Pharmaceutical compositions for gastrointestinal drug delivery

Abstract

A novel pharmaceutical composition, which comprises a therapeutically effective amount of active principle(s) or a pharmaceutically acceptable salt or enantiomer or polymorph thereof, optionally one or more release controlling agent(s) and pharmaceutical acceptable excipient(s) thereof, wherein the composition is formulated to increase the residence time of the said pharmaceutical composition and/or active principle(s) in the gastrointestinal tract. A novel pharmaceutical composition comprising at least two entities wherein one entity is an immediate release/fast release and the other is controlled release. A pharmaceutical composition comprising at least two entities wherein one entity is an immediate release/fast release and the other is bioadhesive. A pharmaceutical composition comprising: at least two entities wherein one entity is controlled release and the other is bioadhesive All the three compositions are formulated to increase the residence time of active principle(s) in the gastrointestinal tract. A multilayered composition with active in a layer which provides immediate release or controlled release of active principles and layer providing increased residence time in the GI tract.

1 - 33 . (canceled) 
     
     
         34 . A pharmaceutical composition, which comprises a therapeutically effective amount of active principle(s), selected from rifaximin, mesalamine, balsalazide, or a pharmaceutically acceptable salt or enantiomer or polymorph thereof,
 one or more release controlling agent(s), wherein the release controlling agent is selected from cellulose, ethyl cellulose, cellulose acetate and hydroxypropyl methyl cellulose and large molecular weight polyanhydrides, waxes, carbomers, polyalkylene polyols, polycarbophils, methacrylic acid, gelatins, gums, polyethylene oxides, and polyvinyl pyrrolidone, or mixtures thereof;   and one or more bioadhesive polymer(s) having affinity for gastrointestinal mucosa that increases the residence time of the pharmaceutical composition and/or active principle(s) in the gastrointestinal tract,   wherein the composition has an adhesive strength, measured as a force of detachment of at least 1000 mN in 30 minutes.   
     
     
         35 . The pharmaceutical composition as in  claim 34 , wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable excipient(s) selected from binders, diluents, lubricants, surfactants and glidants. 
     
     
         36 . The pharmaceutical composition as in  claim 34 , which further comprises one or more solubilizing agent(s) selected from water-soluble or water dispersible nonionic, semi-polar nonionic, anioinic, cationic, amphoteric, or zwitterionic surface-active agents; cyclodextrin; lipophilic substances; vitamin E; monohydric alcohol esters such as trialkyl citrates, lactones and lower alcohol fatty acid esters; nitrogen-containing solvents; phospholipids; glycerol acetates such as acetin, diacetin and triacetin; glycerol fatty acid esters such as mono-, di- and triglycerides and acetylated mono- and diglycerides; propylene glycol esters; ethylene glycol esters or any combination thereof. 
     
     
         37 . The pharmaceutical composition as in  claim 35 , wherein the binder is one or more selected from carbohydrates, celluloses, starches, gums, polyvinylpyrrolidone, povidone, polyethylene oxide, polyacryl amide, poly-N-vinyl amide, sodium carboxymethyl cellulose, polyethylene glycol, gelatin, polyethylene oxide, polypropylene glycol, tragacanth, alginic acid, or any combination thereof. 
     
     
         38 . The pharmaceutical composition as in  claim 35 , wherein diluent is one or more selected from carbohydrates, polyols, sugar alcohols, carbonates, sulphate or phosphate salts of inorganic metals or mixtures thereof. 
     
     
         39 . The pharmaceutical composition as in  claim 35 , wherein the lubricant is one or more selected from magnesium, aluminium, zinc or calcium stearate, polyethylene glycol, mineral oil, sodium stearyl fumarate, stearic acid, hydrogenated vegetable oil, glyceryl behenate, glyceryl palmitostearate, glyceryl stearate, cornstarch, talc, calcium silicate, magnesium silicate, colloidal silicon dioxide, silicon hydrogel, and mixtures thereof. 
     
     
         40 . The pharmaceutical composition as in  claim 35 , wherein the surfactant is selected from ionic or non-ionic or zwitterionic surfactants. 
     
     
         41 . The pharmaceutical composition as in  claim 35 , wherein the glidant is one or more selected from silicon dioxide, colloidal silica, powdered cellulose, talc, tribasic calcium phosphate and mixtures thereof. 
     
     
         42 . The pharmaceutical composition as in  claim 35 , wherein increase in residence time in the gastrointestinal tract is achieved by bioadhesion and/or by delaying expulsion from the gastrointestinal tract. 
     
     
         43 . The pharmaceutical composition as in  claim 42 , wherein bioadhesion is achieved with polymers having affinity for gastrointestinal mucosa selected from polycarbophils, carbomers, lectins, pectine, zein, modified zein, casein, gelatin, gluten, serum albumin, collagen, chitosan, oligosaccharides and polysaccharides, such as cellulose, such as methyl cellulose, ethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxybutylmethyl cellulose, cellulose acetate, cellulose propionate, cellulose acetate butyrate, cellulose acetate phthalate, carboxymethyl cellulose, cellulose triacetate, cellulose sulfate sodium salt, dextrans, tamarind seed polysaccharide, gellan, carrageenan; hyaluronic acid, polyhyaluronic acid, alginic acid, sodium alginate; gums, xanthan gum, guar gum, gum Arabic locust bean gum; poly vinylacetatae, polyvinylalcohol, povidone/polyethylene oxide, acrylic and methacrylic acid their copolymers, polyamides, polycarbonates, polyalkylenes, polyalkylene glycols, polyalkylene oxides, polyalkylene terephthalates, polyvinyl alcohols, polyvinyl ethers, polyvinyl esters, polyvinyl halides, polyvinylpyrrolidone, polyglycolides, polysiloxanes, polyurethanes, polystyrene, polymers of acrylic and methacrylic esters, polylactides, poly(butyric acid), poly(valeric acid), poly(lactide-co-glycolide), polyanhydrides, polyorthoesters, poly(fumaric acid), poly(maleic acid), polymers having a hydrophobic backbone with at least one hydrophilic group pendant from the backbone, polymers having a hydrophobic backbone with at least one hydrophobic group pendant from the backbone, and blends and copolymers or mixtures thereof. 
     
     
         44 . The pharmaceutical composition as in  claim 43 , wherein the bioadhesion is provided for a period greater than 0.5 hours. 
     
     
         45 . The pharmaceutical composition as in  claim 34 , which is formulated as a compressed or compacted dosage form. 
     
     
         46 . The pharmaceutical composition as in  claim 34 , which is formulated as a powder, pellet, bead, granule, tablet, compact, sustained release formulation, capsule, microcapsule, tablet in capsule, tablet in tablet, microsphere, shear form particle, floss, and flakes or mixtures thereof. 
     
     
         47 . The pharmaceutical composition as in  claim 46 , wherein the tablet includes a single layered tablet, multilayered tablet, mini tablet, bioadhesive tablet, caplet, matrix tablet, tablet within a tablet, or mucoadhesive tablet.