Formulations for a tight junction effector

Abstract

Enteric compositions comprising one or more tight junction agonists and/or one or more tight junction antagonists are provided. Compositions of the invention may comprise a delayed-release coating disposed over a tight junction agonist and/or tight junction antagonist layer which may be disposed over an inert core. Delayed-release coatings may be substantially stable in gastric fluid and substantially unstable in intestinal fluid, thus providing for substantial release of the tight junction agonist and/or antagonist from the composition in the duodenum or jejunum of the small intestine.

1 - 59 . (canceled) 
     
     
         60 . An oral dosage composition comprising an effective amount of larazotide acetate (AT1001) in the range of 100-1000 μg, wherein the composition comprises at least two populations of delayed-release particles each comprising:
 a core particle; 
 a base coat comprising larazotide acetate over the core particle; and 
 a delayed-release coating disposed over the base coat, wherein the delayed release coating is substantially stable in an acidic environment and substantially unstable in a near neutral to alkaline environment, 
 wherein the particles contain from 0.1 wt % to 1 wt % larazotide acetate, 
 wherein the at least two populations of delayed release particles have different levels of the delayed release coating so as to begin release of larazotide acetate about 30 minutes apart in the near neutral to alkaline environment, and 
 wherein the composition releases at least 70% of the larazotide by about 90 minutes. 
 
     
     
         61 . The composition of  claim 60 , wherein the composition is in the form of a capsule or tablet. 
     
     
         62 . The composition of  claim 60 , wherein the core particle has an average size of from about 5 to about 50 mesh. 
     
     
         63 . The composition of  claim 62 , wherein the core particle has an average size of from about 15 to about 40 mesh. 
     
     
         64 . The composition of  claim 60 , wherein the core particle comprises an oxide, cellulose, a polymer, an inorganic salt, or a sugar. 
     
     
         65 . The composition of  claim 64 , wherein the core particle comprises a sugar. 
     
     
         66 . The composition of  claim 60 , wherein the delayed-release coating comprises polymethacrylate. 
     
     
         67 . The composition of  claim 66 , wherein the polymethacrylate is a 1:1 copolymer of polymethacrylic acid and ethyl acrylate. 
     
     
         68 . The composition of  claim 60 , further comprising a sealing coat disposed over the coats comprising larazotide acetate. 
     
     
         69 . The composition of  claim 68 , wherein the sealing coat comprises sugar, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl cellulose, methylcellulose, ethylcellulose, and/or hydroxypropylmethylcellulose (HPMC). 
     
     
         70 . The composition of  claim 60 , further comprising a top coat outside of the delayed-release particles. 
     
     
         71 . The composition of  claim 70 , wherein the top coat comprises sugar, polyethylene glycol, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl acetate, hydroxypropyl cellulose, methylcellulose, ethylcellulose, and/or hydroxypropylmethylcellulose (HPMC). 
     
     
         72 . The composition of  claim 60 , wherein the base coat comprising larazotide acetate further comprise a pharmaceutically-acceptable binder. 
     
     
         73 . The composition of  claim 72 , wherein the binder comprises a natural sugar, starch, gelatin, corn sweetener, gum, carboxymethylcellulose, polyvinyl pyrrolidone, hydroxypropyl cellulose, hydroxyethyl cellulose, ethylcellulose, polymethacrylate, polyethylene glycol, or wax. 
     
     
         74 . The composition of  claim 60 , further comprising an inert processing aid and/or plasticizer. 
     
     
         75 . The composition of  claim 74 , wherein the inert processing aid comprises silicon dioxide, talc, and/or magnesium stearate. 
     
     
         76 . The composition of  claim 74 , wherein the plasticizer comprises citric acid ester, triacetin, phthalic acid ester, dibutyl sebacate, cetyl alcohol, polyethylene glycol, and/or polysorbate. 
     
     
         77 . The composition of  claim 60 , wherein the near neutral to alkaline environment is a simulated intestinal fluid having a pH of about 6.