Tablet formulation for cgrp active compounds

Abstract

The present invention is directed to compositions comprising an extrudate or solid solution of a compound, or a salt thereof, of Formula I (API): wherein “R a ” is independently —H or —F, in a water-soluble polymer matrix which further comprises a disintegration system allowing a tablet made therefrom to rapidly disintegrate in the environment in which the API is to be released.

1 . An immediate release pharmaceutical tablet comprising:
 an amorphous solid dispersion of a compound of Formula Ia, in a water-soluble polymer matrix,   
       
         
           
           
               
               
           
         
         
           wherein each of R b  is —H; 
         
         a dispersing agent; and 
         a disintegrant, 
       
       wherein the tablet comprises 50 mg of the compound of Formula Ia. 
     
     
         2 . The tablet according to  claim 1 , which achieves complete disintegration in less than about 5 minutes in a tablet disintegration test complying with USP 31-NF26 Chap. 701 using aqueous HCl at pH 1.8 at 37° C. 
     
     
         3 . The tablet according to  claim 1 , wherein the water-soluble polymer is polyvinylpyrrolidone/vinyl acetate (PVP-VA) copolymer. 
     
     
         4 . The tablet according to  claim 1 , wherein the disintegrant comprises powdered sodium chloride. 
     
     
         5 . The tablet according to  claim 1 , wherein the disintegrant comprises croscarmellose sodium or crospovidone. 
     
     
         6 . The tablet according to  claim 5 , wherein the disintegrant comprises croscarmellose sodium. 
     
     
         7 . The tablet according to  claim 1 , wherein the disintegrant comprises a combination of (i) powdered sodium chloride and (ii) croscarmellose sodium or crospovidone. 
     
     
         8 . The tablet according to  claim 1 , wherein the disintegrant comprises a combination of powdered sodium chloride and croscarmellose sodium. 
     
     
         9 . The tablet according to  claim 1 , wherein the dispersing agent is selected from the group consisting of d-alpha tocopherol polyethyleneglycol succinate (TPGS) and polyethoxylated castor oil. 
     
     
         10 . The tablet according to  claim 9 , wherein the dispersing agent is d-alpha tocopherol polyethyleneglycol succinate (TPGS). 
     
     
         11 . The tablet according to  claim 10 , wherein the disintegrant comprises croscarmellose sodium or crospovidone. 
     
     
         12 . The tablet according to  claim 10 , wherein the disintegrant comprises a combination of (i) powdered sodium chloride and (ii) croscarmellose sodium or crospovidone. 
     
     
         13 . The tablet according to  claim 1 , wherein the amorphous solid dispersion comprises at least about 50 wt % of the tablet. 
     
     
         14 . The tablet according to  claim 1 , which has a hardness of from about 12 kP to about 18 kP. 
     
     
         15 . The tablet according to  claim 1 , wherein when said immediate release solid oral dosage form is subjected to a dissolution test complying with USP 30 NF25 Chapt. 711, in a paddle-stirring apparatus equipped with USP 2 paddles, operated at 50 rpm, in 900 ml of simulated gastric fluid at pH 1.8 at 37° C. releases at least about 90% of the compound of Formula Ia contained therein in less than about 20 minutes. 
     
     
         16 . The tablet according to  claim 3 , wherein the dispersing agent is selected from the group consisting of d-alpha tocopherol polyethyleneglycol succinate (TPGS) and polyethoxylated castor oil. 
     
     
         17 . The tablet according to  claim 16 , wherein the dispersing agent is d-alpha tocopherol polyethyleneglycol succinate (TPGS). 
     
     
         18 . The tablet according to  claim 3 , wherein the disintegrant comprises powdered sodium chloride. 
     
     
         19 . The tablet according to  claim 3 , wherein the disintegrant comprises croscarmellose sodium or crospovidone. 
     
     
         20 . The tablet according to  claim 19 , wherein the disintegrant comprises croscarmellose sodium. 
     
     
         21 . The tablet according to  claim 3 , wherein the disintegrant comprises a combination of (i) powdered sodium chloride and (ii) croscarmellose sodium or crospovidone. 
     
     
         22 . The tablet according to  claim 3 , wherein the disintegrant comprises a combination of powdered sodium chloride and croscarmellose sodium. 
     
     
         23 . The tablet according to  claim 22 , wherein the dispersing agent is d-alpha tocopherol polyethyleneglycol succinate (TPGS). 
     
     
         24 . The tablet according to  claim 1 , wherein the tablet comprises mannitol. 
     
     
         25 . The tablet according to  claim 1 , wherein the tablet comprises colloidal silica. 
     
     
         26 . The tablet according to  claim 1 , wherein the tablet comprises microcrystalline cellulose. 
     
     
         27 . The tablet according to  claim 1 , wherein the tablet comprises sodium stearyl fumarate. 
     
     
         28 . The tablet according to  claim 1 , wherein the tablet comprises mannitol, colloidal silica, microcrystalline cellulose, and sodium stearyl fumarate. 
     
     
         29 . The tablet according to  claim 28 , wherein the water-soluble polymer is polyvinylpyrrolidone/vinyl acetate (PVP-VA) copolymer. 
     
     
         30 . The tablet according to  claim 29 , wherein the disintegrant comprises a combination of powdered sodium chloride and croscarmellose sodium.