Solid dosage forms of elafibranor

1 . An oral solid dosage form in the form of a tablet, comprising:

(a) an internal phase comprising:

i) from 20 to 60% by weight of the tablet, of elafibranor or a pharmaceutically acceptable salt or ester thereof;

ii) a filler selected from the group consisting of mannitol, microcrystalline cellulose, and lactose monohydrate;

iii) a disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium; and

iv) a binder selected from the group consisting of hydroxypropylcellulose, copovidone, povidone, and hydroxypropylmethyl cellulose, and

(b) an external phase comprising a disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium, colloidal silica as a glidant, and magnesium stearate as a lubricant,

wherein the external phase (b) is free of elafibranor; wherein the elafibranor or the pharmaceutically acceptable salt or ester thereof is micronized.

2 . An oral solid dosage form in the form of a tablet, comprising:

(a) an internal phase comprising:

i) from 20 to 60% by weight of the tablet, of elafibranor or a pharmaceutically acceptable salt or ester thereof;

ii) a filler selected from the group consisting of mannitol, microcrystalline cellulose, and lactose monohydrate;

iii) a disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium; and

iv) a binder selected from the group consisting of hydroxypropylcellulose, copovidone, povidone, and hydroxypropylmethyl cellulose, and

(b) an external phase comprising a disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium, colloidal silica as a glidant, and magnesium stearate as a lubricant, wherein the external phase (b) is free of elafibranor;

wherein the elafibranor or the pharmaceutically acceptable salt or ester thereof is in the form of particles, and wherein at least 90% of the particles have a diameter of 15 μm or less.

3 . The oral solid dosage form according to claim 2 , wherein at least 50% of the particles have a diameter of 5 μm or less.

4 . The oral solid dosage form according to claim 1 , wherein the dosage form comprises from 35 to 40% by weight of the elafibranor or the pharmaceutically acceptable salt or ester thereof.

5 . The oral solid dosage form according to claim 1 , wherein the dosage form comprises from 35 mg to 180 mg of the elafibranor or the pharmaceutically acceptable salt or ester thereof.

6 . The oral solid dosage form according to claim 5 , wherein the dosage form comprises from 40 mg to 120 mg of the elafibranor or the pharmaceutically acceptable salt or ester thereof.

7 . The oral solid dosage form according to claim 1 , wherein

(a) the internal phase comprises:

(i) from 30% to 60% by weight of the elafibranor or the pharmaceutically acceptable salt or ester thereof;

(ii) from 20% to 55% by weight of microcrystalline cellulose;

(iii) from 0.8% to 6% by weight of croscarmellose sodium; and

(iv) from 2% to 6% by weight of povidone; and

(b) the external phase comprises:

from 0.2% to 4% by weight of croscarmellose sodium;

from 0.1% to 0.4% by weight of colloidal silica; and

from 0.1% to 2% by weight of magnesium stearate;

relative to the total weight of the tablet.

8 . The oral solid dosage form according to claim 1 , wherein the tablet is obtained by carrying out a step of wet granulation followed by tablet compression and optionally, coating.

9 . The oral solid dosage form according to claim 1 , said dosage form comprising an external coating.

10 . The oral solid dosage form according to claim 9 , wherein the external coating comprises a coloring agent.

11 . A method for treating or preventing primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), cirrhosis, hepatitis C infection, alcoholic liver disease, liver damage due to progressive fibrosis, liver fibrosis or cirrhosis in a patient in need thereof, the method comprising administering the oral solid dosage form according to claim 1 .

12 . The method according to claim 11 , wherein said oral solid dosage form is administered once a day.

13 . The oral solid dosage form according to claim 1 , wherein the elafibranor or the pharmaceutically acceptable salt or ester thereof is the sole active ingredient.

14 . The oral solid dosage form according to claim 1 , consisting of:

(a) the internal phase consisting of:

i) from 20 to 60% by weight of the elafibranor or the pharmaceutically acceptable salt or ester thereof;

ii) the filler selected from the group consisting of mannitol, microcrystalline cellulose, and lactose monohydrate;

iii) the disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium; and

iv) the binder selected from the group consisting of hydroxypropylcellulose, copovidone, povidone, and hydroxypropylmethyl cellulose, and

(b) the external phase consisting of the disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium, colloidal silica as the glidant, and magnesium stearate as the lubricant,

wherein the external phase (b) is free of elafibranor.

15 . The oral solid dosage form according to claim 1 , consisting of:

(a) the internal phase consisting of:

i) from 20 to 60% by weight of the tablet of the elafibranor or the pharmaceutically acceptable salt or ester thereof;

ii) the filler selected from the group consisting of mannitol, microcrystalline cellulose, and lactose monohydrate;

iii) the disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium; and

iv) the binder selected from the group consisting of hydroxypropylcellulose, copovidone, povidone, and hydroxypropylmethyl cellulose,

(b) the external phase consisting of the disintegrating agent selected from the group consisting of crospovidone and croscarmellose sodium, colloidal silica as the glidant and magnesium stearate as the lubricant, and

(c) an external coating,

wherein the external phase (b) and the external coating (c) are free of elafibranor.