FORMULATIONS OF A FARNESOID X RECEPTOR AGONIST
Described herein are pharmaceutical formulations of a farnesoid X receptor agonist, 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl) bicyclo[2.2.2]octan-1-yl)methyl)carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate, and methods of using such pharmaceutical formulations in the treatment of conditions, diseases, or disorders associated with farnesoid X receptor activity.
1 .- 16 . (canceled)
17 . A pharmaceutical formulation in tablet form comprising: a spray-dried solid dispersion comprising (a) 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl) bicyclo[2.2.2]octan-1-yl)methyl) carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate dispersed in a polymer matrix formed from PVP/VA 64; (b) microcrystalline cellulose; (c) lactose monohydrate; (d) croscarmellose sodium; (e) colloidal silicon dioxide; and (f) magnesium stearate.
18 .- 20 . (canceled)
21 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises about 1% by weight to about 30% by weight of the spray-dried solid dispersion.
22 . The pharmaceutical formulation of claim 21 , wherein the tablet comprises about 5% by weight to about 20% by weight of the spray-dried solid dispersion.
23 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises about 1% by weight to about 20% by weight of 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl) bicyclo[2.2.2]octan-1-yl)methyl) carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate.
24 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises about 1 mg, about 5 mg, about 12 mg, or about 25 mg of 4-((4-(1-(tert-butyl)-1H-pyrazol-4-yl)pyridin-2-yl)((4-(4-methoxy-3-methylphenyl) bicyclo[2.2.2]octan-1-yl)methyl) carbamoyl)cyclohexyl 3-hydroxyazetidine-trans-1-carboxylate.
25 .- 56 . (canceled)
57 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises microcrystalline cellulose and lactose monohydrate comprise between about 75% to about 95% by weight.
58 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises croscarmellose sodium between about 5% to about 10% by weight.
59 . The pharmaceutical formulation of claim of claim 58 , wherein the tablet comprises croscarmellose sodium at about 5% by weight.
60 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises colloidal silicon dioxide between about 0.1% to about 2% by weight.
61 . The pharmaceutical formulation of claim 60 , wherein the tablet comprises colloidal silicon dioxide at about 1% by weight.
62 . The pharmaceutical formulation of claim 17 , wherein the tablet comprises magnesium stearate between about 0.1% to about 2% by weight.
63 . The pharmaceutical formulation of claim 62 , wherein the tablet comprises magnesium stearate at about 1% by weight.
64 . A film-coated tablet comprising (a) a tablet core comprising the pharmaceutical formulation of claim 17 , and (b) a film coating surrounding the tablet core.
65 . An enteric-coated pharmaceutical formulation comprising the pharmaceutical formulation of claim 17 and an enteric coating.
66 . A method of treating or preventing a gastrointestinal disease or condition in a mammal, comprising administering to the mammal in need thereof the pharmaceutical formulation of claim 17 , wherein the gastrointestinal disease or condition is necrotizing enterocolitis, gastritis, ulcerative colitis, Crohn's disease, inflammatory bowel disease, irritable bowel syndrome, gastroenteritis, radiation induced enteritis, pseudomembranous colitis, chemotherapy induced enteritis, gastro-esophageal reflux disease (GERD), peptic ulcer, non-ulcer dyspepsia (NUD), celiac disease, intestinal celiac disease, post-surgical inflammation, gastric carcinogenesis, graft versus host disease, or any combination thereof.