Lanifibranor preparations

Abstract

The present invention relates to a pharmaceutical composition useful for treating liver fibrosis, comprising 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of one or more excipients.

Description

[Technical Field]

[0001] The present invention relates to pharmaceutical compositions comprising lanifibranor and to the use of said compositions in therapy, particularly for the treatment of liver fibrosis. [Background technology]

[0002] Lanifibranor, or 1-(6-benzothiazolylsulfonyl)-5-chloro-1H-indole-2-butanoic acid, is a pan-PPAR agonist currently in clinical development for the treatment of subjects with nonalcoholic steatohepatitis (NASH), for which there is currently no approved treatment.

[0003] Lanifibranor is described in Example 117 of WO2007 / 026097, where it is obtained as a pale yellow powder with a melting point of 74-80° C. and has the following structure: [ka]

[0004] The daily dosage regimen of lanifibranor used in the Phase 2 clinical trial was either 800 mg or 1,200 mg, with two or three 400 mg tablets containing 44% lanifibranor by weight administered once daily, depending on the regimen considered. It is planned to follow the same daily dosage regimen using a pharmaceutical formulation containing a higher lanifibranor loading during the upcoming Phase 3 clinical trial. While theoretically it is desirable to incorporate as much active ingredient as possible into a pharmaceutical formulation, challenges exist, for example, regarding the manufacturing process or patient acceptability (due to dosage form size). In particular, incorporating hydrophobic components (as in the case of lanifibranor), especially large amounts of hydrophobic components, into a pharmaceutical formulation is not straightforward, as this can be detrimental to bioavailability.

[0005] The present invention has been made in consideration of the above problems. Summary of the Invention

[0006] In one aspect, the present disclosure provides a composition comprising, based on the total weight of the composition: about 55.0% to about 75.0% by weight of lanifibranol; about 25.0% to about 45.0% by weight of a pharmaceutically acceptable excipient; Including, The present invention relates to a pharmaceutical composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm.

[0007] In some embodiments, the pharmaceutically acceptable excipients comprise two or more of a binder, a disintegrant, a filler, a glidant, a lubricant, and a surfactant. In some embodiments, the pharmaceutically acceptable excipients comprise a binder, a disintegrant, a filler, a glidant, a lubricant, and a surfactant.

[0008] In some embodiments, the pharmaceutical composition is in a solid dosage form, such as a capsule, sachet, lozenge, powder, pill, or tablet.

[0009] In some embodiments, the solid dosage form contains about 200 mg to about 1,200 mg of lanifibranor, for example, 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, or 1,200 mg of lanifibranor.

[0010] In some embodiments, the lanifibranor is present in a crystalline form.

[0011] In some embodiments, the pharmaceutical composition has a dissolution of at least 30% and no more than 60% after 15 minutes, and at least 80%, preferably at least 85%, after 45 minutes, when measured using USP Test Apparatus 1 (10 mesh basket) at 100 rpm in 1000 mL of pH 6.8 sodium phosphate buffer containing about 0.7% to 1.7% tetradecyltrimethylammonium bromide thermostated at 37°C ± 0.5°C.

[0012] In another aspect, the present disclosure relates to a method of treating non-alcoholic fatty liver disease, comprising administering to a subject in need thereof a pharmaceutical composition as defined above.

[0013] In another aspect, the present disclosure relates to a method of treating a subject with cirrhosis at risk of progressing from compensated to decompensated, comprising administering to the subject a pharmaceutical composition as defined above.

[0014] Both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to provide further explanation of the invention as defined in the appended claims. [Brief explanation of the drawings]

[0015] [Figure 1] FIG. 1 shows the dissolution profile of a 600 mg lanifibranor tablet. [Figure 2] FIG. 2 shows the dissolution profile of a 400 mg lanifibranor tablet. DETAILED DESCRIPTION OF THE INVENTION

[0016] As used herein, the articles "a" and "an" are understood to mean one or more of what is claimed or described.

[0017] As used herein, the terms "include", "includes" and "including" are meant to be open-ended.

[0018] As used herein, the term "about xx" refers to a measurable value, such as a parameter, amount, duration, etc., and is intended to encompass a variation of no more than + / -10%, preferably no more than + / -5%, more preferably no more than + / -1%, even more preferably no more than + / -0.5%, more preferably no more than + / -0.05%, even more preferably no more than + / -0.04%, no more than + / -0.03%, no more than + / -0.02%, and no more than + / -0.01% of the specified value, to the extent that such variation is appropriate for the disclosed invention. However, it should be understood that the value to which "about" refers is itself specifically disclosed. In other words, the term "about xx" includes the value "xx."

[0019] It should be understood that concentrations (weight percent (wt %)) disclosed herein are based on the total weight of the pharmaceutical composition or formulation made, unless otherwise indicated.

[0020] The embodiments described herein may be combined.

[0021] In one aspect, the present disclosure provides a composition comprising, based on the total weight of the composition: about 55.0% to about 75.0% by weight of lanifibranol; about 25.0% to about 45.0% by weight of a pharmaceutically acceptable excipient; Including, The present invention relates to a pharmaceutical composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm.

[0022] As used herein, D50 and D90 (sometimes referred to as D(v; 0.5) and D(v; 0.9), respectively) are the size distribution points at which 50% and 90% of the total volume of material in a sample is "contained," respectively. For example, D90≦50 μm means that 90% of the sample has a size of up to 50 μm. D50 and D90 were measured using a laser diffraction / scattering particle size distribution analyzer (e.g., available from Malvern).

[0023] In some embodiments, the particle size distribution of the lanifibranor is such that it has a D50≦10 μm and a D90≦30 μm, and advantageously, the lanifibranor has a D90≦15 μm.

[0024] In some embodiments, the lanifibranor has a particle size distribution such that both its D90 and its D50 are ≦5 μm, eg, both D90 and D50 values ​​are within the range of about 200 nm to about 2000 nm.

[0025] As used herein, "lanifibranor" refers to lanifibranor, which is referred to under CAS No. 927961-18-0 (also known as IVA337) or described in Example 117 of WO 2007 / 026097. In some embodiments, the term "lanifibranor" also includes deuterated derivatives of lanifibranor. In some embodiments, the lanifibranor is in a crystalline form. Examples of crystalline forms of lanifibranor are described in WO 2023 / 194339, WO 2023 / 016319, WO 2022 / 122014, WO 2022 / 261410, or WO 2022 / 258060, all of which are incorporated herein by reference.

[0026] In some embodiments, the deuterated derivative of lanifibranor is a compound of formula (I) [ka] and As described in WO 2020 / 021215, at least one of groups R1-R7 is a deuterium (D) atom and the other groups R1-R7 are hydrogen (H) atoms. In some embodiments, at least group R1 is D. In some embodiments, at least one of groups R2-R7 is D, particularly at least one of groups R2 and R3 and / or at least one of groups R4 and R5 and / or at least one of groups R6 and R7 is D. In preferred embodiments, each of R2, R3, R4, R5, R6 and R7 is D. Preferred compounds of formula (I) include 4-(1-(2-deuterio-1,3-benzothiazol-6-yl)sulfonyl)-5-chloro-1H-indol-2-yl)butanoic acid and 4-[1-(1,3-benzothiazol-6-ylsulfonyl)-5-chloro-indol-2-yl]-2,2,3,3,4,4-hexadeuteriobutanoic acid.

[0027] In some embodiments, lanifibranor or its deuterated derivative is in the form of a pharmaceutically acceptable salt or solvate. The term "solvate" is used herein to describe a molecular complex containing lanifibranor or its deuterated derivative and one or more pharmaceutically acceptable solvent molecules, such as ethanol. The term "hydrate" is used when the solvent is water. Pharmaceutically acceptable salts of lanifibranor or its deuterated derivative include its base addition salts. Base addition salts can be prepared from inorganic and organic bases. Examples of inorganic bases include sodium hydroxide, potassium hydroxide, magnesium hydroxide, and calcium hydroxide. Examples of organic bases include amines, amino alcohols, basic amino acids such as lysine or arginine, and quaternary ammonium compounds such as betaine or choline.

[0028] In some embodiments, the lanifibranor is about 55.0% to about 75.0% by weight, e.g., about 55.0% to about 70.0% by weight, e.g., about 55.0% to about 65.0% by weight, e.g., about 55.0% to about 60.0% by weight. In some embodiments, the lanifibranor is about 56.0% to about 75.0% by weight, e.g., about 56.0% to about 70.0% by weight, e.g., about 56.0% to about 65.0% by weight, e.g., about 56.0% to about 60.0% by weight. In some embodiments, the lanifibranor is, for example, about 57.0% to about 75.0% by weight, e.g., about 57.0% to about 70.0% by weight, e.g., about 57.0% to about 65.0% by weight, e.g., about 57.0% to about 60.0% by weight. In some embodiments, lanifibranor is about 55.0% by weight, about 55.1% by weight, about 55.2% by weight, about 55.3% by weight, about 55.4% by weight, about 55.5% by weight, about 55.6% by weight, about 55.7% by weight, about 55.8% by weight, about 55.9% by weight, about 56.0% by weight, about 56.1% by weight, about 56.2% by weight, about 56.3% by weight, about 56.4% by weight, about 56.5% by weight %, about 56.6% by weight, about 56.7% by weight, about 56.8% by weight, about 56.9% by weight, about 57.0% by weight, about 57.1% by weight, about 57.2% by weight, about 57.3% by weight, about 57.4% by weight, Approximately 57.5% by weight, approximately 57.6% by weight, approximately 57.7% by weight, approximately 57.8% by weight, approximately 57.9% by weight, approximately 58.0% by weight, approximately 58.1% by weight, approximately 58.2% by weight, approximately 58.3% by weight, approximately 58 .4% by weight, approximately 58.5% by weight, approximately 58.6% by weight, approximately 58.7% by weight, approximately 58.8% by weight, approximately 58.9% by weight, approximately 59.0% by weight, approximately 59.1% by weight, approximately 59.2% by weight, approximately 59.3 Weight%, about 59.4% by weight, about 59.5% by weight, about 59.6% by weight, about 59.7% by weight, about 59.8% by weight, about 59.9% by weight, about 60.0% by weight, about 60.1% by weight, about 60.2% by weight , about 60.3% by weight, about 60.4% by weight, about 60.5% by weight, about 60.6% by weight, about 60.7% by weight, about 60.8% by weight, about 60.9% by weight, about 61.0% by weight, about 61.1% by weight, about 61.2% by weight, approximately 61.3% by weight, approximately 61.4% by weight, approximately 61.5% by weight, approximately 61.6% by weight, approximately 61.7% by weight, approximately 61.8% by weight, approximately 61.9% by weight, approximately 62.0% by weight, approximately 62.1% by weight, approximately 62.2% by weight, approximately 62.3% by weight, approximately 62.4% by weight, approximately 62.5% by weight, approximately 62.6% by weight, approximately 62.7% by weight, approximately 62.8% by weight, approximately 62.9% by weight, approximately 63.0% by weight, approximately 63.1% by weight, approximately 63.2% by weight, approximately 63.3% by weight, approximately 63.4% by weight, approximately 63.5% by weight, approximately 63.6% by weight, approximately 63.7% by weight, approximately 63.8% by weight, approximately 63.9% by weight, approximately 64.0% by weight, approximately 64.1% by weight, approximately 64.2% by weight, approximately 64.3% by weight, approximately 64.4% by weight, approximately 64.5% by weight, approximately 64.6% by weight, approximately 64.7% by weight, approximately 64.8% by weight, approximately 64.9% by weight, approximately 65.0% by weight, approximately 65.1% by weight, approximately 65.2% by weight, approximately 65.3% by weight, approximately 65.4% by weight, approximately 65.5% by weight, approximately 65.6% by weight, approximately 65.7% by weight, approximately 65.8% by weight, approximately 65.9% by weight, approximately 66.0% by weight, approximately 66.1% by weight, approximately 66.2% by weight, approximately 66.3% by weight, approximately 66.4% by weight, approximately 66.5% by weight, approximately 66.6% by weight, approximately 66.7% by weight, approximately 66.8% by weight, approximately 66.9% by weight, approximately 67.0% by weight, approximately 67.1% by weight, approximately 67.2% by weight, approximately 67.3% by weight, approximately 67.4% by weight, approximately 67.5% by weight, approximately 67.6% by weight Approximately 67.7% by weight, approximately 67.8% by weight, approximately 67.9% by weight, approximately 68.0% by weight, approximately 68.1% by weight, approximately 68.2% by weight, approximately 68.3% by weight, approximately 68.4% by weight, approximately 68.5% by weight, approximately 68.6% by weight, approximately 68.7% by weight, approximately 68.8% by weight, approximately 68.9% by weight, approximately 69.0% by weight, approximately 69.1% by weight, approximately 69.2% by weight, approximately 69.3% by weight, approximately 69.4% by weight, approximately 69.5% by weight, approximately 69.6% by weight, approximately 69.7% by weight, approximately 69.8% by weight, approximately 69.9% by weight, approximately 70.0% by weight, approximately 70.1% by weight, approximately 70.2% by weight, approximately 70.3% by weight, approximately 70.4% by weight. Weight%, approximately 70.5% by weight, approximately 70.6% by weight, approximately 70.7% by weight, approximately 70.8% by weight, approximately 70.9% by weight, approximately 71.0% by weight, approximately 71.1% by weight, approximately 71.2% by weight, approximately 71.3% by weight, approximately 71.4% by weight, approximately 71.5% by weight, approximately 71.6% by weight, approximately 71.7% by weight, approximately 71.8% by weight, approximately 71.9% by weight, approximately 72.0% by weight, approximately 72.1% by weight, approximately 72.2% by weight, approximately 72.3% by weight, approximately 72.4% by weight, approximately 72.5% by weight, approximately 72.6% by weight, approximately 72.7% by weight, approximately 72.8% by weight, approximately 72.9% by weight, approximately 73.0% by weight, approximately 73.1% by weight, approximately 73%.2% by weight, about 73.3% by weight, about 73.4% by weight, about 73.5% by weight, about 73.6% by weight, about 73.7% by weight, about 73.8% by weight, about 73.9% by weight, about 74.0% by weight, about 74.1% by weight, about 74.2% by weight, about 74.3% by weight, about 74.4% by weight, about 74.5% by weight, about 74.6% by weight, about 74.7% by weight, about 74.8% by weight, about 74.9% by weight, and about 75.0% by weight.

[0029] The inventors have surprisingly demonstrated that a specific distribution of lanifibranor (as the active ingredient) and pharmaceutically acceptable excipients makes it possible to obtain an immediate release pharmaceutical composition that is stable, easy to compress into tablets, has a good dissolution profile and is well tolerated.

[0030] In some embodiments, the pharmaceutically acceptable excipients comprise two or more of a binder, a disintegrant, a filler, a glidant, a lubricant, and a surfactant. In some embodiments, the pharmaceutically acceptable excipients comprise a binder, a disintegrant, a filler, a glidant, a lubricant, and a surfactant.

[0031] Filler In some embodiments, the pharmaceutically acceptable excipient comprises a filler, and the filler is present in an amount of about 10.0 wt% to about 35.0 wt%, for example about 11.0 wt% to about 35.0 wt%, for example about 12.0 wt% to about 35.0 wt%, for example about 13.0 wt% to about 35.0 wt%, for example about 14.0 wt% to about 35.0 wt%, for example about 15.0 wt% to about 35.0 wt%, for example about 16.0 wt% to about 35.0 wt%, for example about 17.0 wt% to about 35.0 wt%, for example about 18.0 wt% to about 35.0 wt%, for example about 19.0 wt% to about 35.0 wt%, of the total weight of the composition. 0.0% by weight, for example, about 20.0% by weight to about 35.0% by weight, for example, about 21.0% by weight to about 35.0% by weight, for example, about 22.0% by weight to about 35.0% by weight, for example, about 23.0% by weight to about 35.0% by weight, for example, about 24.0% by weight to about 35.0% by weight, for example, about 25.0% by weight to about 35.0% by weight, for example, about 26.0% by weight to about 35.0% by weight, for example, about 27.0% by weight to about 35.0% by weight, for example, about 28.0% by weight to about 35.0% by weight, for example, about 29.0% by weight to about 35.0% by weight, for example, about 30.0% by weight to about 35.0% by weight, for example, about 31.0% by weight to about 35.0% by weight, for example, about 32.0% by weight to about 35.0% by weight, for example, about 33.0% by weight to about 35.0% by weight, for example, about 34.0% by weight to about 35.0% by weight, for example, about 10.0% by weight to about 34.0% by weight, for example, about 11.0% by weight to about 34.0% by weight, for example, about 12.0% by weight to about 34.0% by weight, for example, about 13.0% by weight to about 34.0% by weight, for example, about 14.0% by weight to about 34.0% by weight, for example, about 15.0% by weight to about 34.0% by weight, for example, about 16.0% by weight to about 34.0% by weight, for example, about 17.0% by weight to about 34.0% by weight, for example, about 18.0% by weight Amount % to about 34.0 wt%, for example, about 19.0 wt% to about 34.0 wt%, for example, about 20.0 wt% to about 34.0 wt%, for example, about 21.0 wt% to about 34.0 wt%, for example, about 22.0 wt% to about 34.0 wt%, for example, about 23.0 wt% to about 34.0 wt%, for example, about 24.0 wt% to about 34.0 wt%, for example, about 25.0 wt% to about 34.0 wt%, for example, about 26.0 wt% to about 34.0 wt%, for example, about 27.0 wt% to about 34.0 wt%, for example, about 28.0 wt% to about 34.0 wt%, for example, about 29.0 wt% to about 34.0 wt%, for example, about 30.0% by weight to about 34.0% by weight, for example, about 31.0% by weight to about 34.0% by weight, for example, about 32.0% by weight to about 34.0% by weight, for example, about 33.0% by weight to about 34.0% by weight, for example, about 10.0% by weight to about 33.0% by weight, for example, about 11.0% by weight to about 33.0% by weight, for example, about 12.0% by weight to about 33.0% by weight, for example, about 13.0% by weight to about 33.0% by weight, for example, about 14.0% by weight to about 33.0% by weight, for example, about 15.0% by weight to about 33.0% by weight, for example, about 16.0% by weight to about 33.0% by weight, for example, about 17.0% by weight to about 33.0% by weight, for example, 18.0% by weight to about 33.0% by weight, for example about 19.0% by weight to about 33.0% by weight, for example about 20.0% by weight to about 33.0% by weight, for example about 21.0% by weight to about 33.0% by weight, for example about 22.0% by weight to about 33.0% by weight, for example about 23.0% by weight to about 33.0% by weight, for example about 24.0% by weight to about 33.0% by weight, for example about 25.0% by weight to about 33.0% by weight, for example about 26.0% by weight to about 33.0% by weight, for example about 27.0% by weight to about 33.0% by weight, for example about 28.0% by weight to about 33.0% by weight, for example about 29.0% by weight to about 33.0% by weight, For example, about 30.0 wt% to about 33.0 wt%, for example, about 31.0 wt% to about 33.0 wt%, for example, about 32.0 wt% to about 33.0 wt%, for example, about 10.0 wt% to about 32.0 wt%, for example, about 11.0 wt% to about 32.0 wt%, for example, about 12.0 wt% to about 32.0 wt%, for example, about 13.0 wt% to about 32.0 wt%, for example, about 14.0 wt% to about 32.0 wt%, for example, about 15.0 wt% to about 32.0 wt%, for example, about 16.0 wt% to about 32.0 wt%, for example, about 17.0 wt% to about 32.0 wt%, for example, about 18.0 wt% to about 32.0 wt% %, for example, about 19.0 wt % to about 32.0 wt %, for example, about 20.0 wt % to about 32.0 wt %, for example, about 21.0 wt % to about 32.0 wt %, for example, about 22.0 wt % to about 32.0 wt %, for example, about 23.0 wt % to about 32.0 wt %, for example, about 24.0 wt % to about 32.0 wt %, for example, about 25.0 wt % to about 32.0 wt %, for example, about 26.0 wt % to about 32.0 wt %, for example, about 27.0 wt % to about 32.0 wt %, for example, about 28.0 wt % to about 32.0 wt %, for example, about 29.0 wt % to about 32.0 wt %, for example, about 30.0 wt % to about 32.0% by weight, for example, about 31.0% by weight to about 32.0% by weight, for example, about 10.0% by weight to about 31.0% by weight, for example, about 11.0% by weight to about 31.0% by weight, for example, about 12.0% by weight to about 31.0% by weight, for example, about 13.0% by weight to about 31.0% by weight, for example, about 14.0% by weight to about 31.0% by weight, for example, about 15.0% by weight to about 31.0% by weight, for example, about 16.0% by weight to about 31.0% by weight, for example, about 17.0% by weight to about 31.0% by weight, for example, about 18.0% by weight to about 31.0% by weight, for example, about 19.0% by weight to about 31.0% by weight, for example, about 20.0% by weight to about 31.0% by weight, for example, about 21.0% by weight to about 31.0% by weight, for example, about 22.0% by weight to about 31.0% by weight, for example, about 23.0% by weight to about 31.0% by weight, for example, about 24.0% by weight to about 31.0% by weight, for example, about 25.0% by weight to about 31.0% by weight, for example, about 26.0% by weight to about 31.0% by weight, for example, about 27.0% by weight to about 31.0% by weight, for example, about 28.0% by weight to about 31.0% by weight, for example, about 29.0% by weight to about 31.0% by weight, for example, about 30.0% by weight to about 31.0% by weight, for example, about 10.0% by weight to about 30.0% by weight, for example, about 11.0% by weight to about 30.0 wt%, for example, about 12.0 wt% to about 30.0 wt%, for example, about 13.0 wt% to about 30.0 wt%, for example, about 14.0 wt% to about 30.0 wt%, for example, about 15.0 wt% to about 30.0 wt%, for example, about 16.0 wt% to about 30.0 wt%, for example, about 17.0 wt% to about 30.0 wt%, for example, about 18.0 wt% to about 30.0 wt%, for example, about 19.0 wt% to about 30.0 wt%, for example, about 20.0 wt% to about 30.0 wt%, for example, about 21.0 wt% to about 30.0 wt%, for example, about 22.0 wt% to about 30.0 wt%, for example, about 23.0 wt% Amount % to about 30.0 wt%, for example, about 24.0 wt% to about 30.0 wt%, for example, about 25.0 wt% to about 30.0 wt%, for example, about 26.0 wt% to about 30.0 wt%, for example, about 27.0 wt% to about 30.0 wt%, for example, about 28.0 wt% to about 30.0 wt%, for example, about 29.0 wt% to about 30.0 wt%, for example, about 10.0 wt% to about 29.0 wt%, for example, about 11.0 wt% to about 29.0 wt%, for example, about 12.0 wt% to about 29.0 wt%, for example, about 13.0 wt% to about 29.0 wt%, for example, about 14.0 wt% to about 29.0 wt%, for example, about 15.0% by weight to about 29.0% by weight, for example, about 16.0% by weight to about 29.0% by weight, for example, about 17.0% by weight to about 29.0% by weight, for example, about 18.0% by weight to about 29.0% by weight, for example, about 19.0% by weight to about 29.0% by weight, for example, about 20.0% by weight to about 29.0% by weight, for example, about 21.0% by weight to about 29.0% by weight, for example, about 22.0% by weight to about 29.0% by weight, for example, about 23.0% by weight to about 29.0% by weight, for example, about 24.0% by weight to about 29.0% by weight, for example, about 25.0% by weight to about 29.0% by weight, for example, about 26.0% by weight to about 29.0% by weight, for example, about 27.0 wt% to about 29.0 wt%, for example, about 28.0 wt% to about 29.0 wt%, for example, about 10.0 wt% to about 28.0 wt%, for example, about 11.0 wt% to about 28.0 wt%, for example, about 12.0 wt% to about 28.0 wt%, for example, about 13.0 wt% to about 28.0 wt%, for example, about 14.0 wt% to about 28.0 wt%, for example, about 15.0 wt% to about 28.0 wt%, for example, about 16.0 wt% to about 28.0 wt%, for example, about 17.0 wt% to about 28.0 wt%, for example, about 18.0 wt% to about 28.0 wt%, for example, about 19.0 wt% to about 28.0 wt%, e.g. For example, about 20.0 wt% to about 28.0 wt%, for example, about 21.0 wt% to about 28.0 wt%, for example, about 22.0 wt% to about 28.0 wt%, for example, about 23.0 wt% to about 28.0 wt%, for example, about 24.0 wt% to about 28.0 wt%, for example, about 25.0 wt% to about 28.0 wt%, for example, about 26.0 wt% to about 28.0 wt%, for example, about 27.0 wt% to about 28.0 wt%, for example, about 10.0 wt% to about 27.0 wt%, for example, about 11.0 wt% to about 27.0 wt%, for example, about 12.0 wt% to about 27.0 wt%, for example, about 13.0 wt% to about 27.0 wt% %, for example, about 14.0 wt % to about 27.0 wt %, for example, about 15.0 wt % to about 27.0 wt %, for example, about 16.0 wt % to about 27.0 wt %, for example, about 17.0 wt % to about 27.0 wt %, for example, about 18.0 wt % to about 27.0 wt %, for example, about 19.0 wt % to about 27.0 wt %, for example, about 20.0 wt % to about 27.0 wt %, for example, about 21.0 wt % to about 27.0 wt %, for example, about 22.0 wt % to about 27.0 wt %, for example, about 23.0 wt % to about 27.0 wt %, for example, about 24.0 wt % to about 27.0 wt %, for example, about 25.0 wt % to about 27.0% by weight, for example, about 26.0% by weight to about 27.0% by weight, for example, about 10.0% by weight to about 26.0% by weight, for example, about 11.0% by weight to about 26.0% by weight, for example, about 12.0% by weight to about 26.0% by weight, for example, about 13.0% by weight to about 26.0% by weight, for example, about 14.0% by weight to about 26.0% by weight, for example, about 15.0% by weight to about 26.0% by weight, for example, about 16.0% by weight to about 26.0% by weight, for example, about 17.0% by weight to about 26.0% by weight, for example, about 18.0% by weight to about 26.0% by weight, for example, about 19.0% by weight to about 26.0% by weight, for example, about 20.0% by weight to about 26.0% by weight, for example, about 21.0% by weight to about 26.0% by weight, for example, about 22.0% by weight to about 26.0% by weight, for example, about 23.0% by weight to about 26.0% by weight, for example, about 24.0% by weight to about 26.0% by weight, for example, about 25.0% by weight to about 26.0% by weight, for example, about 10.0% by weight to about 25.0% by weight, for example, about 11.0% by weight to about 25.0% by weight, for example, about 12.0% by weight to about 25.0% by weight, for example, about 13.0% by weight to about 25.0% by weight, for example, about 14.0% by weight to about 25.0% by weight, for example, about 15.0% by weight to about 25.0% by weight, for example, about 16.0% by weight to about 25.0 wt%, for example, about 17.0 wt% to about 25.0 wt%, for example, about 18.0 wt% to about 25.0 wt%, for example, about 19.0 wt% to about 25.0 wt%, for example, about 20.0 wt% to about 25.0 wt%, for example, about 21.0 wt% to about 25.0 wt%, for example, about 22.0 wt% to about 25.0 wt%, for example, about 23.0 wt% to about 25.0 wt%, for example, about 24.0 wt% to about 25.0 wt%, for example, about 10.0 wt% to about 24.0 wt%, for example, about 11.0 wt% to about 24.0 wt%, for example, about 12.0 wt% to about 24.0 wt%, for example, about 13.0 wt% to about 24.0 wt%, Amount % to about 24.0 wt%, for example, about 14.0 wt% to about 24.0 wt%, for example, about 15.0 wt% to about 24.0 wt%, for example, about 16.0 wt% to about 24.0 wt%, for example, about 17.0 wt% to about 24.0 wt%, for example, about 18.0 wt% to about 24.0 wt%, for example, about 19.0 wt% to about 24.0 wt%, for example, about 20.0 wt% to about 24.0 wt%, for example, about 21.0 wt% to about 24.0 wt%, for example, about 22.0 wt% to about 24.0 wt%, for example, about 23.0 wt% to about 24.0 wt%, for example, about 10.0 wt% to about 23.0 wt%, for example, about 11.0% by weight to about 23.0% by weight, for example, about 12.0% by weight to about 23.0% by weight, for example, about 13.0% by weight to about 23.0% by weight, for example, about 14.0% by weight to about 23.0% by weight, for example, about 15.0% by weight to about 23.0% by weight, for example, about 16.0% by weight to about 23.0% by weight, for example, about 17.0% by weight to about 2. 3.0% by weight, for example, about 18.0% by weight to about 23.0% by weight, for example, about 19.0% by weight to about 23.0% by weight, for example, about 20.0% by weight to about 23.0% by weight, for example, about 21.0% by weight to about 23.0% by weight, for example, about 22.0% by weight to about 23.0% by weight, for example, about 10.0% by weight to about 22.0% by weight, for example, about 11.0% by weight to about 22.0% by weight, for example, about 12.0% by weight to about 22.0% by weight, for example, about 13.0% by weight to about 22.0% by weight, for example, about 14.0% by weight to about 22.0% by weight, for example, about 15.0% by weight to about 22.0% by weight, for example, about 16.0% by weight to about 22.0% by weight, for example, about 17.0% by weight to about 22.0% by weight, for example, about 18.0% by weight to about 22.0% by weight, for example, about 19.0% by weight to about 22.0% by weight, for example, about 20.0% by weight to about 22.0% by weight, for example, about 21.0% by weight to about 22.0% by weight, for example, about 10.0% by weight to about 21.0% by weight, for example, about 11.0% by weight to about 21.0% by weight, for example, about 12.0% by weight to about 21.0% by weight, for example, about 13.0% by weight to about 21.0% by weight, for example, about 14.0% by weight to about 21.0% by weight, for example, about 15.0% by weight to about 21.0% by weight, for example, about 16.0% by weight % to about 21.0 wt%, for example, about 17.0 wt% to about 21.0 wt%, for example, about 18.0 wt% to about 21.0 wt%, for example, about 19.0 wt% to about 21.0 wt%, for example, about 20.0 wt% to about 21.0 wt%, for example, about 10.0 wt% to about 20.0 wt%, for example, about 11.0 wt% to about 20.0 wt%, for example, about 12.0 wt% to about 20.0 wt%, for example, about 13.0 wt% to about 20.0 wt%, for example, about 14.0 wt% to about 20.0 wt%, for example, about 15.0 wt% to about 20.0 wt%, for example, about 16.0 wt% to about 20.0 wt%, for example, about 17.0 % to about 20.0% by weight, for example, about 18.0% to about 20.0% by weight, for example, about 19.0% to about 20.0% by weight, for example, about 10.0% to about 19.0% by weight, for example, about 11.0% to about 19.0% by weight, for example, about 12.0% to about 19.0% by weight, for example, about 13.0% to about 19.0% by weight, for example, about 14.0% to about 19.0% by weight, for example, about 15.0% to about 19.0% by weight, for example, about 16.0% to about 19.0% by weight, for example, about 17.0% to about 19.0% by weight, for example, about 18.0% to about 19.0% by weight, for example, about 10.0% by weight to about 18.0% by weight, for example, about 11.0% by weight to about 18.0% by weight, for example, about 12.0% by weight to about 18.0% by weight, for example, about 13.0% by weight to about 18.0% by weight, for example, about 14.0% by weight to about 18.0% by weight, for example, about 15.0% by weight to about 18.0% by weight, for example, about 16.0% by weight to about 18.0% by weight, for example, about 17.0% by weight to about 18.0% by weight, for example, about 10.0% by weight to about 17.0% by weight, for example, about 11 0.0% by weight to about 17.0% by weight, for example, about 12.0% by weight to about 17.0% by weight, for example, about 13.0% by weight to about 17.0% by weight, for example, about 14.0% by weight to about 17.0% by weight, for example, about 15.0% by weight to about 17.0% by weight, for example, about 16.0% by weight to about 17.0% by weight, for example, about 10.0% by weight to about 16.0% by weight, for example, about 11.0% by weight to about 16.0% by weight, for example, about 12.0% by weight to about 16.0% by weight, for example, about 1 3.0% by weight to about 16.0% by weight, for example, about 14.0% by weight to about 16.0% by weight, for example, about 15.0% by weight to about 16.0% by weight, for example, about 10.0% by weight to about 15.0% by weight, for example, about 11.0% by weight to about 15.0% by weight, for example, about 12.0% by weight to about 15.0% by weight, for example, about 13.0% by weight to about 15.0% by weight, for example, about 14.0% by weight to about 15.0% by weight, for example, about 10.0% by weight to about 14.0% by weight, for example, about 11.0% by weight to about 14.0% by weight, for example, about 12.0% by weight to about 14.0% by weight, for example, about 13.0% by weight to about 14.0% by weight, for example, about 10.0% by weight to about 13.0% by weight, for example, about 11.0% by weight to about 13.0% by weight, for example, about 12.0% by weight to about 13.0% by weight, for example, about 10.0% by weight to about 12.0% by weight, for example, about 11.0% by weight to about 12.0% by weight, for example, about 10.0% by weight to about 11.0% by weight.

[0032] In some embodiments, the filler is about 10.0% by weight, about 10.1% by weight, about 10.2% by weight, about 10.3% by weight, about 10.4% by weight, about 10.5% by weight, about 10.6% by weight, about 10.7% by weight, about 10.8% by weight, about 10.9% by weight, about 11.0% by weight, about 11.1% by weight, about 11.2% by weight, about 11.3% by weight, about 11.4% by weight, about 11.5% by weight, about 11.6% by weight, about 11.7% by weight, about 11.8% by weight, about 11.9% by weight, about 12.0% by weight, about 12.1% by weight, about 12.2% by weight, about 12.3% by weight, about 12.4% by weight, about 12.5% ​​by weight, about 12.6% by weight, about 12.7% by weight, about 12.8% by weight, about 12.9% by weight, about 13.0% by weight, about 13.1% by weight, about 13.2% by weight, about 13.3% by weight, about 13.4% by weight, about 13.5% by weight, about 13.6% by weight, about 13.7% by weight, about 13.8% by weight, about 13.9% by weight, about 14.0% by weight, about 14.1% by weight, about 14.2% by weight, about 14.3% by weight, about 14.4% by weight, about 14.5% by weight, about 14.6% by weight, about 14.7% by weight, about 14.8% by weight, about 14.9% by weight, about 1 5% by weight, approximately 12.6% by weight, approximately 12.7% by weight, approximately 12.8% by weight, approximately 12.9% by weight, approximately 13.0% by weight, approximately 13.1% by weight, approximately 13.2% by weight, approximately 13.3% by weight, approximately 13.4% by weight, approximately 13.5% by weight, approximately 13.6% by weight, approximately 13.7% by weight, approximately 13.8% by weight, approximately 1 3.9% by weight, approximately 14.0% by weight, approximately 14.1% by weight, approximately 14.2% by weight, approximately 14.3% by weight, approximately 14.4% by weight, approximately 14.5% by weight, approximately 14.6% by weight, approximately 14.7% by weight, approximately 14.8% by weight, approximately 14.9% by weight, approximately 15.0% by weight, approximately 15.1% by weight, approximately 15.2% by weight, approximately 15.3% by weight, approximately 15.4% by weight, approximately 15.5% by weight, approximately 15.6% by weight, approximately 15.7% by weight, approximately 15.8% by weight, approximately 15.9% by weight, approximately 16.0% by weight, approximately 16.1% by weight, approximately 16.2% by weight, approximately 16.3% by weight, approximately 16.4% by weight, approximately 16.5% by weight, approximately 16.6% by weight , about 16.7% by weight, about 16.8% by weight, about 16.9% by weight, about 17.0% by weight, about 17.1% by weight, about 17.2% by weight, about 17.3% by weight, about 17.4% by weight, about 17.5% by weight, about 17.6% by weight, about 17.7% by weight, about 17.8% by weight, about 17.9% by weight, about 18.0% by weight %, about 18.1% by weight, about 18.2% by weight, about 18.3% by weight, about 18.4% by weight, about 18.5% by weight, about 18.6% by weight, about 18.7% by weight, about 18.8% by weight, about 18.9% by weight, about 19.0% by weight, about 19.1% by weight, about 19.2% by weight, about 19.3% by weight, about 19.4 Weight%, about 19.5% by weight, about 19.6% by weight, about 19.7% by weight, about 19.8% by weight, about 19.9% ​​by weight, about 20.0% by weight, about 20.1% by weight, about 20.2% by weight, about 20.3% by weight, about 20.4% by weight, about 20.5% by weight, about 20.6% by weight, about 20.7% by weight, about 20.8% by weight, approximately 20.9% by weight, approximately 21.0% by weight, approximately 21.1% by weight, approximately 21.2% by weight, approximately 21.3% by weight, approximately 21.4% by weight, approximately 21.5% by weight, approximately 21.6% by weight, approximately 21.7% by weight, approximately 21.8% by weight, approximately 21.9% by weight, approximately 22.0% by weight, approximately 22.1% by weight, approximately 22.2% by weight, approximately 22.3% by weight, approximately 22.4% by weight, approximately 22.5% by weight, approximately 22.6% by weight, approximately 22.7% by weight, approximately 22.8% by weight, approximately 22.9% by weight, approximately 23.0% by weight, approximately 23.1% by weight, approximately 23.2% by weight, approximately 23.3% by weight, approximately 23.4% by weight, approximately 23.5% by weight, approximately 23.6% by weight, approximately 23.7% by weight, approximately 23.8% by weight, approximately 23.9% by weight, approximately 24.0% by weight, approximately 24.1% by weight, approximately 24.2% by weight, approximately 24.3% by weight, approximately 24.4% by weight, approximately 24.5% by weight, approximately 24.6% by weight, approximately 24.7% by weight, approximately 24.8% by weight, approximately 24.9% by weight, approximately 25.0% by weight, approximately 25.1% by weight, approximately 25.2% by weight, approximately 25.3% by weight, approximately 25.4% by weight, approximately 25.5% by weight, approximately 25.6% by weight, approximately 25.7% by weight, approximately 25.8% by weight, approximately 25.9% by weight, approximately 26.0% by weight, approximately 26.1% by weight, approximately 26.2% by weight, approximately 26.3% by weight Approximately 26.4% by weight, approximately 26.5% by weight, approximately 26.6% by weight, approximately 26.7% by weight, approximately 26.8% by weight, approximately 26.9% by weight, approximately 27.0% by weight, approximately 27.1% by weight, approximately 27.2% by weight, approximately 27.3% by weight, approximately 27.4% by weight, approximately 27.5% by weight, approximately 27.6% by weight, approximately 27.7% by weight, approximately 27.8% by weight, approximately 27.9% by weight, approximately 28.0% by weight, approximately 28.1% by weight, approximately 28.2% by weight, approximately 28.3% by weight, approximately 28.4% by weight, approximately 28.5% by weight, approximately 28.6% by weight, approximately 28.7% by weight, approximately 28.8% by weight, approximately 28.9% by weight, approximately 29.0% by weight, approximately 29.1% by weight. Weight%, approximately 29.2% by weight, approximately 29.3% by weight, approximately 29.4% by weight, approximately 29.5% by weight, approximately 29.6% by weight, approximately 29.7% by weight, approximately 29.8% by weight, approximately 29.9% by weight, approximately 30.0% by weight, approximately 30.1% by weight, approximately 30.2% by weight, approximately 30.3% by weight, approximately 30.4% by weight, approximately 30.5% by weight, approximately 30.6% by weight, approximately 30.7% by weight, approximately 30.8% by weight, approximately 30.9% by weight, approximately 31.0% by weight, approximately 31.1% by weight, approximately 31.2% by weight, approximately 31.3% by weight, approximately 31.4% by weight, approximately 31.5% by weight, approximately 31.6% by weight, approximately 31.7% by weight, approximately 31.8% by weight, approximately 31%.9% by weight, approximately 32.0% by weight, approximately 32.1% by weight, approximately 32.2% by weight, approximately 32.3% by weight, approximately 32.4% by weight, approximately 32.5% by weight, approximately 32.6% by weight, approximately 32 .7% by weight, approximately 32.8% by weight, approximately 32.9% by weight, approximately 33.0% by weight, approximately 33.1% by weight, approximately 33.2% by weight, approximately 33.3% by weight, approximately 33.4% by weight, approximately 33 0.5%, about 33.6%, about 33.7%, about 33.8%, about 33.9%, about 34.0%, about 34.1%, about 34.2%, about 34.3%, about 34.4%, about 34.5%, about 34.6%, about 34.7%, about 34.8%, about 34.9%, and about 35.0% by weight. Examples of fillers include lactose monohydrate, anhydrous lactose, modified starch, mannitol, and mixtures thereof. In one embodiment, the filler comprises lactose monohydrate and / or anhydrous lactose.

[0033] surfactants In some embodiments, the pharmaceutically acceptable excipient comprises a surfactant, and the surfactant is present in an amount of about 1.0 wt% to about 5.0 wt%, such as about 1.5 wt% to about 5.0 wt%, for example, about 2.0 wt% to about 5.0 wt%, for example, about 2.5 wt% to about 5.0 wt%, for example, about 3.0 wt% to about 5.0 wt%, for example, about 3.5 wt% to about 5.0 wt%, for example, about 4.0 wt% to about 5.0 wt%, for example, For example, about 4.5% by weight to about 5.0% by weight, for example, about 1.0% by weight to about 4.5% by weight, for example, about 1.5% by weight to about 4.5% by weight, for example, about 2.0% by weight to about 4.5% by weight, for example, about 2.5% by weight to about 4.5% by weight, for example, about 3.0% by weight to about 4.5% by weight, for example, about 3.5% by weight to about 4.5% by weight, for example, about 4.0% by weight to about 4.5% by weight, for example, about 1.0% by weight to about 4.0% by weight, for example, about 1.5% by weight to about 4.0 % by weight, for example, about 2.0% by weight to about 4.0% by weight, for example, about 2.5% by weight to about 4.0% by weight, for example, about 3.0% by weight to about 4.0% by weight, for example, about 3.5% by weight to about 4.0% by weight, for example, about 1.0% by weight to about 3.5% by weight, for example, about 1.5% by weight to about 3.5% by weight, for example, about 2.0% by weight to about 3.5% by weight, for example, about 2.5% by weight to about 3.5% by weight, for example, about 3.0% by weight to about 3.5% by weight, for example, about 1.0% by weight % to about 3.0% by weight, for example, about 1.5% by weight to about 3.0% by weight, for example, about 2.0% by weight to about 3.0% by weight, for example, about 2.5% by weight to about 3.0% by weight, for example, about 1.0% by weight to about 2.5% by weight, for example, about 1.5% by weight to about 2.5% by weight, for example, about 2.0% by weight to about 2.5% by weight, for example, about 1.0% by weight to about 2.0% by weight, for example, about 1.5% by weight to about 2.0% by weight, for example, about 1.0% by weight to about 1.5% by weight.

[0034] In some embodiments, the surfactant is present in an amount of about 1.0%, about 1.1%, about 1.2%, about 1.3%, about 1.4%, about 1.5%, about 1.6%, about 1.7%, about 1.8%, about 1.9%, about 2.0%, about 2.1%, about 2.2%, about 2.3%, about 2.4%, about 2.5%, about 2.6%, about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5.0%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 5.6%, about 5.7%, about 5.8%, about 5.9%, about 6.0%, about 6.1%, about 6.2%, about 6.3%, about 6.4%, about 6.5%, about 6.6%, about 6.7%, about 6.8%, about 6.9%, about 7.0%, about 7.1%, about 7.2%, about 7.3%, about 7.4%, about 7.5%, about 7.6%, about 7.7%, about 7.8%, about 7.9%, about 8.0%, about 8.1%, about 8.2%, about 8.3%, about 8.4%, about 8.5%, about 8.6%, about 8.7%, about 8.8%, about 8.9%, about 9.0%, about 9.1%, about 9.1%, about 2.5% by weight, approximately 2.51% by weight, approximately 2.52% by weight, approximately 2.53% by weight, approximately 2.54% by weight, approximately 2.55% by weight, approximately 2.56% by weight, approximately 2.57% by weight, approximately 2.58 Weight%, about 2.59 weight%, about 2.6 weight%, about 2.61 weight%, about 2.62 weight%, about 2.63 weight%, about 2.64 weight%, about 2.65 weight%, about 2.66 weight%, about 2.67% by weight, approximately 2.68% by weight, approximately 2.69% by weight, approximately 2.7% by weight, approximately 2.71% by weight, approximately 2.72% by weight, approximately 2.73% by weight, approximately 2.74% by weight, approximately 2.75 Weight%, about 2.76 weight%, about 2.77 weight%, about 2.78 weight%, about 2.79 weight%, about 2.8 weight%, about 2.9 weight%, about 3.0 weight%, about 3.1 weight%, about 3.2 %, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, and about 5.0 wt%.

[0035] In some embodiments, the surfactant is selected from nonionic surfactants, anionic surfactants, cationic surfactants, and mixtures thereof. In some embodiments, the surfactant is selected from nonionic surfactants, anionic surfactants, and mixtures thereof.

[0036] Examples of anionic surfactants include those having at least one hydrophobic chain containing between 4 and 20 carbon atoms. Exemplary surfactants are those having the formula: RX - -R'M + and may contain multiple hydrophobic chains, i.e., at least two separate straight or branched chain alkyl or alkaryl (i.e., alkyl chains bearing aromatic substituents such as benzyl groups) moieties, as shown in During the ceremony, X represents any of the common polar hydrophilic groups known in anionic surfactants, such as carboxylate, sulfate, sulfonate, ether sulfate, sulfosuccinate, glutamate, or phosphate; R represents a linear or branched alkyl group or an alkaryl group, each having 4 to 20 carbon atoms, preferably 4 to 16 carbon atoms, and more preferably 4 to 12 carbon atoms; R' can be either a hydrogen atom or R, and M + is a pharmaceutically acceptable cation as defined below.

[0037] In one embodiment, the anionic surfactant is -Formula R-Ar-SO3 - M + wherein R is a C4 to C6 alkylbenzene sulfonate. 20 is an alkyl or alkenyl group, Ar is a phenyl group, and M + is a pharmaceutically acceptable cation selected from, for example, ammonium ion, charged alkanolamine ion (such as cationic triethanolamine), alkali metal ion (such as sodium ion or potassium ion), and mixtures thereof, and examples of alkylbenzenesulfonates include sodium tridecylbenzenesulfonate, sodium dodecylbenzenesulfonate, and mixtures thereof; and -Formula R-OSO3 - M + wherein R and M are alkyl sulfates having the formula +are each as defined above, and examples of alkyl sulfates include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric acid monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, and monoethanolamine lauryl sulfate. alkyl sulfates; -Formula: RO(C2H4O) y SO3 - M + wherein R and M are alkyl ether sulfates having the formula + are each independently as defined above, and y is an integer between 1 and 10, inclusive; and -Formula RO-P(=O)(OR')O - M + wherein R, R′ and M + are each independently as defined above, preferably the alkyl phosphate is a dialkyl phosphate; -Formula ROC(=O)-C2H4-SO3 - M + wherein R and M are alkyl isethionates having the formula + each of which is as defined above; and Formula: R—(C═O)—NH—(C2H4COOH)—COO - M + wherein R and M are alkyl glutamates having the formula +each of which is as defined above; and sulfosuccinates, such as dialkyl sulfosuccinates, examples of which include disodium N-octadecyl sulfosuccinate, disodium lauryl sulfosuccinate, diammonium lauryl sulfosuccinate, tetrasodium N-(1,2-dicarboxyethyl)-N-octadecyl sulfosuccinate, diamyl sodium sulfosuccinate, dihexyl sodium sulfosuccinate, dioctyl sodium sulfosuccinate, and mixtures thereof; is selected from the group consisting of:

[0038] In some embodiments, the anionic surfactant is selected from alkyl sulfates, sulfosuccinates, and mixtures thereof. In one embodiment, the anionic surfactant comprises sodium lauryl sulfate and / or dioctyl sodium sulfosuccinate (also known as docusate sodium).

[0039] Examples of nonionic surfactants include ethoxylated and / or propoxylated C4-C6 surfactants containing 5 to 60 EO or PO units. 20 Fatty alkyl ethers are included. The aliphatic groups can be derived from petrochemical sources, but are preferably derived from vegetable oils such as coconut oil, palm oil, and rapeseed oil, and contain both saturated and unsaturated alkyl chains. Commercially available examples of suitable alkyl ethoxylate ethers are those known under the trade name Genapol™. Other suitable nonionic surfactants are polyethylene glycol sorbitan esters containing 3 to 30 ethoxylate units, such as sorbitan esters with lauric acid, oleic acid, myristic acid, stearic acid, and palmitic acid, known under the trade name Tween™ from Croda or Glycosperse™ from Lonza. Other suitable nonionic surfactants are C8-C6 alkyl ethers with 20 to 80 ethoxylate groups, such as glycerol-polyethylene glycol oxystearate, marketed by BASF under the trade name Cremophor™.20 Ethoxylated polyglyceryl esters of fatty acids are also suitable nonionic surfactants; these esters contain 1 to 10 glycerin units and 1 or 2 C4-C6 alkyl esters. 20 Contains aliphatic alkyl groups. Examples are available from Lonza under the trade name Polyaldo™.

[0040] Further suitable nonionic surfactants include those in which the acyl group is C8-C 20 These surfactants are N-alkyl-N-acylglucamines (also called glucamides) derived from fatty acids. Preferably, the fatty acids are derived from plant materials such as coconut oil and palm oil. Examples of these surfactants include lauroyl / myristoyl methyl glucamide, cocoyl methyl glucamide, and capryloyl / caproyl methyl glucamide. Commercially, these surfactants are available as Glucotain Flex™, Glucotain Care™, and Glucotain Clear™, respectively.

[0041] Other suitable nonionic surfactants are C6-C monosaccharide, disaccharide or polysaccharide surfactants. 20 Suitable nonionic surfactants include C8-C9 ethers or esters, such as sucrose esters with lauric acid, oleic acid, palmitic acid, or stearic acid, such as Ryoto™ Sugar Esters, available from Mitsubishi-Kagaku Foods Corporation. 20 Other sugar surfactants include those in the Oramix series by Seppic, those in the Sepiclear series by Seppic, such as Sepiclear G7, or those in the Sisterna series, such as L70-C by Sisterna. Further suitable nonionic surfactants include those in the C6-C8 series by Sisterna, such as Sisterna L70-C, ... 16 ) alkyl glucoside (sold under the name Plantacare® by Cognis, e.g., C sold as Plantacare® 1200UP)12 ~C 16 fatty alcohol polyglycosides).

[0042] In some embodiments, the nonionic surfactant is a sorbitan ester of lauric acid, oleic acid, myristic acid, stearic acid, or palmitic acid and a C8-C 20 Sucrose esters with fatty acids containing 1 to 10 glycerol units and 1 or 2 C4-C 20 Polyglyceryl esters containing aliphatic alkyl groups (C6-C 16 ) alkyl glucosides, glucamides, and mixtures thereof.

[0043] Binder In some embodiments, the pharmaceutically acceptable excipient comprises a binder, and the binder is present in an amount of about 1.0 wt% to about 10.0 wt%, such as 1.5 wt% to about 10.0 wt%, for example, 2.0 wt% to about 10.0 wt%, for example, 2.5 wt% to about 10.0 wt%, for example, 3.0 wt% to about 10.0 wt%, for example, 3.5 wt% to about 10.0 wt%, for example, 4.0 wt% to about 10.0 wt%, for example, 4.5 wt% to about 10.0 wt%, for example, 5.0 wt% to about 10.0 wt%, for example, 5.5 wt% to about 10.0 wt%, for example, 6.0 wt% to about 10.0 wt%, for example, 7.0 wt% to about 10.0 wt%, for example, 8.0 wt% to about 10.0 wt%, for example, 9.0 wt% to about 10.0 wt%, for example, 10.0 wt% to about 10.0 wt%, for example, 11.0 wt% to about 10.0 wt%, for example, 12.0 wt% to about 10.0 wt%, for example, 13.0 wt% to about 10.0 wt%, for example, 14.0 wt% to about 10.0 wt%, for example, 15.0 wt% to about 10.0 wt%, for example, 16.0 wt% to about 10.0 wt%, for example, 17.0 wt% to about 10.0 wt%, for example, 18.0 wt% to about 10.0 wt%, for example, 19.0 wt% to about 10.0 wt%, for 0.0% by weight, for example 6.5% by weight to about 10.0% by weight, for example 7.0% by weight to about 10.0% by weight, for example 7.5% by weight to about 10.0% by weight, for example 8.0% by weight to about 10.0% by weight, for example 8.5% by weight to about 10.0% by weight, for example 9.0% by weight to about 10.0% by weight, for example 9.5% by weight to about 10.0% by weight, for example about 1.0% by weight to about 9.5% by weight, for example 1.5% by weight to about 9.5% by weight, for example 2.0% by weight to about 9.5% by weight, for example 2.5% by weight to about 9.5% by weight, for example 3.0% by weight to about 9.5% by weight, for example 3.5% by weight to about 9.5% by weight, for example For example, 4.0% by weight to about 9.5% by weight, for example, 4.5% by weight to about 9.5% by weight, for example, 5.0% by weight to about 9.5% by weight, for example, 5.5% by weight to about 9.5% by weight, for example, 6.0% by weight to about 9.5% by weight, for example, 6.5% by weight to about 9.5% by weight, for example, 7.0% by weight to about 9.5% by weight, for example, 7.5% by weight to about 9.5% by weight, for example, 8.0% by weight to about 9.5% by weight, for example, 8.5% by weight to about 9.5% by weight, for example, 9.0% by weight to about 9.5% by weight, for example, about 1.0% by weight to about 9.0% by weight, for example, 1.5% by weight to about 9.0% by weight, for example, 2.0% by weight to about 9.0% by weight %, for example, 2.5% by weight to about 9.0% by weight, for example, 3.0% by weight to about 9.0% by weight, for example, 3.5% by weight to about 9.0% by weight, for example, 4.0% by weight to about 9.0% by weight, for example, 4.5% by weight to about 9.0% by weight, for example, 5.0% by weight to about 9.0% by weight, for example, 5.5% by weight to about 9.0% by weight, for example, 6.0% by weight to about 9.0% by weight, for example, 6.5% by weight to about 9.0% by weight, for example, 7.0% by weight to about 9.0% by weight, for example, 7.5% by weight to about 9.0% by weight, for example, 8.0% by weight to about 9.0% by weight, for example, 8.5% by weight to about 9.0% by weight, for example, about 1.0% by weight to about 8.5% by weight, for example, 1.5% by weight to about 8.5% by weight, for example, 2.0% by weight to about 8.5% by weight, for example, 2.5% by weight to about 8.5% by weight, for example, 3.0% by weight to about 8.5% by weight, for example, 3.5% by weight to about 8.5% by weight, for example, 4.0% by weight to about 8.5% by weight, for example, 4.5% by weight to about 8.5% by weight, for example, 5.0% by weight to about 8.5% by weight, for example, 5.5% by weight to about 8.5% by weight, for example, 6.0% by weight to about 8.5% by weight, for example, 6.5% by weight to about 8.5% by weight, for example, 7.0% by weight to about 8.5% by weight, for example, 7.5% by weight to about 8.5% by weight, for example, 8.0% by weight to about 8.5% by weight, for example, about 1.0% by weight to about 8.0% by weight, 1.5% by weight to about 8.0% by weight, for example, 2.0% by weight to about 8.0% by weight, for example, 2.5% by weight to about 8.0% by weight, for example, 3.0% by weight to about 8.0% by weight, for example, 3.5% by weight to about 8.0% by weight, for example, 4.0% by weight to about 8.0% by weight, for example, 4.5% by weight to about 8.0% by weight, for example, 5.0% by weight to about 8.0% by weight, for example, 5.5% by weight to about 8.0% by weight, for example, 6.0% by weight to about 8.0% by weight, for example, 6.5% by weight to about 8.0% by weight, for example, 7.0% by weight to about 8.0% by weight, for example, 7.5% by weight to about 8.0% by weight, for example, about 1.0% by weight to about 7.5% by weight, for example, 1.5% by weight to about 7.5% by weight, for example, 2.0% by weight to about 7.5% by weight, for example, 2.5% by weight to about 7.5% by weight, for example, 3.0% by weight to about 7.5% by weight, for example, 3.5% by weight to about 7.5% by weight, for example, 4.0% by weight to about 7.5% by weight, for example, 4.5% by weight to about 7.5% by weight, for example, 5.0% by weight to about 7.5% by weight, for example, 5.5% by weight to about 7.5% by weight, for example, 6.0% by weight to about 7.5% by weight, for example, 6.5% by weight to about 7.5% by weight, for example, 7.0% by weight to about 7.5% by weight, for example, about 1.0% by weight Amount % to about 7.0 wt%, for example 1.5 wt% to about 7.0 wt%, for example 2.0 wt% to about 7.0 wt%, for example 2.5 wt% to about 7.0 wt%, for example 3.0 wt% to about 7.0 wt%, for example 3.5 wt% to about 7.0 wt%, for example 4.0 wt% to about 7.0 wt%, for example 4.5 wt% to about 7.0 wt%, for example 5.0 wt% to about 7.0 wt%, for example 5.5 wt% to about 7.0 wt%, for example 6.0 wt% to about 7.0 wt%, for example 6.5 wt% to about 7.0 wt%, for example about 1.0 wt% to about 6.5 wt%, for example 1.5 wt% to about 6.5 wt%, for example 2.0% by weight to about 6.5% by weight, for example 2.5% by weight to about 6.5% by weight, for example 3.0% by weight to about 6.5% by weight, for example 3.5% by weight to about 6.5% by weight, for example 4.0% by weight to about 6.5% by weight, for example 4.5% by weight to about 6.5% by weight, for example 5.0% by weight to about 6.5% by weight, for example 5.5% by weight to about 6.5% by weight, for example 6.0% by weight to about 6.5% by weight, for example about 1.0% by weight to about 6.0% by weight, for example 1.5% by weight to about 6.0% by weight, for example 2.0% by weight to about 6.0% by weight, for example 2.5% by weight to about 6.0% by weight, for example about 3.0% by weight to about 6.0% by weight, For example, 3.5% by weight to about 6.0% by weight, for example, 4.0% by weight to about 6.0% by weight, for example, 4.5% by weight to about 6.0% by weight, for example, 5.0% by weight to about 6.0% by weight, for example, 5.5% by weight to about 6.0% by weight, for example, about 1.0% by weight to about 5.5% by weight, for example, 1.5% by weight to about 5.5% by weight, for example, 2.0% by weight to about 5.5% by weight, for example, 2.5% by weight to about 5.5% by weight, for example, 3.0% by weight to about 5.5% by weight, for example, 3.5% by weight to about 5.5% by weight, for example, 4.0% by weight to about 5.5% by weight, for example, 4.5% by weight to about 5.5% by weight, for example, 5.0% by weight to about 5.5% by weight %, for example, about 1.0 wt % to about 5.0 wt %, for example, 1.5 wt % to about 5.0 wt %, for example, 2.0 wt % to about 5.0 wt %, for example, 2.5 wt % to about 5.0 wt %, for example, about 3.0 wt % to about 5.0 wt %, for example, 3.5 wt % to about 5.0 wt %, for example, 4.0 wt % to about 5.0 wt %, for example, 4.5 wt % to about 5.0 wt %, for example, about 1.0 wt % to about 4.5 wt %, for example, 1.5 wt % to about 4.5 wt %, for example, 2.0 wt % to about 4.5 wt %, for example, 2.5 wt % to about 4.5 wt %, for example, 3.0 wt % to about 4.5 wt %, for example, 3.5 wt % to about 4.5% by weight, for example, 4.0% by weight to about 4.5% by weight, for example, about 1.0% by weight to about 4.0% by weight, for example, 1.5% by weight to about 4.0% by weight, for example, 2.0% by weight to about 4.0% by weight, for example, 2.5% by weight to about 4.0% by weight, for example, about 3.0% by weight to about 4.0% by weight, for example, 3.5% by weight to about 4.0% by weight, for example, about 1.0% by weight to about 3.5% by weight, for example, 1.5% by weight to about 3.5% by weight, for example, 2.0% by weight to about 3.5% by weight, for example, 2.5% by weight to about 3.5% by weight, for example, 3.0% by weight to about 3.5% by weight, for example, about 1.0% by weight to about 3.0% by weight, for example, 1.5% by weight to about 3.0% by weight, for example, 2.0% by weight to about 3.0% by weight, for example, 2.5% by weight to about 3.0% by weight, for example, about 1.0% by weight to about 2.5% by weight, for example, 1.5% by weight to about 2.5% by weight, for example, 2.0% by weight to about 2.5% by weight, for example, about 1.0% by weight to about 2.0% by weight, for example, 1.5% by weight to about 2.0% by weight, for example, 1.0% by weight to about 1.5% by weight. In some embodiments, the binder is about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, or about 3.4 wt% of the total weight of the composition. Weight %, about 3.3 weight %, about 3.4 weight %, about 3.5 weight %, about 3.6 weight %, about 3.7 weight %, about 3.8 weight %, about 3.9 weight %, about 4.0 weight %, about 4.1 weight %, about 4.11 weight %, about 4.12 weight %, about 4.13 weight %, about 4.14% by weight, approximately 4.15% by weight, approximately 4.16% by weight, approximately 4.17% by weight, approximately 4.18% by weight, approximately 4.19% by weight, approximately 4.2% by weight, approximately 4.21% by weight, approximately 4.22% by weight, approximately 4.23% by weight, approximately 4.24% by weight, approximately 4.25% by weight %, about 4.26% by weight, about 4.27% by weight, about 4.28% by weight, about 4.29% by weight, about 4.3% by weight, about 4.31% by weight, about 4.32% by weight, about 4.33% by weight, about 4.34% by weight, about 4.35% by weight, about 4.36% by weight, about 4.3 7% by weight, approximately 4.38% by weight, approximately 4.39% by weight, approximately 4.4% by weight, approximately 4.41% by weight, approximately 4.42% by weight, approximately 4.43% by weight, approximately 4.44% by weight, approximately 4.45% by weight, approximately 4.46% by weight, approximately 4.47% by weight, approximately 4.48% by weight, approximately 4.49% by weight, approximately 4.5% by weight, approximately 4.6% by weight, approximately 4.7% by weight, approximately 4.8% by weight, approximately 4.9% by weight, approximately 5.0% by weight, approximately 5.1% by weight, approximately 5.2% by weight, approximately 5.3% by weight, approximately 5.31% by weight, approximately 5.32% by weight, approximately 5.33% by weight Amount %, about 5.34% by weight, about 5.35% by weight, about 5.36% by weight, about 5.37% by weight, about 5.38% by weight, about 5.39% by weight, about 4.4% by weight, about 4.41% by weight, about 4.42% by weight, about 4.43% by weight, about 4.44% by weight, about 4.45% by weight, approximately 4.46% by weight, approximately 4.47% by weight, approximately 4.48% by weight, approximately 4.49% by weight, approximately 5.4% by weight, approximately 5.5% by weight, approximately 5.6% by weight, approximately 5.7% by weight, approximately 5.8% by weight, approximately 5.9% by weight, approximately 6.0% by weight, approximately 6.1% by weight , about 6.2% by weight, about 6.3% by weight, about 6.4% by weight, about 6.5% by weight, about 6.6% by weight, about 6.7% by weight, about 6.8% by weight, about 6.9% by weight, about 7.0% by weight, about 7.1% by weight, about 7.2% by weight, about 7.3% by weight, about 7.4% by weight, about 7.5% by weight, about 7.6% by weight, about 7.7% by weight, about 7.8% by weight, about 7.9% by weight, about 8.0% by weight, about 8.1% by weight, about 8.2% by weight, about 8.3% by weight, about 8.4% by weight, about 8.5% by weight, about 8.6% by weight, about 8.7% by weight, about 8.8% by weight, about 8.9% by weight, about 9.0% by weight, about 9.1% by weight, about 9.2% by weight, about 9.3% by weight, about 9.4% by weight, about 9.5% by weight, about 9.6% by weight, about 9.7% by weight, about 9.8% by weight, about 9.9% by weight, about 10.0% by weight. Examples of binders include cellulose, modified cellulose (such as ethyl cellulose, methylhydroxyethyl cellulose, and hydroxypropyl methylcellulose), microcrystalline cellulose (such as Avicel® PH101 and Avicel® PH102), polyvinylpyrrolidone, and mixtures thereof. In one embodiment, the binder is hydroxypropyl methylcellulose.

[0044] lubricant In some embodiments, the pharmaceutically acceptable excipient comprises a lubricant, and the lubricant is present in an amount of about 0.5 wt% to about 5.0 wt%, such as about 1.0 wt% to about 5.0 wt%, for example, 1.5 wt% to about 5.0 wt%, for example, 2.0 wt% to about 5.0 wt%, for example, 2.5 wt% to about 5.0 wt%, for example, about 3.0 wt% to about 5.0 wt%, for example, 3.5 wt% to about 5.0 wt%, for example, 4.0 wt% to about 5.0 wt%, for example, 4.5 wt% to about 5.0 wt%, for example, about 0.5 wt% % to about 4.5% by weight, for example, about 1.0% to about 4.5% by weight, for example, 1.5% to about 4.5% by weight, for example, 2.0% to about 4.5% by weight, for example, 2.5% to about 4.5% by weight, for example, 3.0% to about 4.5% by weight, for example, 3.5% to about 4.5% by weight, for example, 4.0% to about 4.5% by weight, for example, about 0.5% to about 4.0% by weight, for example, about 1.0% to about 4.0% by weight, for example, 1.5% to about 4.0% by weight, for example, 2.0% to about 4.0% by weight, for example, 2.5% by weight % to about 4.0% by weight, for example, about 3.0% to about 4.0% by weight, for example, 3.5% to about 4.0% by weight, for example, about 0.5% to about 3.5% by weight, for example, about 1.0% to about 3.5% by weight, for example, 1.5% to about 3.5% by weight, for example, 2.0% to about 3.5% by weight, for example, 2.5% to about 3.5% by weight, for example, 3.0% to about 3.5% by weight, for example, about 0.5% to about 3.0% by weight, for example, about 1.0% to about 3.0% by weight, for example, 1.5% to about 3.0% by weight, for example, 2.0 % by weight to about 3.0% by weight, for example, 2.5% by weight to about 3.0% by weight, for example, about 0.5% by weight to about 2.5% by weight, for example, about 1.0% by weight to about 2.5% by weight, for example, 1.5% by weight to about 2.5% by weight, for example, 2.0% by weight to about 2.5% by weight, for example, about 0.5% by weight to about 2.0% by weight, for example, about 1.0% by weight to about 2.0% by weight, for example, 1.5% by weight to about 2.0% by weight, for example, about 0.5% by weight to about 1.5% by weight, for example, 1.0% by weight to about 1.5% by weight, for example, about 0.5% by weight to about 1.0% by weight.In some embodiments, the lubricant is about 0.5 wt%, about 0.6 wt%, about 0.7 wt%, about 0.8 wt%, about 0.9 wt%, about 1.0 wt%, about 1.1 wt%, about 1.2 wt%, about 1.3 wt%, about 1.4 wt%, about 1.5 wt%, about 1.6 wt%, about 1.7 wt%, about 1.8 wt%, about 1.9 wt%, about 2.0 wt%, about 2.1 wt%, about 2.2 wt%, about 2.3 wt%, about 2.4 wt%, about 2.5 wt%, about 2.6 wt%, about 2.7 wt%, about 2.8 wt%, about 2.9 wt%, about 3.0 wt%, about 3.1 wt%, about 3.2 wt%, about 3.3 wt%, about 3.4 wt%, about 3.5 wt%, about 3.6 wt%, about 3.7 wt%, about 3.8 wt%, about 3.9 wt%, about 4.0 wt%, about 4.1 wt%, about 4.2 wt%, about 4.3 wt%, about 4.4 wt%, about 4.5 wt%, about 4.6 wt%, about 4.7 wt%, about 4.8 wt%, about 4.9 wt%, about 5.0 wt%, about 5.1 wt%, about 5.1 wt%, about 5.2 wt%, about 5.3 wt%, about 5.4 wt%, about 5.5 wt%, about 5.6 wt%, about 5.7 wt%, about 5.8 wt%, about 5.9 wt%, about 6.0 wt%, about 6.1 wt%, about 6.2 wt%, about 6.3 wt%, about 6.4 wt%, about 6.5 wt%, about 6.6 The lubricant content is about 2.7%, about 2.8%, about 2.9%, about 3.0%, about 3.1%, about 3.2%, about 3.3%, about 3.4%, about 3.5%, about 3.6%, about 3.7%, about 3.8%, about 3.9%, about 4.0%, about 4.1%, about 4.2%, about 4.3%, about 4.4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, and about 5.0% by weight. Examples of lubricants include talc, stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica gel, and mixtures thereof. In one embodiment, the lubricant is magnesium stearate.

[0045] Disintegrant In some embodiments, the pharmaceutically acceptable excipient comprises a disintegrant, and the disintegrant is present in an amount of about 1.0 wt% to about 8.0 wt%, for example, 1.5 wt% to about 8.0 wt%, for example, 2.0 wt% to about 8.0 wt%, for example, 2.5 wt% to about 8.0 wt%, for example, 3.0 wt% to about 8.0 wt%, for example, 3.5 wt% to about 8.0 wt%, for example, 4.0 wt% to about 8.0 wt%, for example, 4.5 wt% to about 8.0 wt%, for example, 5.0 wt% to about 8.0 wt%, for example, 5.5 wt% to about 8.0 wt%, for example, 6.0 wt% to about 8.0 wt%, for example, 6.5 ... % by weight to about 8.0% by weight, for example, 7.0% by weight to about 8.0% by weight, for example, 7.5% by weight to about 8.0% by weight, for example, about 1.0% by weight to about 7.5% by weight, for example, 1.5% by weight to about 7.5% by weight, for example, 2.0% by weight to about 7.5% by weight, for example, 2.5% by weight to about 7.5% by weight, for example, 3.0% by weight to about 7.5% by weight, for example, 3.5% by weight to about 7.5% by weight, for example, 4.0% by weight to about 7.5% by weight, for example, 4.5% by weight to about 7.5% by weight, for example, 5.0% by weight to about 7.5% by weight, for example, 5.5% by weight to about 7.5% by weight, for example, 6.0% by weight to about 7.5% by weight, for example 6.5 wt% to about 7.5 wt%, for example, 7.0 wt% to about 7.5 wt%, for example, about 1.0 wt% to about 7.0 wt%, for example, 1.5 wt% to about 7.0 wt%, for example, 2.0 wt% to about 7.0 wt%, for example, 2.5 wt% to about 7.0 wt%, for example, 3.0 wt% to about 7.0 wt%, for example, 3.5 wt% to about 7.0 wt%, for example, 4.0 wt% to about 7.0 wt%, for example, 4.5 wt% to about 7.0 wt%, for example, 5.0 wt% to about 7.0 wt%, for example, 5.5 wt% to about 7.0 wt%, for example, 6.0 wt% to about 7.0 wt%, for example, 6.5 wt% to about 7.0 wt%, For example, about 1.0 wt% to about 6.5 wt%, for example, 1.5 wt% to about 6.5 wt%, for example, 2.0 wt% to about 6.5 wt%, for example, 2.5 wt% to about 6.5 wt%, for example, 3.0 wt% to about 6.5 wt%, for example, 3.5 wt% to about 6.5 wt%, for example, 4.0 wt% to about 6.5 wt%, for example, 4.5 wt% to about 6.5 wt%, for example, 5.0 wt% to about 6.5 wt%, for example, 5.5 wt% to about 6.5 wt%, for example, 6.0 wt% to about 6.5 wt%, for example, about 1.0 wt% to about 6.0 wt%, for example, 1.5 wt% to about 6.0 wt%, for example, about 2.0 wt% to about 6.0% by weight, for example, 2.5% by weight to about 6.0% by weight, for example, about 3.0% by weight to about 6.0% by weight, for example, 3.5% by weight to about 6.0% by weight, for example, 4.0% by weight to about 6.0% by weight, for example, 4.5% by weight to about 6.0% by weight, for example, 5.0% by weight to about 6.0% by weight, for example, 5.5% by weight to about 6.0% by weight, for example, about 1.0% by weight to about 5.5% by weight, for example, 1.5% by weight to about 5.5% by weight, for example, 2.0% by weight to about 5.5% by weight, for example, 2.5% by weight to about 5.5% by weight, for example, 3.0% by weight to about 5.5% by weight, for example, 3.5% by weight to about 5.5% by weight Amount %, for example 4.0% by weight to about 5.5% by weight, for example 4.5% by weight to about 5.5% by weight, for example 5.0% by weight to about 5.5% by weight, for example about 1.0% by weight to about 5.0% by weight, for example 1.5% by weight to about 5.0% by weight, for example 2.0% by weight to about 5.0% by weight, for example 2.5% by weight to about 5.0% by weight, for example about 3.0% by weight to about 5.0% by weight, for example 3.5% by weight to about 5.0% by weight, for example 4.0% by weight to about 5.0% by weight, for example 4.5% by weight to about 5.0% by weight, for example about 1.0% by weight to about 4.5% by weight, for example 1.5% by weight to about 4.5% by weight , for example, 2.0% by weight to about 4.5% by weight, for example, 2.5% by weight to about 4.5% by weight, for example, 3.0% by weight to about 4.5% by weight, for example, 3.5% by weight to about 4.5% by weight, for example, 4.0% by weight to about 4.5% by weight, for example, about 1.0% by weight to about 4.0% by weight, for example, 1.5% by weight to about 4.0% by weight, for example, 2.0% by weight to about 4.0% by weight, for example, 2.5% by weight to about 4.0% by weight, for example, about 3.0% by weight to about 4.0% by weight, for example, 3.5% by weight to about 4.0% by weight, for example, about 1.0% by weight to about 3.5% by weight, for example, 1.5% by weight to about 3.5% by weight, e.g. For example, 2.0% to about 3.5% by weight, for example, 2.5% to about 3.5% by weight, for example, 3.0% to about 3.5% by weight, for example, about 1.0% to about 3.0% by weight, for example, 1.5% to about 3.0% by weight, for example, 2.0% to about 3.0% by weight, for example, 2.5% to about 3.0% by weight, for example, about 1.0% to about 2.5% by weight, for example, 1.5% to about 2.5% by weight, for example, 2.0% to about 2.5% by weight, for example, about 1.0% to about 2.0% by weight, for example, 1.5% to about 2.0% by weight, for example, 1.0% to about 1.5% by weight. In some embodiments, the binder is present in an amount of about 1.0% by weight, about 1.1% by weight, about 1.0% by weight, about 1.5 ...2% by weight, approximately 1.3% by weight, approximately 1.4% by weight, approximately 1.5% by weight, approximately 1.6% by weight, approximately 1.7% by weight, approximately 1.8% by weight, approximately 1.9% by weight, approximately 2.0% by weight, approximately 2.1% by weight, approximately 2.2% by weight, approximately 2.3% by weight, approximately 2.4% by weight, approximately 2.5% by weight, approximately 2.6% by weight, approximately 2.7% by weight, approximately 2.8% by weight, approximately 2.9% by weight, approximately 3.0% by weight, approximately 3.1% by weight, approximately 3.2% by weight, approximately 3.3% by weight, approximately 3.4% by weight, approximately 3.5% by weight, approximately 3.6% by weight, approximately 3.7% by weight, approximately 3.8% by weight, approximately 3.9% by weight, approximately 4.0% by weight, approximately 4.1% by weight, approximately 4.11% by weight, approximately 4. 12% by weight, approximately 4.13% by weight, approximately 4.14% by weight, approximately 4.15% by weight, approximately 4.16% by weight, approximately 4.17% by weight, approximately 4.18% by weight, approximately 4.19% by weight, approximately 4.2% by weight, approximately 4.21% by weight, approximately 4.22% by weight, approximately 4.23% by weight, approximately 4.24% by weight, approximately 4.25% by weight, approximately 4.26% by weight, approximately 4.27% by weight, approximately 4.28% by weight, approximately 4.29% by weight, approximately 4.3% by weight, approximately 4.31% by weight, approximately 4.32% by weight, approximately 4.33% by weight, approximately 4.34% by weight, approximately 4.35% by weight, approximately 4.36% by weight, approximately 4.37% by weight, approximately 4.38% by weight, approximately 4.39% by weight, approximately 4. 4% by weight, approximately 4.41% by weight, approximately 4.42% by weight, approximately 4.43% by weight, approximately 4.44% by weight, approximately 4.45% by weight, approximately 4.46% by weight, approximately 4.47% by weight, approximately 4.48% by weight, approximately 4.49% by weight, approximately 4.5% by weight, approximately 4.6% by weight, approximately 4.7% by weight, approximately 4.8% by weight, approximately 4.9% by weight, approximately 5.0% by weight, approximately 5.1% by weight, approximately 5.2% by weight, approximately 5.3% by weight, approximately 5.3% by weight, approximately 5.31% by weight, approximately 5.32% by weight, approximately 5.33% by weight, approximately 5.34% by weight, approximately 5.35% by weight, approximately 5.36% by weight, approximately 5.37% by weight, approximately 5.38% by weight, approximately 5.39% by weight, approximately 4.4% by weight, approximately 4 0.41 wt%, approximately 4.42 wt%, approximately 4.43 wt%, approximately 4.44 wt%, approximately 4.45 wt%, approximately 4.46 wt%, approximately 4.47 wt%, approximately 4.48 wt%, approximately 4.49 wt%, approximately 5.4 wt%, approximately 5.5 wt%, approximately 5.6 wt%, approximately 5.7 wt%, approximately 5.8 wt%, approximately 5.9 wt%, approximately 6.0 wt%, approximately 6.1 wt%, approximately 6.2 wt%, approximately 6.3 wt%, approximately 6.4 wt%, approximately 6.5 wt%, approximately 6.6 wt%, approximately 6.7 wt%, approximately 6.8 wt%, approximately 6.9 wt%, approximately 7.0 wt%, approximately 7.1 wt%, approximately 7.2 wt%, approximately 7.3 wt%, approximately 7.4 wt%, approximately 7.5% by weight, about 7.6% by weight, about 7.7% by weight, about 7.8% by weight, about 7.9% by weight, and about 8.0% by weight.

[0046] Examples of disintegrants include starch, modified starch, croscarmellose sodium, crospovidone, sodium starch glycolate, and mixtures thereof. In some embodiments, the disintegrant is sodium starch glycolate.

[0047] Glidants In some embodiments, the pharmaceutically acceptable excipient comprises a glidant, and the glidant is present in an amount of about 0.1 wt% to about 5.0 wt%, such as about 0.2 wt% to about 5.0 wt%, for example about 0.3 wt% to about 5.0 wt%, for example about 0.4 wt% to about 5.0 wt%, such as about 0.5 wt% to about 5.0 wt%, for example about 0.6 wt% to about 5.0 wt%, for example about 0.7 wt% to about 5.0 wt%, for example about 0.8 wt% to about 5.0 wt%, such as about 0.9 wt% to about 5.0 wt%, for example about 1.0 wt% to about 5.0 wt%, for example about 1.5 wt% of the total weight of the composition. % to about 5.0 wt%, for example, about 2.0 wt% to about 5.0 wt%, for example, about 2.5 wt% to about 5.0 wt%, for example, about 3.0 wt% to about 5.0 wt%, for example, about 3.5 wt% to about 5.0 wt%, for example, about 4.0 wt% to about 5.0 wt%, for example, about 4.5 wt% to about 5.0 wt%, for example, about 0.1 wt% to about 4.5 wt%, for example, about 0.2 wt% to about 4.5 wt%, for example, about 0.3 wt% to about 4.5 wt%, for example, about 0.4 wt% to about 4.5 wt%, for example, about 0.5 wt% to about 4.5 wt%, for example, about 0.6 wt% to about 4.5 wt%, for example, about 0.7 wt% about 4.5% by weight, for example, about 0.8% by weight to about 4.5% by weight, for example, about 0.9% by weight to about 4.5% by weight, for example, about 1.0% by weight to about 4.5% by weight, for example, about 1.5% by weight to about 4.5% by weight, for example, about 2.0% by weight to about 4.5% by weight, for example, about 2.5% by weight to about 4.5% by weight, for example, about 3.0% by weight to about 4.5% by weight, for example, about 3.5% by weight to about 4.5% by weight, for example, about 4.0% by weight to about 4.5% by weight, for example, about 0.1% by weight to about 4.0% by weight, for example, about 0.2% by weight to about 4.0% by weight, for example, about 0.3% by weight to about 4.0% by weight, for example, about 0.4% by weight to about 4.0% by weight, for example, about 0.5% by weight to about 4.0% by weight, for example, about 0.6% by weight to about 4.0% by weight, for example, about 0.7% by weight to about 4.0% by weight, for example, about 0.8% by weight to about 4.0% by weight, for example, about 0.9% by weight to about 4.0% by weight, for example, about 1.0% by weight to about 4.0% by weight, for example, about 1.5% by weight to about 4.0% by weight, for example, about 2.0% by weight to about 4.0% by weight, for example, about 2.5% by weight to about 4.0% by weight, for example, about 3.0% by weight to about 4.0% by weight, for example, about 3.5% by weight to about 4.0% by weight, for example, about 0.1% by weight to about 3.5% by weight, for example, about 0.2% by weight to about 3.5% by weight, for example, about 0.3% by weight to about 3.5% by weight, for example, about 0.4% by weight to about 3.5% by weight, for example, about 0.5% by weight to about 3.5% by weight, for example, about 0.6% by weight to about 3.5% by weight, for example, about 0.7% by weight to about 3.5% by weight, for example, about 0.8% by weight to about 3.5% by weight, for example, about 0.9% by weight to about 3.5% by weight, for example, about 1.0% by weight to about 3.5% by weight, for example, about 1.5% by weight to about 3.5% by weight, for example, about 2.0% by weight to about 3.5% by weight, for example, about 2.5% by weight to about 3.5% by weight, for example, about 3.0% by weight to about 3.5% by weight, for example, about 0.1% by weight to about 3.0% by weight Amount %, for example, about 0.2% by weight to about 3.0% by weight, for example, about 0.3% by weight to about 3.0% by weight, for example, about 0.4% by weight to about 3.0% by weight, for example, about 0.5% by weight to about 3.0% by weight, for example, about 0.6% by weight to about 3.0% by weight, for example, about 0.7% by weight to about 3.0% by weight, for example, about 0.8% by weight to about 3.0% by weight, for example, about 0.9% by weight to about 3.0% by weight, for example, about 1.0% by weight to about 3.0% by weight, for example, about 1.5% by weight to about 3.0% by weight, for example, about 2.0% by weight to about 3.0% by weight, for example, about 2.5% by weight to about 3.0% by weight, for example, about 0.1% by weight to about 2.5% by weight, For example, about 0.2% by weight to about 2.5% by weight, for example, about 0.3% by weight to about 2.5% by weight, for example, about 0.4% by weight to about 2.5% by weight, for example, about 0.5% by weight to about 2.5% by weight, for example, about 0.6% by weight to about 2.5% by weight, for example, about 0.7% by weight to about 2.5% by weight, for example, about 0.8% by weight to about 2.5% by weight, for example, about 0.9% by weight to about 2.5% by weight, for example, about 1.0% by weight to about 2.5% by weight, for example, about 1.5% by weight to about 2.5% by weight, for example, about 2.0% by weight to about 2.5% by weight, for example, about 0.1% by weight to about 2.0% by weight, for example, about 0.2% by weight to about 2.0% by weight, About 0.3% by weight to about 2.0% by weight, for example, about 0.4% by weight to about 2.0% by weight, for example, about 0.5% by weight to about 2.0% by weight, for example, about 0.6% by weight to about 2.0% by weight, for example, about 0.7% by weight to about 2.0% by weight, for example, about 0.8% by weight to about 2.0% by weight, for example, about 0.9% by weight to about 2.0% by weight, for example, about 1.0% by weight to about 2.0% by weight, for example, about 1.5% by weight to about 2.0% by weight, for example, about 0.1% by weight to about 1.5% by weight, for example, about 0.2% by weight to about 1.5% by weight, for example, about 0.3% by weight to about 1.5% by weight, for example, about 0.4% by weight to about 1.5% by weight, for example, about 0.5% by weight to about 1.5% by weight, for example, about 0.6% by weight to about 1.5% by weight, for example, about 0.7% by weight to about 1.5% by weight, for example, about 0.8% by weight to about 1.5% by weight, for example, about 0.9% by weight to about 1.5% by weight, for example, about 1.0% by weight to about 1.5% by weight, for example, about 0.1% by weight to about 1.0% by weight, for example, about 0.2% by weight to about 1.0% by weight, for example, about 0.3% by weight to about 1.0% by weight, for example, about 0.4% by weight to about 1. 0% by weight, for example, about 0.5% by weight to about 1.0% by weight, for example, about 0.6% by weight to about 1.0% by weight, for example, about 0.7% by weight to about 1.0% by weight, for example, about 0.8% by weight to about 1.0% by weight, for example, about 0.9% by weight to about 1.0% by weight, for example, about 0.1% by weight to about 0.5% by weight, for example, about 0.2% by weight to about 0.5% by weight, for example, about 0.3% by weight to about 0.5% by weight, for example, about 0.4% by weight to about 0.5% by weight. In some embodiments, the glidant is about 0.1 wt%, about 0.11 wt%, about 0.12 wt%, about 0.13 wt%, about 0.14 wt%, about 0.15 wt%, about 0.16 wt%, about 0.17 wt%, about 0.18 wt%, about 0.19 wt%, about 0.2 wt%, about 0.21 wt%, about 0.22 wt%, about 0.23 wt%, about 0.24 wt%, about 0.25 wt%, about 0.26 wt%, about 0.27 wt%, about 0.28 wt%, about 0.29 wt%, about 0.30 wt%, about 0.31 wt%, about 0.32 wt%, about 0.33 wt%, about 0.34 wt%, about 0.35 wt%, about 0.36 wt%, about 0.37 wt%, about 0.38 wt%, about 0.39 wt%, about 0.40 wt%, about 0.41 wt%, about 0.42 wt%, about 0.43 wt%, about 0.44 wt%, about 0.45 wt%, about 0.46 wt%, about 0.47 wt%, about 0.48 wt%, about 0.49 wt%, about 0.50 wt%, about 0.51 wt%, about 0.52 wt%, about 0.53 wt%, about 0.54 wt%, about 0.55 wt%, about 0.56 wt%, about 0.57 wt%, about 0.58 wt%, about 0.59 wt%, about 0.60 wt%, about 0.61 wt%, about 0.62 wt%, about 0.63 wt%, about 0.64 wt%, about 0.65 wt%, Amount%, about 0.25% by weight, about 0.26% by weight, about 0.27% by weight, about 0.28% by weight, about 0.29% by weight, about 0.3% by weight, about 0.31% by weight, about 0.32% by weight, about 0.33% by weight Amount%, about 0.34 weight%, about 0.35 weight%, about 0.36 weight%, about 0.37 weight%, about 0.38 weight%, about 0.39 weight%, about 0.4 weight%, about 0.41 weight%, about 0.42 weight% Amount%, about 0.43% by weight, about 0.44% by weight, about 0.45% by weight, about 0.46% by weight, about 0.47% by weight, about 0.48% by weight, about 0.49% by weight, about 0.5% by weight, about 0.51 Weight%, about 0.52 weight%, about 0.53 weight%, about 0.54 weight%, about 0.55 weight%, about 0.56 weight%, about 0.57 weight%, about 0.58 weight%, about 0.59 weight%, about 0.6 Weight%, about 0.61 weight%, about 0.62 weight%, about 0.63 weight%, about 0.64 weight%, about 0.65 weight%, about 0.66 weight%, about 0.67 weight%, about 0.68 weight%, about 0.6 9% by weight, approximately 0.7% by weight, approximately 0.8% by weight, approximately 0.9% by weight, approximately 1.0% by weight, approximately 1.1% by weight, approximately 1.2% by weight, approximately 1.3% by weight, approximately 1.4% by weight, approximately 1.5% by weight, approximately 1.6% by weight, about 1.7% by weight, about 1.8% by weight, about 1.9% by weight, about 2.0% by weight, about 2.1% by weight, about 2.2% by weight, about 2.3% by weight, about 2.4% by weight, about 2.5% by weight, about 2.6% by weight, about 2.7% by weight, about 2.8% by weight, about 2.9% by weight, about 3.0% by weight, about 3.1% by weight, about 3.2% by weight, about 3.3% by weight, about 3.4% by weight, about 3.5% by weight, about 3.6% by weight, about 3.7% by weight, about 3.8% by weight, about 3.9% by weight, about 4.0% by weight, about 4.1% by weight, about 4.2% by weight, about 4.3% by weight, about 4.4% by weight, about 4.5% by weight, about 4.6% by weight, about 4.7% by weight, about 4.8% by weight, about 4.9% by weight, and about 5.0% by weight. Examples of glidants include ascorbyl palmitate, calcium palmitate, fumed silica (colloidal silicon dioxide), and mixtures thereof. In some embodiments, the glidant is colloidal silicon dioxide.

[0048] Other excipients The pharmaceutical composition may optionally further comprise one or more additional excipients, such as colorants, flavoring agents, preservatives, and / or sweeteners. Examples of sweeteners include any natural or artificial sweetener (such as sucrose, xylitol, sodium saccharin, cyclamate, aspartame, and acesulfame). Examples of flavoring agents include Magnasweet®, bubblegum flavor, and fruit flavors. Examples of preservatives include potassium sorbate, methylparaben, propylparaben, benzoic acid and its salts, other esters of parahydroxybenzoic acid such as butylparaben, alcohols such as ethyl alcohol or benzyl alcohol, phenolic compounds such as phenol, or quaternary compounds such as benzalkonium chloride.

[0049] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Includes.

[0050] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% to about 5.0% by weight of the total weight of the composition.

[0051] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% to about 3.0% by weight of the total weight of the composition.

[0052] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 10.0% to 35.0% by weight of a filler, advantageously 15.0% to 35.0% by weight of a filler, advantageously 20.0% to 35.0% by weight of a filler, 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant; 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder; 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant; 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant; optionally one or more additional excipients as defined above; Including, The sum of the above mentioned ingredients is 100% by weight.

[0053] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; It essentially consists of:

[0054] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; and among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% to about 5.0% by weight of the total weight of the composition.

[0055] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; and among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% by weight to about 3.0% by weight of the total weight of the composition.

[0056] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 10.0% to 35.0% by weight of a filler, advantageously 15.0% to 35.0% by weight of a filler, advantageously 20.0% to 35.0% by weight of a filler, 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant; 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder; 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant; 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant; optionally one or more additional excipients as defined above; It essentially consists of:

[0057] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; It consists of:

[0058] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% by weight to about 5.0% by weight of the total weight of the composition.

[0059] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Among the pharmaceutically acceptable excipients, the surfactant accounts for about 1.0% by weight to about 3.0% by weight of the total weight of the composition.

[0060] In some embodiments, the pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 10.0% to 35.0% by weight of a filler, advantageously 15.0% to 35.0% by weight of a filler, advantageously 20.0% to 35.0% by weight of a filler, 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant; 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder; 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant; 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant; optionally one or more additional excipients as defined above; It consists of:

[0061] In some embodiments, the pharmaceutical composition is in a solid dosage form.Exemplary solid dosage forms include tablets, capsules, stick packs, sachets, lozenges, powders, pills, or granules.Preferred solid dosage forms include tablets, capsules, and stick packs, with tablets being particularly preferred.

[0062] In some embodiments, the pharmaceutical composition contains 200 mg to 1,200 mg of lanifibranor. Exemplary pharmaceutical compositions contain 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, or 1,200 mg of lanifibranor.

[0063] In any of the above embodiments, the lanifibranor may be present in the pharmaceutical composition in a crystalline form.

[0064] Dissolution Profile When the pharmaceutical composition of the present invention is in the form of a solid dosage form, said form has a fast dissolution profile, specifically, a dissolution profile in which at least 30% and at most 60% of the composition is dissolved within 15 minutes, and at least 80%, advantageously at least 85%, of the composition is dissolved within 45 minutes.

[0065] Dissolution is preferably measured in a discriminatory medium. Such a dissolution medium generates two very different dissolution curves for two products with very different dissolution profiles in gastric fluid. That is, the dissolution medium predicts the in vivo dissolution of the composition. An exemplary dissolution medium is an aqueous medium containing about 0.7% to about 1.7% tetradecyltrimethylammonium bromide (cetrimide). Specifically, dissolution was measured using USP Test Apparatus 1 (10 mesh basket) at 100 rpm in 1000 mL of pH 6.8 sodium phosphate buffer containing about 0.7% to about 1.7% cetrimide, thermostated at 37°C ± 0.5°C. One skilled in the art can determine the appropriate cetrimide concentration by applying sink conditions (i.e., the ability of the dissolution medium to dissolve at least three times the amount of drug present in the dosage form).

[0066] In some embodiments, the pharmaceutical compositions of the present invention have the following dissolution profile: -30% to 60% is released within 15 minutes of oral ingestion. - at least 80%, advantageously at least 85%, released within 45 minutes after oral ingestion, These were measured using USP Test Apparatus 1 (10 mesh basket) at 100 rpm in 1000 mL of sodium phosphate buffer, pH 6.8, containing approximately 0.7% to approximately 1.7% cetrimide, thermostated at 37°C ± 0.5°C.

[0067] Due to their fast dissolution profile, the pharmaceutical compositions of the present invention are stable immediate-release pharmaceutical compositions. As used herein, the term "immediate-release" refers to any type of release of the active ingredient (lanifibranor) from the pharmaceutical compositions of the present invention that results in an in vitro release within a short period of time, i.e., less than 1 hour. Preferably, more than 85% of the lanifibranor is released within 45 minutes after oral ingestion.

[0068] Advantageously, the pharmaceutical composition of the present invention releases approximately 30-60% of the lanifibranor within 15 minutes after oral ingestion.

[0069] Advantageously, the pharmaceutical composition of the present invention releases at least 80%, preferably at least 85%, of the lanifibranor within 45 minutes after oral ingestion.

[0070] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranol and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition, wherein the immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: -30% to 60% is released within 15 minutes of oral ingestion. - at least 80%, advantageously at least 85%, released within 45 minutes after oral ingestion

[0071] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0072] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition, wherein the surfactants, among the pharmaceutically acceptable excipients, comprise about 1.0% to about 5.0% by weight, advantageously about 1.0% to about 3.0% by weight of the total weight of the immediate release pharmaceutical composition.

[0073] In some embodiments, the immediate release pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; - 10.0% to 35.0% by weight of fillers, advantageously 15.0% to 35.0% by weight of fillers, advantageously 20.0% to 35.0% by weight of fillers, - 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, - 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, optionally one or more additional excipients as defined above, Comprising, consisting essentially of, or consisting of.

[0074] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition; - the immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0075] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition; - among the pharmaceutically acceptable excipients, surfactants represent about 1.0% to 5.0% by weight, advantageously about 1.0% to 3.0% by weight of the total weight of the immediate release pharmaceutical composition; - the immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: Approximately 30% to 60% is released within 15 minutes of oral ingestion. At least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion.

[0076] In some embodiments, the immediate release pharmaceutical composition comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the composition; - among the pharmaceutically acceptable excipients, surfactants represent about 1.0% to 5.0% by weight, advantageously about 1.0% to 3.0% by weight of the total weight of the immediate release pharmaceutical composition; - the immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0077] In some embodiments, the immediate release pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; - 10.0% to 35.0% by weight of fillers, advantageously 15.0% to 35.0% by weight of fillers, advantageously 20.0% to 35.0% by weight of fillers, - 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, - 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, and optionally one or more additional excipients as defined above, comprising, consisting essentially of, or consisting of, The immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: -30% to 60% is released within 15 minutes of oral ingestion. - at least 80%, advantageously at least 85%, released within 45 minutes after oral ingestion

[0078] In some embodiments, the immediate release pharmaceutical composition comprises, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; - 10.0% to 35.0% by weight of fillers, advantageously 15.0% to 35.0% by weight of fillers, advantageously 20.0% to 35.0% by weight of fillers, - 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, - 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, and optionally one or more additional excipients as defined above, comprising, consisting essentially of, or consisting of, - the immediate release pharmaceutical composition has a lanifibranol dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0079] In some embodiments, the above-mentioned immediate release pharmaceutical composition is a solid dosage form.Advantageously, the solid dosage form comprises tablets, capsules, stick packs, sachets, lozenges, powders, pills, or granules.Preferred solid dosage forms include tablets, capsules, and stick packs, and tablets are particularly preferred.

[0080] In some embodiments, the immediate release pharmaceutical composition contains 200 mg to 1,200 mg of lanifibranor. Advantageously, the pharmaceutical composition contains 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, or 1,200 mg of lanifibranor.

[0081] In some embodiments, the immediate release pharmaceutical composition is for oral administration.

[0082] In another aspect, the present invention discloses an immediate release tablet comprising, consisting essentially of, or consisting of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet.

[0083] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet, wherein the immediate release tablet has a lanifibranor dissolution profile with the following constraints: -30% to 60% is released within 15 minutes of oral ingestion. - at least 80%, advantageously at least 85%, released within 45 minutes after oral ingestion

[0084] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet, and the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0085] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet; - the immediate release tablet has a lanifibranor dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0086] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet, wherein among the pharmaceutically acceptable excipients, surfactants comprise 1.0% to 5.0% by weight, advantageously 1.0% to 3.0% by weight of the total weight of the immediate release tablet.

[0087] In some embodiments, the immediate release tablet contains, based on the total weight of the tablet: 55.0% to 75.0% by weight of lanifibranol; - 10.0% to 35.0% by weight of fillers, advantageously 15.0% to 35.0% by weight of fillers, advantageously 20.0% to 35.0% by weight of fillers, - 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, - 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, and optionally one or more additional excipients as defined above, Comprising, consisting essentially of, or consisting of.

[0088] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet; - among the pharmaceutically acceptable excipients, surfactants represent 1.0% to 5.0% by weight, advantageously 1.0% to 3.0% by weight, of the total weight of the immediate release tablet; - the immediate release tablet has a lanifibranor dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, At least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion.

[0089] In some embodiments, the immediate release tablet comprises, consists essentially of, or consists of 55.0% to 75.0% by weight of lanifibranor and 25.0% to 45.0% by weight of pharmaceutically acceptable excipients, based on the total weight of the tablet; - among the pharmaceutically acceptable excipients, surfactants represent 1.0% to 5.0% by weight, advantageously 1.0% to 3.0% by weight, of the total weight of the immediate release tablet; - the immediate release tablet has a lanifibranor dissolution profile with the following constraints: ○ 30% to 60% is released within 15 minutes after oral ingestion, at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0090] In some embodiments, the immediate release tablet contains, based on the total weight of the tablet: 55.0% to 75.0% by weight of lanifibranol; - 10.0% to 35.0% by weight of fillers, advantageously 15.0% to 35.0% by weight of fillers, advantageously 20.0% to 35.0% by weight of fillers, - 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, - 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, and optionally one or more additional excipients as defined above, comprising, consisting essentially of, or consisting of, The immediate release tablet has a lanifibranol dissolution profile with the following constraints: -30% to 60% is released within 15 minutes of oral ingestion. - at least 80%, advantageously at least 85%, released within 45 minutes after oral ingestion

[0091] In some embodiments, the immediate release tablet contains, based on the total weight of the tablet: - about 55.0% to 75.0% by weight of lanifibranol; - approximately 10.0% to 35.0% by weight of filler, advantageously 15.0% to 35.0% by weight of filler, advantageously 20.0% to 35.0% by weight of filler, about 1.0% to 5.0% by weight of a surfactant, advantageously 1.0% to 3.0% by weight of a surfactant, - approximately 1.0% to 10.0% by weight of a binder, advantageously 2.0% to 8.0% by weight of a binder, advantageously 3.0% to 6.0% by weight of a binder, about 0.5% to 5.0% by weight of a lubricant, advantageously 0.5% to 3.0% by weight of a lubricant, about 1.0% to 8.0% by weight of a disintegrant, advantageously 2.0% to 6.0% by weight of a disintegrant, - about 0.1% to 5.0% by weight of a glidant, advantageously 0.1% to 2.0% by weight of a glidant, and optionally one or more additional excipients as defined above, comprising, consisting essentially of, or containing where: - the immediate release tablet has a lanifibranor dissolution profile with the following constraints: Approximately 30% to 60% is released within 15 minutes of oral ingestion. at least 80%, advantageously at least 85%, is released within 45 minutes after oral ingestion, - the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0092] In some embodiments, the immediate release tablets contain 200 mg to 1,200 mg of lanifibranor. Advantageously, the immediate release tablets contain 200 mg, 400 mg, 600 mg, 800 mg, 1,000 mg, or 1,200 mg of lanifibranor.

[0093] In some embodiments, the immediate release tablets are for oral administration.

[0094] Methods of Using Lanifibranol Compositions The pharmaceutical compositions, immediate-release pharmaceutical compositions, and immediate-release tablets of the present invention are useful for treating fibrotic conditions such as non-alcoholic fatty liver disease (NAFLD), including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH). The pharmaceutical compositions, immediate-release pharmaceutical compositions, and immediate-release tablets of the present invention are also useful for treating subjects with cirrhosis who are at risk of progressing from compensated to decompensated liver disease. The pharmaceutical compositions, immediate-release pharmaceutical compositions, and immediate-release tablets of the present invention are also useful for treating diseases selected from cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, and liver cirrhosis.

[0095] Therefore, in one aspect, the present disclosure relates to a pharmaceutical composition, immediate-release pharmaceutical composition, or immediate-release tablet as defined above for use in a method for treating NAFLD, including non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).The present disclosure also relates to a pharmaceutical composition, immediate-release pharmaceutical composition, or immediate-release tablet as defined above for use in a method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated.The present disclosure also relates to a pharmaceutical composition, immediate-release pharmaceutical composition, or immediate-release tablet as defined above for use in a method for treating a disease selected from cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, and liver cirrhosis.

[0096] In one aspect, the present disclosure relates to a method for treating non-alcoholic fatty liver disease (NAFLD), comprising administering to a subject in need thereof a pharmaceutical composition, immediate release pharmaceutical composition, or immediate release tablet as defined above. The present disclosure also relates to a method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated, comprising administering to the subject a pharmaceutical composition, immediate release pharmaceutical composition, or immediate release tablet as defined above.

[0097] The present disclosure also relates to a method of treating a disease selected from cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, or liver cirrhosis, comprising administering to a subject in need thereof the pharmaceutical composition, immediate release pharmaceutical composition, or immediate release tablet as defined above.

[0098] As used herein, the term "subject" refers to an animal, preferably a mammal, including a human or non-human. A subject is, for example, a human or animal prone to having a fibrotic condition or suffering from such a disease. A subject is advantageously a human. A patient may be a child (a human patient under the age of 18) or an adult (a human patient over the age of 18). In some embodiments, a subject is a non-human animal, including, but not limited to, a dog, a cat, a guinea pig, a rabbit, a rat, a mouse, a horse, a cow, a bear, a cow, an ape, a monkey, an orangutan, and a chimpanzee. The terms patient and subject may be used interchangeably.

[0099] In some embodiments, a daily dosage of 400 mg to 1,200 mg of lanifibranor is administered to a patient, for example, 400 mg, 600 mg, 800 mg, 1,000 mg, or 1,200 mg.

[0100] Method for producing a lanifibranol composition Reference is made below to a suitable process for preparing tablets, although it should be understood that other solid dosage forms can be prepared by suitable techniques known to those skilled in the art. Exemplary pharmaceutical compositions containing as excipients binders, disintegrants, fillers, glidants, lubricants and surfactants include: a) providing lanifibranol having a particle size distribution such that D50≦30 μm and D90≦50 μm; b) providing a granulation solution comprising an aqueous solution of a surfactant; c) preparing a blend of lanifibranor, a filler, a disintegrant and a binder; d) spraying the granulation solution (obtained in step b) onto the resulting blend to obtain a granulation (wet granulation); e) preparing a blend of a filler and a glidant, and then adding another portion of a filler and a disintegrant to the blend; f) mixing the granulation obtained in step d) with the blend obtained in step e) and a lubricant, and then mixing the resulting blend; g) processing the blend obtained in step f) into a desired dosage form; The composition can be prepared by a process including:

[0101] In some embodiments, the aqueous surfactant solution used in step c) comprises about 80.0% to about 90.0% (purified) water by weight. In some embodiments, the surfactant comprises about 10.0% to about 20.0% by weight of the aqueous solution and is a mixture of sodium lauryl sulfate (SLS) and dioctyl sodium sulfosuccinate (DOSS) in a weight ratio (SLS / DOSS) of about 2.5 to about 5.0.

[0102] In some embodiments, the binder is added last during the blending process in step c).

[0103] The wet granulation in step d) is carried out by methods known in the art, for example, by a high shear mixer. In some embodiments, the granulation time is from about 10 seconds to about 30 minutes, for example, from about 30 seconds to about 15 minutes.

[0104] In some embodiments, the same filler is used twice in step e). In some embodiments, different fillers are used in step e). In the latter embodiment, at least one filler used is the same as the filler used in step c).

[0105] In some embodiments, the desired dosage form is a tablet and the method defined above may further comprise the step of film-coating the tablet.

[0106] The invention is illustrated by the following non-limiting examples. [Example]

[0107] In the following examples, lanifibranor was provided in crystalline form characterized by XRPD, DSC, and TGA, as described in Example 5. It was micronized prior to processing so that its particle size distribution was characterized by D50≦10 μm and D90≦30 μm.

[0108] XRPD Powder X-ray diffraction analysis was performed using a Panalytical Empyrean S3 diffractometer equipped with a Cu source (Cu wavelength = 1.5406 Å). Analysis was performed in transmission mode (samples placed between Kapton® and polypropylene foil) over an angular range of 2θ = 2–50°, with a step size of 0.026° and a time per step of 20.4 s.

[0109] DSC DSC analyses were performed on a Mettler Toledo DSC3+ calorimeter. Samples of several milligrams were placed in 40 μL sealed aluminum pans, punctured prior to analysis, and flushed with nitrogen at 50 mL / min. The temperature range was scanned from 20 °C to 300 °C at a rate of 10 °C / min.

[0110] TGA TGA analyses were performed on a Mettler Toledo TGA / DSC3+ thermogravimetric analyzer. Samples were measured using a few milligrams of sample in a 100 μL sealed aluminum pan, punctured prior to analysis, and flushed with nitrogen at 50 mL / min. The temperature range was scanned from 25 °C to 300 °C at a rate of 10 °C / min.

[0111] Example 1 Wettability Test A blend and granulation solution (GS) was prepared by combining the ingredients listed in Table 1. [Table 1]

[0112] A sample of each blend was spread on a flat surface by lightly pressing it to make the powder bed approximately flat. Using a dropper, a droplet of either GS1 or GS2 was gently placed on the powder bed. If the droplet remained on the powder, the blend had poor wetting; if the droplet spread over the surface and penetrated the powder, it had good wetting. The results are shown in Table 2. [Table 2]

[0113] These observations confirmed that lanifibranor is hydrophobic, as it exhibited poor wettability with water alone (GS1). When the granulation solution contained a surfactant, lanifibranor was wetted, regardless of the presence or absence of lactose.

[0114] Example 2 Lanifibranor Formulation The objective of this example was to prepare lanifibranor tablets by combining the ingredients listed in Table 3 using the general method described above (i.e., the tablets were prepared using a spray granulation process). During tablet manufacturing, care was taken to adhere to the required weight percentages of lanifibranor and excipients, respectively (i.e., 55-75% by weight lanifibranor and 25-45% by weight excipients). [Table 3]

[0115] Example 3 Stability Test Using the materials listed in Table 3 and the general method described above, 600 mg lanifibranor tablets were prepared so that the lanifibranor content in the tablets was 57% by weight. Stability tests were performed on these tablets, which were packed in HDPE bottles fitted with PP caps equipped with silica gel cartridges. The results are shown in Table 4. [Table 4]

[0116] As can be seen from the table above, no OOT (out of trend) / OOS (out of specification) was observed after 6 months of storage. Specifically, no significant changes were observed in the appearance, assay, impurity profile, disintegration time, crush resistance, loss on drying, or dissolution of the formulation after 6 months of storage in HDPE bottles sealed with desiccant at 25°C / 60%RH, 30°C / 70%RH, and 40°C / 75%RH.

[0117] As can be seen from the table above, no OOT (out of trend) / OOS (out of specification) was observed after 24 months of storage. Specifically, no significant changes were observed in the appearance, assay, impurity profile, disintegration time, crush resistance, loss on drying, and dissolution of the formulation after 24 months of storage at 25°C / 60% RH and 30°C / 70% RH.

[0118] Example 4 Dissolution Profile The dissolution profile of 600 mg lanifibranor tablets (used in stability studies) was measured using USP Apparatus 1 (10 mesh basket) at 100 rpm in 1000 mL of pH 6.8 sodium phosphate buffer containing 1.7% tetradecyltrimethylammonium bromide thermostated at 37° C. ± 0.5° C. The results are shown in Table 5. [Table 5]

[0119] Example 5 Dissolution Profile Using the materials listed in Table 3 and the general method described above, 400 mg lanifibranor tablets were prepared to provide a lanifibranor content of 57% by weight in the tablets. The dissolution profiles of these tablets were measured using USP Apparatus 1 (10 mesh basket) at 100 rpm in 1000 mL of pH 6.8 sodium phosphate buffer containing 1.7% tetradecyltrimethylammonium bromide thermostated at 37°C ± 0.5°C. The results are shown in Table 6. [Table 6]

[0120] Example 6 Crystallography The active pharmaceutical ingredient (API), lanifibranol, present in the 600 mg tablets of Example 3 was analyzed by XRPD. Its characteristics were found to be identical to those of the starting API before processing into tablets. In particular, the lanifibranol analyzed from the tablets was -having an XRPD pattern containing the peaks shown in Table 7 (2θ positions may show some variation, typically as much as ±0.2°, and relative peak intensities may show instrument-to-instrument variation). [Table 7]

[0121] Example 7 Preparation of a scale-up batch of coated tablets a) A granulating solution was prepared using 1125.0 g of sodium lauryl sulfate and 300.0 g of docusate sodium in 6750.0 g of water, which was stirred until completely dissolved.

[0122] b) Separately, a mixture of lanifibranor (30,000.0 g), lactose monohydrate (12,150 g), sodium starch glycolate (1,500.0 g), and hydroxypropyl methylcellulose (2,250.0 g) was prepared by blending together.

[0123] c) The blend obtained in step b) was sprayed with the granulating solution and the resulting granulation was dried.

[0124] d) A blend of lactose spray dried monohydrate (3650.0 g), sodium starch glycolate (700.0 g) and colloidal silicon dioxide (240 g) was then prepared.

[0125] e) The granulation from step c), the blend from step d) and magnesium stearate (500.0 g) were mixed together in a final blend.

[0126] f) The blend obtained in step e) was processed into tablets using a tablet press equipped with metal checks.

[0127] g) Finally, the tablets obtained in step f) were coated with Opadry™.

[0128] Example 8 Effect of surfactants on granulation and tableting performance Pharmaceutical compositions according to the present invention as set forth in Table 8 were prepared and tested. [Table 8]

[0129] For each pharmaceutical composition in Table 8, sodium lauryl sulfate and docusate sodium were mixed with water and stirred until completely dissolved to obtain a granulation solution. A mixture of lanifibranol, lactose monohydrate, sodium starch glycolate, and hydroxypropyl methylcellulose was prepared by blending them separately. The granulation process was carried out by spraying the granulation solution onto the blend. This process formed a granulation, which was then dried. A blend of lactose monohydrate, sodium starch glycolate, and colloidal silicon dioxide was then prepared. The granulation, blend, and magnesium stearate were mixed together to obtain the final blend. Tablets were prepared from the final blend using a tablet press equipped with metal checks and coated with Opadry™.

[0130] Observations made during the preparation of the tablets are reported in Table 9. [Table 9]

[0131] These observations confirmed that varying the amount of surfactant affected the granulation process and tableting. In fact, even if granulation was possible, a significant amount of lanifibranol remained on the walls of the granulator when the total amount of surfactant was less than 1.0%. Furthermore, tablets could not be obtained with surfactant amounts less than 1.0% by weight. Therefore, the amount of surfactant plays an important role in the success of granulation and tableting.

[0132] Aspects of the present disclosure are further described with reference to the following non-limiting embodiments.

[0133] 1. A pharmaceutical composition comprising, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, A pharmaceutical composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0134] 2. The pharmaceutical composition described in paragraph 1, wherein the pharmaceutical composition releases 30-60% of the lanifibranor within 15 minutes after oral ingestion.

[0135] 3. The pharmaceutical composition of any one of paragraphs 1 to 2, wherein the pharmaceutical composition releases at least 80% of the lanifibranor within 45 minutes after oral ingestion.

[0136] 4. The pharmaceutical composition of any one of paragraphs 1 to 3, wherein the pharmaceutically acceptable excipients comprise two or more of binders, colorants, disintegrants, fillers, glidants, lubricants, preservatives, surfactants, and sweeteners.

[0137] 5. The pharmaceutical composition of any one of paragraphs 1 to 4, wherein the pharmaceutically acceptable excipient comprises a filler, and the filler accounts for 10.0% by weight to 35.0% by weight of the total weight of the composition.

[0138] 6. The pharmaceutical composition according to paragraph 5, wherein the filler is selected from lactose monohydrate, anhydrous lactose, starch, modified starch, mannitol and mixtures thereof.

[0139] 7. The pharmaceutical composition of any one of paragraphs 1 to 6, wherein the pharmaceutically acceptable excipient comprises a surfactant, and the surfactant comprises 1.0% by weight to 5.0% by weight of the total weight of the composition.

[0140] 8. The pharmaceutical composition according to paragraph 7, wherein the surfactant is selected from nonionic surfactants, anionic surfactants, cationic surfactants, and mixtures thereof.

[0141] 9. The pharmaceutical composition of any one of paragraphs 1 to 8, wherein the pharmaceutically acceptable excipient comprises a binder, and the binder comprises 1.0% by weight to 10.0% by weight of the total weight of the composition.

[0142] 10. The pharmaceutical composition according to paragraph 9, wherein the binder is selected from cellulose, modified cellulose, microcrystalline cellulose, polyvinylpyrrolidone and mixtures thereof.

[0143] 11. The pharmaceutical composition of any one of paragraphs 1 to 10, wherein the pharmaceutically acceptable excipient comprises a lubricant, and the lubricant accounts for 0.5% to 5.0% by weight of the total weight of the composition.

[0144] 12. The pharmaceutical composition according to paragraph 11, wherein the lubricant is selected from talc, stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica gel, and mixtures thereof.

[0145] 13. The pharmaceutical composition of any one of paragraphs 1 to 12, wherein the pharmaceutically acceptable excipient comprises a disintegrant, and the disintegrant accounts for 1.0% by weight to 8.0% by weight of the total weight of the composition.

[0146] 14. The pharmaceutical composition according to paragraph 13, wherein the disintegrant is selected from starch, modified starch, croscarmellose sodium, crospovidone, sodium starch glycolate, and mixtures thereof.

[0147] 15. The pharmaceutical composition of any one of paragraphs 1 to 14, wherein the pharmaceutically acceptable excipient comprises a glidant, and the glidant comprises 0.1% by weight to 5.0% by weight of the total weight of the composition.

[0148] 16. The pharmaceutical composition of any one of paragraphs 1 to 15, which is a solid dosage form.

[0149] 17. The pharmaceutical composition according to paragraph 16, which is a tablet, capsule or stick pack, preferably a tablet.

[0150] 18. The pharmaceutical composition according to paragraph 16 or 17, comprising 200 mg to 1,200 mg of lanifibranor.

[0151] 19. The pharmaceutical composition of any one of paragraphs 1 to 18, wherein the lanifibranor is in a crystalline form.

[0152] 20. A pharmaceutical composition according to any one of paragraphs 1 to 19 for use in a method for treating non-alcoholic fatty liver disease (NAFLD).

[0153] 21. The pharmaceutical composition for use according to paragraph 20, wherein NAFLD includes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).

[0154] 22. The pharmaceutical composition of any one of paragraphs 1 to 19 for use in a method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated.

[0155] 23. The pharmaceutical composition of any one of paragraphs 1 to 19 for use in a method for treating cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, or liver cirrhosis.

[0156] 24. A method for treating non-alcoholic fatty liver disease (NAFLD), comprising administering to a subject in need thereof a pharmaceutical composition described in any one of paragraphs 1 to 19.

[0157] 25. The method of paragraph 24, wherein NAFLD includes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).

[0158] 26. A method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated, comprising administering to the subject a pharmaceutical composition described in any one of paragraphs 1 to 19.

[0159] 27. A method for treating a disease selected from cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, or liver cirrhosis, comprising administering to a subject in need thereof the pharmaceutical composition of any one of paragraphs 1 to 19.

[0160] 28. The method of any one of paragraphs 24 to 27, wherein a daily dose of 400 mg to 1,200 mg of lanifibranor is administered to the subject.

[0161] 29. Based on the total weight of the composition, 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm; 4. The pharmaceutical composition of any one of paragraphs 1 to 3, wherein, among the pharmaceutically acceptable excipients, surfactants account for 1.0% to 5.0% by weight of the total weight of the composition.

[0162] 30. A stable immediate release pharmaceutical composition comprising, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, A stable immediate release pharmaceutical composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0163] 31. The stable immediate release pharmaceutical composition according to paragraph 30, wherein the pharmaceutical composition releases 30 to 60% of the lanifibranor within 15 minutes after oral ingestion.

[0164] 32. The stable immediate release pharmaceutical composition according to any one of paragraphs 30 to 31, wherein the pharmaceutical composition releases at least 80% of the lanifibranor within 45 minutes after oral ingestion.

[0165] 33. The stable immediate release pharmaceutical composition according to any one of paragraphs 30 to 32, wherein the pharmaceutically acceptable excipients comprise two or more of binders, colorants, disintegrants, fillers, glidants, lubricants, preservatives, surfactants, and sweeteners.

[0166] 34. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 33, wherein the pharmaceutically acceptable excipient comprises a filler, and the filler accounts for 10.0% to 35.0% by weight of the total weight of the composition.

[0167] 35. The stable immediate release pharmaceutical composition according to paragraph 34, wherein the filler is selected from lactose monohydrate, anhydrous lactose, starch, modified starch, mannitol, and mixtures thereof.

[0168] 36. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 35, wherein the pharmaceutically acceptable excipient comprises a surfactant, and the surfactant accounts for 1.0% to 5.0% by weight of the total weight of the composition.

[0169] 37. The stable immediate release pharmaceutical composition according to paragraph 36, wherein the surfactant is selected from nonionic surfactants, anionic surfactants, cationic surfactants, and mixtures thereof.

[0170] 38. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 37, wherein the pharmaceutically acceptable excipient comprises a binder, and the binder accounts for 1.0% by weight to 10.0% by weight of the total weight of the composition.

[0171] 39. The stable immediate-release pharmaceutical composition according to paragraph 38, wherein the binder is selected from cellulose, modified cellulose, microcrystalline cellulose, polyvinylpyrrolidone and mixtures thereof.

[0172] 40. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 39, wherein the pharmaceutically acceptable excipients comprise a lubricant, and the lubricant accounts for 0.5% to 5.0% by weight of the total weight of the composition.

[0173] 41. The stable immediate-release pharmaceutical composition according to paragraph 40, wherein the lubricant is selected from talc, stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica gel, and mixtures thereof.

[0174] 42. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 41, wherein the pharmaceutically acceptable excipient comprises a disintegrant, and the disintegrant accounts for 1.0% to 8.0% by weight of the total weight of the composition.

[0175] 43. The stable immediate-release pharmaceutical composition according to paragraph 42, wherein the disintegrant is selected from starch, modified starch, croscarmellose sodium, crospovidone, sodium starch glycolate, and mixtures thereof.

[0176] 44. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 33, wherein the pharmaceutically acceptable excipient comprises a glidant, and the glidant comprises 0.1% by weight to 5.0% by weight of the total weight of the composition.

[0177] 45. The stable immediate release pharmaceutical composition of any one of paragraphs 30 to 44, which is a solid dosage form.

[0178] 46. ​​The stable immediate release pharmaceutical composition according to paragraph 45, which is a tablet, capsule or stick pack, preferably a tablet.

[0179] 47. The stable immediate release pharmaceutical composition of paragraph 45 or 46, comprising 200 mg to 1,200 mg of lanifibranor.

[0180] 48. The stable immediate release pharmaceutical composition according to any one of paragraphs 30 to 47, wherein the lanifibranor is in a crystalline form.

[0181] 49. A stable immediate-release tablet comprising, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, A stable immediate release tablet, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

[0182] 50. The stable immediate-release tablet of paragraph 49, wherein the tablet releases 30 to 60% of the lanifibranor within 15 minutes after oral ingestion.

[0183] 51. The stable immediate-release tablet of any one of paragraphs 49 to 50, wherein the tablet releases at least 80% of the lanifibranor within 45 minutes after oral ingestion.

[0184] 52. The stable immediate-release tablet of any one of paragraphs 49 to 51, wherein the pharmaceutically acceptable excipients comprise two or more of a binder, a colorant, a disintegrant, a filler, a glidant, a lubricant, a preservative, a surfactant, and a sweetener.

[0185] 53. The stable immediate-release tablet of any one of paragraphs 49 to 52, wherein the pharmaceutically acceptable excipients comprise a filler, and the filler accounts for 10.0% to 35.0% by weight of the total weight of the composition.

[0186] 54. The stable immediate-release tablet according to paragraph 53, wherein the filler is selected from lactose monohydrate, anhydrous lactose, starch, modified starch, mannitol, and mixtures thereof.

[0187] 55. The stable immediate-release tablet of any one of paragraphs 49 to 54, wherein the pharmaceutically acceptable excipient comprises a surfactant, and the surfactant comprises 1.0% by weight to 5.0% by weight of the total weight of the composition.

[0188] 56. The stable immediate-release tablet according to paragraph 55, wherein the surfactant is selected from nonionic surfactants, anionic surfactants, cationic surfactants, and mixtures thereof.

[0189] 57. The stable immediate-release tablet of any one of paragraphs 49 to 56, wherein the pharmaceutically acceptable excipients comprise a binder, and the binder accounts for 1.0% by weight to 10.0% by weight of the total weight of the composition.

[0190] 58. The stable immediate-release tablet according to paragraph 57, wherein the binder is selected from cellulose, modified cellulose, microcrystalline cellulose, polyvinylpyrrolidone, and mixtures thereof.

[0191] 59. The stable immediate-release tablet of any one of paragraphs 49 to 58, wherein the pharmaceutically acceptable excipients comprise a lubricant, and the lubricant accounts for 0.5% to 5.0% by weight of the total weight of the composition.

[0192] 60. The stable immediate-release tablet according to paragraph 59, wherein the lubricant is selected from talc, stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica gel, and mixtures thereof.

[0193] 61. The stable immediate-release tablet of any one of paragraphs 49 to 60, wherein the pharmaceutically acceptable excipients comprise a disintegrant, and the disintegrant accounts for 1.0% to 8.0% by weight of the total weight of the composition.

[0194] 62. The stable immediate-release tablet according to paragraph 61, wherein the disintegrant is selected from starch, modified starch, croscarmellose sodium, crospovidone, sodium starch glycolate, and mixtures thereof.

[0195] 63. The stable immediate-release tablet of any one of paragraphs 49 to 62, wherein the pharmaceutically acceptable excipients comprise a glidant, and the glidant comprises 0.1% to 5.0% by weight of the total weight of the composition.

[0196] 64. The stable immediate-release pharmaceutical composition of any one of paragraphs 30 to 48 or the stable immediate-release tablet of any one of paragraphs 49 to 63 for use in a method for treating non-alcoholic fatty liver disease (NAFLD).

[0197] 65. The stable immediate-release pharmaceutical composition of any one of paragraphs 30 to 48 or the stable immediate-release tablet of any one of paragraphs 49 to 63 for use in a method for treating non-alcoholic fatty liver disease (NAFLD), wherein NAFLD includes non-alcoholic fatty liver and non-alcoholic steatohepatitis (NASH).

[0198] 66. A stable immediate-release pharmaceutical composition according to any one of paragraphs 30 to 48 or a stable immediate-release tablet according to any one of paragraphs 49 to 63 for use in a method for treating a subject with cirrhosis at risk of progression from compensated to decompensated liver disease.

[0199] 67. The stable immediate-release pharmaceutical composition of any one of paragraphs 30 to 48 or the stable immediate-release tablet of any one of paragraphs 49 to 63 for use in a method for treating cirrhosis, liver fibrosis, hepatic steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure (ACLF), acute liver failure (ALF), decompensated cirrhosis, compensated cirrhosis, metabolically associated fatty liver disease (MAFLD), metabolically associated steatohepatitis (MASH), diabetes, or liver cirrhosis.

Claims

1. 1. A pharmaceutical composition comprising, based on the total weight of the composition: 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, A pharmaceutical composition, wherein the lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm.

2. 10. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition releases about 30-60% of the lanifibranor within 15 minutes after oral ingestion.

3. 3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition releases at least 80% of the lanifibranor within 45 minutes after oral ingestion.

4. 4. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipients comprise two or more of a binder, a colorant, a disintegrant, a filler, a glidant, a lubricant, a preservative, a surfactant, and a sweetener.

5. 5. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a filler, and the filler accounts for 10.0% to 35.0% by weight of the total weight of the composition.

6. 6. The pharmaceutical composition of claim 5, wherein the filler is selected from lactose monohydrate, anhydrous lactose, starch, modified starch, mannitol, and mixtures thereof.

7. 7. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a surfactant, and the surfactant comprises 1.0% to 5.0% by weight of the total weight of the composition.

8. 8. The pharmaceutical composition of claim 7, wherein the surfactant is selected from a nonionic surfactant, an anionic surfactant, a cationic surfactant, and mixtures thereof.

9. 9. The pharmaceutical composition of claim 1, wherein the pharmaceutically acceptable excipient comprises a binder, and the binder comprises 1.0% to 10.0% by weight of the total weight of the composition.

10. 10. The pharmaceutical composition of claim 9, wherein the binder is selected from cellulose, modified cellulose, microcrystalline cellulose, polyvinylpyrrolidone, and mixtures thereof.

11. 11. The pharmaceutical composition of any one of claims 1 to 10, wherein the pharmaceutically acceptable excipients comprise a lubricant, and the lubricant accounts for 0.5% to 5.0% by weight of the total weight of the composition.

12. 12. The pharmaceutical composition of claim 11, wherein the lubricant is selected from talc, stearic acid, magnesium stearate, calcium stearate, sodium stearyl fumarate, silica gel, and mixtures thereof.

13. 13. The pharmaceutical composition of any one of claims 1 to 12, wherein the pharmaceutically acceptable excipients comprise a disintegrant, and the disintegrant accounts for 1.0% to 8.0% by weight of the total weight of the composition.

14. 14. The pharmaceutical composition of claim 13, wherein the disintegrant is selected from starch, modified starch, croscarmellose sodium, crospovidone, sodium starch glycolate, and mixtures thereof.

15. 15. The pharmaceutical composition of any one of claims 1 to 14, wherein the pharmaceutically acceptable excipient comprises a glidant, and the glidant comprises 0.1% to 5.0% by weight of the total weight of the composition.

16. based on the total weight of the composition 55.0% to 75.0% by weight of lanifibranol; 10.0 wt.% to 35.0 wt.% of a filler; 1.0 wt % to 5.0 wt % of a surfactant; 1.0 wt % to 10.0 wt % of a binder; 0.5% to 5.0% by weight of a lubricant; 1.0% to 8.0% by weight of a disintegrant; 0.1% to 5.0% by weight of a glidant; 16. The pharmaceutical composition of claim 1, comprising:

17. 17. The pharmaceutical composition of any one of claims 1 to 16, which is in a solid dosage form.

18. 18. A pharmaceutical composition according to claim 17, which is a tablet, capsule or stick pack, preferably a tablet.

19. 19. The pharmaceutical composition of claim 17 or claim 18, comprising 200 mg to 1,200 mg of lanifibranor.

20. 20. The pharmaceutical composition of any one of claims 1 to 19, wherein the lanifibranor is in a crystalline form.

21. 21. A pharmaceutical composition according to any one of claims 1 to 20 for use in a method for treating non-alcoholic fatty liver disease (NAFLD).

22. 22. The pharmaceutical composition for use according to claim 21, wherein NAFLD includes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).

23. 21. A pharmaceutical composition according to any one of claims 1 to 20 for use in a method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated stage.

24. 21. The pharmaceutical composition of any one of claims 1 to 20 for use in a method for treating liver cirrhosis, liver fibrosis, liver steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure, acute liver failure, decompensated cirrhosis, compensated cirrhosis, metabolically related fatty liver disease, metabolically related steatohepatitis, diabetes, or liver cirrhosis.

25. based on the total weight of the composition 55.0% to 75.0% by weight of lanifibranol; 25.0% to 45.0% by weight of a pharmaceutically acceptable excipient; Including, Lanifibranor has a particle size distribution such that D50≦30 μm and D90≦50 μm, preferably D50≦10 μm and D90≦30 μm; 4. The pharmaceutical composition according to claim 1, wherein, among the pharmaceutically acceptable excipients, surfactants account for 1.0% to 5.0% by weight of the total weight of the composition.

26. 26. The pharmaceutical composition of claim 25, wherein the pharmaceutically acceptable excipients further comprise two or more of a binder, a colorant, a disintegrant, a filler, a glidant, a lubricant, a preservative, a surfactant, and a sweetener.

27. 27. The pharmaceutical composition of claim 25 or claim 26, which is in a solid dosage form.

28. 28. A pharmaceutical composition according to any one of claims 25 to 27, which is a tablet, capsule or stick pack, preferably a tablet.

29. 29. The pharmaceutical composition of any one of claims 25 to 28, comprising 200 mg to 1,200 mg of lanifibranor.

30. 30. The pharmaceutical composition of any one of claims 25 to 29, wherein the lanifibranor is in a crystalline form.

31. 31. The pharmaceutical composition of any one of claims 25 to 30 for use in a method for treating non-alcoholic fatty liver disease (NAFLD).

32. 32. The pharmaceutical composition for use according to claim 31, wherein NAFLD includes non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH).

33. 31. A pharmaceutical composition according to any one of claims 25 to 30 for use in a method for treating a subject with cirrhosis at risk of progressing from compensated to decompensated stage.

34. 31. The pharmaceutical composition of any one of claims 25 to 30 for use in a method for treating liver cirrhosis, liver fibrosis, liver steatosis, fatty liver disease, acute decompensation, acute exacerbation of chronic liver failure, acute liver failure, decompensated cirrhosis, compensated cirrhosis, metabolically related fatty liver disease, metabolically related steatohepatitis, diabetes, or liver cirrhosis.

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