Procedure for preparing enteric-coated pellets containing a proton pump inhibitor and multi-particle pharmaceutical compositions containing them

Abstract

Pharmaceutical compositions are provided which include enteric-coated pellets. The enteric-coated pellets include pure cellulose cores. A coating is present on the cores which contains 1) a proton pump inhibitor with benzimidazole structure in an amount greater than 10.5% by weight with respect to the total weight of the enteric-coated pellets, 2) one or more of lysine, histidine, and L-arginine, and 3) polyvinylpyrrolidone, wherein the dibasic amino acid is present in an amount less than or equal to 10% by weight in relation to the weight of the proton pump inhibitor. An enteric coating disposed over said coating. Enteric-coated pellets that contain pure cellulose cores having an average diameter between 150 and 300 microns have an average diameter between 350 and 590 microns and the enteric-coated pellets that contain pure cellulose cores with an average diameter between 300 and 500 microns have an average diameter between 500 and 710 microns.

1 . A pharmaceutical composition, comprising:
 enteric-coated pellets having an average diameter between 350 and 710 microns, the enteric-coated pellets comprising:
 pure cellulose cores, wherein the cores have a particle size range between 150 and 500 microns, 
   a coating disposed on the pure cellulose cores, the coating containing each of: a proton pump inhibitor with benzimidazole structure in an amount greater than 10.5% by weight with respect to the total weight of the enteric-coated pellets, a dibasic amino acid selected from the group consisting of lysine, histidine and L-arginine, and polyvinylpyrrolidone, wherein the dibasic amino acid is present in an amount less than or equal to 10% by weight in relation to the weight of the proton pump inhibitor, and
 an enteric coating disposed over said coating, 
   wherein enteric-coated pellets that contain pure cellulose cores having an average diameter between 150 and 300 microns have an average diameter between 350 and 590 microns and enteric-coated pellets that contain pure cellulose cores with an average diameter between 300 and 500 microns have an average diameter between 500 and 710 microns.   
     
     
         2 . The pharmaceutical composition according to  claim 1 , wherein the enteric-coated pellets are present in an amount of 20 to 35% by weight, with respect to the total weight of the pharmaceutical composition, wherein the pharmaceutical composition further comprises one or more pharmaceutically-acceptable excipients, and wherein the pharmaceutical composition is an oral disintegration tablet. 
     
     
         3 . The composition according to  claim 2 , wherein the oral disintegration tablet has a disintegration time in a buccal cavity of less than 30 seconds. 
     
     
         4 . The pharmaceutical composition according to  claim 1 , wherein the enteric-coated pellets are present in an amount between 2 and 4% by weight, with respect to the total weight of the pharmaceutical composition, wherein the pharmaceutical composition further comprises:
 between 10 and 30% by weight, of a mixture of microcrystalline cellulose and carboxymethyl cellulose;   between 2 and 6%, of citric acid; and   at least one flavoring, wherein the pharmaceutical composition is a powder formulated for oral suspension.   
     
     
         5 . The pharmaceutical composition according to  claim 1 , wherein the enteric-coated pellets are disposed in a gelatin capsule smaller than capsule size No. 2. 
     
     
         6 . The pharmaceutical composition according to  claim 1 , wherein the pharmaceutical composition comprises 10, 20 or 40 mg of the proton pump inhibitor. 
     
     
         7 . The pharmaceutical composition according to  claim 1 , formulated as a single or multiple dose pharmaceutical composition. 
     
     
         8 . The pharmaceutical composition according to  claim 1 , further comprising enteric-coated microcapsules of diclofenac. 
     
     
         9 . The pharmaceutical composition according to  claim 8 , wherein the proton pump inhibitor is present in an amount in the range of 10 to 40 mg and the diclofenac is present in an amount in the range of 25 to 100 mg. 
     
     
         10 . The pharmaceutical composition according to  claim 8 , wherein the proton pump inhibitor is omeprazole or esomeprazole.