Controlled release metformin compositions

Abstract

A composition for treating patients having non-insulin-dependent diabetes mellitus (NIDDM) by administering a controlled release oral solid dosage form containing preferably a biguanide drug such as metformin, on a once-a-day basis. The dosage form provides a mean time to maximum plasma concentration (T max ) of the drug which occurs at 5.5 to 7.5 hours after oral administration on a once-a-day basis to human patients. Preferably, the dose of drug is administered at dinnertime to a patient in the fed state.

1 - 42 . (canceled)  
     
     
         43 . A controlled release oral dosage form for the reduction of serum glucose levels in human patients with NIDDM, comprising a core comprising metformin or a pharmaceutically acceptable salt thereof and a membrane coating surrounding said core, said dosage form being suitable for providing once-a-day oral administration of the metformin or pharmaceutically acceptable salt thereof, wherein the dosage form provides a mean maximum plasma concentration (C max ) of metformin from about 1500 ng/ml to about 3000 ng/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         44 . The controlled release oral dosage form of  claim 43 , which provides a mean maximum plasma concentration (C max ) of metformin from about 750 ng/ml to about 1500 ng/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         45 . The controlled release oral dosage form of  claim 43 , which provides a mean maximum plasma concentration (C max ) of metformin from about 1125 ng/ml to about 2250 ng/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         46 . The controlled release oral dosage form of  claim 43 , which provides a mean maximum plasma concentration (C max ) of metformin from about 1875 ng/ml to about 3750 ng/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         47 . The controlled release oral dosage form of  claim 43 , wherein said core further comprises a binding agent.  
     
     
         48 . The controlled release oral dosage form of  claim 47 , wherein said core further comprises an absorption enhancer.  
     
     
         49 . The controlled release oral dosage form of  claim 43 , further comprising a passageway in the membrane.  
     
     
         50 . The controlled release oral dosage form of  claim 43 , wherein said membrane comprises a polymer selected from the group consisting of cellulose esters, cellulose diesters, cellulose triesters, cellulose ethers, cellulose ester-ether, cellulose acylate, cellulose diacylate, cellulose triacylate, cellulose acetate, cellulose diacetate, cellulose triacetate, cellulose acetate propionate, and cellulose acetate butyrate  
     
     
         51 . The controlled release oral dosage form of  claim 50 , wherein said membrane further comprises a plasticizer.  
     
     
         52 . A controlled release oral dosage form for the reduction of serum glucose levels in human patients with NIDDM, comprising a plurality of multiparticulates comprising metformin or a pharmaceutically acceptable salt thereof and a controlled release material, said dosage form being suitable for providing once-a-day oral administration of the metformin or pharmaceutically acceptable salt thereof, wherein the dosage form provides a mean maximum plasma concentration (C max ) of metformin from about 1500 ng/ml to about 3000 ng/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         53 . The controlled release oral dosage form of  claim 52 , which provides a mean maximum plasma concentration (C max ) of metformin from about 750 ng/ml to about 1500 ng/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         54 . The controlled release oral dosage form of  claim 52 , which provides a mean maximum plasma concentration (C max ) of metformin from about 1125 ng/ml to about 2250 ng/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         55 . The controlled release oral dosage form of  claim 52 , which provides a mean maximum plasma concentration (C max ) of metformin from about 1875 ng/ml to about 3750 ng/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         56 . The controlled release oral dosage form of  claim 52 , wherein said multiparticulates are selected from the group consisting of granules, spheroids, beads and pellets.  
     
     
         57 . The controlled release oral dosage form of  claim 52 , wherein said multiparticulates are coated with the controlled release material.  
     
     
         58 . The controlled release oral dosage form of  claim 52 , wherein the controlled release material is selected from the group consisting of an alkylcellulose and a polymeric glycol.  
     
     
         59 . The controlled release oral dosage form of  claim 52 , wherein said multiparticulates are incorporated into a capsule.  
     
     
         60 . The controlled release oral dosage form of  claim 43 , which provides a mean AUC 0-24hr  of metformin from about 17200 ng.hr/ml to about 33900 ng.hr/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         61 . The controlled release oral dosage form of  claim 60 , which provides a mean AUC 0-24hr  of metformin from about 8600 ng/ml to about 16950 ng/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         62 . The controlled release oral dosage form of  claim 60 , which provides a mean AUC 0-24hr  of metformin from about 12900 ng/ml to about 25425 ng/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         63 . The controlled release oral dosage form of  claim 60 , which provides a mean AUC 0-24hr  of metformin from about 21500 ng/ml to about 42375 ng/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         64 . The controlled release oral dosage form of  claim 43 , wherein said dosage form comprising said metformin or pharmaceutically acceptable salt thereof is contained in two formulations.  
     
     
         65 . The controlled release oral dosage form of  claim 43 , wherein said core is a tablet core and said membrane comprise a hydrophobic material.