Orally disintegrating compositions

Abstract

An orally disintegrating dosage form of a proton pump inhibitor, methods for its production and use thereof are provided. The dosage form includes a plurality of pellets containing a proton pump inhibitor admixed with a disintegrant to afford rapid

1 . An orally disintegrating composition comprising (i) enteric coated active cores comprising a therapeutically effective amount of a proton pump inhibitor; and (ii) at least one pharmaceutically acceptable excipient comprising a disintegrant, wherein the composition substantially disintegrates in the oral cavity of a subject in need thereof within less than about 60 seconds after administration, and wherein in vitro drug release in 15 minutes at 0.1N HCl and 40% ethanol is less than about 20%. 
     
     
         2 . The orally disintegrating composition of  claim 1 , wherein after administration the composition provides a release profile of the proton pump inhibitor which is substantially the same as the release profile of a non-orally disintegrating composition in the absence of alcohol. 
     
     
         3 . The orally disintegrating composition of  claim 1 , wherein after administration the composition provides a release profile of the proton pump inhibitor in the presence of up to 40% ethanol which is substantially the same as the release profile of the composition in the absence of alcohol. 
     
     
         4 . The orally disintegrating composition of  claim 1 , wherein after administration the composition results in a C max  or AUC substantially equivalent to a non-orally disintegrating composition in the absence of alcohol. 
     
     
         5 . The orally disintegrating composition of  claim 1  in the form of an orally disintegrating tablet. 
     
     
         6 . The orally disintegrating composition of  claim 5 , wherein the tablet is characterized by hardness of at least 20 Newtons. 
     
     
         7 . The orally disintegrating composition of  claim 1 , wherein the proton pump inhibitor comprises lansoprazole, omeprazole, pantoprazole, leminoprazole, perprazole, rabeprazole, or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The orally disintegrating composition of  claim 1 , wherein the active cores comprise a plurality of inert seeds coated with a therapeutically effective amount of a proton pump inhibitor. 
     
     
         9 . The orally disintegrating composition of  claim 8 , wherein the inert seeds comprise sugar spheres. 
     
     
         10 . The orally disintegrating composition of  claim 1 , wherein the active cores further comprise at least one excipient selected from a binder, a filler, a surfactant, and a combination thereof. 
     
     
         11 . The orally disintegrating composition of  claim 1 , wherein the active cores further comprise an alkalizing agent. 
     
     
         12 . The orally disintegrating composition of  claim 1 , wherein the enteric coated active cores comprise one or more enteric polymers over the active cores, wherein the enteric polymer is selected from the group consisting of cellulose acetate phthalate (CAP), hydroxypropyl methylcellulose phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMCAS), polyvinyl acetate phthalate, cellulose acetate trimellitate, polymethacrylic acid, polymethyl methacrylate, and polyethyl methacrylate. 
     
     
         13 . The orally disintegrating composition of  claim 1 , wherein the enteric coated active cores comprise a subcoating layer over the active cores and an enteric coating over the subcoating layer. 
     
     
         14 . The orally disintegrating composition of  claim 13 , wherein the subcoating layer comprises at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, polyvinylpyrrolidone, polyethylene glycol, and polyvinyl alcohol. 
     
     
         15 . The orally disintegrating composition of  claim 1 , wherein the disintegrant is selected from the group consisting of crospovidone, croscarmelose sodium, a sugar alcohol, a cellulose derivative, cross-linked derivatives of starch, pregelatinized starch and a combination or mixture thereof. 
     
     
         16 . The orally disintegrating composition of  claim 15 , wherein the sugar alcohol is selected from the group consisting of mannitol, sorbitol, maltitol, xylitol, and a combination or mixture thereof. 
     
     
         17 . The orally disintegrating composition of  claim 15 , wherein the cellulose derivative is selected from the group consisting of methylcellulose, cross-linked carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose, low substituted hydroxypropylcellulose, microcrystalline cellulose and a combination or mixture thereof. 
     
     
         18 . The orally disintegrating composition of  claim 15 , wherein the cross-linked derivatives of starch comprise sodium starch glycolate. 
     
     
         19 . The orally disintegrating composition of  claim 1 , comprising:
 (a) inert seeds in an amount of about 2% to about 10% by weight of the total composition;   (b) a proton pump inhibitor in an amount of about 3% to about 9% by weight of the total composition;   (c) a subcoating layer in an amount of about 5% to about 15% by weight of the total composition;   (d) an enteric coating in an amount of about 10% to about 25% by weight of the total composition;   (e) at least one disintegrant in an amount of about 2% to about 15% by weight of the total composition; and   (f) optionally one or more excipients selected from a binder, a filler, an anti-tacking agent, an alkalizing agent, a lubricant, a glidant, a surfactant, a plasticizer or a combination thereof in an amount of not more than about 30% by weight of the total composition,   wherein presence of all components add to 100% (w/w).   
     
     
         20 . The orally disintegrating composition of  claim 19 , further comprising at least one alkalizing agent in an amount of about 1% to about 5% by weight of the total composition. 
     
     
         21 . (canceled) 
     
     
         22 . (canceled) 
     
     
         23 . A method of inhibiting gastric acid secretion, the method comprising administering to a subject in need thereof the orally disintegrating composition of  claim 1 . 
     
     
         24 . A method of treating a disease or disorder selected from gastroesophageal reflux disease, gastritis, peptic ulcers (duodenal and gastric) and erosive esophagitis, the method comprising administering to a subject in need thereof the orally disintegrating composition of  claim 1 .