COMPOSITIONS OF OBETICHOLIC ACID AND METHODS OF USE
The disclosure relates to obeticholic acid formulations with improved stability, dissolution, and/or solubility, methods of preparing the same for use and methods of treating various diseases and conditions.
1 . A pharmaceutical composition comprising an active pharmaceutical ingredient, which is obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof, and one or more pharmaceutically acceptable excipients,
which provides a peak plasma concentration (C max ) of obeticholic acid in a subject at a median time (T max ) of approximately 2 hours after administration of the pharmaceutical composition to the subject.
2 . The pharmaceutical composition of claim 1 , which provides formation of glyco-obeticholic acid and/or tauro-obeticholic acid after the administration of the pharmaceutical composition to the subject and which provides a peak plasma concentration (C max ) of glyco-obeticholic acid or of tauro-obeticholic acid at a median time (T max ) of approximately 10 hours after the administration.
3 . The pharmaceutical composition of claim 1 , wherein said one or more pharmaceutically acceptable excipients have a total alcohol impurity having a primary alcohol group content of less than about 6% (wt/wt).
4 . The pharmaceutical composition of claim 3 , wherein said one or more pharmaceutically acceptable excipients having a total alcohol impurity having a primary alcohol group content of less than about 6% (wt/wt) is sodium starch glycolate.
5 . The pharmaceutical composition of claim 1 , wherein said one or more pharmaceutically acceptable excipients includes a viscosity enhancer.
6 . The pharmaceutical composition of claim 5 , wherein the viscosity enhancer is colloidal silicon dioxide.
7 . The pharmaceutical composition of claim 1 , wherein the active pharmaceutical ingredient is obeticholic acid.
8 . The pharmaceutical composition of claim 7 , wherein the obeticholic acid is present in an amount of 25 mg.
9 . The pharmaceutical composition of claim 1 , in the form of an oral dosage form.
10 . The pharmaceutical composition of claim 9 , wherein the oral dosage form is a tablet.
11 . The pharmaceutical composition of claim 1 , wherein the active pharmaceutical ingredient is the only active pharmaceutical ingredient in the pharmaceutical composition.
12 . A method of treating nonalcoholic steatohepatitis (NASH), comprising administering to a subject the pharmaceutical composition of claim 1 .
13 . The method of claim 12 , wherein the active pharmaceutical ingredient is obeticholic acid.
14 . The method of claim 13 , wherein the obeticholic acid is present in an amount of 25 mg.
15 . The method of claim 12 , wherein the active pharmaceutical ingredient is the only active pharmaceutical ingredient in the pharmaceutical composition.
16 . A method of treating nonalcoholic steatohepatitis (NASH) comprising administering to a subject a pharmaceutical composition,
the pharmaceutical composition comprises an active pharmaceutical ingredient, which is obeticholic acid or a pharmaceutically acceptable salt or amino acid conjugate thereof, and one or more pharmaceutically acceptable excipients,
which provides a peak plasma concentration (C max ) of obeticholic acid in a subject at a median T max of approximately 1.5 hours after administration of the pharmaceutical composition to the subject.
17 . The method of claim 16 , wherein the active pharmaceutical ingredient is obeticholic acid.
18 . The method of claim 17 , wherein the obeticholic acid is present in an amount of 25 mg.
19 . The method of claim 16 , wherein the active pharmaceutical ingredient is the only active pharmaceutical ingredient in the pharmaceutical composition.