TABLET FORMULATION FOR CGRP ACTIVE COMPOUNDS
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.