Dispersible formulations of n-((r)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benazmide 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 tablet comprising:
a. about 0.5 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I)
wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.1 wt/wt % to about 7 wt/wt % of the tablet;
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. optionally one or more flavoring agents;
e. optionally one or more sweeteners; and
f. about 0 wt/wt % to about 5 wt/wt % of one or more lubricants.
2. The tablet of claim 1 , wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is crystalline.
3. The tablet of claim 1 , wherein the crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is characterized by an XRPD pattern having peaks at 4.6±0.2, 7.3±0.2, and 14.6±0.2 degrees two theta.
4. The tablet of claim 1 , wherein the tablet is orodispersible.
5. The tablet of claim 1 , comprising:
a. about 0.5 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.2 wt/wt % to about 1.5 wt/wt % of the tablet;
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.
6. The tablet of claim 1 , comprising:
a. about 0.5 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide;
b. about 60.60 mg of microcrystalline cellulose;
c. about 3.25 mg of croscarmellose sodium;
d. grape flavor;
e. 0.65 mg sucralose; and
f. about 0.65 mg magnesium stearate.
7. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising orally administering the tablet of claim 1 .
8. The method of claim 7 , wherein the subject is a pediatric patient.
9. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising (i) combining a tablet of claim 1 with a potable liquid to form a solution, and (ii) orally administering the solution to the subject.
10. The method of claim 9 , wherein the tablet disintegrates or dissolves within 10 minutes after being combined with a potable liquid.
11. A method of treating a human subject who has neurofibromatosis type 1 comprising (i) combining a tablet of claim 1 with a potable liquid to form a solution, and (ii) orally administering the solution to the subject.
12. The method of claim 11 , wherein the subject has a neurofibroma associated with neurofibromatosis type 1.
13. The method of claim 11 , wherein the potable liquid is water.
14. A dispersible tablet comprising:
a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide of Formula (I)
wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.1 wt/wt % to about 7 wt/wt % of the tablet;
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. optionally one or more flavoring agents;
e. optionally one or more sweeteners; and
f. about 0 wt/wt % to about 5 wt/wt % of one or more lubricants.
15. The tablet of claim 14 , wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is crystalline.
16. The tablet of claim 14 , wherein the crystalline form of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide is characterized by an XRPD pattern having peaks at 4.6±0.2, 7.3±0.2, and 14.6±0.2 degrees two theta.
17. The tablet of claim 14 , wherein the tablet is orodispersible.
18. The tablet of claim 14 , comprising:
a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide, wherein the N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide constitutes about 0.2 wt/wt % to about 1.5 wt/wt % of the tablet;
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.
19. The tablet of claim 14 , comprising:
a. about 1 mg of N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide;
b. about 121.20 mg of microcrystalline cellulose;
c. about 6.5 mg of croscarmellose sodium;
d. grape flavor;
e. 1.30 mg sucralose; and
f. about 1.30 mg magnesium stearate.
20. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising orally administering the tablet of claim 14 .
21. The method of claim 20 , wherein the subject is a pediatric patient.
22. A method of administering N—((R)-2,3-dihydroxypropoxy)-3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-benzamide to a subject in need thereof comprising (i) combining a tablet of claim 14 with a potable liquid to form a solution, and (ii) orally administering the solution to the subject.
23. The method of claim 22 , wherein the tablet disintegrates or dissolves within 10 minutes after being combined with a potable liquid.