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
AssigneeAbbVie Inc.
InventorsAyman Allian, Jayanthy Jayanth, Ben Klünder, Mohamed-Eslam F. Mohamed, Ahmed A. Othman, Patrick J. Marroum, Peter T. Mayer
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Abstract
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.
Claims11
An oral extended release once-daily pharmaceutical composition comprising (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 15 mg, per unit dosage form, 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 free base equivalent,
- wherein administration of a single dose of the oral extended release once-daily pharmaceutical composition to healthy adult subjects results in a mean AUCinf from about 220 ng·hours/mL to about 450 ng·hours/mL 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
- wherein administration of a single dose of the oral extended release once-daily pharmaceutical composition to healthy adult subjects under fasting conditions results in a mean Cmax from about 25 ng/mL to about 40 ng/mL 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-carboxide.
An oral extended release once-daily pharmaceutical composition comprising (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 15 mg, per unit dosage form, 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 free base equivalent, wherein the oral extended release once-daily pharmaceutical composition is bioequivalent to an oral extended release once-daily film-coated tablet consisting of:
- (i) in the intragranular core:
- 15.4 mg of Freebase Hydrate Form C, 40.0 mg of microcrystalline cellulose, and 4.8 mg of hydroxypropyl methyl cellulose;
- (ii) in the extragranular core:
- 122.5 mg of Microcrystalline cellulose, 100.6 mg of mannitol, 96.0 mg of tartaric acid, 91.2 mg of hydroxypropyl methyl cellulose, 2.4 mg of colloidal silicon dioxide/silica, and 7.2 mg of magnesium stearate;
- and
- (iii) 14.4 mg of a film coat comprising polyvinyl alcohol, titanium dioxide, polyethylene glycol 3350, talc, and iron oxide.
Dependencies are inferred from the claim text.