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) about 15 mg, about 30 mg or about 45 mg 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;
(b) microcrystalline cellulose;
(c) mannitol;
(d) at least one release control polymer;
(f) colloidal silica; and
(g) magnesium stearate.
2. 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.
3. An extended release tablet for oral administration, comprising:
(a) about 15 mg, about 30 mg or about 45 mg 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;
(b) microcrystalline cellulose;
(c) about 21 w/w % mannitol;
(d) about 20 w/w % of at least one release control polymer;
(e) about 20 w/w % tartaric acid;
(f) about 0.5 w/w % colloidal silica; and
(g) about 1.5 w/w % magnesium stearate.
4. The extended release tablet of claim 3 , 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.
5. The extended release tablet of claim 1 , further comprising tartaric acid.
6. The extended release tablet of claim 2 , further comprising tartaric acid.
7. The extended release tablet of claim 1 , wherein the at least one release control polymer is hydroxypropyl methylcellulose.
8. The extended release tablet of claim 7 , further comprising citric acid.
9. The extended release tablet of claim 7 , further comprising succinic acid.
10. The extended release tablet of claim 7 , further comprising fumaric acid.
11. The extended release tablet of claim 7 , further comprising tartaric acid.