Title of Invention

"PHARMACEUTICAL COMPOSITIONS AND METHODS THEREOF"

Abstract

Disclosed herein is a synergistic pharmaceutical composition comprising synergistic effective amount of Nitazoxanide and Ofloxacin or pharmaceutically acceptable salts thereof with pharmaceutically acceptable inert excipients selected from diluents, binders, disintegrating agents, glidants or lubricants. Further, the composition is provided in a solid oral dosage form, preferably tablets comprising single layer or bilayer tablets.

Full Text

United States Patent No. 5,886,013 to Rossignol, discloses a composition comprising Nitazoxanide for a substantially immediate action against viruses or a substantially immediate treatment of liver trouble. Such a composition has been disclosed as suitable for treating human viral infections, such as diseases of the liver. United States Patent No. 5,968,961 and 6,117,894, to Rossignol, disclose a pharmaceutical composition of Nitazoxanide and/or Tizoxanide for oral administration, as a solid dosage form, or a liquid suspension, and also composition for topical or intravaginal application as a paste ointment or cream. Also disclosed is that the oral administration of a single dose of 50 mg per kg of solid particles of the actives having a particle size smaller than 5 µm caused severe adverse effects in the animals. Accordingly it has been disclosed that for a safe and effective treatment of infections caused by parasites, fungi, bacteria and viruses in humans and animals, solid particles having a particle size smaller than 200 µm and greater than 10 µm are to be used. United States Patent No. 5,965,590 to Rossignol, et al., discloses a method for treatment or prevention of infections, and particularly opportunistic infections in persons with compromised or suppressed immune systems by administering a pharmaceutical composition containing an active selected from Nitazoxanide and Tizoxanide. United States Patent No. 5,859,038 to Rossignol, discloses a method for treating Helicobacter pylori bacteria by administering an effective amount of a compound selected from the group consisting of Nitazoxanide and Tizoxanide and a mixture of said compounds, prior to administering to the subject a compound selected from the group consisting of metronidazole, ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, piperacillin, cefoxitin, imipenem and clindamycin. United States Patent No. 5,935,591 to Rossignol, et al., discloses a method for treatment or prevention of equine protozoal myeloencephalitis by administering a pharmaceutical composition comprising, as active agent, one or more derivatives of 2-benzamido-5-nitro-thiazole. United States Patent No. 6,180,136 and 6,423,338 to Larson, et al., discloses pharmaceutical compositions containing phospholipid coated microcrystals, which offer significantly longer sustained release times. Also disclosed are methods for treating infections caused by bacteria, fungi, protozoa, or any type of parasitic organism which has invaded the body, in a variety of mammals which involves the administration of said compositions. Also disclosed are pharmaceutical compositions for the sustained release of pharmacologically active compounds and methods of their manufacture and use for treating respiratory diseases, infections, inflammation, and pain in a variety of mammals, wherein the pharmacologically active compounds are selected from cephalone, tilmicosin, or nitazoxanide, fioroquinolone such as ofloxacin, sarafloxicin, or ciprofloxaicin, cephalosporin such as cefazolin, cefuroxine or a derivative of cefuroxine, cefoperazone, or cefoclor, tetracycline such as oxytetracycline, fioroquinolone and a cephalosporin in combined form. The pharmacologically active compound may also be an antiinflammatory agent, such as flunixin, an anesthetic, such as propofal, or an anti-protozoan agent, such as nitazoxanide. WO 9,619,220 to Schickander et al., discloses a pharmaceutical composition for treatment of H. pylori related infections comprising combination of nitazoxanide with an anti-ulcer agent selected from cimetidine, ranitidine, famotidine, nizatidine and pharmaceutically acceptable salts thereof and an antibacterial agent, bismuth salts such as selected from bismuth citrate, bismuth subcitrate, bismuth salicylate, bismuth subsalicylate, bismuth nitrate, bismuth galate, dibismuth trietraoxidialuminate and hydrate thereof. Summary of the Invention It is an object of the present invention to provide a therapeutic synergistic combination of Nitazoxanide and a fluoroquinolone or pharmaceutically acceptable salts thereof, in pharmaceutically administrable dosage form. Preferably the fluoroquinolone used is Ofloxacin. This and other objects of the invention are attained in accordance with the present invention wherein there is provided several embodiments. In accordance with one preferred embodiment of the present invention, there is provided a pharmaceutical composition comprising a therapeutic synergistic combination of Nitazoxanide and Ofloxacin, which is effectively used for the treatment of infections caused by gram +ve and gram -ve aerobic bacteria, anaerobic bacteria including strains resistant to Metronidazole, mixed parasitic (protozoal and helminthic) and bacterial infections, Trichomonas vaginalis infections including strains resistant to Metronidazole, H. pylori infections, etc. In accordance with further embodiment, the present invention provides for determining the role of a therapeutically effective combination of Nitazoxanide and Ofloxacin against Enterocolitis (mixed parasitic and bacterial infections), combined aerobic & anaerobic urogenital infections including Pelvic inflammatory diseases (also including Trichomonas vaginalis infection which has developed resistance to Metronidazole), Skin & Soft tissue infections, post-operative anaerobic infections (esp. in abdominal & gynecological surgeries), Suppurative Pulmonary diseases, Peptic Ulcer and Gastric Cancer {Helicobacter pylori infections). In another preferred embodiment, there is provided a synergistic composition comprising a therapeutically effective amount of Nitazoxanide and Ofloxacin, or salts thereof, and pharmaceutically acceptable inert excipients, wherein the excipients are selected from diluents, binders, disintegrating agents, glidants and lubricants. In another preferred embodiment of the present invention, there is provided a fixed dose synergistic combination of Nitazoxanide 500 mg and Ofloxacin in the range of 100 mg to 400 mg, preferably 200 mg, wherein the dosage form is solid oral dosage form, preferably tablet. According to further embodiment of the present invention, said tablet dosage form includes both single layer and bilayer tablets. Each type of tablet further comprises of two parts, one part is wet granulation part comprising Ofloxacin and inert pharmaceutical excipients and another is dry mixing part comprising Nitazoxanide and directly compressible excipients. In another embodiment, there is provided a single layer or bilayer tablet dosage form comprising a dry mixture of Ofloxacin and Nitazoxanide, prepared together or separately with suitable directly compressible pharmaceutical excipients. In accordance with another embodiment, there is provided a method of preparing a composition wherein there is provided a synergistic combination of Nitazoxanide and Ofloxacin in an oral dosage form, wherein the oral dosage form is single layer or bilayer tablet form, wherein the method comprises separately preparing wet granulation part of Ofloxacin employing pharmaceutically acceptable inert excipients and dry mixing part of Nitazoxanide employing directly compressible inert excipients, and compressing the two parts into single layer or bilayer tablets. The tablets may further be film coated. In accordance with another embodiment of the present invention, there is provided a method of preparing a composition wherein there is provided a synergistic combination of Nitazoxanide and Ofloxacin in an oral dosage form, wherein the oral dosage form is single layer or bilayer tablet form, the method comprising separately preparing a dry mixture of Nitazoxanide and of Ofloxacin, each employing suitable directly compressible pharmaceutically acceptable inert excipients, and compressing the two parts into single layer or bilayer tablets. These tablets may further be film coated. In another embodiment of the invention, the fixed dose combination of Nitazoxanide and Ofloxacin shows more efficacy and safety in the treatment of enterocolitis, urogenital infections including PID, suppurative pulmonary infections and skin & soft tissue infections as compared to the fixed dose combination of Metronidazole and Ofloxacin. Detailed Description of the Invention Nitazoxanide is highly effective against anaerobic strains susceptible to Metronidazole. For some strains with decreased susceptibility or increased resistance to Metronidazole (B. fragilis, Eubactrium spp & Bifidobacterium spp.), Nitazoxanide has shown high efficacy. Also Nitazoxanide is highly effective against a broad spectrum of protozoal parasites and helminths that infect the intestinal tract of humans including Entamoeba histolytica, Giardia lamblia and Cryptosporidium parvum. Ofloxacin has a broad spectrum of activity against aerobic gram +ve as well as gram -ve bacteria. The synergistic combination of a broad spectrum antiparasitic having susceptibility to a wide range of anaerobic bacteria - Nitazoxanide and a broad spectrum fluorinated quinolone antibacterial agent - Ofloxacin of the present invention provides a substitute to the existing Metronidazole and Ofloxacin combination where resistance to Metronidazole is fast developing. The synergistic composition of Nitazoxanide and Ofloxacin or their pharmaceutically acceptable salts can be prepared in different pharmaceutical dosage forms. The preferred dosage form of the present invention is tablet dosage form. The synergistic composition of Nitazoxanide and Ofloxacin is provided as a fixed dose combination comprising 500 mg Nitazoxanide and 100, 200 or 400 mg Ofloxacin preferably 200 mg. The preferred dosage forms are single layer or bilayer tablets. The tablets further comprise two parts, one part is wet granulation part comprising Ofloxacin and another is dry mixing part comprising Nitazoxanide. Wet granulation part consists of Ofloxacin or pharmaceutically acceptable salts thereof in combination with pharmaceutically acceptable inert excipients and dry mixing part contains Nitazoxanide in combination with pharmaceutically acceptable directly compressible inert excipients. Nitazoxanide is taken in dry granulation part because of its instability in the presence of moisture. Ofloxacin can be taken in dry granulation part as well, with pharmaceutically acceptable directly compressible excipients. The pharmaceutically acceptable excipients were chosen in each part based on the incompatibility studies between them and the active ingredient concerned, conducted at preformulation stage under different storage conditions. Pharmaceutically inert excipients include diluents, binders, disintegrating agents, glidants and lubricants. Diluents may be selected from Lactose, Dicalcium Phosphate, Microcrystalline Cellulose, Starch, all other Starch and Cellulose derivatives and combinations thereof. Disintegrants may be selected from Starch, Croscarmellose Sodium, Crospovidone, Sodium Starch Glycolate, Pregelatinized Starch and all other Starch and Cellulose derivatives and combinations thereof. Binders may be selected from Polyvinylpyrollidone, Starch, Pregelatinized Starch, Hydrogenated Castor Oil, Hydroxypropyl Methycellulose, all other Starch and Cellulose derivatives and combinations thereof. Glidants and lubricants may be selected from Talcum, Stearic Acid, Sodium Stearyl Fumarate, Hydrogenated Castor Oil and Magnesium Stearate. Coating material may be combination of any of the following - Talcum, Titanium dioxide, Quinoline yellow aluminium lake or any other suitable lake or pigment, Lactose, Hydroxypropyl Methylcellulose, Polyvinyl Alcohol, Acrylic polymer, all other cellulose derivatives, Polyethylene glycols, Triethyl Citrate, Tributyl citrate, Dibutyl sebacate, Diethyl sebacate, Triacetin, Lecithin Tween 80 and Sodium lauryl sulphate. Most preferred diluents in the present invention are Microcrystalline Cellulose and Lactose. The amount of diluent in the composition generally varies from 10% to 55% by weight of the composition. Preferably the amount of diluent varies from 15% to 50% by weight of the composition. Further, the amount of diluent in the granulation part varies from 1% to 65% by weight of the granulation part composition and in dry mixing part varies from 10% to 50% by weight of the dry mixing part composition. Most preferred disintegrants in the present invention are Croscarmellose Sodium and Pregelatinised starch. The amount of disintegrant in the composition generally varies from 1% to 10% by weight of the composition. Preferably the amount of disintegrant varies from 2% to 5% by weight of the composition. Further, the amount of disintegrant in the granulation part generally varies from 1% to 8% by weight of the granulation part composition and in dry mixing part varies from 1% to 5% by weight of the dry mixing part composition. Most preferred binder in the granulation part is Starch and in dry mixing part is Hydrogenated Castor Oil or Pregelatinized Starch or combinations thereof. The amount of binder in the composition generally varies from 1% to 8% by weight of the composition. The amount of binder in the granulation part generally varies from 1% to 8% by weight of the granulation part composition. Preferably the amount of binder varies from 3% to 6% by weight of the granulation part composition. Further, the amount of binder in the dry mixing part generally varies from 1% to 8% by weight of the dry mixing part composition. Preferably the amount of binder varies from 3% to 6% by weight of the dry mixing part composition. Most preferred glidant is Talcum. The amount of glidant in the composition generally varies from 1% to 3% by weight of the composition. Preferably the amount of glidant varies from 1.0% to 2.0% by weight of the composition. Most preferred lubricants are Magnesium Stearate and Hydrogenated Castor Oil. The amount of lubricant in the composition generally varies from 1% to 5% by weight of the composition. Preferably the amount of lubricant varies from 1% to 3% by weight of the composition. Coating composition in the present invention varies from 1% to 5% by weight of the composition. Preferably, the weight gain of the tablet with coating material varies from 2% to 3% by weight of the composition. Further, for bilayer tablets, coloring agent may be included in the granulation part. Most preferred coloring agent is Quinoline yellow aluminium lake. The amount of coloring agent generally varies from 0.5% to 2% by weight of the composition. Preferably the amount of coloring agent varies from 0.5% to 1% by weight of the composition. The following non-limiting examples illustrate specific embodiments of the present invention. They are, however, not intended to be limiting the scope of the present invention in any way. Example 1 Preparation of combination tablet of Nitazoxanide and Ofloxacin in single layer (Table Removed) Procedure: Wet Granulation Part Ofloxacin is sifted through a suitable mesh and dry mixed with Lactose and Microcrystalline Cellulose sifted through 40# mesh. The blend of Ofloxacin, Lactose and Microcrystalline cellulose is mixed geometrically with Sodium Starch Glycolate sifted through 60# mesh. This blend is granulated with Starch paste prepared in Purified water. The Granules are dried in Fluidised Bed Drier (FBD) or any suitable drying apparatus to a moisture content of less than 2%. Dry Granulation Part Nitazoxanide is sifted through a suitable mesh and is mixed geometrically with Hydrogenated Castor Oil sifted through 60# mesh. This blend is further mixed with directly compressible Microcrystalline Cellulose sifted through 40# mesh. Croscarmellose Sodium and Talcum are sifted through 60# mesh and mixed geometrically with the above blend. Now this blend is mixed with dried granules of Ofloxacin and then mixed with Sodium Stearyl Fumarate sifted through 60# mesh. This final blend is compressed into tablets. These tablets may be further film coated. Example 2 Preparation of combination tablet of Nitazoxanide and Ofloxacin in single layer (Table Removed) Procedure: Wet Granulation Part Ofloxacin is sifted through a suitable mesh and dry mixed with Microcrystalline Cellulose sifted through 40# mesh. This blend of Ofloxacin and Microcrystalline Cellulose is mixed geometrically with Pregelatinized starch sifted through 60# mesh. This blend is granulated with Starch paste prepared in Purified water. The granules are dried in FBD or any suitable drying apparatus to a moisture content of less than 2%. Dry Granulation Part Nitazoxanide is sifted through suitable mesh and mixed geometrically with Hydrogenated castor oil sifted through 60# mesh. This blend is further mixed with directly compressible Microcrystalline Cellulose and Lactose sifted through 40# mesh. Croscarmellose Sodium and Talcum are sifted through 60# mesh and geometrically mixed with the above blend. Now this blend is mixed with dried granules of Ofloxacin and then mixed with Stearic Acid and Magnesium Stearate sifted through 60# mesh. This final blend is compressed into tablets. These tablets may be further film coated. Example 3 Preparation of combination tablet of Nitazoxanide and Ofloxacin in single layer (Table Removed) Procedure: Wet Granulation Part Ofloxacin is sifted through a suitable mesh and dry mixed with Microcrystalline Cellulose sifted through 40# mesh. The blend of Ofloxacin and Microcrystalline Cellulose is mixed geometrically with Croscarmellose Sodium sifted through 60# mesh. This blend is granulated with binder solution of Polyvinylpyrollidone in Purified water. The granules are dried in FBD or any suitable drying apparatus to a moisture content of less than 2%. Dry Granulation Part Nitazoxanide is sifted through a suitable mesh and mixed geometrically with Hydrogenated Castor Oil sifted through 60# mesh. This blend is further mixed with directly compressible Microcrystalline Cellulose sifted through 40# mesh. Croscarmellose Sodium and Talcum are sifted through 60# mesh and mixed geometrically with the above blend. Now this blend is mixed with dried granules of Ofloxacin and then mixed with Magnesium Stearate sifted through 60# mesh. This final blend is compressed into tablets. These tablets may be further film coated. Field of the Invention In general, the invention relates to pharmaceutical compositions containing a broad-spectrum antiparasitic and a fluoroquinolone. More particularly, the present invention provides for a pharmaceutical composition comprising a synergistic combination of Nitazoxanide and Ofloxacin, methods for producing the same and use thereof. Background of the Invention A combination of Metronidazole and Ofloxacin is the first line of treatment in Pelvic Inflammatory Diseases (PDD). It is also used popularly post surgically and for selective decontamination of the bowels in neutropenic patients. The literature reports problems connected with the development of resistance to Metronidazole. Nitazoxanide (NTZ) is an anti-protozoal drug active against a broad spectrum of protozoa and helminths that infect the intestinal tract of humans. Nitazoxanide is highly effective against anaerobic strains susceptible to Metronidazole (METRO). Nitazoxanide is highly effective against anaerobic strains susceptible to Metronidazole. For some strains with decreased susceptibility or increased resistance to Metronidazole (B. fragilis, Eubactrium spp & Bifidobacterium spp.), Nitazoxanide has shown high efficacy. Ofloxacin (OFLOX) has a broad spectrum of activity against aerobic gram +ve as well as gram -ve bacteria. Related Art United States Patent No. 5,387,598 to Rossignol, discloses compositions of Nitazoxanide for the treatment of diarrhea. The composition may also contain other active agents like an anthelmintic agent such as febantel, praziquantel, levamisole, albendazole, oxfendazole, moxidectin, ivermectin, milbemycins, etc. United States Patent No. 5,856,348 to Rossignol, discloses the use of a pharmaceutical composition containing Tizoxanide and Nitazoxanide for the treatment of a parasitic infection of a trematode selected from the group consisting of Schistosoma, Fasciola, Fasciolopsis, Dicrocoelium, Heterophyes and Metagonimus. Example 4 Preparation of combination tablet of Nitazoxanide and Ofloxacin in Bilayer (Table Removed) Procedure; Ofloxacin Layer Ofloxacin is sifted through a suitable mesh and mixed geometrically with Quinoline yellow aluminium lake sifted through 100# mesh. The blend of Ofloxacin and Quinoline yellow aluminium lake is mixed geometrically with Croscarmellose Sodium sifted through 60# mesh. This blend is granulated with Starch paste prepared in purified water. The granules are dried in FBD or any suitable drying apparatus to a moisture content of less than 2%. Directly compressible Microcrystalline Cellulose is sifted through 40# mesh and mixed with dried granules. Magnesium Stearate is sifted through 60# mesh and mixed with the above blend of granules. Nitazoxanide Layer Nitazoxanide is sifted through a suitable mesh and mixed geometrically with Hydrogenated Castor Oil sifted through 60# mesh. This blend is fiirther mixed with directly compressible Lactose and Microcrystalline Cellulose sifted through 40# mesh. Croscarmellose Sodium is sifted through 60# mesh and mixed geometrically with the above blend. Now this blend is mixed with Talcum. Ofloxacin layer and Nitazoxanide layer are compressed into bilayer tablets. These tablets may be fiirther film coated. Example 5 Preparation of combination tablet of Nitazoxanide and Ofloxacin in Bilayer (Table Removed) Procedure: Ofloxacin Layer Ofloxacin is sifted through a suitable mesh and mixed geometrically with Quinoline yellow aluminium lake sifted through 100# mesh. The blend of Ofloxacin and Quinoline yellow aluminium lake is mixed geometrically with Croscarmellose Sodium sifted through 60# mesh. This blend is granulated with Purified water. The granules are dried in FBD or any suitable drying apparatus to a moisture content of less than 2%. Directly compressible Microcrystalline Cellulose and Lactose are sifted through 40# mesh and mixed geometrically with Quinoline yellow aluminium lake sifted through 100# mesh. This blend is mixed geometrically with Croscarmellose Sodium sifted through 60# mesh and then with dried granules. Magnesium Stearate is sifted through 60# mesh and mixed with the above blend of granules. Nitazoxanide Layer Nitazoxanide is sifted through a suitable mesh and mixed geometrically with Hydrogenated Castor Oil sifted through 60# mesh. This blend is further mixed with directly compressible Microcrystalline Cellulose sifted through 40# mesh. Croscarmellose Sodium is sifted through 60# mesh and mixed geometrically with the above blend. Now this blend is mixed with Talcum. Ofloxacin layer and Nitazoxanide layer are compressed into bilayer tablets. These tablets may be further film coated. Example 6 Preparation of combination tablet of Nitazoxanide and Ofloxacin in single layer (Table Removed) Procedure: Ofloxacin is sifted through a suitable mesh and dry mixed with directly compressible Microcrystalline Cellulose and Lactose sifted through 40# mesh. Nitazoxanide is sifted through a suitable mesh and mixed geometrically with Hydrogenated Castor Oil sifted through 60# mesh. The blend of Ofloxacin, Lactose and Microcrystalline Cellulose is mixed with blend of Nitazoxanide and Hydrogenated Castor Oil. Pregelatinised starch, Croscarmellose Sodium and Talcum are sifted through 60# mesh and mixed geometrically with the above blend. Now this blend is mixed with Magnesium Stearate sifted through 60# mesh. This final blend is compressed into tablets. These tablets may be further film coated. Example 7 Preparation of combination tablet of Nitazoxanide and Ofloxacin in bilayer tablet (Table Removed) Procedure; Ofloxacin Layer Ofloxacin passed through a suitable mesh is mixed geometrically with Quinoline yellow lake passed through 100# mesh. It is then mixed geometrically with Croscarmellose Sodium and Pregelatinised starch passed through 60# mesh. Directly compressible Microcrystalline Cellulose and Lactose passed through 40# mesh are then mixed with this blend and finally lubricated with Magnesium Stearate passed through 60# mesh. Nitazoxanide Layer Nitazoxanide passed through a suitable mesh is mixed geometrically with Hydrogenated Castor Oil passed through 60# mesh. It is then mixed geometrically with Croscarmellose Sodium, Pregelatinised starch and Talc passed through 60# mesh. Directly compressible Microcrystalline Cellulose sifted through 40# mesh is then mixed with this blend. Both the above-mentioned layers are then compressed into Bilayer tablets, which may further be film coated. The clinical study shows that the fixed dose synergistic combination of Nitazoxanide and Ofloxacin is more effective and safe in the treatment of enterocolitis, urogenital infections including PID, suppurative pulmonary infections and skin & soft tissue infections than the fixed dose combination of Metronidazole and Ofloxacin. The double blind trial of Nitazoxanide and Ofloxacin conducted for the treatment of enterocolitis, urogenital infections including PID, suppurative pulmonary infections and skin & soft tissue infections provided a comparative analysis of the efficacy and safety of the investigational product with the conventional treatment i.e. Metronidazole and Ofloxacin. Analysis of the 100 patients data obtained from the study demonstrates that clinical response rate of Nitazoxanide and Ofloxacin combination was more as compared to the conventionally used Metronidazole and Ofloxacin combination. This trial confirmed that the fixed dose combination of Nitazoxanide and Ofloxacin administered at a dose of 500 and 200 mg respectively, twice daily for 5-7 consecutive days was more effective in enterocolitis, urogenital infections including PID and skin and soft tissue infections and equally effective for the treatment of suppurative pulmonary infections. The treatment schedule followed in this study was comparable to the standard schedule of Metronidazole and Ofloxacin combination. In addition, Nitazoxanide was very well tolerated and only minimal side effects such as nausea or loss of appetite were recorded, with no significant change in the haematological and clinical chemistry values. Further, certain modifications and improvements of the disclosed invention will occur to those skilled in the art without departing from the scope of invention, which is limited only by the appended claims. We Claim: 1. A pharmaceutical composition comprising synergistic effective amount of Nitazoxanide and a fluoroquinolone or pharmaceutically acceptable salts thereof with pharmaceutically acceptable inert excipients. 2. The composition according to claim 1, wherein the fluoroquinolone is preferably Ofloxacin. 3. The composition according to claim 1 or 2, wherein the synergistic composition is provided in a solid oral dosage form. 4. The composition according to claim 3, wherein the oral dosage form is preferably tablets comprising single layer or bilayer tablets. 5. The composition according to claim 4, wherein the single layer or bilayer tablet comprises dry mixtures of Nitazoxanide and Ofloxacin. 6. The composition according to claim 4, wherein the single layer or bilayer tablet comprises two parts, one part is wet granulation part and another is dry mixing part. 7. The composition according to claim 6, wherein said wet granulation part comprises Ofloxacin or pharmaceutically acceptable salts thereof in combination with pharmaceutically acceptable inert excipients. 8. The composition according to claim 6, wherein said dry mixing part comprises Nitazoxanide in combination with pharmaceutically acceptable inert excipients. 9. The composition according to any of the claims 1, 7 or 8, wherein the pharmaceutically inert excipients are selected from diluents, binders, disintegrating agents, glidants, or lubricants. 10. The composition according to claim 9, wherein the diluent is selected from a group comprising Lactose, Starch, Dicalcium Phosphate, Microcrystalline Cellulose, all other Starch derivatives and all other Cellulose derivatives or combinations thereof, most preferably Microcrystalline Cellulose and Lactose. 11. The composition according to claim 10, wherein the diluent used in the composition generally varies from 10% to 55% by weight of the composition, preferably from 15% to 50% by weight of the composition and in the granulation part varies from 1% to 65% by weight of the granulation part composition and in dry mixing part varies from 10% to 50% by weight of the dry mixing part composition. 12. The composition according to claim 9, wherein the disintegrating agent is selected from the group comprising Starch, Croscarmellose Sodium, Crospovidone, Sodium Starch Glycolate, Pregelatinized Starch and all other Starch or Cellulose derivatives or combinations thereof, most preferably Croscarmellose Sodium and Pregelatinised starch. 13. The composition according to claim 12, wherein the disintegrating agent used in the composition generally varies from 1% to 10% by weight of the composition, preferably from 2% to 5% by weight of the composition and in the granulation part generally varies from 1% to 8% by weight of the granulation part composition and in dry mixing part varies from 1% to 5% by weight of the dry mixing part composition. 14. The composition according to claim 9, wherein the binder is selected from a group comprising Polyvinylpyrollidone, Starch, Hydrogenated Castor Oil, Pregelatinized Starch, Hydroxypropyl Methycellulose and all other Starch or Cellulose derivatives or combinations thereof, preferably Starch, Hydrogenated Castor Oil or Pregelatinized Starch. 15. The composition according to claim 14, wherein the binder used in the composition varies from 1% to 8% by weight of the composition, and the binder used in the granulation part varies from 1% to 8% by weight of the granulation part composition, preferably from 3% to 6% by weight of the granulation part composition and in the dry mixing part varies from 1% to 8% by weight of the dry mixing part composition, preferably from 3% to 6% by weight of the dry mixing part composition. 16. The composition according to claim 9, wherein the glidants and lubricants are selected from the group comprising Talcum, Stearic Acid, Sodium Stearyl Fumarate, Hydrogenated Castor Oil or Magnesium Stearate, preferred glidant being Talcum and the preferred lubricants being Magnesium Stearate and Hydrogenated Castor Oil. 17. The composition according to claim 16, wherein the glidant used in the composition varies from 1% to 3% by weight of the composition, preferably from 1.0% to 2.0% by weight of the composition. 18. The composition according to claim 16, wherein the lubricant used in the composition varies from 1% to 5% by weight of the composition, preferably from 1% to 3% by weight of the composition. 19. A method of preparing a composition providing a synergistic combination of Nitazoxanide and Ofloxacin in an oral dosage form, preferably single layer or bilayer tablets form, the method comprising separately preparing wet granulation part of Ofloxacin employing pharmaceutically acceptable inert excipients and dry mixing part of Nitazoxanide employing pharmaceutically acceptable inert excipients, compressing the two parts into single or bilayer tablets. 20. A method of preparing a composition providing a synergistic combination of Nitazoxanide and Ofloxacin in an oral dosage form, preferably single layer or bilayer tablets form, the method comprising separately preparing dry mixing part of Ofloxacin employing pharmaceutically acceptable inert excipients and dry mixing part of Nitazoxanide employing pharmaceutically acceptable inert excipients, compressing the two parts into single or bilayer tablets. 21. The method according to claim 19 or 20, wherein the tablet is further coated employing a coating material and aqueous/non aqueous solvents. 22. The method according to claim 21, wherein the coating material may be a combination of any of the following - Talcum, Titanium Dioxide, Quinoline yellow aluminium lake or any other suitable lake or pigments, Lactose, Hydroxypropyl Methylcellulose, Acrylic polymers, Polyvinyl Alcohol, all other cellulose derivatives, Polyethylene Glycols, Triethyl Citrate, Tributyl Citrate, Dibutyl Sebacate, Diethyl Sebacate, Triacetin, Lecithin, Tween 80 and Sodium Lauryl Sulphate. 23. The method according to claim 19 or 20, wherein the granulation part contains a coloring agent, preferably Quinoline yellow aluminium lake. 24. The method according to claim 23, wherein the coloring agent varies from 0.5% to 2% by weight of the composition, preferably from 0.5% to 1% by weight of the composition. 25. Use of the composition according to any of the preceding claims for the treatment of infections caused by gram +ve and gram -ve aerobic bacteria, anaerobic bacteria including strains resistant to Metronidazole, mixed parasitic (protozoal and helminthic) and bacterial infections, Trichomonas vaginalis infections including strains resistant to Metronidazole, or H. pylori infections.

Documents:

1675-del-2004-Abstract-(20-05-2013).pdf

1675-del-2004-abstract.pdf

1675-del-2004-Assignment-(13-11-2014).pdf

1675-del-2004-Claims-(13-11-2014).pdf

1675-del-2004-Claims-(20-05-2013).pdf

1675-del-2004-claims.pdf

1675-del-2004-Correspondance Others-(13-11-2014).pdf

1675-del-2004-Correspondence-Others-(20-05-2013).pdf

1675-del-2004-Correspondence-Others-(22-05-2013).pdf

1675-del-2004-correspondence-others.pdf

1675-del-2004-description (complete).pdf

1675-del-2004-description (provisional).pdf

1675-del-2004-Form-1-(20-05-2013).pdf

1675-del-2004-form-1.pdf

1675-del-2004-form-18.pdf

1675-del-2004-form-2.pdf

1675-del-2004-form-3.pdf

1675-del-2004-form-5.pdf

1675-del-2004-GPA-(20-05-2013).pdf

1675-del-2004-GPA-(22-05-2013).pdf

1675-DEL-2004-OTHERS-131114.pdf

1675-del-2004-Petition-137-(20-05-2013).pdf