Novel substituted benzimidazole dosage forms and method of using same

Abstract

A method of treating gastric acid disorders by administering to a patient a pharmaceutical composition comprising a proton pump inhibitor (PPI) in a pharmaceutically acceptable carrier. The present invention provides an oral solution/suspension comprising a proton pump inhibitor and at least one buffering agent. The PPI can be any substituted benzimidazole compound having H + ,K + -ATPase inhibiting activity and being unstable to acid. Omeprazole and lansoprazole are the preferred PPIs for use in oral suspensions in concentrations of at least greater than 1.2 mg/ml and 0.3 mg, respectively. The liquid oral compositions can be further comprised of parietal cell activators, anti-foaming agents and/or flavoring agents. The inventive compositions can alternatively be formulated as a powder, tablet, suspension tablet, chewable tablet, capsule, effervescent powder, effervescent tablet, pellets and granules. Such dosage forms are advantageously devoid of any enteric coating or delayed or sustained-release delivery mechanisms, and comprise a PPI and at least one buffering agent to protect the PPI against acid degradation. Similar to the liquid dosage form, the dry forms can further include anti-foaming agents, parietal cell activators and flavoring agents. Kits utilizing the inventive dry dosage forms are also disclosed herein to provide for the easy preparation of a liquid composition from the dry forms. In accordance with the present invention, there is further provided a method of treating gastric acid disorders by administering to a patient a pharmaceutical composition comprising a proton pump inhibitor in a pharmaceutically acceptable carrier and at least one buffering agent wherein the administering step comprises providing a patient with a single dose of the composition without requiring further administering of the buffering agent. Additionally, the present invention relates to a method for enhancing the pharmacological activity of an intravenously administered proton pump inhibitor in which at least one parietal cell activator is orally administered to the patient before, during or after the intravenous administration of the proton pump inhibitor.

I claim:  
     
         1 . A liquid oral pharmaceutical composition, comprising: 
 a) a proton pump inhibitor; and    b) at least one buffering agent;    wherein if said proton pump inhibitor is omeprazole, it must be present in a concentration greater than 1.2 mg/ml, and if said inhibitor is lansoprazole, it must be present in a concentration greater than 0.3 mg/ml.    
     
     
         2 . The liquid oral pharmaceutical composition as recited in  claim 1  further comprising a parietal cell activator.  
     
     
         3 . The liquid oral pharmaceutical composition as recited in  claim 2  wherein said activator is selected from the group consisting of chocolate, sodium bicarbonate, a calcium salt, peppermint oil, spearmint oil, coffee, tea, cola, caffeine, theophylline, theobromine, at least one amino acid, and combinations thereof.  
     
     
         4 . The liquid oral pharmaceutical composition as recited in  claim 1  further comprising an anti-foaming agent.  
     
     
         5 . The liquid oral pharmaceutical composition as recited in  claim 1  further comprising a flavoring agent.  
     
     
         6 . A liquid oral pharmaceutical composition, comprising: 
 a) a proton pump inhibitor; and    b) at least one buffering agent;    wherein said proton pump inhibitor is selected from the group consisting of omeprazole (in a concentration greater than 1.2 mg/ml), lansoprazole (in a concentration greater than 0.3 mg/ml), pantoprazole, rabeprazole, dontoprazole, perprazole, habeprazole, ransoprazole, pariprazole, and leminoprazole.    
     
     
         7 . A solid oral pharmaceutical composition, comprising: 
 a) a proton pump inhibitor; and    b) at least one buffering agent;    wherein said composition is in a dosage form selected from the group consisting of a powder, a tablet, a suspension tablet, a chewable tablet, a capsule, an effervescent powder, an effervescent tablet, pellets and granules, and wherein said dosage form is not enteric coated or time-released.    
     
     
         8 . The solid oral pharmaceutical composition as recited in  claim 7  further comprising a parietal cell activator.  
     
     
         9 . The solid oral pharmaceutical composition as recited in  claim 7  further comprising an anti-foaming agent.  
     
     
         10 . The solid oral pharmaceutical composition as recited in  claim 7  wherein said composition is in the form of a tablet, said tablet comprising a central core of said proton pump inhibitor uniformly surrounded by the at least one buffering agent.  
     
     
         11 . The tablet composition as recited in  claim 10  wherein the buffering agent is sodium bicarbonate in an amount of approximately 1 mEq to approximately 25 mEq.  
     
     
         12 . The solid oral pharmaceutical composition as recited in  claim 7  wherein said composition is in the form of a tablet, said tablet comprising a substantially homogeneous mixture of said proton pump inhibitor and said at least one buffering agent.  
     
     
         13 . The tablet composition as recited in  claim 12  wherein the buffering agent is sodium bicarbonate in an amount of approximately 1 mEq to approximately 25 mEq.  
     
     
         14 . The solid oral pharmaceutical composition as recited in  claim 7  wherein said composition is in the form of an effervescent tablet, said tablet further comprising an effervescing agent.  
     
     
         15 . A method of treating gastric acid disorders comprising administering to a patient an oral pharmaceutical composition comprising a proton pump inhibitor and at least one buffering agent wherein said administering step comprises providing a patient with a single dose of the pharmaceutical composition without requiring further administration of the at least one buffering agent.  
     
     
         16 . A kit for the preparation of a liquid oral pharmaceutical composition, comprising: 
 a) a powder comprising a proton pump inhibitor; and    b) a liquid buffering agent to be mixed with said powder to form said liquid composition.    
     
     
         17 . A kit for the preparation of a liquid oral pharmaceutical composition, comprising a proton pump inhibitor in combination with at least one buffering agent, said combination in a dry form, and a diluent to be mixed with said dry form to create said composition.  
     
     
         18 . An oral pharmaceutical composition to be administered in combination with a proton pump inhibitor, comprising at least one buffering agent, wherein said composition is in a dosage form selected from the group consisting of a powder, a tablet, a chewable tablet, a capsule, an effervescent powder, an effervescent tablet, pellets and granules, and wherein said dosage form is not enteric coated or time-released.  
     
     
         19 . The oral pharmaceutical composition of  claim 18  further comprising a parietal cell activator.  
     
     
         20 . The oral pharmaceutical composition of  claim 18  further comprising a flavoring agent.  
     
     
         21 . A method for enhancing the pharmacological activity of a proton pump inhibitor intravenously administered to a patient, comprising orally administering to the patient at least one parietal cell activator at a time interval selected from the group consisting of before, during and after the intravenous administration of the proton pump inhibitor.  
     
     
         22 . The method as recited in  claim 21  wherein the parietal cell activator is selected from the group consisting of chocolate, sodium bicarbonate, a calcium salt, peppermint oil, spearmint oil, coffee, tea, cola, caffeine, theophylline, theobromine, at least one amino acid, and combinations thereof.