Dispersible formulations of N-((R)-2,3-dihydroxypropoly)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide and uses thereof
The present disclosure relates to dispersible pharmaceutical compositions comprising N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, and, optionally, a pharmaceutically acceptable carrier.
1. A dispersible pharmaceutical composition that disintegrates or dissolves within 10 minutes after being combined with a potable liquid, comprising:
a. about 0.1 mg to about 20 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I)
corresponding to about 0.1 wt/wt % to about 7 wt/wt % of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide;
b. about 50 wt/wt % to about 98 wt/wt % of one or more diluents;
c. about 1 wt/wt % to about 10 wt/wt % of one or more disintegrants;
d. one or more flavoring agents;
e. one or more sweeteners; and
f. about 0 wt/wt % to about 5 wt/wt % of one or more lubricants.
2. The pharmaceutical composition of claim 1 , wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is crystalline.
3. The pharmaceutical composition of claim 2 , wherein the crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is selected from the group consisting of:
a) a crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide characterized by an XRPD pattern having peaks at 4.6±0.2, 7.3±0.2, and 14.6±0.2 degrees two theta;
b) a crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide characterized by an XRPD pattern having peaks at one or more of 10.6±0.2, 13.7±0.2, 19.0±0.2, and 23.7±0.2 degrees two theta; and
c) a crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide characterized by an XRPD pattern having peaks at one or more of 5.5±0.2 and 19.6±0.2 degrees two theta.
4. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is orodispersible.
5. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is a tablet, a powder, granules, minitablets, or pellets.
6. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is a powder that is a dispersible powder.
7. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is granules that are dispersible granules.
8. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is minitablets that are dispersible minitablets.
9. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is in the form of pellets that are dispersible pellets.
10. The pharmaceutical composition of claim 5 , wherein the pharmaceutical composition is a dispersible tablet.
11. The pharmaceutical composition of claim 1 , comprising:
a. about 0.5 wt/wt % to about 1.2 wt/wt % of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide;
b. about 85 wt/wt % to about 95 wt/wt % of one or more diluents;
c. about 3.5 wt/wt % to about 6 wt/wt % of one or more disintegrants;
d. grape flavor;
e. sucralose; and
f. about 0.5 wt/wt % to about 2 wt/wt % of one or more lubricants.