Treatment of migraine
The present disclosure provides methods for the acute treatment of migraine with or without aura, comprising the administration of ubrogepant. In particular, the present disclosure provides methods for the acute treatment of migraine in patients having hepatic impairment; in patients with renal impairment; and in patients concurrently taking CYP3A4 modulators or BCRP and/or P-gp only inhibitors.
1. A rapidly disintegrating pharmaceutical tablet, wherein the tablet comprises:
(i) amorphous compound of formula Ia:
Formulia Ia
wherein each of R b is hydrogen; and
(ii) a disintegration system,
wherein the tablet achieves complete disintegration in less than about 5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
2. The tablet according to claim 1 , wherein the tablet comprises an amorphous dispersion of the compound of Formulia Ia.
3. The tablet according to claim 2 , wherein the dispersion comprises a polymer matrix.
4. The tablet according to claim 3 , wherein the polymer matrix comprises an excipient selected from polyvinylpyrrolidone-vinyl acetate copolymer and HPMCAS.
5. The tablet according to claim 3 , wherein the dispersion comprises a dispersing agent.
6. The tablet according to claim 1 , wherein the disintegration system comprises a disintegrant selected from croscarmellose sodium and crospovidone.
7. The tablet according to claim 1 , wherein the disintegration system comprises sodium chloride.
8. The tablet according to claim 6 , wherein the disintegration system comprises sodium chloride.
9. The tablet according to claim 3 , wherein the disintegration system comprises croscarmellose sodium and sodium chloride, and wherein the tablet comprises about 50 mg of the compound of Formula Ia.
10. The tablet according to claim 4 , wherein the disintegration system comprises croscarmellose sodium and sodium chloride.
11. The tablet according to claim 1 , wherein the tablet further comprises at least one additional excipient selected from a diluent, a glidant, and a lubricant.
12. The tablet according to claim 1 , wherein the tablet comprises at least one excipient selected from mannitol, colloidal silica, microcrystalline cellulose, and sodium stearyl fumarate.
13. The tablet according to claim 1 , wherein the tablet achieves complete disintegration in less than about 1.5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
14. The tablet according to claim 7 , wherein the tablet achieves complete disintegration in less than about 1.5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
15. The tablet according to claim 8 , wherein the tablet achieves complete disintegration in less than about 1.5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
16. The tablet according to claim 15 , wherein the tablet comprises at least one excipient selected from mannitol, colloidal silica, microcrystalline cellulose, and sodium stearyl fumarate, and wherein the tablet comprises about 50 mg of the compound of formula Ia.
17. A rapidly disintegrating pharmaceutical tablet, wherein the tablet comprises
(i) amorphous compound of formula Ia:
Formulia Ia
wherein each of R b is hydrogen and
(ii) a disintegrant,
wherein the tablet achieves complete disintegration in less than about 5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
18. The tablet according to claim 17 , wherein the tablet comprises an amorphous dispersion of the compound of Formula Ia.
19. The tablet according to claim 17 , wherein the tablet comprises a salt.
20. The tablet according to claim 18 , wherein the tablet comprises a salt.
21. The tablet according to claim 19 , wherein the salt is sodium chloride.
22. The tablet according to claim 20 , wherein the salt is sodium chloride.
23. The tablet according to claim 17 , wherein the disintegrant is selected from the group consisting of croscarmellose sodium and crospovidone.
24. The tablet according to claim 19 , wherein the disintegrant is selected from the group consisting of croscarmellose sodium and crospovidone.
25. The tablet according to claim 21 , wherein the disintegrant is selected from the group consisting of croscarmellose sodium and crospovidone.
26. The tablet according to claim 18 , wherein the dispersion comprises a polymer matrix.
27. The tablet according to claim 26 , wherein the disintegrant is selected from the group consisting of croscarmellose sodium and crospovidone, and the wherein the tablet further comprises sodium chloride.
28. The tablet according to claim 17 , wherein the tablet achieves complete disintegration in less than about 1.5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
29. The tablet according to claim 25 , wherein the tablet achieves complete disintegration in less than about 1.5 minutes in a tablet disintegration test complying with USP31-NF26 Chapt. 701 using aqueous HCl at pH 1.8 at 37° C.
30. The tablet according to claim 29 , wherein the tablet comprises at least one excipient selected from mannitol, colloidal silica, microcrystalline cellulose, and sodium stearyl fumarate, and wherein the tablet comprises about 50 mg of the compound of Formula Ia.