Immediate Release Compositions and Methods For Delivering Drug Formulations Using Weak Acid Ion Exchange Resins In Abnormally High pH Environments

Abstract

Multi-layer solid oral dosage immediate release and extended release compositions and methods for delivering drugs in abnormally high pH environments wherein the extended release layer is formed from a drug resinate of a strong acid ion-exchange resin and a release rate retarding polymer compressed together.

What is claimed is: 
     
         1 . A multi-layer solid oral pharmaceutical composition comprising:
 (i) a first distinct layer comprising:
 (a) a first pharmaceutically active agent bound to a weak acid ion exchange resin to form a weak acid ion-exchange resinate; and 
 (b) a release-enhancing agent consisting of FeCl 3 ; 
   (ii) at least a second distinct layer comprising:
 (a) a drug selected from the group consisting of said first pharmaceutically active agent and a second pharmaceutically active agent, said drug being bound to a strong acid ion exchange resin to form a strong acid ion-exchange resinate; and 
 (b) a release rate retarding polymer susceptible to gastrointestinal dissolution to slow and extend release of the drug contained in said at least second layer; 
   wherein said strong acid ion-exchange resinate and said polymer have been compressed together and   
       wherein said pharmaceutical composition is capable of immediate release of said first pharmaceutically active agent from said weak acid resinate at a pH of at least 1.5, immediate release being defined as at least 80% release of said pharmaceutically active agent within 45 minutes in a standard dissolution apparatus according to USP 34 NF 26 section 711; and, wherein said release of the drug from said strong acid resinate continues over a period of at least 8 hours after ingestion. 
     
     
         2 . The multi-layer solid oral pharmaceutical composition of  claim 1  having at least three distinct layers, each said layer comprising pharmaceutically active agents in a form selected from the group consisting of ion-exchange resinates and unbound pharmaceutically active agents. 
     
     
         3 . The multi-layer solid oral pharmaceutical composition of  claim 1  where said first layer comprises a member of the group consisting of hydrocodone bitartrate polacrilex weak acid resinate, codeine polacrilex weak acid resinate and dextromethorphan polacrilex weak acid resinate; and said second layer comprises a member of the group consisting of hydrocodone polistirex strong acid resinate, codeine polistirex strong acid resinate and dextromethorphan polistirex strong acid resinate. 
     
     
         4 . The multi-layer solid oral pharmaceutical composition of  claim 2 , wherein, at least one of said layers comprises an unbound pharmaceutically active agent. 
     
     
         5 . The multi-layer solid oral pharmaceutical composition of  claim 4  wherein said first layer comprises a member of the group consisting of hydrocodone bitartrate polacrilex weak acid resinate, codeine polacrilex weak acid resinate and dextromethorphan polacrilex weak acid resinate; and said second layer comprises a member of the group consisting of hydrocodone polistirex strong acid resinate, codeine polistirex strong acid resinate and dextromethorphan polistirex strong acid resinate; and
 wherein a third layer consists of an unbound pharmaceutically active agent. 
 
     
     
         6 . A method of treating a patient with a stomach pH of at least about 1.5 comprising administration of a multilayer solid oral dosage form, said dosage form comprising:
 (i) a first distinct layer comprising:
 (a) a first pharmaceutically active agent bound to a weak acid ion exchange resin to form a weak acid ion-exchange resinate; and 
 (b) a release-enhancing agent selected from the group consisting of an inorganic salt and an organic base; 
   (ii) at least a second distinct layer comprising:
 (a) a drug selected from the group consisting of said first pharmaceutically active agent and a second pharmaceutically active agent, said drug being bound to a strong acid ion exchange resin to form a strong acid ion-exchange resinate; and, 
 b) a release rate retarding polymer susceptible to gastrointestinal dissolution to slow and extend release of the drug contained in said at least second layer; 
   wherein said strong acid ion-exchange resinate and said polymer have been compressed together; and   
       wherein said pharmaceutical composition is capable of immediate release of said first pharmaceutically active agent from said weak acid resinate at a pH of at least 1.5, immediate release being defined as at least 80% release of said pharmaceutically active agent within 45 minutes in a standard dissolution apparatus according to USP 34 NF 26 section 711; and, 
       wherein release of the drug from said strong acid resinate continues over a period of at least 8 hours after ingestion. 
     
     
         7 . The method of treating a patient with a stomach pH of at least about 1.5 as in  claim 6 , wherein said patient has a first condition and a second condition, said first condition being selected from the group consisting of  Helicobacter pylori  infection, atrophic gastritis, hypochlorhydria and achlorhydria in the stomach; and wherein said second condition is a condition other than said first condition. 
     
     
         8 . The method of treating a patient with a stomach pH of at least about 1.5 as in  claim 6 , wherein the patient has within the past 24 hours been administered a compound selected from the group consisting of a proton pump inhibitor, an H2 receptor antagonist. 
     
     
         9 . A method of delivering a pharmaceutically active agent to a patient, said method comprising orally administering a solid oral dosage composition comprising:
 (i) a first distinct layer comprising:
 (a) a first pharmaceutically active agent bound to a weak acid ion exchange resin to form a weak acid ion-exchange resinate; and 
 (b) a release-enhancing agent selected from the group consisting of an inorganic salt and an organic base; 
   (ii.) at least a second distinct layer comprising:
 (a) pharmaceutically active agent selected from the group consisting of said first pharmaceutically active agent and a second pharmaceutically active agent, said pharmaceutically active agent bound to a strong acid ion exchange resin to form a strong acid ion-exchange resinate; and, 
 b) a release rate retarding polymer susceptible to gastrointestinal dissolution to slow and extend release of the drug contained in said at least second layer; 
   wherein said strong acid ion-exchange resinate and said polymer have been compressed together; and   
       wherein said pharmaceutical composition is capable of immediate release of said first pharmaceutically active agent from said weak acid resinate at a pH of at least 1.5, immediate release being defined as at least 80% release of said pharmaceutically active agent within 45 minutes in a standard dissolution apparatus according to USP 34 NF 26 section 711; and, wherein release of the drug from said strong acid resinate continues over a period of at least 8 hours after ingestion. 
     
     
         10 . The multi-layer solid oral pharmaceutical composition of  claim 1 , wherein the release rate retarding polymer is selected from the group consisting of hydroxypropyl methylcellulose, ethyl cellulose, polyethylene oxide, polyvinyl alcohol, hydrogenated vegetable oil, methacrylate copolymers, polyacrylic acid, and their combinations. 
     
     
         11 . The method of delivering a pharmaceutically active agent to a patient of  claim 9 , wherein the release rate retarding polymer is selected from the group consisting of hydroxypropyl methylcellulose, ethyl cellulose, polyethylene oxide, polyvinyl alcohol, hydrogenated vegetable oil, methacrylate copolymers, polyacrylic acid, and their combinations. 
     
     
         12 . The method of treating a patient with a stomach pH of at least about 1.5 of  claim 6 , wherein the release rate retarding polymer is selected from the group consisting of hydroxypropyl methylcellulose, ethyl cellulose, polyethylene oxide, polyvinyl alcohol, hydrogenated vegetable oil, methacrylate copolymers, polyacrylic acid, and their combination.