Novel pharmaceutical formulation containing a biguanide and a thiazolidinedione derivative

Abstract

A pharmaceutical dosage form comprising a controlled release component comprising an antihyperglycemic drug in combination with a second component comprising a thiazolidinedione derivative is herein disclosed and described.

1 . A pharmaceutical dosage form having a first and second active drug, said dosage form comprising:
 (a) a controlled release core comprising an antihyperglycemic drug and at least one pharmaceutically acceptable excipient; and   (b) an immediate release thiazolidinedione derivative containing component wherein not less than 85%, of the thiazolidinedione is released from the dosage form within 45 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0.   
     
     
         2 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 90%, of the thiazolidinedione is released from the dosage form within 45 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         3 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 95%, of the thiazolidinedione is released from the dosage form within 45 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         4 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 100%, of the thiazolidinedione is released from the dosage form within 45 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         5 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 85%, of the thiazolidinedione is released from the dosage form within 40 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         6 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 90%, of the thiazolidinedione is released from the dosage form within 40 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         7 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 95%, of the thiazolidinedione is released from the dosage form within 40 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         8 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 100%, of the thiazolidinedione is released from the dosage form within 40 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         9 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 85%, of the thiazolidinedione is released from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         10 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 90%, of the thiazolidinedione is released from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         11 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 95%, of the thiazolidinedione is released from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         12 . The pharmaceutical dosage form as defined in  claim 1  wherein not less than 100%, of the thiazolidinedione is released from the dosage form within 30 minutes when tested according to the United States Pharmacopeia (USP) 26, with Apparatus 1 at 100 rpm, 37° C. and 900 ml of 0.3 M KCl—HCl Buffer, pH 2.0. 
     
     
         13 . A pharmaceutical dosage form having a first and second active drug, said dosage form comprising:
 (a) a controlled release core comprising an antihyperglycemic drug and at least one pharmaceutically acceptable excipient; and   (b) an immediate release thiazolidinedione derivative containing component wherein the total thiazolidinedione related compounds or impurities in the final dosage form are not more than 0.6 as determined by high performance liquid chromatography.   
     
     
         14 . The pharmaceutical dosage form as defined in  claim 13  wherein the total thiazolidinedione related compounds are not more than 0.5%. 
     
     
         15 . The pharmaceutical dosage form as defined in  claim 13  wherein the total thiazolidinedione related compounds are not more than 0.5%. 
     
     
         16 . The pharmaceutical dosage form as defined in  claim 13  wherein each individual thiazolidinedione related compound or impurity in the final dosage form is not more than 0.25%. 
     
     
         17 . The pharmaceutical dosage form as defined in  claim 16  wherein each individual thiazolidinedione related compound or impurity in the final dosage form is not more than 0.20%. 
     
     
         18 . The pharmaceutical dosage form as defined in  claim 17  wherein each individual thiazolidinedione related compound or impurity in the final dosage form is not more than 0.10%. 
     
     
         19 . The dosage form of  claim 1  wherein said controlled release core is an osmotic tablet. 
     
     
         20 . The dosage form of  claim 19  wherein the osmotic tablet comprises:
 (a) a core comprising:
 (i) 50-98% of said antihyperglycemic drug; 
 (ii) 0.1-40% of a binding agent; 
 (iii) 0-20% of an absorption enhancer; and 
 (iv) 0-5% of a lubricant; 
 
 (b) optionally a seal coat surrounding the core; and 
 (c) a sustained release membrane comprising:
 (i) 50-99% of a polymer; 
 (ii) 0-40% of a flux enhancer and 
 (iii) 0-25% of a plasticizer, said membrane having at least one passageway formed therein for release of the antihyperglycemic drug. 
 
 
     
     
         21 - 34 . (canceled)