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 - 116 . (canceled)
117 . An extended-release pharmaceutical tablet comprising:
(a) 15 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 (Compound 1);
(b) an acidic pH modifier;
(c) a release control polymer; and
(d) at least one filler.
118 . The tablet of claim 117 , wherein the extended-release pharmaceutical tablet provides for the release of Compound 1 upon entry into a use environment at a rate substantially independent of the pH of the use environment, wherein the use environment has a pH range from about 1.2 to about 6.8.
119 . The extended-release pharmaceutical tablet of claim 117 , wherein:
a single administration of the tablet to healthy adult subjects results in a mean AUC inf from about 220 ng·hours/mL to about 450 ng·hours/mL of Compound 1; and
a single administration of the tablet to healthy adult subjects results in a mean C max from about 25 ng/mL to about 40 ng/ml of Compound 1.
120 . The extended-release pharmaceutical tablet of claim 119 , wherein:
a single administration of the tablet to healthy adult subjects results in a mean AUC inf from about 220 ng·hours/mL to about 450 ng·hours/mL of Compound 1; and
a single administration of the tablet to healthy adult subjects results in a mean C max from about 25 ng/ml to about 40 ng/ml of Compound 1.
121 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, lactose, sucrose and sorbitol.
122 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, and sorbitol.
123 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of lactose and sucrose.
124 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one lubricant selected from the group consisting of polyethylene glycol, magnesium stearate, calcium stearate, sodium stearate, sodium stearyl fumarate and talc.
125 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one lubricant selected from the group consisting of magnesium stearate, calcium stearate and sodium stearate.
126 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one lubricant selected from the group consisting of calcium stearate and sodium stearate.
127 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one glidant selected from the group consisting of colloidal silicon dioxide, calcium silicate, magnesium silicate, and talc.
128 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one glidant selected from the group consisting of colloidal silicon dioxide and calcium silicate.
129 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises at least one glidant which is colloidal silicon dioxide.
130 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, lactose, sucrose and sorbitol; and
the tablet further comprises at least one lubricant selected from the group consisting of polyethylene glycol, magnesium stearate, calcium stearate, sodium stearate, sodium stearyl fumarate and talc.
131 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose and sorbitol; and
the tablet further comprises at least one lubricant selected from the group consisting of magnesium stearate.
132 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, lactose, sucrose and sorbitol; and
the tablet further comprises at least one glidant selected from the group consisting of colloidal silicon dioxide, calcium silicate, magnesium silicate, and talc.
133 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, and sorbitol; and
the tablet further comprises at least one glidant which is colloidal silicon dioxide.
134 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises:
at least one lubricant selected from the group consisting of magnesium stearate, calcium stearate and sodium stearate; and
at least one glidant selected from the group consisting of colloidal silicon dioxide and calcium silicate.
135 . The extended-release pharmaceutical tablet of claim 120 , wherein the tablet further comprises:
at least one lubricant which is magnesium stearate; and
at least one glidant which is colloidal silicon dioxide.
136 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, lactose, sucrose and sorbitol; and
the tablet further comprises:
at least one lubricant selected from the group consisting of magnesium stearate, calcium stearate and sodium stearate; and
at least one glidant selected from the group consisting of colloidal silicon dioxide, calcium silicate, magnesium silicate, and talc.
137 . The extended-release pharmaceutical tablet of claim 120 , wherein the at least one filler is selected from the group consisting of microcrystalline cellulose, mannitol, and sorbitol; and
the tablet further comprises:
at least one lubricant which is magnesium stearate; and
at least one glidant which is colloidal silicon dioxide.
138 . The extended-release pharmaceutical tablet of claim 117 , wherein the release control polymer is hydroxypropyl methylcellulose.
139 . The extended-release pharmaceutical tablet of claim 118 , wherein the release control polymer is hydroxypropyl methylcellulose.
140 . The extended-release pharmaceutical tablet of claim 119 , wherein the release control polymer is hydroxypropyl methylcellulose.
141 . The extended-release pharmaceutical tablet of claim 120 , wherein the release control polymer is hydroxypropyl methylcellulose.
142 . The extended-release pharmaceutical tablet of claim 117 , wherein the acidic pH modifier is tartaric acid.
143 . The extended-release pharmaceutical tablet of claim 118 , wherein the acidic pH modifier is tartaric acid.
144 . The extended-release pharmaceutical tablet of claim 119 , wherein the acidic pH modifier is tartaric acid.
145 . The extended-release pharmaceutical tablet of claim 120 , wherein the acidic pH modifier is tartaric acid.
146 . The extended-release tablet of claim 117 , wherein the 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.