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 metformin or a pharmaceutically acceptable salt thereof and a controlled-release carrier, said dosage form (i) providing an in-vitro dissolution of metformin or salt thereof of from 0-30% at 2 hours when tested in a USP type II apparatus at 75 rpm in 900 mL of pH 7.5 phosphate buffer and at 37 degrees C.; and (ii) being suitable for providing once-a-day oral administration of the metformin or pharmaceutically acceptable salt thereof and providing 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 to human patients.  
     
     
         44 . The controlled release oral dosage form of  claim 43 , 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.  
     
     
         45 . The controlled release oral dosage form of  claim 43 , 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.  
     
     
         46 . The controlled release oral dosage form of  claim 43 , 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.  
     
     
         47 . A controlled release oral dosage form for the reduction of serum glucose levels in human patients with NIDDM, comprising metformin or a pharmaceutically acceptable salt thereof and a controlled-release carrier, said dosage form (i) providing an in-vitro dissolution of metformin or salt thereof of from 0-30% at 2 hours when tested in a USP type II apparatus at 75 rpm in 900 mL of pH 7.5 phosphate buffer and at 37 degrees C; and (ii) being suitable for providing once-a-day oral administration of the metformin or pharmaceutically acceptable salt thereof and providing a mean AUC 0-24hr  of metformin from about 16140 ng.hr/ml to about 33870 ng.hr/ml, based on administration of a 2000 mg once-a-day dose of metformin to human patients.  
     
     
         48 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin from about 8070 ng.hr/ml to about 16935 ng.hr/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         49 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin from about 12105 ng.hr /ml to about 25403 ng.hr/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         50 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin from about 20175 ng.hr /ml to about 42338 ng.hr /ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         51 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 22590 ng.hr/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         52 . The controlled release oral dosage form of  claim 51 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 11295 ng.hr/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         53 . The controlled release oral dosage form of  claim 51 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 16943 ng.hr/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         54 . The controlled release oral dosage form of  claim 51 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 28238 ng.hr/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         55 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 24136 ng.hr/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         56 . The controlled release oral dosage form of  claim 55 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 12068 ng.hr/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         57 . The controlled release oral dosage form of  claim 55 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 18102 ng.hr/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         58 . The controlled release oral dosage form of  claim 55 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 30170 ng.hr/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         59 . The controlled release oral dosage form of  claim 47 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 26818 ng.hr/ml, based on administration of a 2000 mg once-a-day dose of metformin.  
     
     
         60 . The controlled release oral dosage form of  claim 59 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 13409 ng.hr/ml upon administration of a 1000 mg once-a-day dose of metformin.  
     
     
         61 . The controlled release oral dosage form of  claim 59 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 201135 ng.hr/ml upon administration of a 1500 mg once-a-day dose of metformin.  
     
     
         62 . The controlled release oral dosage form of  claim 59 , which provides a mean AUC 0-24hr  of metformin therapeutically equivalent to 33523 ng.hr/ml upon administration of a 2500 mg once-a-day dose of metformin.  
     
     
         63 . The controlled release oral dosage form of  claim 43 , which 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.  
     
     
         64 . The controlled release oral dosage form of claim  21 , 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.  
     
     
         65 . The controlled release oral dosage form of claim  21 , 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.  
     
     
         66 . The controlled release oral dosage form of claim  21 , 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.  
     
     
         67 . 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.  
     
     
         68 . The controlled release oral dosage form of  claim 43 , wherein said core is a tablet core and said membrane comprise a hydrophobic material.