Viscous budesonide for the treatment of inflammatory diseases of the gastrointestinal tract

Abstract

Provided herein are methods for preventing or alleviating the symptoms of and inflammation associated with inflammatory diseases and conditions of the gastrointestinal tract, for example, those involving the esophagus. Also provided herein are pharmaceutical compositions useful for the methods of the present invention.

What is claimed is: 
     
         1 . A method of preventing or alleviating esophageal inflammation in an individual comprising orally administering to said individual a corticosteroid in association with at least one viscosity enhancing excipient, wherein upon oral administration, the corticosteroid is present in a medium with a viscosity of at least 2 cP at 25 degrees Celcius and a shear rate of about 13.2 sec −1 . 
     
     
         2 . The method of  claim 1 , wherein the corticosteroid is administered in a pharmaceutical composition comprising the corticosteroid and the at least one viscosity enhancing excipient. 
     
     
         3 . The method of  claim 2 , wherein the pharmaceutical composition further comprises a liquid vehicle. 
     
     
         4 . The method of  claim 3 , wherein the pharmaceutical composition is a suspension comprising corticosteroid microparticles. 
     
     
         5 . The method of  claim 3 , wherein the viscosity of the pharmaceutical composition is at least 10 cP at 25 degrees Celcius and a shear rate of about 13.2 sec −1 . 
     
     
         6 . The method of  claim 2 , wherein the pharmaceutical composition is in the form of a dissolvable tablet, a dissolvable wafer, or a dissolvable capsule. 
     
     
         7 . The method of  claim 2 , wherein the pharmaceutical composition is administered once a day, twice a day, or three times a day. 
     
     
         8 . The method of  claim 2 , wherein the pharmaceutical composition is administered no more than once a day. 
     
     
         9 . The method of  claim 1 , wherein said corticosteroid is a topical corticosteroid. 
     
     
         10 . The method of  claim 1 , wherein said corticosteroid is Budesonide. 
     
     
         11 . The method of  claim 1 , wherein the viscosity enhancing excipient is selected from the group consisting of lactose, sucrose, sucralose, maltodextrin, dextrose, mannitol, sorbitol, honey, maize starch, wheat starch, rice starch, potato starch, gelatin, gum tragacanth, methyl cellulose, hydroxypropylmethyl-cellulose, a carboxymethyl cellulose (CMC), sodium carboxymethyl-cellulose (NaCMC), polyvinylpyrrolidone (PVP: povidone), and combinations thereof. 
     
     
         12 . The method of  claim 1 , wherein the esophageal inflammation is eosinophilic esophagitis. 
     
     
         13 . The method of  claim 1 , wherein said individual has been diagnosed with a disease or condition selected from the group consisting of eosinophilic esophagitis, inflammatory bowel diseases involving the esophagus, Crohn's disease, esophageal inflammation secondary to caustic/irritant ingestion, persistent/recurrent esophageal strictures of any cause and including caustic/irritant ingestion, pill-induced esophagitis, systemic diseases, congenital diseases, and post-surgery inflammation. 
     
     
         14 . The method of  claim 1 , wherein 0.5-10 mg corticosteroid per day is administered to said individual. 
     
     
         15 . The method of  claim 2 , wherein oral administration of the pharmaceutical composition provides a decreased systemic load of corticosteroid, as measured by plasma AUC 0-∞ , when compared to inhaled administration delivering an identical amount of corticosteroid. 
     
     
         16 . The method of  claim 2 , wherein the pharmaceutical composition comprises corticosteroid microparticles, wherein at least 95% of the corticosteroid microparticles have a diameter of less than 10 microns. 
     
     
         17 . An oral pharmaceutical composition comprising a therapeutically effective amount of a corticosteroid, and a liquid vehicle, wherein the pharmaceutical composition has a viscosity of greater than 2 cP at 25° C. and a shear rate of about 13.2 sec −1 , and wherein the pharmaceutical composition is suitable for oral administration. 
     
     
         18 . The oral pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition has a viscosity about 50 cP or greater at 25° C. and a shear rate of about 13.2 sec −1 . 
     
     
         19 . The oral pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition has a viscosity of about 200 cP at 25° C. and a shear rate of about 13.2 sec −1 . 
     
     
         20 . The oral pharmaceutical composition of  claim 17 , wherein the oral pharmaceutical composition is thixatropic. 
     
     
         21 . The oral pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition has a volume of about 2 mL to about 20 mL. 
     
     
         22 . The oral pharmaceutical composition of  claim 17 , wherein the corticosteroid is a topical corticosteroid. 
     
     
         23 . The oral pharmaceutical composition of  claim 22 , wherein the topical corticosteroid is budesonide. 
     
     
         24 . The oral pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition comprises about 250 μg to about 10 mg of corticosteroid. 
     
     
         25 . The oral pharmaceutical composition of  claim 17  further comprising a viscosity enhancing agent. 
     
     
         26 . The oral pharmaceutical composition of  claim 25 , wherein the wherein the viscosity enhancing agent is selected from a crosslinked poly(acrylic acid), a carbomer homopolymer, a carbomer copolymer, acacia (gum arabic), agar, aluminum magnesium silicate, sodium alginate, sodium stearate, bladderwrack, bentonite, carbomer, carrageenan, Carbopol, a cellulose, ceratonia, chondrus, dextrose, furcellaran, gelatin, Ghatti gum, guar gum, hectorite, lactose, sucrose, maltodextrin, mannitol, sorbitol, honey, maize starch, wheat starch, rice starch, potato starch, gelatin, sterculia gum, xanthum gum, polyethylene glycol, gum tragacanth, ethyl cellulose, ethylhydroxyethyl cellulose, ethylmethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, poly(hydroxyethyl methacrylate), oxypolygelatin, pectin, polygeline, povidone, propylene carbonate, methyl vinyl ether/maleic anhydride copolymer (PVM/MA), poly(methoxyethyl methacrylate), poly(methoxyethoxyethyl methacrylate), hydroxypropyl cellulose, hydroxypropylmethyl-cellulose, a carboxymethyl-cellulose (CMC), silicon dioxide, polyvinylpyrrolidone (PVP: povidone) and combinations thereof. 
     
     
         27 . The oral pharmaceutical composition of  claim 17 , wherein the pharmaceutical composition is a suspension, solution, syrup, or slurry. 
     
     
         28 . The oral pharmaceutical composition of  claim 17 , the pharmaceutical composition comprises corticosteroid microparticles, wherein at least 95% of the corticosteroid microparticles have a diameter of less than 10 microns.