pharmaceutical composition, according to the present invention, may be seal coated. Preferably, the tablet may be seal coated and finally film coated or the tablet may be seai coated and further enteric coated.
According to an embodiment of the present invention, pharmaceutical composition may be film coated with Ready colour mix systems (such as Opadry colour mix systems).
According to another embodiment of the present invention, there is a seal coat between the core containing rifaximin, and the enteric coat. The seal coat comprises one or more pharmaceutically acceptable film-forming polymers and pharmaceutically acceptable excipients(s). The seal coat provides a smooth base for the application of the enteric coat, prolongs the resistance of the core to the acidic conditions, improves stability by minimizing the interaction between drug in the core and the enteric polymer in the enteric layer from coming into direct contact with each other; and also improves stability of drug from light exposure. The smoothing function of the separating coat is purely mechanical, the objective of which is to improve the coverage of the enteric coat and to avoid thin spots in it, caused by bumps and irregularities on the core.
According to the present invention, the seal coat comprises film forming polymeric materials, such as but not limited to, hydroxypropylmethylcellulose,

hydroxypropylcellulose, polyvinylpyrrolidone, methylcellulose, carboxymethylcellulose, hypromellose, acacia, gelatin to increase adherence and coherence of the seal coat.
According to another embodiment of the present invention, the enteric coat is present over the seal coat. The enteric coat comprises of materials such as, but not limited to, neutralized methacrylic acid copolymer such as, EUDRAGIT L 30 D-55, EUDRAGIT L100-55, EUDRAGIT S 100, EASTACRYL 30D, KOLLICOAT MAE 30 DP, KOLLICOAT MAE 100 P; cellulose acetate phthalate, hydroxypropyl methylcellulose phthalate and combinations thereof.
In a further embodiment, the pharmaceutical composition according to the present invention may be used to treat a bacterial infection, e.g., acute hemorrhoidal disease, irritable bowel syndrome, traveler's diarrhea, small intestinal anal disease, Crohn's disease, chronic pancreatitis, pancreatic insufficiency, colitis, hepatic encephalopathy, antibiotic associated colitis, and/or diverticular disease.
Further, the pharmaceutical composition according to the present invention may further comprise at least one additional active ingredient.
Additional active agents may be selected from, but not limited to one or more of antiinflammatory agents, steroids (e.g. corticosteroids), additional antibiotics, anti-fungal agents, anti-viral agents, analgesics, or anti-neoplastic agents.
Suitable antibiotics include, but are not limited to, dapsone, chloramphenicol, neomycin, cefaclor, cefadroxil, cephalexin, cephradine, erythromycin, clindamycin, lincomycin, amoxicillin, ampicillin, bacampicillin, carbenicillin, dicl oxacillin, cyclacillin, picloxacillin, hetaciHin, methicillin, nafcillin, penicillin, polymyxin, tetracycline, amphotericin-b, candicidin, dermostatin, filipin, fungichromin, hachimycin, hamycin, lucensomycin, mepartricin, natamycin, nystatin, pecilocin, perimycin, azaserine, griseofulvin, oligomycins, neomycin undecylenate, pyrroinitrin, siccanin, tubercidin, viridin, picloxacillin, hetacillin, methicillin, nafcillin, penicillin, polymyxin or tetracycline.

Suitable anitfungal agents include but are not limited to, allylamines such as butenafine, naftifine, imidazoles such as bifonazole, butoconazole, chlordantoin, chlormidazole, cloconazole, clotrimazole, econazole, enilconazole, fenticonazole, flutrimazole, isoconazole, ketoconazole, lanoconazole, miconazole, omoconazole, oxiconazole nitrate, sertaconazole, sulconazole, tioconazole, triazoles such as fluconazole, itraconazole, saperconazole, terconazole, and others such as acrisorcin, amorolf[iota]ne, biphenamine, bromosalicylchloranilide, buclosamide, calcium propionate, chlophenesin, ciclopirox, cloxyquin, coparaff[iota]nate, diamthazole, dihydrochloride, exalamide, flucytosine, halethazole,hexetidine, Ioflucarban, nifuratel, potassium iodide, propionates, propionic acid, pyrithione, salicylanilide, sulbentine, tenonitrozole, triacetin, ujothion, undecylenic acid.
Antifungal agents may also include, polyenes such as amphotericin-b, candicidin, dermostatin, filipin, fungichromin, hachimycin, hamycin, lucensomycin, mepartricin, natamycin, nystatin, pecilocin, perimycin, azaserine, griseofulvin, oligomycins, neomycin undecylenate, pyrroinitrin, siccanin, rubercidin, viridin, allylamines such as butenafine, naftifine, imidazoles such as bifonazole, butoconazole, chlordantoin, chlormidazole, cloconazole, clotrimazole, econazole, enilconazole, fenticonazole, flutrimazole, isoconazole, ketoconazole, lanoconazole, miconazole, omoconazole, oxiconazole nitrate, sertaconazole, sulconazole, tioconazole, triazoles such as fluconazole, itraconazole, saperconazole, terconazole, acrisorcin, amorolf[iota]ne, biphenamine, bromosalicylchloranilide, buclosamide, calcium propionate, chlophenesin, ciclopirox, cloxyquin,coparaffiota]nate,diamthazole, dihydrochloride, exalamide, flucytosine, halethazole, hexetidine, Ioflucarban, nifuratel, potassium iodide, propionates, propionic acid, pyrithione, salicylanilide, sulbentine, tenonitrozole, triacetin, ujothion or undecylenic acid.
Other therapeutic agents can include a steroidal or non-steroidal antiinflammatory agent. Non-steroidal anti-inflammatory agents, include, but are not limited to, aspirin, ibuprofen, diclofenac, naproxen, benoxaprofen, flurbiprofen, fenoprofen, flubufen, ketoprofen, indoprofen, piroprofen, carprofen, oxaprozin, pramoprofen, muroprofen, trioxaprofen, suprofen, aminoprofen, tiaprofenic acid, fluprofen, bucloxic acid, indomethacin, sulindac, tolmetin, zomepirac, tiopinac, zidometacin, acemetacin, fentiazac, clidanac, oxpinac,

mefenamic acid, meclofenamic acid, flufenamic acid, niflum[iota]c acid, tolfenamic acid, diflurisal, flufenisal, piroxicam, sudoxicarn, isoxicam; salicylic acid derivatives, including aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salicylsalcyiclacid, sulfasalazine, and olsalazin; para-am inophennol derivatives including acetaminophen and phenacetin; indole and indene acetic acids, including indomethacin, sulindac, and etodolac; heteroaryl acetic acids, including tolmetin, diclofenac, and ketorolac; anthranific acids (fenamates), including mefenamic acid, and meclofenamic acid; enolic acids, including oxicams (piroxicam, tenoxicam), and pyrazolidinediones (phenylbutazone, oxyphenthartazone); and alkanones, including nabumetone and pharmaceuticalacceptable salts thereof and mixtures thereof.
Suitable corticosteroids include but are not limited to, hydrocortisone, i.e., 11-17- 21-trihydroxypregn-4-ene-3,20-dione or Cortisol, Cortisol acetate, hydrocortisone phosphate, hydrocortisone 21 -sodium succinate, hydrocortisone tebutate, corticosterone, corticosterone acetate, cortisone, cortisone acetate, cortisone 21B-cydopentanepropionate, cortisone phosphate, triamcinolone hexacetonide, dexamethasone phosphate, desonide, betamethasone dipropionate, mometasone furate.
Antineoplastic agents may also be included in the pharmaceutical composition of the present invention along with rifaximin which include, but are not limited to, vincristine, vinblastine, vindesine, busulfan, chlorambucil, spiroplatin, cisplatin, carboplatin, methotrexate, adriamycin, mitomycin, bleomycin, cytosi[pi]e arabinoside, arabinosyl adenine, mercaptopurine, mitotane, procarbazine, dactinomycin (antinomycin D), daunorubicin, doxorubicin hydrochloride, taxol, plicamycin, aminoglutethimide, estramustine, flutamide, leuprolide, megestrol acetate, tamoxifen, testolactone, trilostane, amsacrine (m-AMSA), asparaginase (L-asparaginase), etoposide, and interferon α-2a and 2b.
Antiviral agents may also be included in the pharmaceutical composition of the present invention along with the rifaximin which include, but are not limited to, acyclovir, amantadine, azidothymidine, ribavirin and vidarabine.

The following examples are for the purpose of illustration of the invention only and are not intended in any way to limit the scope of the present invention.
Example 1

Sr. No. Ingredients Qty/Tab (mg)
Dry Mix
1. Rifaximin 400.0
2. Copovidone 400.0
3. Polyethylene Oxide (Polyox N80) 400.0
4. Glycerol Palmitostearate 80.0
Blending & Lubrication
5. Microcrystalline Cellulose 240.0
6. Sodium Starch Glycolate 96.0
7. Colloidal Silicon Dioxide 8.0
8. Magnesium Stearate 16.0
Seal Coating
9. Hydroxypropylmethy 1 cell u lose 6cps 10.0
10. Isopropyl Alcohol q.s.
11. Purified Water q.s.
Film Coating
12. Ready Colour Mix System 30.00
13. Purified Water q.s.
Total 1680.0
Process:
1) All ingredients were sifted through the required specific mesh.
2) Rifaximin, copovidone, polynox N80 and glycerol palmitosterate were mixed in an octagonal blender.
3) The mixture obtained in step (2) was hot melt extruded at 150°C.

4) The extrudates obtained in step (3) were further milled and sized which was followed by addition of microcrystalline cellulose, sodium starch glycolate, and colloidal silicon dioxide and further lubricated with magnesium stearate.
5) The lubricated mixture obtained in step (3) was compressed to form a tablet which was seal coated and finally film coated.

Sr.No Ingredients Qty/Tab (mg)
1. Rifaximin 150.0
Binder
2. Disodium EDTA 1.125
3. Hypromellose 7.50
4. Purified Water q.s.
5. Isopropyl Alcohol q.s.
Blending & Lubrication
6. Macrocrystalline Cellulose 79.125
7. Sodium Starch Glycolate 10.5
8. Colloidal Silicon Dioxide 2.25
9. Magnesium Stearate 4.5
Total 255.0
Seal coating
10. Hypromellose 5.00
11. Purified Water q.s.
Enteric ( boating
10. EudragitLlOO 55 25.00
11. Talc 5.00
12. Triethyl citrate 5.00
13. Purified Water q.s.
Total 295.00

Process:
1) All ingredients were sifted through the required specific mesh.
2) Rifaximin, hypromellose, disodium EDTA was mixed with purified water and isopropyl alcohol.
3) The mixture obtained in step (2) was granulated in the extrusion apparatus to obtain the dried granules.
4) The granules obtained in step (3) were sized which was followed by addition of microcrystalline cellulose, sodium starch glycolate, and colloidal silicon dioxide and further lubricated with magnesium stearate.
5) The lubricated mixture obtained in step (3) was compressed to form a tablet which was seal coated and finally enteric coated.
It will be readily apparent to one skilled in the art that varying substitutions and modifications may be made to the invention disclosed herein without departing from the spirit of the invention. Thus, it should be understood that although the present invention has been specifically disclosed by the preferred embodiments and optional features, modification and variation of the concepts herein disclosed may be resorted to by those skilled in the art, and such modifications and variations are considered to be falling within the scope of the invention.
It is to be understood that the phraseology and terminology used herein is for the purpose of description and should not be regarded as limiting. The use of "including," "comprising," or "having" and variations thereof herein is meant to encompass the items listed thereafter and equivalents thereof as well as additional items.
It must be noted that, as used in this specification and the appended claims, the singular forms "a," "an" and "the" include plural references unless the context clearly dictates otherwise. Thus, for example, reference to "a propellant" includes a single propellant as well as two or more different propellants; reference to a "cosolvent" refers to a single cosolvent or to combinations of two or more cosolvents, and the like.

We Claim:
1) A pharmaceutical composition comprising rifaximin or its pharmaceutically acceptable salts, solvates, derivatives, hydrates, anhydrates, enantiomers, polymorphs, prodrugs or complexes or mixtures thereof and atleast one pharmaceutically acceptable polymer.
2) A pharmaceutical composition as claimed in claim 1, wherein the pharmaceutically acceptable polymer is water soluble and/or a water insoluble polymer.
3) A pharmaceutical composition as claimed in any of the preceding claims, further comprising one or more pharmaceutically acceptable excipient/s.
4) A pharmaceutical composition as claimed in claim 3, wherein the pharmaceutically acceptable excipient/s comprises one or more plasticizer, disintegrating agents, lubricants, glidants, diluents, binders, chelating agents.
5) A pharmaceutical composition as claimed in any of the preceding claims, obtainable by melt extruding rifaximin with at least one pharmaceutically acceptable polymer, and optionally one or more pharmaceutically acceptable excipients to form exudates, and optionally admixing the extrudate with one or more further pharmaceutically acceptable excipients.
6) A pharmaceutical composition as claimed in claim 6, wherein the extrudate, and optional pharmaceutically acceptable excipient or excipients, is compressed to form a tablet.
7) A pharmaceutical composition as claimed in claim 6, wherein the tablet is seal coated and film coated or the tablet is seal coated and further enteric coated.
8) A process for preparing the pharmaceutical composition comprising hot melt extrusion of rifaximin to form an extrudate,

9) A process as claimed in claim 8, wherein rifaximin is mixed with a water soluble polymer and/or a water insoluble polymer prior to the hot melt extrusion step.
10) A process as claimed in claim 8, wherein rifaximin is mixed with a water soluble polymer and/or a water insoluble polymer and extruded by hot melt granulation process or melt granulation process.
11) A process as claimed in claim 8 or 9 or 10, comprising preparing a substantially homogeneous melt of rifaximin and optionally one or more excipients, extruding the melt, and cooling the melt until it solidifies.
12) A process according to claim 11, wherein rifaximin, polymer, and optionally one or more excipients are processed to form a powder blend which is transferred through the heated barrel of the extruder, whereby the powder blend melts and a molten solution product is formed, which is allowed to cool to form an extrudate.
13) A process according to claim 12, comprising processing the cooled extrudate into a desired pharmaceutical dosage form.
14) A pharmaceutical composition according to any one of the preceding claims further comprising one or more active(s) selected from anti-inflammatory agents, corticosteroids, antibiotics, anti-fungal agents, anti-viral agents, analgesics, antineoplastic agents or their pharmaceutically acceptable salts, solvates, tautomers, derivatives, enantiomers, isomers, hydrates, prodrugs or polymorphs thereof.
15) A pharmaceutical composition substantially herein described with reference to the accompanying examples.