Composition

Abstract

A pharmaceutical composition comprising an immediate release phase and a sustained release phase of paracetamol is described which has a unique in vitro dissolution profile resulting in advantageous pharmacokinetic properties.

1 . A pharmaceutical composition comprising a bilayer tablet having an immediate release phase of paracetamol and a sustained release phase of paracetamol for oral administration every 8 hours wherein,
 the immediate release phase being in one layer and comprising from about 10 to 45% by weight of the total paracetamol; and   the sustained release phase being in the other layer, and the sustained release layer comprising paracetamol comprising from about 55% to 90% by weight of the total paracetamol in admixture with a matrix forming water soluble polymer which is selected from two different viscosities of hydroxypropylmethylcellulose present in an amount from 0.5 to 10% by weight of the sustained release phase and wherein the hydroxypropylmethylcellulose is present as a low viscosity hydroxypropylmethylcellulose and a high viscosity hydroxypropylmethylcellulose in a ratio of about 1:2; said composition comprising from 600 to 700 mg of paracetamol per unit dose and   a pharmaceutically acceptable carrier, characterized in having an in vitro paracetamol dissolution profile (as determined by the USP type III apparatus, reciprocating basket, with 250 ml of 0.1M HCl at 37 C set at a cycle speed of 15 strokes/min) with the following constraints:
 30 to 48% released after 15 minutes 
 56 to 75% released after 60 minutes 
 >85% released after 180 minutes. 
   
     
     
         2 . The composition according to  claim 1  in which the in vitro dissolution profile has the following constraints:
 35 to 47% released after 15 minutes 
 58 to 73% released after 60 minutes 
 >90% released after 180 minutes. 
 
     
     
         3 . The composition according to  claim 1  in which the in vitro dissolution profile has the following constraints:
 38 to 44% released after 15 minutes 
 62 to 70% released after 60 minutes 
 >95% released after 180 minutes. 
 
     
     
         4 . The composition according to  claim 1  in which the paracetamol is present in an amount of 630 to 680 mg per unit dose. 
     
     
         5 . The composition according to  claim 4  in which the paracetamol is present in an amount of 650 to 667 mg per unit dose. 
     
     
         6 . The composition according to  claim 1  in which the matrix forming polymer is present in an amount from 1 to 6% by weight of the sustained release phase. 
     
     
         7 . The composition according to  claim 6  in which the matrix forming polymer is present in an amount from 2 to 4% by weight of the sustained release phase. 
     
     
         8 . The composition according to  claim 1  in which the sustained release phase comprises from 65 to 75% by weight of the total paracetamol. 
     
     
         9 . The composition according to  claim 8  in which the immediate release phase comprises from 25 to 35% by weight of the total paracetamol. 
     
     
         10 . A composition according to  claim 1  in which the sustained release phase comprises from 60 to 80% by weight of the total paracetamol, and the immediate release phase comprises from 20 to 40% by weight of the total paracetamol.