Pharmaceutical formulations useful for inhibiting acid secretion and methods for making and using them

Abstract

In one general aspect of the present invention, pharmaceutical formulations comprising both a proton pump inhibitor microencapsulated or dry coated with a material that enhances the shelf-life of the pharmaceutical composition and one or more antacid are described. In another general aspect of the present invention, pharmaceutical formulations comprising both a proton pump inhibitor microencapsulated or dry coated with a taste-masking material and one or more antacid are described.

What is claimed is: 
     
         1 . A pharmaceutical formulation comprising (a) at least one non-enteric coated acid-labile proton pump inhibitor that is dry coated, and (b) at least one antacid;
 wherein an initial serum concentration of the proton pump inhibitor is greater than about 0.1 μg/ml within about 30 minutes after administration of the pharmaceutical formulation to a subject.   
     
     
         2 . A pharmaceutical formulation according to  claim 1 , wherein at least some of the antacid is used to dry coat the proton pump inhibitor. 
     
     
         3 . A pharmaceutical formulation according to  claim 1 , wherein part of the antacid is used to dry coat the proton pump inhibitor and part of the antacid is combined with the dry coated proton pump inhibitor. 
     
     
         4 . A pharmaceutical formulation according to  claim 3 , wherein the antacid combined with the dry coated proton pump inhibitor comprises at least one antacid that is different from the antacid used to dry coat the proton pump inhibitor. 
     
     
         5 . A pharmaceutical formulation according to  claim 2 , wherein the antacid used to dry coat the proton pump inhibitor comprises an alkaline metal salt or a Group IA metal selected from a bicarbonate salt of a Group IA metal, a carbonate salt of a Group IA metal. 
     
     
         6 . A pharmaceutical formulation according to  claim 5 , wherein the material used to dry coat the proton pump inhibitor further comprises sodium bicarbonate or sodium carbonate. 
     
     
         7 . A pharmaceutical formulation according to  claim 2 , wherein the material used to dry coat the proton pump inhibitor further comprises a binder. 
     
     
         8 . A pharmaceutical formulation according to  claim 6 , wherein the material used to dry coat the proton pump inhibitor further comprises a sweetener selected from sucralose, xylitol or mixtures thereof. 
     
     
         9 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is a substituted bicyclic aryl-imidazole selected from the group consisting of omeprazole, hydroxyomeprazole, esomeprazole, tenatoprazole, lansoprazole, pantoprazole, rabeprazole, dontoprazole, habeprazole, perprazole, ransoprazole, pariprazole, leminoprazole; or a free base, free acid, salt, hydrate, ester, amide, enantiomer, isomer, tautomer, polymorph, or prodrug thereof. 
     
     
         10 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is selected from omeprazole, or a free base, free acid, salt, hydrate, polymorph, or prodrug thereof. 
     
     
         11 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is selected from lansoprazole, or a free base, free acid, salt, hydrate, polymorph, or prodrug thereof. 
     
     
         12 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is selected from esomeprazole, or a free base, free acid, salt, hydrate, polymorph, or prodrug thereof. 
     
     
         13 . A pharmaceutical formulation according to  claim 1  comprising about 5 mgs to about 200 mgs of the proton pump inhibitor. 
     
     
         14 . A pharmaceutical formulation according to  claim 1  comprising about 10 mgs, or about 15 mgs, or about 20 mgs, or about 30 mgs, or about 40 mgs, or about 60 mgs, or about 80 mgs of the proton pump inhibitor. 
     
     
         15 . A pharmaceutical formulation according to  claim 1 , wherein the antacid is selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium carbonate, aluminum hydroxide, and mixtures thereof. 
     
     
         16 . A pharmaceutical formulation according to  claim 1 , wherein the antacid comprises at least one soluble buffer. 
     
     
         17 . A pharmaceutical formulation according to  claim 16 , wherein the soluble buffer is present in at least about 5 mEq. 
     
     
         18 . A pharmaceutical formulation according to  claim 1 , wherein the antacid is present in an amount of between about 5 mEq to about 60 mEq. 
     
     
         19 . A pharmaceutical formulation according to  claim 1  comprising about 500 to about 2000 mg of antacid. 
     
     
         20 . A pharmaceutical formulation according to  claim 1 , wherein the pharmaceutical formulation has less than 5% total new impurities after 1 year of storage at room temperature. 
     
     
         21 . A pharmaceutical formulation according to  claim 1  in the form of a capsule, a chewable tablet, a tablet, a caplet, or a capsule. 
     
     
         22 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is dry coated using a dry granulation technique. 
     
     
         23 . A pharmaceutical formulation according to  claim 1 , wherein the proton pump inhibitor is dry coated using a nano particle coating technique. 
     
     
         24 . A pharmaceutical formulation according to  claim 1 , wherein serum concentration of the proton pump inhibitor is greater than about 0.5 μg/ml within about 1 hour after administration of the pharmaceutical formulation to a subject. 
     
     
         25 . A pharmaceutical formulation according the  claim 1 , wherein the average particle size of the dry blended proton pump inhibitor is between about 100 to about 1000 microns in diameter. 
     
     
         26 . A pharmaceutical formulation according the  claim 1 , wherein the average particle size of the dry blended proton pump inhibitor is between about 100 to about 1000 microns in diameter. 
     
     
         27 . A pharmaceutical formulation according the  claim 1 , wherein the average particle size of the dry blended proton pump inhibitor is between about 300 to about 700 microns in diameter. 
     
     
         28 . A pharmaceutical formulation according to  claim 1 , wherein a maximum serum concentration is reached within about 45 minutes after administration of the pharmaceutical formulation to a fasting subject. 
     
     
         29 . A pharmaceutical formulation according to  claim 1 , wherein a maximum serum concentration is reached within about 60 minutes after administration of the pharmaceutical formulation to a fasting subject. 
     
     
         30 . A pharmaceutical formulation according to  claim 1 , wherein the drug loading of the proton pump inhibitor in the dry coated granules is greater than about 10 wt-% of proton pump inhibitor. 
     
     
         31 . A pharmaceutical formulation according to  claim 1 , wherein the drug loading of the proton pump inhibitor in the dry coated granules is between about 5 wt-% to about 40 wt-% of proton pump inhibitor. 
     
     
         32 . A method of treating an acid related gastrointestinal disorder in a subject in need thereof by administering the pharmaceutical formulation of  claim 1 . 
     
     
         33 . A chewable tablet comprising:
 (a) between about 10-80 mgs of a proton pump inhibitor which is microencapsulated with a material comprising a cellulose hydroxypropyl ether;   (b) between about 10 mEq and about 100 mEq of antacid selected from sodium bicarbonate, sodium carbonate, calcium carbonate, magnesium oxide, potassium bicarbonate, magnesium hydroxide, magnesium carbonate, and mixtures thereof; and   (c) at least one flavoring agent;   wherein the drug loading of the proton pump inhibitor into microspheres is between about 20 wt-% to about 50 wt-% of proton pump inhibitor to microencapsulated proton pump inhibitor.   
     
     
         34 . A chewable tablet according to  claim 33 , wherein the flavoring agent comprises peach, menthol, aspartame, sucralose, sucrose, xylitol, mint, or a mixture thereof. 
     
     
         35 . A chewable tablet according to  claim 33 , wherein the antacid is a mixture of sodium bicarbonate and magnesium hydroxide. 
     
     
         36 . A chewable tablet according to  claim 33 , wherein the drug loading of the proton pump inhibitor into microspheres is about 37 wt-% of proton pump inhibitor. 
     
     
         37 . A chewable tablet according to  claim 33 , wherein a serum concentration of the proton pump inhibitor is greater than about 0.5 μg/ml within about 1 hour after administration of the pharmaceutical formulation to a subject. 
     
     
         38 . A chewable tablet according to  claim 33 , wherein upon administration of the chewable tablet to a fasted subject, the maximum serum concentration of the proton pump inhibitor is reached within about 45 minutes after administration. 
     
     
         39 . A chewable tablet according to  claim 33 , wherein greater than about 70% of the proton pump inhibitor is released from the composition within about 1.5 hours after exposure to gastrointestinal fluid.