Processes for the preparation of (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]-pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide and solid state forms thereof
The present disclosure relates to processes for preparing (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide, solid state forms thereof, and corresponding pharmaceutical compositions, methods of treatment (including treatment of rheumatoid arthritis), kits, methods of synthesis, and products-by-process.
1. An extended release tablet for oral administration, comprising:
a. (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver about 7.5 mg, about 15 mg, about 30 mg or about 45 mg (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide freebase equivalent;
b. at least one filler;
c. at least one a release control polymer; and
d. at least one additional pharmaceutically acceptable excipient selected from the group consisting of: (i) one or more pH modifiers, (ii) one or more glidants, (iii) one or more surfactants, and (iv) one or more lubricants.
2. The extended release tablet of claim 1 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, lactose, sucrose and sorbitol.
3. The extended release tablet of claim 1 , wherein the at least one release control polymer is selected from the group consisting of a cellulose derivative, copolymers of acrylic acid crosslinked with a polyalkenyl polyether, non-ionic homopolymers of ethylene oxide, water soluble natural gums of polysaccharides, starch, polyvinyl acetate and polyvinylpyrrolidone.
4. The extended release tablet of claim 1 , wherein the one or more pH modifiers is selected from the group consisting of phosphoric acid, citric acid, succinic acid, malic acid, fumaric acid, tartaric acid, sodium citrate, magnesium carbonate, calcium carbonate, magnesium bicarbonate, and calcium bicarbonate.
5. The extended release tablet of claim 1 , wherein the one or more glidants is selected from the group consisting of silicon dioxide, calcium silicate, magnesium silicate and talc.
6. The extended release tablet of claim 1 , wherein the one or more surfactants is selected from the group consisting of sodium lauryl sulfate and polysorbate.
7. The extended release tablet of claim 1 , wherein the one or more lubricants is selected from the group consisting of polyethylene glycol, magnesium stearate, calcium stearate, sodium stearate, sodium stearyl fumarate and talc.
8. The extended release tablet of claim 2 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, lactose and sucrose.
9. The extended release tablet of claim 2 , wherein the at least one filler is selected from the group consisting of mannitol and sorbitol.
10. The extended release tablet of claim 8 , wherein the at least one filler is microcrystalline cellulose.
11. The extended release tablet of claim 9 , wherein the release control polymer is selected from the group consisting of hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose, copolymers of acrylic acid crosslinked with a polyalkenyl polyether, non-ionic homopolymers of ethylene oxide, water soluble natural gums of polysaccharides, starch, polyvinyl acetate and polyvinylpyrrolidone.
12. The extended release tablet of claim 11 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose, copolymers of acrylic acid crosslinked with a polyalkenyl polyether, non-ionic homopolymers of ethylene oxide, water soluble natural gums of polysaccharides, starch, polyvinyl acetate and polyvinylpyrrolidone.
13. The extended release tablet of claim 12 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose, non-ionic homopolymers of ethylene oxide, water soluble natural gums of polysaccharides, starch, polyvinyl acetate and polyvinylpyrrolidone.
14. The extended release tablet of claim 13 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose, water soluble natural gums of polysaccharides, starch, polyvinyl acetate and polyvinylpyrrolidone.
15. The extended release tablet of claim 14 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose, starch, polyvinyl acetate and polyvinylpyrrolidone.
16. The extended release tablet of claim 15 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose, polyvinyl acetate and polyvinylpyrrolidone.
17. The extended release tablet of claim 16 , wherein the release control polymer is selected from the group consisting of hydroxypropyl methylcellulose and polyvinylpyrrolidone.
18. The extended release tablet of claim 17 , wherein the release control polymer is hydroxypropyl methylcellulose.
19. The extended release tablet of claim 6 , wherein the at least one surfactant is polysorbate.
20. The extended release tablet of claim 1 , comprising at least one pharmaceutically acceptable excipient selected from the group consisting of silicon dioxide, calcium silicate, magnesium silicate, polyethylene glycol, magnesium stearate, sodium stearate, sodium stearyl fumarate and talc.
21. The extended release tablet of claim 20 , comprising at least one pharmaceutically acceptable excipient selected from the group consisting of silicon dioxide and calcium silicate.
22. The extended release tablet of claim 20 , comprising at least one pharmaceutically acceptable excipient selected from the group consisting of magnesium silicate and polyethylene glycol.
23. The extended release tablet of claim 20 , comprising at least one pharmaceutically acceptable excipient selected from the group consisting of magnesium stearate and sodium stearate.
24. The extended release tablet of claim 20 , comprising at least one pharmaceutically acceptable excipient selected from the group consisting of sodium stearyl fumarate and talc.
25. The extended release tablet of claim 21 , comprising silicon dioxide.
26. The extended release tablet of claim 22 , comprising polyethylene glycol.
27. The extended release tablet of claim 23 , comprising magnesium stearate.
28. The extended release tablet of claim 24 , comprising talc.
29. An extended release tablet for oral administration, comprising:
a. (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver about 7.5 mg, about 15 mg, about 30 mg or about 45 mg (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide freebase equivalent;
b. microcrystalline cellulose;
c. mannitol;
d. hydroxypropyl methylcellulose;
e. tartaric acid;
f. colloidal silica; and
g. magnesium stearate.
30. An extended release tablet for oral administration, comprising:
a. (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide in an amount sufficient to deliver about 7.5 mg, about 15 mg, about 30 mg or about 45 mg (3S,4R)-3-ethyl-4-(3H-imidazo[1,2-a]pyrrolo[2,3-e]pyrazin-8-yl)-N-(2,2,2-trifluoroethyl)pyrrolidine-1-carboxamide freebase equivalent;
b. about 33.8 w/w % microcrystalline cellulose;
c. about 21 w/w % mannitol;
d. about 20 w/w % hydroxypropyl methylcellulose;
e. about 20 w/w % tartaric acid;
f. about 0.5 w/w % colloidal silica; and
g. about 1.5 w/w % magnesium stearate.