Solid dosage form

Abstract

A solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) preferably is prepared by compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler; and a disintegrant. Said composition for use in the treatment of a TLR7 / 8-related autoimmune disease.

Description

SOLID DOSAGE FORMTECHNICAL FIELD OF INVENTION

[0001] The present invention relates to a solid dosage form preferably comprising a toll-like receptor 7 / 8 (TLR7 / 8) antagonists, particularly enpatoran. The present invention also relates to a method for preparing the solid dosage form, to a powder mixture for tableting; and to uses and methods related thereto; and to the use of the solid dosage form in the medical treatment, especially the treatment of TLR7 / 8-related autoimmune diseases.BACKGROUND OF THE INVENTION

[0002] Toll-like receptors (TLR) currently comprising a gene family of 10 receptors with different specificities are part of the cellular pathogen pattern recognition system, which has evolved for defense against a variety of infections (bacteria, virus, fungi). Activation of TLRs leads to cytokine responses, e.g. with release of interferons and activation of specified immune cells.

[0003] TLRs have been implicated in various autoimmune and inflammatory diseases, with the clearest example being the role played by TLR7 in the pathogenesis of systemic lupus erythematosus (Barrat and Coffman, Immunol Rev, 223:271-283, 2008). TLR7 has also been implicated in systemic sclerosis, myositis and rheumatoid arthritis (Duffy and O’Reilly, Immunotargets Ther. 2016; 5: 69-80). TLR8 in turn has inter alia been associated with rheumatoid arthritis and systemic sclerosis (Duffy and O’Reilly, loc. cit).

[0004] Enpatoran, which has the IIIPAC name 5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile, is a compound having the following structure:>

[0006] Enpatoran is a potent and selective small molecule inhibitor of the Toll-Like-Receptor (TLR) 7 and 8 in clinical development for autoimmune diseases, including for the treatment of cutaneous and systemic lupus erythematosus (CLE / SLE). The compound may be prepared according to the methods provided in WO 2017 / 106607.

[0007] When used for treating humans, it is important that a therapeutic agent, like enpatoran (i.e. 5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile), or a salt or hydrate thereof, retains appropriate polymorphic and chemical stability, solubility, and other physicochemical properties overtime and among various manufactured batches of the agent. Polymorphism refers to the occurrence of different crystalline forms of a single compound. A single compound may give rise to a variety of polymorphic forms, each having different solid-state physical properties, such as different solubility, melting point, stability, dissolution rates and / or different X-ray diffraction peaks. The existence of particular polymorphic forms and their physical properties is unpredictable.

[0008] If the physical or chemical properties of a therapeutic agent vary with time and / or among batches, the administration of a therapeutically effective dose may become problematic and may lead to inconsistent dosages or to ineffective therapy. Therefore, it is important to choose a physicochemical form, including a polymorphic form, of the agent that is stable, is manufactured reproducibly, and has physicochemical properties favorable for its use as a therapeutic agent.

[0009] Due to the possibility of variable solubility and / or stability of solid state forms, identifying the existence of distinct solid state forms of pharmaceutical compounds, including different polymorphs, is important for providing pharmaceutical products having predictable solubility profiles. However, the art remains unable to predict, which physicochemical form of a therapeutic agent will have a combination of the desired properties, including stability, dissolution and flow properties, and will be suitable for human administration, and how to make the agent in such a form, in particular in such crystalline form. Similarly, the solid state form of a therapeutic agent needs to be suitable for a certain method for preparation of a pharmaceutical composition, and in particular a solid dosage form such as a tablet for oral administration.

[0010] Apart from the solid state form of enpatoran, also the composition and properties of the pharmaceutical composition, such as a solid dosage form, e.g. a tablet for oral use, may affect stability, dissolution and / or absorption of an active ingredient. It is therefore crucial to carefullyselect and calibrate the excipients of a solid dosage form to ensure reproducible stability, release and absorption of the active ingredient.

[0011] There is a need for a solid oral dosage form of a TLR 7 / 8 inhibitor, such as enpatoran, in particular an immediate release solid oral dosage form for oral use, which is simple to prepare, stable in storage and use, and ensures consistency between batches with regard to desired properties (preparability, stability, disintegration & dissolution behavior, etc.).

[0012] It is thus an object of the present invention to provide a solid dosage form, in particular a tablet formulation, that is suitable for a range of drug loads and in particular also lower and higher drug loads, and to obtain tablets with an acceptable size and weight for easy oral administration. Furthermore, the solid dosage form should comprise a TLR 7 / 8 inhibitor, such as enpatoran, with desirable physicochemical properties that are conducive to easy processing for preparation of solid dosage forms, in particular tableting by compression such as direct compression; and the resulting solid dosage form should have good stability and dissolution properties to allow long-term storage and reproducibly fast and complete release of the active ingredient.SUMMARY OF THE INVENTION

[0013] After considering various solid dosage form designs, the present inventors found an advantageous immediate release solid dosage form comprising an active ingredient, such as enpatoran H1. The solid oral dosage form of the present invention comprises a core (1) comprising the active ingredient, and optionally an immediate release coating covering the core. The ingredients and composition of the solid dosage form are carefully selected to ensure the desired disintegration and dissolution profile after administration.

[0014] It was found that the engineered H1 polymorph of enpatoran is much more conducive to tablet preparation by compression than other polymorphic forms. In particular, it was found that the H1 polymorph of enpatoran, due to its favorable and more controllable properties (e.g., monomodal and tight particle size distribution, high bulk density, equant particle shape) is particularly suitable for direct compression, a preparation process, which would not have been considered with polymorphic forms of enpatoran showing less ideal properties. This, together with the variable, and high, drug load requirement, was taken as an initiative to develop a solid dosage form, such as a tablet formulation, for compression, and in particular direct compression.

[0015] Thus, the present invention provides a novel solid dosage form preferably for oral use, comprising an active ingredient, such as enpatoran H 1 , in a core (1), which may be prepared by direct compression, and which optionally is covered with a coating; and a method for its preparation as well as its use in the treatment of certain autoimmune disease, including lupus (such as SLE, CLE and LN), myositis (such as PM and DM) and Sjogren's disease; and related products, uses and methods.

[0016] The present invention relates to the subject matter defined in the following items:[1] A solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is preferably prepared by compression, more preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a binder; a filler; and / or a disintegrant; and optionally one or more further pharmaceutically acceptable excipients.[2] A solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is prepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a (e.g. one or two) binder; a filler; and a disintegrant; and optionally one or more further pharmaceutically acceptable excipients.[3] The solid dosage form of item 1 or 2, wherein the core (1) comprises a binder selected from microcrystalline cellulose, powdered cellulose, copovidone, and combinations thereof.[4] A solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) preferably is prepared by compression, more preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof.[5] The solid dosage form of any of the preceding items, wherein the core (1) further comprises a glidant and / or a lubricant.[6] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose sodium (i.e. croscarmellose-sodium); and optionally a glidant, preferably silicon dioxide and / or a lubricant, preferably magnesium stearate, and optionally one more additional pharmaceutically acceptable excipient.[7] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably silicon dioxide; a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipient.[8] The solid dosage form of any of the preceding items, wherein the solid dosage form comprises, or consists of, a core (1) comprising, or consisting of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium (i.e. croscarmellose-sodium); a glidant, preferably silicon dioxide; a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipients; and an optional immediate release coating (2) covering the core.[9] The solid dosage form of any of items 3 to 8, wherein the copovidone is characterized by one or more of the following:particle size of < 45 % is <50 pm and < 15 % is > 250 pm, preferably < 40 % is <50 pm and < 10 % is > 250 pm, more preferably < 35 % is <50 pm and < 7 % is > 250 pm; and / ora bulk density of 0.03-0.23 g / ml, preferably 0.05-0.18 g / ml, more preferably 0.08-015 g / ml; and / ora molecular weight (Mw) of 55,000 - 80,000, preferably 50,000 - 75,000, more preferably 45,000 - 70,000.

[0010] The solid dosage form of any of items 3 to 9, wherein the microcrystalline cellulose is microcrystalline cellulose grade 101, grade 102, grade 200, grade 301, or grade 302, or a combination thereof, preferably microcrystalline cellulose grade 102.

[0011] The solid dosage form of any of items 3 to 10, wherein the core (1) comprises as a binder microcrystalline cellulose, preferably microcrystalline cellulose grade 102.

[0012] The solid dosage form of any of items 3 to 11, wherein the microcrystalline cellulose is characterized by one or more of the following:average particle size (laser diffraction) of 80-180 pm, preferably 100-160 pm, more preferably 120-140 pm, even more preferably 125-135 pm, e.g. about 130 pm; and / or a bulk density of 0.24-0.37 g / ml, preferably 0.26-0.35 g / ml, more preferably 0.28-0.33 g / ml.

[0013] The solid dosage form of any of the preceding items, wherein the core (1) comprises a filler selected from the group consisting of mannitol, sucrose, maltose, lactose, trehalose, glycerol, maltitol, isomalt, sorbitol, xylitol, and combinations thereof, preferably mannitol.

[0014] The solid dosage form of any of the preceding items, wherein the core (1) comprises mannitol as a filler.

[0015] The solid dosage form of any of the preceding items, wherein the core (1) comprises one filler, which is mannitol.

[0016] The solid dosage form of any of items 4 to 15, wherein the mannitol is characterized by one or more of the following:particle size of < 25 % is < 53 pm and < 25 % is > 500 pm, preferably < 20 % is < 53 pm and < 20 % is > 500 pm, more preferably < 15 % is < 53 pm and < 15 % is > 500 pm; and / ora pH value (10 % in water) of 4.2 - 81 , preferably, 4.3 - 7.8, more preferably 4.5 - 7.5; and / orloss on drying of <2 %, preferably, <1 %, more preferably <0.5 %.

[0017] The solid dosage form of any of the preceding items, wherein the core (1) comprises a disintegrant, preferably selected from carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose or a pharmaceutically acceptable salt thereof (e.g. croscarmellose sodium); crospovidone (polyvinylpolypyrrolidone); and starch (e.g. carboxy starch glycolate, or partially pregelatinized maize starch); and combinations thereof; preferably croscarmellose or a pharmaceutically acceptable salt thereof and / or crospovidone.

[0018] The solid dosage form of any of items 4 to 17, wherein the crospovidone is characterized by one or more of the following:a bulk density of 0.10 to 0.40 g / ml, preferably 0.15 to 0.31 g / ml, more preferably 0.18 to 0.28 g / ml; and / ora specific surface area (N2-BET) of 1-5 m2 / g, preferably 2-4 m2 / g, more preferably 2.5- 3.5 m2 / g about 3 m2 / g; and / ora particle size of < 60 % is > 50 pm and < 25 % is > 100 pm, preferably < 40 % is > 50 pm and < 15 % is > 100 pm, more preferably < 30 % is > 50 pm and < 10 % is > 100 pm; and / ora content of water-soluble material of <15 %, preferably, <12 %, more preferably <10 %; and / ora hydration capacity of 3-10 g water / g poiymer, preferably 6.5-9 g water / g polymer, more preferably 7-8.5 g water / g polymer.

[0019] The solid dosage form of item 17 or 18, wherein the disintegrant is croscarmellose or a pharmaceutically acceptable salt thereof, preferably croscarmellose sodium (i.e. croscarmellose-sodium).

[0020] The solid dosage form of any of items 4 to 19, wherein the croscarmellose or a pharmaceutically acceptable salt thereof is characterized by one or more of the following: a degree of substitution (on dried basis) of 0.50-0.95, preferably 0.55-0.90, more preferably 0.60-0.85, e.g. about 0.7; and / ora content of water-soluble material of <15 %, preferably <12 %, more preferably <10 %; and / ora settling volume of 5-40 ml, preferably 8-35 ml, more preferably 10-30 ml; and / or a pH value (1 % in water) of 4.6 - 7.4, preferably, 4.8 - 7.2, more preferably 5 - 7; and / orloss on drying (according to Ph.Eur., 2.2.32, no 99) of <15 %, preferably <12 %, more preferably <10 %.

[0021] The solid dosage form of any of the preceding items, wherein the core (1) comprises powdered cellulose.

[0022] The solid dosage form of item 21, wherein the powdered cellulose is characterized by a particle size distribution (e.g. retained on air jet sieve):up to 65 %, preferably up to 55 %, more preferably up to 50 %, or up to 48 %, or up to 47 %, or up to 46 %, e.g. about 45 %, particles with >32 pm (450 mesh); and / or up to 35 %, preferably up to 25 %, more preferably up to 20 %, or up to 18 %, or up to 16 %, or up to 15 %, e.g. about 14 %, particles with > 63 pm (230 mesh); and / or up to 2 % particles, preferably up to 1 %, more preferably up to 0.5 %, or up to 0.2 %, or up to 0.1 %, or up to 0.05 %, e.g. 0 %, with >125 pm (120 mesh).

[0023] The solid dosage form of item 21 or 22, wherein the powdered cellulose is characterized by a bulk density of 80 to 400 g / L, preferably 100 to 300 g / L, more preferably 140 to 280 g / L, 160 to 260 g / L, 180 to 240 g / L.

[0024] The solid dosage form of any of items 5 to 23, wherein the glidant is silicon dioxide (silica), talc, or tribasic calcium phosphate, preferably silicon dioxide, more preferably highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide; and / or wherein the lubricantis stearic acid or a pharmaceuticai acceptable salt thereof, glycerol fatty acid esters and sodium stearyl fumarate, preferably stearic acid or a pharmaceutical acceptable salt thereof, more preferably magnesium stearate (Mg stearate), calcium stearate (Ca-stearate), or stearic acid, more preferably magnesium stearate.

[0025] The solid dosage form of any of items 5 to 24, wherein the glidant is silicon dioxide (silica), preferably highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide.

[0026] The solid dosage form of item 5 or 25, wherein the glidant is silicon dioxide, which is characterized by one or more of the following:specific surface area (BET method) of 100-300 m2 / g, preferably 150-250 m2 / g, more preferably 175-225 m2 / g, e.g. about 200 m2 / g; and / ora tamped density of 30-70 g / l, preferably 40-60 g / l, more preferably 45-55 g / l, e.g. about 50 g / l; and / ora SiC>2 content of >99 %, preferably >99.5 %, more preferably >99.8 %; and / or a pH value of 3.4 - 4.8, preferably, 3.6 - 4.6, more preferably 3.7 - 4.5; and / or loss on drying of <3 %, preferably, <2 %, more preferably <1.5 %.

[0027] The solid dosage form of any of items 5 to 26, wherein the lubricant is stearic acid or a pharmaceutical acceptable salt thereof, preferably magnesium stearate (Mg stearate), calcium stearate (Ca-stearate), or stearic acid, more preferably magnesium stearate.

[0028] The solid dosage form of any of items 5 to 27, wherein the lubricant is magnesium stearate, e.g. magnesium stearate vs.

[0029] The solid dosage form of any of items 5 to 28, wherein the lubricant is magnesium stearate, which is characterized by one or more of the following:a specific surface area of 3-13 m2 / g, preferably 5-11 m2 / g, more preferably 6-10 m2 / g; and ora median particle size (D50): 4-14 pm, preferably 6-12 pm, more preferably 7-11 pm; and / orloss on drying (Ph.Eur. 2.2.32, no 99) of <10 %, preferably, <8 %, more preferably <6%.

[0030] The solid dosage form of any of items 1 to 29, wherein the active ingredient is enpatoran, preferably enpatoran H1; the binder is microcrystalline cellulose; the filler is mannitol; the disintegrant is selected from crospovidone, carboxy starch glycolate, carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose sodium;the glidant is selected from silicon dioxide and derivatives thereof; and / or the lubricant is selected from magnesium stearate, calcium stearate, stearic acid, glycerol fatty acid esters and sodium stearyl fumarate.

[0031] The solid dosage form of any of items 1 to 30, wherein the active ingredient is enpatoran, preferably enpatoran H1; the binder is microcrystalline cellulose; the filler is mannitol; the disintegrant is croscarmellose sodium; the glidant is highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide; and / or the lubricant is magnesium stearate.

[0032] The solid dosage form any of the preceding items, wherein the core (1) comprises 0.1-200 mg, preferably 1-150 mg, more preferably 2-100 mg, even more preferably 5-60 mg, even more preferably 6-55 mg, or 7-54 mg, 8-53 mg, or 9-52 mg, active ingredient, preferably enpatoran.

[0033] The solid dosage form any of the preceding items, wherein the core (1) comprises 0.1-200 mg, preferably 1-150 mg, more preferably 5-100 mg, even more preferably 15-75 mg, even more preferably 40-65 mg, or 40-60 mg, 45-55 mg, or 47-53 mg, or 48-52 mg, or 49-51 mg, active ingredient, preferably enpatoran,.

[0034] The solid dosage form any of the preceding items, wherein the core (1) comprises 0.1-150 mg, preferably 0.5-100 mg, more preferably 1-75 mg, even more preferably 3-50 mg, even more preferably 5-45 mg, or 10-40 mg, or 15-35 mg, or 20-30 mg, or 22-28 mg, or 23-27 mg, or 24-26 mg, or 24.5-25.5 mg, active ingredient, preferably enpatoran.

[0035] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35-42 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, e.g. about 38.63 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core.

[0036] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35-42 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, e.g. about 38.63 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0037] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 20 wt.-%, or at least 25 wt.-%, or at least 30 wt.-%, or at least 33 wt.-%, or at least 35 wt.-%, or at least 35.6 wt.-%, or at least37.6 wt.-%, or at least 38.1 wt.-%, or at least 38.3 wt.-%; and / or less than 75 wt.-%, preferably less than 70 wt.-%, more preferably less than 65 wt.-%, even more preferably less than 60 wt.-%, or less than 55 wt.-%, or less than 50 wt.-%, or less than 45 wt.-%, or less than 43 wt.-%, or less than 42 wt.-%, or less than 41.6 wt.-%, or less than 40.6 wt.-%, or less than 39.6 wt.-%, or less than 39.1 wt.-%, or less than 38.9 wt.-%; binder, preferably microcrystalline cellulose, relative to the total weight of the core.

[0038] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 20 wt.-%, or at least 25 wt.-%, or at least 30 wt.-%, or at least 33 wt.-%, or at least 35 wt.-%, or at least 35.6 wt.-%, or at least 37.6 wt.-%, or at least 38.1 wt.-%, or at least 38.3 wt.-%; and / or less than 75 wt.-%, preferably less than 70 wt.-%, more preferably less than 65 wt.-%, even more preferably less than 60 wt.-%, or less than 55 wt.-%, or less than 50 wt.-%, or less than 45 wt.-%, or less than 43 wt.-%, or less than 42 wt.-%, or less than 41.6 wt.-%, or less than 40.6 wt.-%, or less than 39.6 wt.-%, or less than 39.1 wt.-%, or less than 38.9 wt.-%; binder, preferably microcrystalline cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0039] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-50 wt.-%, preferably 2-48 wt.-%, more preferably 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.- %, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23-28 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25-26.5 wt.-%, or 25.25-26.25 wt.-%, or 25.55-25.95 wt.-%, e.g. about 25.76 wt.-%, filler, preferably mannitol, relative to the total weight of the core.

[0040] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-50 wt.-%, preferably 2-48 wt.-%, more preferably 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.- %, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23-28 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25-26.5 wt.-%, or 25.25-26.25 wt.-%, or 25.55-25.95 wt.-%, e.g. about 25.76 wt.-%, filler, preferably mannitol, relative to the total weight of the final powder blend used to prepare the core.

[0041] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.-%, or at least 21 wt.-%, or at least 22 wt.-%, or at least 23 wt.-%, or at least 23.75 wt.-%, or at least 24.75 wt.-%, or at least 25 wt.-%, or at least 25.25 wt.-%, or at least 25.55 wt.-%; and / or less than 55 wt.-%, preferably less than 50 wt.-%, more preferably less than 45 wt.-%, even more preferably less than 40 wt.-%, or less than 35 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.75 wt.-%, or less than26.75 wt.-%, or less than 26.5 wt.-%, or less than 26.25 wt.-%, or less than 25.95 wt.-% filler, preferably mannitol, relative to the total weight of the core.

[0042] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.-%, or at least 21 wt.-%, or at least 22 wt.-%, or at least 23 wt.-%, or at least 23.75 wt.-%, or at least 24.75 wt.-%, or at least 25 wt.-%, or at least 25.25 wt.-%, or at least 25.55 wt.-%; and / or less than 55 wt.-%, preferably less than 50 wt.-%, more preferably less than 45 wt.-%, even more preferably less than 40 wt.-%, or less than 35 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.75 wt.-%, or less than 26.75 wt.-%, or less than 26.5 wt.-%, or less than 26.25 wt.-%, or less than 25.95 wt.-%; filler, preferably mannitol, relative to the total weight of the final powder blend used to prepare the core.

[0043] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.25-3 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.- %, or 0.5-1.5 wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, e.g. about 1 wt.-%, disintegrant, preferably croscarmellose, relative to the total weight of the core.

[0044] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.2-6 wt.-%, or 0.3-4 wt.-%, or 0.4-3 wt.-%, or 0.5-2 wt.-%, or 0.55-1.8 wt.-%, or 0.65-1.6 wt.- %, or 0.7-1.5 wt.-%, or 0.75-1.4 wt.-%, or 0.8-1.3 wt.-%, or 0.85-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, e.g. about 1 wt.-%, disintegrant, preferably croscarmellose sodium, relative to the total weight of the final powder blend used to prepare the core.

[0045] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 0.01 wt.-%, preferably at least 0.05 wt.-%, more preferably at least 0.1 wt.-%, even more preferably at least 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.7 wt.-%, or at least 0.75 wt.- %, or at least 0.80 wt.-%, or at least 0.85 wt.-%, or at least 0.90 wt.-%, or at least 0.95 wt.-%; and / or less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, even more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.6 wt.-%, or less than 1.5 wt.-%, or less than 1.4 wt.-%, or less than 1.3 wt.-%, or less than 1.2 wt.-%, or less than 1.1 wt.-%, or less than 1.05 wt.-%; disintegrant, preferably croscarmellose, relative to the total weight of the core.

[0046] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least at least 0.01 wt.-%, preferably at least 0.05 wt.-%, more preferably at least 0.1 wt.-%, even more preferably at least 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.7 wt.-%, or at least 0.75 wt.-%, or at least 0.80 wt.-%, or at least 0.85 wt.-%, or at least 0.90 wt.-%, or at least 0.95 wt.-%; and / or less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, even more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.6 wt.-%, or less than 1.5 wt.-%, or less than 1.4 wt.-%, or less than 1.3 wt.-%, or less than 1.2 wt.-%, or less than 1.1 wt.-%, or less than 1.05 wt.-%; disintegrant, preferably croscarmellose sodium, relative to the total weight of the final powder blend used to prepare the core.

[0047] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-40 wt.-%, preferably 0.2-25 wt.-%, more preferably 0.5-15 wt.-%, even more preferably 1- 10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 3.5-6.5 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7- 5.3 wt.-%, or 4.75-5.25 wt.-%, or 4.8-5.2 wt.-%, or 4.85-5.15 wt.-%, or 4.9-5.1 wt.-%, or 4.95- 5.05 wt.-%, e.g. about 5 wt.-%, powdered cellulose, relative to the total weight of the core.

[0048] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-40 wt.-%, preferably 0.2-25 wt.-%, more preferably 0.5-15 wt.-%, even more preferably 1- 10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 3.5-6.5 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7- 5.3 wt.-%, or 4.75-5.25 wt.-%, or 4.8-5.2 wt.-%, or 4.85-5.15 wt.-%, or 4.9-5.1 wt.-%, or 4.95- 5.05 wt.-%, e.g. about 5 wt.-%, powdered cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0049] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 0.05 wt.-%, preferably at least 0.1 wt.-%, more preferably at least 0.2 wt.-%, even more preferably at least 0.5 wt.-%, or at least 1 wt.-%, or at least 2 wt.-%, or at least 3 wt.-%, or at least 3.5 wt.-%, or at least 4 wt.-%, or at least 4.5 wt.-%, or at least 4.7 wt.-%, or at least 4.75 wt.-%, or at least 4.8 wt.-%, or at least 4.85 wt.-%, or at least 4.9 wt.-%, or at least 4.95 wt.-%; and / or less than 50 wt.-%, preferably less than 40 wt.-%, more preferably less than 25 wt.-%, even more preferably less than 15 wt.-%, or less than 10 wt.-%, or less than 8 wt.-%, or less than 7 wt.-%, or less than 6.5 wt.-%, or less than 6 wt.-%, or less than 5.5 wt.-%, or less than 5.3 wt.-%, or less than 5.25 wt.-%, or less than 5.2 wt.-%, or less than 5.15 wt.-%, or less than 5.1 wt.-%, or less than 5.05 wt.-%; powdered cellulose, relative to the total weight of the core.

[0050] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least at least 0.05 wt.-%, preferably at least 0.1 wt.-%, more preferably at least 0.2 wt.-%, even more preferably at least 0.5 wt.-%, or at least 1 wt.-%, or at least 2 wt.-%, or at least 3wt.-%, or at least 3.5 wt.-%, or at least 4 wt.-%, or at least 4.5 wt.-%, or at least 4.7 wt.-%, or at least 4.75 wt.-%, or at least 4.8 wt.-%, or at least 4.85 wt.-%, or at least 4.9 wt.-%, or at least 4.95 wt.-%; and / or less than 50 wt.-%, preferably less than 40 wt.-%, more preferably less than 25 wt.-%, even more preferably less than 15 wt.-%, or less than 10 wt.-%, or less than 8 wt.-%, or less than 7 wt.-%, or less than 6.5 wt.-%, or less than 6 wt.-%, or less than 5.5 wt.-%, or less than 5.3 wt.-%, or less than 5.25 wt.-%, or less than 5.2 wt.-%, or less than 5.15 wt.-%, or less than 5.1 wt.-%, or less than 5.05 wt.-%; powdered cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0051] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.8 wt.-%, or 0.45-1.65 wt.-%, or 0.55-1.55 wt.-%, or 0.65-1.45 wt.-%, or 0.75-1.35 wt.-%, or 0.85-1.25 wt.-%, or 0.95- 1.15 wt.-%, or 1.0-1.1 wt.-%, e.g. about 1.05 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed silicon dioxide), relative to the total weight of the core.

[0052] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.8 wt.-%, or 0.45-1.65 wt.-%, or 0.55-1.55 wt.-%, or 0.65-1.45 wt.-%, or 0.75-1.35 wt.-%, or 0.85-1.25 wt.-%, or 0.95- 1.15 wt.-%, or 1.0-1.1 wt.-%, e.g. about 1.05 wt.-%, glidant, preferably silicon dioxide, relative to the total weight of the final powder blend used to prepare the core.

[0053] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 0.01 wt.-%, more preferably at least 0.05 wt.-%, even more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.25 wt.-%, or at least 0.3 wt.-%, or at least 0.35 wt.-%, or at least 0.4 wt.-%, or at least 0.45 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.75 wt.-%, or at least 0.85 wt.-%, or at least 0.95 wt.-%, or at least 1.0 wt.-%; and / or less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, even more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.- %, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.65 wt.-%, or less than 1.55 wt.- %, or less than 1.45 wt.-%, or less than 1.35 wt.-%, or less than 1.25 wt.-%, or less than 1.15 wt.-%, or less than 1.1 wt.-%; glidant, preferably silicon dioxide (e.g. highly dispersed silicon dioxide), relative to the total weight of the core.

[0054] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least at least 1 wt.-%, preferably at least 0.01 wt.-%, more preferably at least 0.05 wt.-%, even more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.25 wt.-%, or at least 0.3 wt.-%, or at least 0.35 wt.-%, or at least 0.4 wt.-%, or at least 0.45 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.75 wt.-%, or at least 0.85 wt.-%, or at least 0.95 wt.-%, or at least 1.0 wt.-%; and / or less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, even more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.65 wt.-%, or less than 1.55 wt.-%, or less than 1.45 wt.-%, or less than 1.35 wt.-%, or less than 1.25 wt.-%, or less than 1.15 wt.-%, or less than 1.1 wt.-%; glidant, preferably silicon dioxide, relative to the total weight of the final powder blend used to prepare the core.

[0055] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-18 wt.-%, preferably 0.05-15 wt.-%, more preferably 0.1-10 wt.-%, even more preferably 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt.-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, or 1.47- 1.53 wt.-%, e.g. about 1.5 wt.-%, lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the core.

[0056] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt.-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, or 1.47- 1.53 wt.-%, e.g. about 1.5 wt.-%, lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the final powder blend used to prepare the core.

[0057] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 0.01 wt.-%, more preferably at least 0.05 wt.-%, even more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.6 wt.-%, or at least 0.8 wt.-%, or at least 1.0 wt.-%, or at least 1.2 wt.-%, or at least 1.3 wt.-%, or at least 1.4 wt.-%, or at least 1.45 wt.-%, or at least 1.47 wt.-%; and / or less than 18 wt.-%, preferably less than 15 wt.-%, more preferably less than 10 wt.-%, even more preferably less than 8 wt.-%, or less than 7 wt.-%, or less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2.4 wt.-%, or less than 2.2 wt.- %, or less than 2.0 wt.-%, or less than 1.8 wt.-%, or less than 1.7 wt.-%, or less than 1.6 wt.- %, or less than 1.55 wt.-%, or less than 1.53 wt.-%; lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the core.

[0058] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least at least 1 wt.-%, preferably at least 0.01 wt.-%, more preferably at least 0.05 wt.-%, even more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.6 wt.-%, or at least 0.8 wt.-%, or at least 1.0 wt.- %, or at least 1.2 wt.-%, or at least 1.3 wt.-%, or at least 1.4 wt.-%, or at least 1.45 wt.-%, orat least 1.47 wt.-%; and / or less than 18 wt.-%, preferably less than 15 wt.-%, more preferably less than 10 wt.-%, even more preferably less than 8 wt.-%, or less than 7 wt.-%, or less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2.4 wt.-%, or less than 2.2 wt.-%, or less than 2.0 wt.-%, or less than 1.8 wt.-%, or less than 1.7 wt.-%, or less than 1.6 wt.-%, or less than 1.55 wt.-%, or less than 1.53 wt.-%; lubricant, preferably stearic add or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the final powder blend used to prepare the core.

[0059] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-60 wt.-%, preferably 0.5-55 wt.-%, more preferably 1-50 wt.-%, even more preferably 2- 45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 18-36 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.5-27.5 wt.-%, or 26.75-27.35 wt.-%, or 26.85-27.25 wt.-%, or 26.95-27.15 wt.-%, or 27.0-27.1 wt.-%, e.g. about 27.05 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the core.

[0060] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-60 wt.-%, preferably 0.5-55 wt.-%, more preferably 1-50 wt.-%, even more preferably 2- 45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 18-36 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.5-27.5 wt.-%, or 26.75-27.35 wt.-%, or 26.85-27.25 wt.-%, or 26.95-27.15 wt.-%, or 27.0-27.1 wt.-%, e.g. about 27.05 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the final powder blend used to prepare the core.

[0061] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.-%, or at least 22 wt.-%, or at least 24 wt.-%, or at least 25 wt.-%, or at least 26 wt.-%, or at least 26.5 wt.-%, or at least 26.75 wt.-%, or at least 26.85 wt.-%, or at least 26.95 wt.-%, or at least 27 wt.-%; and / or less than 60 wt.-%, preferably less than 55 wt.-%, more preferably less than 50 wt.-%, even more preferably less than 45 wt.-%, or less than 40 wt.-%, or less than 36 wt.- %, or less than 34 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.5 wt.-%, or less than 27.35 wt.-%, or less than 27.25 wt.-%, or less than 27.15 wt.-%, or less than 27.1 wt-%; active ingredient, preferably enpatoran, relative to the total weight of the core.

[0062] The solid dosage form of any of the preceding items, wherein the core (1) comprises at least at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.- %, or at least 22 wt.-%, or at least 24 wt.-%, or at least 25 wt.-%, or at least 26 wt.-%, or at least 26.5 wt.-%, or at least 26.75 wt.-%, or at least 26.85 wt.-%, or at least 26.95 wt.-%, or atleast 27 wt.-%; and / or less than 60 wt.-%, preferably less than 55 wt.-%, more preferably less than 50 wt.-%, even more preferably less than 45 wt.-%, or less than 40 wt.-%, or less than 36 wt.-%, or less than 34 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.5 wt.-%, or less than 27.35 wt.-%, or less than 27.25 wt.-%, or less than 27.15 wt.-%, or less than 27.1 wt-%; active ingredient, preferably enpatoran, relative to the total weight of the final powder blend used to prepare the core.

[0063] The solid dosage form of any of any of the preceding items, wherein the core (1) comprises 1-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, even more preferably 10-65 wt.-%, or 15-62 wt.-%, or 20-60 wt.-%, or 25-59 wt.-%, or 30-58 wt.-%, or 35- 57 wt.-%, or 38-56 wt.-%, or 41-55 wt.-%, or 42-54 wt.-%, or 44-53 wt.-%, or 45-52 wt.-%, or 46-51 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core.

[0064] The solid dosage form of item 58, wherein the core (1) comprises 42.5-44 wt.-%, or 43-44.5 wt.-%, or 43.5-45 wt.-%, or 44-45.5 wt.-%, or 44.5-46 wt.-%, or 45-46.5 wt.-%, or 45.5- 47 wt.-%, or 46-47.5 wt.-%, or 46.5-48 wt.-%, or 47-48.5 wt.-%, or 47.5-49 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core.

[0065] The solid dosage form of any of the preceding items, wherein the core (1) comprises 11-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, even more preferably 10-65 wt.-%, or 15-62 wt.-%, or 20-60 wt.-%, or 25-59 wt.-%, or 30-58 wt.-%, or 35-57 wt.-%, or 38- 56 wt.-%, or 41-55 wt.-%, or 42-54 wt.-%, or 44-53 wt.-%, or 45-52 wt.-%, or 46-51 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0066] The solid dosage form of item 60, wherein the core (1) comprises 42.5-44 wt.-%, or 43-44.5 wt.-%, or 43.5-45 wt.-%, or 44-45.5 wt.-%, or 44.5-46 wt.-%, or 45-46.5 wt.-%, or 45.5- 47 wt.-%, or 46-47.5 wt.-%, or 46.5-48 wt.-%, or 47-48.5 wt.-%, or 47.5-49 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the final powder blend used to prepare the core.

[0067] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-55 wt.-%, or 2-50 wt.-%, or 5-48 wt.-%, or 10-45 wt.-%, or 15-42 wt.-%, or 20-40 wt.-%, or 24-39 wt.-%, or 26-38 wt.-%, or 28-36 wt.-%, or 30-34 wt.-%, or 31.25-33.25 wt.-%, or 31.75- 32.75 wt.-%, or31-31.5wt.-%, filler, preferably mannitol, relative to the total weight of the core.

[0068] The solid dosage form of item 67, wherein the core (1) comprises 28-29.5 wt.-%, or 28.5-30 wt.-%, or 29-30.5 wt.-%, or 29.5-31 wt.-%, or 30-31.5 wt.-%, or 30.5-32 wt.-%, or 31- 32.5 wt.-%, or 31.5-33 wt.-%, or 32-33.5 wt.-%, or 32.5-34 wt.-%, or 33-34.5 wt.-%, or 33.5- 35 wt.-%, or 34-35.5 wt.-%, or 34.5-36 wt.-%, or 35-36.5 wt.-%, or 35.5-37 wt.-%, or 36-37.5wt.-%, or 36.5-38 wt.-% , filler, preferably mannitol, mannitol, relative to the total weight of the core.

[0069] The solid dosage form of any of the preceding items, wherein the core (1) comprises 1-55 wt.-%, or 2-50 wt.-%, or 5-48 wt.-%, or 10-45 wt.-%, or 15-42 wt.-%, or 20-40 wt.-%, or 24-39 wt.-%, or 26-38 wt.-%, or 28-36 wt.-%, or 30-34 wt.-%, or 31.25-33.25 wt.-%, or 31.75- 32.75 wt.-%, or 31-31.5 wt.-%, filler, preferably mannitol, relative to the total weight of the final powder blend used to prepare the core.

[0070] The solid dosage form of item 69, wherein the core (1) comprises 28-29.5 wt.-%, or 28.5-30 wt.-%, or 29-30.5 wt.-%, or 29.5-31 wt.-%, or 30-31.5 wt.-%, or 30.5-32 wt.-%, or 31- 32.5 wt.-%, or 31.5-33 wt.-%, or 32-33.5 wt.-%, or 32.5-34 wt.-%, or 33-34.5 wt.-%, or 33.5- 35 wt.-%, or 34-35.5 wt.-%, or 34.5-36 wt.-%, or 35-36.5 wt.-%, or 35.5-37 wt.-%, or 36-37.5 wt.-%, or 36.5-38 wt.-%, filler, preferably mannitol, relative to the total weight of the final powder blend used to prepare the core.

[0071] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-45 wt.-%, preferably 0.5-30 wt.-%, more preferably 1-25 wt.-%, even more preferably 2- 20 wt.-%, or 5-15 wt.-%, or 6-14 wt.-%, or 7-13 wt.-%, or 8-12 wt.-%, or 8.5-11.5 wt.-%, or 9- 11 wt.-%, or 9.5-10.5 wt.-%, or 9.6-10.4 wt.-%, or 9.7-10.3 wt.-%, or 9.8-10.2 wt.-%, or 9.9- 10.1 wt.-%, or 9.95-10.05 wt.-%, e.g. about 10.0 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the core.

[0072] The solid dosage form of any of the preceding items, wherein the core (1) comprises 0.1-45 wt.-%, preferably 0.5-30 wt.-%, more preferably 1-25 wt.-%, even more preferably 2- 20 wt.-%, or 5-15 wt.-%, or 6-14 wt.-%, or 7-13 wt.-%, or 8-12 wt.-%, or 8.5-11.5 wt.-%, or 9- 11 wt.-%, or 9.5-10.5 wt.-%, or 9.6-10.4 wt.-%, or 9.7-10.3 wt.-%, or 9.8-10.2 wt.-%, or 9.9- 10.1 wt.-%, or 9.95-10.05 wt.-%, e.g. about 10.0 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the final powder blend used to prepare the core.

[0073] The solid dosage form any of the preceding items, wherein the core (1) comprises 0.1- 100 mg, preferably 0.5-75 mg, more preferably 1-50 mg, even more preferably 2-30 mg, even more preferably 3-20 mg, or 4-17 mg, or 5-15 mg, 6-14 mg, or 7-13 mg, or 8-12 mg, or 9-11 mg, or 9.5-10.5 mg, or 9.7-10.3 mg, active ingredient, preferably enpatoran.

[0074] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 23-31 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, or 26.85-27.25 wt.-%, active ingredient, preferably enpatoran; and / or- 1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6- 39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, or 38.4-38.8 wt.-%, binder, preferably microcrystalline cellulose; and / or- 1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.- %, or 25.55-25.95 wt.-%, filler, preferably mannitol; and / or0.05-10 wt.-%, or 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.-%, or 0.5-1.5wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7-5.3 wt.-%, or 4.8-5.2 wt.-%, or 4.9-5.1 wt.-%, or 4.95-5.05 wt.- %, powdered cellulose; and / or- 0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.8 wt.-%, or 0.45-1.65 wt.-%, orO.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt.-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.- %, or 1.45-1.55 wt.-%, lubricant, preferably magnesium stearate (i.e. magnesium¬ stearate),relative to the total weight of the core (1).

[0075] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,- 23-31 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, or 26.85-27.25 wt.- %, active ingredient, preferably enpatoran; and / or- 34-43 wt.-%, or 36.6-40.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.4-38.8 wt.-%, binder, preferably microcrystalline cellulose; and / or- 22-29 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.-%, or 25.55-25.95 wt.-%, filler, preferably mannitol; and / or0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.5-15 wt.-%, or 1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.8-5.2 wt.- %, or 4.9-5.1 wt.-%, powdered cellulose; and / or0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or 0.3-5 wt.-%, or 0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45- 1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0076] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,24-30 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, active ingredient, preferably enpatoran; and / or35.6-41.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, binder, preferably microcrystalline cellulose; and / or- 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.-%, filler, preferably mannitol; and / or0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.9-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and / or1-10 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, powdered cellulose; and / or0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.95-1.15 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.4-1.6 wt.-%, lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0077] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,0.1-45 wt.-%, or 0.5-30 wt.-%, or 2-20 wt.-%, or 5-15 wt.-%, or 8-12 wt.-%, or 8.5-11.5 wt.-%, or 9-11 wt.-%, or 9.5-10.5 wt.-%, or 9.6-10.4 wt.-%, or 9.8-10.2 wt.-%, or 9.9- 10.1 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 20-60 wt.-%, or 30-58 wt.-%, or 38-56 wt.-%, or 41-55 wt.-%, or 44-53 wt.-%, or 45-52 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose; and / or1-55 wt.-%, or 10-45 wt.-%, or 20-40 wt.-%, or 24-39 wt.-%, or 26-38 wt.-%, or 28-36 wt.-%, or 30-34 wt.-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt.-%, or 32-32.5 wt.-%, filler, preferably mannitol; and / or0.05-10 wt.-%, or 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.-%, or 0.5-1.5wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7-5.3 wt.-%, or 4.8-5.2 wt.-%, or 4.9-5.1 wt.-%, or 4.95-5.05 wt.- %, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.8 wt.-%, or 0.45-1.65 wt.-%, orO.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or - 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt.-%, or 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0078] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,2-20 wt.-%, or 5-15 wt.-%, or 9-11 wt.-%, or 9.5-10.5 wt.-%, or 9.8-10.2 wt.-%, or 9.9- 10.1 wt.-%, active ingredient, preferably enpatoran; and / or41-55 wt.-%, or 45-52 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose; and / or- 26-38 wt.-%, or 30-34 wt.-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt.-%, or 32-32.5 wt.-%, filler, preferably mannitol; and / or0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.5-15 wt.-%, or 1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.8-5.2 wt.- %, or 4.9-5.1 wt.-%, powdered cellulose; and / or0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or - 0.3-5 wt.-%, or 0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45- 1.55 wt.-%, lubricant, preferably magnesium stearate (i.e. magnesium-stearate),relative to the total weight of the core (1).

[0079] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of,5-15 wt.-%, or 8-12 wt.-%, or 9.5-10.5 wt.-%, active ingredient, preferably enpatoran; and / or44-53 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, binder, preferably microcrystalline cellulose; and / or28-36 wt.-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt.-%, filler, preferably mannitol; and / or0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.9-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and / or1-10 wt.-%, or 3-7 wt.-%, or4-6 wt.-%, or 4.8-5.2 wt.-%, powdered cellulose; and / or 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.95-1.15 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.4-1.6 wt.-%, lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0080] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 2-55 wt.-% active ingredient, preferably enpatoran, 5-70 wt.-% binder, preferably microcrystalline cellulose; 5-45 wt.-% filler, preferably mannitol; 0.15-6 wt.-%, disintegrant, preferably croscarmellose sodium; 0.5-15 wt.-% powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0081] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder, preferably microcrystalline cellulose; 18-34 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0082] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 1-20 wt.-% active ingredient, preferably enpatoran, 40-57 wt.-% binder, preferably microcrystalline cellulose; 24-40 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose, 0.2-6 wt.-%glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0083] The solid dosage form of any of items 74 to 82, wherein, instead of relative to the total weight of the core (1), the weight percentages (wt.-%) are relative to the total weight of the final powder blend used to prepare the core.

[0084] The solid dosage form of any of items 35 to 83, wherein, instead of relative to the total weight of the core (1), the weight percentages (wt.-%) are relative to the total weight of the solid dosage form.

[0085] The solid dosage form of any of the preceding items, the solid dosage form comprising, 0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 21-32 wt.-%, or 22-31 wt.-%, or 23-29 wt.-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26 -26.5 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 19-54 wt.-%, or 26-49 wt.-%, or 31-44 wt.-%, or 33-42 wt.-%, or 34.5-40.5 wt.-%, or 35.5-39.5 wt.-%, or 36.5- 38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.-%, or 37.3-37.7 wt.-%, binder, preferably microcrystalline cellulose; and / or1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 20.5- 29.5 wt.-%, or 21.5-28.5 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, or 24.7-25.3 wt.-%, or 24.8-25.2 wt.-%, filler, preferably mannitol; and / or0.05-10 wt.-%, or 0.1-6 wt.-%, or 0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.25-1.8 wt.-%, or 0.3- 1.6 wt.-%, or 0.4-1.5 wt.-%, or 0.5-1.4 wt.-%, or 0.6-1.3 wt.-%, or 0.7-1.2 wt.-%, or 0.8- 1.1 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or 0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.6-5.1 wt.-%, or 4.75-4.95 wt.-%, or 4.8-4.9 wt.-%, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.7 wt.-%, or 0.45-1.6 wt.-%, or 0.62-1.42 wt.-%, or 0.82-1.22 wt.-%, or 0.92-1.12 wt.- %, or 0.97-1.07 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.0-1.9 wt.-%, or 1.1-1.8 wt.-%, or 1.25-1.7 wt.-%, or 1.35- 1.55 wt.-%, or 1.40-1.50 wt.-%, lubricant, preferably magnesium stearate; relative to the total weight of the solid dosage form.

[0086] The solid dosage form of item 85, the solid dosage form comprising 0.1-35 wt.-%, or 0.2-15 wt.-%, or 0.3-10 wt.-%, or 0.5-8 wt.-%, or 0.7-7 wt.-%, or 0.9-6 wt.-%, or 1.4-4.4 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3.0 wt.-%, or 2.85-2.95 wt.-%, immediate release coating, relative to the total weight of the solid dosage form.

[0087] The solid dosage form of item 85, the solid dosage form consisting of components of item 85 and 86.

[0088] The solid dosage form of any of the preceding items, the solid dosage form comprising, or consisting of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 21-32 wt.-%, or 22-31 wt.-%, or 23-29 wt.-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 19-54 wt.-%, or 26-49 wt.-%, or 31-44 wt.-%, or 33-42 wt.-%, or 34.5-40.5 wt.-%, or 35.5-39.5 wt.-%, or 36.5- 38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.-%, or 37.3-37.7 wt.-%, binder, preferably microcrystalline cellulose; and / or1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 20.5- 29.5 wt.-%, or 21.5-28.5 wt.-%, or 22-28 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5- 25.5 wt.-%, or 24.7-25.3 wt.-%, or 24.8-25.2 wt.-%, filler, preferably mannitol; and / or 0.05-10 wt.-%, or 0.1-6 wt.-%, or 0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.25-1.8 wt.-%, or 0.3-1.6 wt.-%, or 0.4-1.5wt.-%, or 0.5-1.4 wt.-%, or 0.6-1.3 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.6-5.1 wt.-%, or 4.75-4.95 wt.-%, or 4.8-4.9 wt.-%, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.7 wt.-%, or 0.45-1.6 wt.-%, or 0.62-1.42 wt.-%, or 0.82-1.22 wt.-%, or 0.92-1.12 wt.- %, or 0.97-1.07 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.0-1.9 wt.-%, or 1.1-1.8 wt.-%, or 1.25-1.7 wt.-%, or 1.35- 1.55 wt.-%, or 1.40-1.50 wt.-%, lubricant, preferably magnesium stearate; and / or 0.1-35 wt.-%, or 0.2-15 wt.-%, or 0.3-10 wt.-%, or 0.5-8 wt.-%, or 0.7-7 wt.-%, or 0.9-6 wt.-%, or 1.4-4.4 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3.0 wt.-%, or 2.85-2.95 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0089] The solid dosage form of any of the preceding items, the solid dosage form comprising, or consisting of,- 22-31 wt.-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and / or33-42 wt.-%, or 35.5-39.5 wt.-%, or 36.5-38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.- %, binder, preferably microcrystalline cellulose; and / or- 20.5-29.5 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, or 24.7-25.3 wt.- %, filler, preferably mannitol; and / or0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.4-1.5 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.5-15 wt.-%, or 1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and / or0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.- %, glidant, preferably silicon dioxide (highly dispersed); and / or0.4-4 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and / or0.3-10 wt.-%, or 0.7-7 wt.-%, or 1.4-4.4 wt.-%, or 2.4-3.4 wt.-%, 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0090] The solid dosage form of any of the preceding items, the solid dosage form comprising, or consisting of,23-29 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, active ingredient, preferably enpatoran; and / or34.5-40.5 wt.-%, or 36.5-38.5 wt.-%, or 37-38 wt.-%, binder, preferably microcrystalline cellulose; and / or21.5-28.5 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, filler, preferably mannitol; and / or 0.2-2 wt.-%, or 0.6-1.3 wt.-%, 0.8-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and / or1-10 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, powdered cellulose; and / or0.35-2 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or0.5-3 wt.-%, or 1.0-1.9 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and / or0.5-8 wt.-%, or 0.9-6 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0091] The solid dosage form of any of the preceding items, the solid dosage form comprising, or consisting of,0.5-55 wt.-%, or 1-35 wt.-%, or 2-25 wt.-%, or 3-20 wt.-%, or 5-16 wt.-%, or 6-15 wt.-%, or 7- 14 wt.-%, or 8-13 wt.-%, or 8.5-12 wt.-%, or 9-11 wt.-%, or 9.5-10.5 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 15-65 wt.-%, or 20-60 wt.-%, or 30-58 wt.-%, or 35-56 wt.-%, or 38-55 wt.-%, or 40-54 wt.-%, or 41-53 wt.-%, or 42-52 wt.-%, or 43-51 wt.-%, or 44-50 wt.-%, or 45-49 wt.-%, or 46-48 wt.-%, or 46.5-47.5 wt.-%, binder, preferably microcrystalline cellulose; and / or1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 20-35 wt.-%, or 23-40 wt.-%, or 25-38 wt.-%, or 26-37wt.-%, or 27-36 wt.-%, or 28-35 wt.-%, or 29-34 wt.-%, or 29.5-33.5 wt.-%, or 30.5-32.5 wt.-%, or 31-32 wt.-%, filler, preferably mannitol; and / or0.05-10 wt.-%, or 0.1-6 wt.-%, or 0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.25-1.8 wt.-%, or 0.3-1.6 wt.-%, or 0.4-1.5 wt.-%, or 0.5-1.4 wt.-%, or 0.6-1.3 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35- 5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.6-5.1 wt.-%, or 4.75-4.95 wt.-%, or 4.8-4.9 wt.-%, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.- %, or 0.45-1.6 wt.-%, or 0.62-1.42 wt.-%, or 0.82-1.22 wt.-%, or 0.92-1.12 wt.-%, or 0.97-1.07 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.0-1.9 wt.-%, or 1.1-1.8 wt.-%, or 1.25-1.7 wt.-%, or 1.35-1.55 wt.-%, or 1.40-1.50 wt.-%, lubricant, preferably magnesium stearate; and / or0.1-35 wt.-%, or 0.2-15 wt.-%, or 0.3-10 wt.-%, or 0.5-8 wt.-%, or 0.7-7 wt.-%, or 0.9-6 wt.-%, or 1.4-4.4 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3.0 wt.-%, or 2.85- 2.95 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0092] The solid dosage form of any of the preceding items, the solid dosage form comprising, or consisting of,3-20 wt.-%, 6-15 wt.-%, or 8-13 wt.-%, or 8.5-12 wt.-%, or 9-11 wt.-%, active ingredient, preferably enpatoran; and / or35-56 wt.-%, or 40-54 wt.-%, or 43-51 wt.-%, or 44-50 wt.-%, or 45-49 wt.-%, or 46-48 wt.-%, binder, preferably microcrystalline cellulose; and / or23-40 wt.-%, or 25-38 wt.-%, or 27-36 wt.-%, or 29-34 wt.-%, or 29.5-33.5 wt.-%, or 30.5-32.5 wt.-%, filler, preferably mannitol; and / or0.2-2 wt.-%, or 0.3-1.6 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and / or2-8 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and / or0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.-%, glidant, preferably silicon dioxide (highly dispersed); and / or0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and optionally0.5-8 wt.-%, or 0.9-6 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0093] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 2-45 wt.-% active ingredient, preferably enpatoran, 1-70 wt.-% binder, preferably microcrystalline cellulose; 1-45 wt.-% filler, preferably mannitol; 0.05-10 wt.-%, disintegrant, preferably croscarmellose sodium; 0.2-25 wt.-%, powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the solid dosage form.

[0094] The solid dosage form of any of the preceding items, wherein solid dosage form comprises, or consists of, 2-45 wt.-% active ingredient, preferably enpatoran, 5-70 wt.-% binder, preferably microcrystalline cellulose; 5-45 wt.-% filler, preferably mannitol; 0.15-6 wt.-%, disintegrant, preferably croscarmellose sodium; 0.5-15 wt.-% powdered cellulose; 0.2-6wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0095] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder, preferably microcrystalline cellulose; 18-34 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0096] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 23-29 wt.-% active ingredient, preferably enpatoran, 34.5-40.5 wt.-% binder, preferably microcrystalline cellulose; 22-28 wt.-% filler, preferably mannitol; 0.3-1.6 wt.-% disintegrant, preferably croscarmellose sodium; 3-7 wt.-% powdered cellulose; 0.4-1.7 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.8-2.1 wt.-% lubricant, preferably magnesium stearate; and optionally 1.9-3.9 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0097] The solid dosage form of any of the preceding items, wherein the core (1) comprises, or consists of, 1-20 wt.-% active ingredient, preferably enpatoran, 38-55 wt.-% binder, preferably microcrystalline cellulose; 23-40 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0098] The solid dosage form of any of the preceding items, wherein the solid dosage form is prepared by compression using direct compression.

[0099] The solid dosage form of any of the preceding items, wherein the core (1) is prepared by direct compression.

[0100] The solid dosage form of any of the preceding items, wherein the solid dosage form comprises an immediate release coating (2), which preferably is based on polyvinyl alcohol and / or hypromellose.

[0101] The solid dosage form of any of the preceding items, wherein the immediate release coating is a film coating suitable for immediate release of the active ingredient.T1

[0102] The solid dosage form of any of the preceding items, wherein the immediate release coating is a cosmetic coating.

[0103] The solid dosage form of any of the preceding items, wherein the immediate release coating provides color, protection (e.g. light, environmental and moisture protection) and / or taste-masking for the core (1).

[0104] The solid dosage form of any of the preceding items, wherein immediate release coating (2) is applied to the core (1) by applying an immediate release coating liquid using spray coating, preferably fluidized-bed spray coating, and drying the wet coated solid dosage form, simultaneously or concomitantly, preferably using a fluidized bed or an oven.

[0105] The solid dosage form of any of the preceding items, wherein the solid dosage form comprises a immediate release coating (2), comprising, or consisting of, polyvinyl alcohol, macrogol, talcum, titanium dioxide, glycerol monocaprylocaprat, and iron oxide yellow; or polyvinyl alcohol (e.g. part, hydr.), calcium carbonate, talcum, hypromellose, glycerin-monocaprylocaprat, and iron oxide-yellow / red and black.

[0106] The solid dosage form of any of the preceding items, wherein the solid dosage form comprises 0.1-20 wt.-%, preferably 0.5-15 wt.-%, more preferably 1-10 wt.-%, even more preferably 1.5-5 wt.-%, or 1.6-4.8 wt.-%, or 1.8-4.6 wt.-%, or 2-3.8 wt.-%, or 2.2-3.6 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3 wt.-%, immediate release coating (2), relative to the total weight of the solid dosage form.

[0107] The solid dosage form of any of the preceding items, comprising less than 5 wt.- %, preferably less than 2 wt.-% more preferably less than 1 wt.- %, water, relative to the total weight of the solid dosage form.

[0108] The solid dosage form of any of the preceding items, wherein the core (1) (inert core unit (1)) is a pellet with a particle size distribution such that at least 85 % of the dosage forms have a particle size of 2-10 mm, preferably 3-7 mm.

[0109] The solid dosage form according to any one of the preceding items, wherein the solid dosage form is an oral dosage form.

[0110] The solid dosage form according to any one of the preceding items, wherein the solid dosage form is a tablet or mini-tablet, a pellet, or a granule, preferably a tablet.

[0111] The solid dosage form of any of the preceding items, wherein the active ingredient is a TLR 7 / 8 inhibitor, preferably wherein the TLR 7 / 8 inhibitor is a TLR7 and / or TLR8 small molecule inhibitor.

[0112] The solid dosage form of item 111, wherein the TLR 7 / 8 inhibitor is selected from the group consisting of 5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile (enpatoran); (3R,5S)-1-(8-methoxy-1 ,7-naphthyridin-5-yl)-5-methylpiperidin-3-amine; 2-{4-[2-(7, 8-dimethyl[1 ,2,4]triazolo[1 ,5-a]pyridin-6-yl)-3-(propan-2-yl)-1 H-indol-5-yl]piperidin-1-yl}acetamide; rel-(2R,6R)-4-(8-cyanoquinolin-5yl)-N-((3R,4S)-4-fluoropyrrolidin-3-yl)-6-methylmorpholine-2-carboxamide hydrochloride; (S)-N-(4-((5-(1 ,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide; and (R)-N-(4-((5-(1 ,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide or a pharmaceutically acceptable salt of any of these compounds

[0113] The solid dosage form of item 112, wherein the wherein the TLR 7 / 8 inhibitor is enpatoran.

[0114] The oral dosage form of any of the preceding items, wherein the active ingredient is enpatoran.

[0115] The solid dosage form of item 114, wherein enpatoran is present in the core (1) as a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0116] The solid dosage form of any of the preceding items, the core (1) comprising a crystalline polymorph of enpatoran, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0117] The solid dosage form of any of the preceding items, wherein the active ingredient is a crystalline polymorph of enpatoran, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0118] The solid dosage form of any of the preceding items, wherein the active ingredient is enpatoran, which comprises, or consists of, a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0119] The solid dosage form of any of the preceding items, wherein at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 % by weight, of the enpatoran is a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0120] The solid dosage form of any of items 115 to 119, wherein the crystalline hemihydrate is polymorphic form H1.

[0121] The solid dosage form of any of items 115 to 120, wherein the crystalline polymorph of enpatoran is a hemihydrate, preferably characterized by one or more peaks from the powderX-ray diffraction (PXRD), wherein the peaks, expressed in degrees 20 ±0.2°, comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9.

[0122] The solid dosage form of any of items 115 to 121, wherein the crystalline polymorph of enpatoran is characterized by two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, or each of the PXRD peaks, expressed in degrees 20 ±0.2°, 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9.

[0123] The solid dosage form of any of items 115 to 122, wherein the crystalline polymorph of enpatoran is characterized by PXRD peaks, expressed in degrees 20 ±0.2°, comprising a peak at 13.4.

[0124] The solid dosage form of any of items 115 to 123, wherein the crystalline polymorph of enpatoran is characterized by PXRD peaks, expressed in degrees 20 ±0.2°, comprising peaks at 9.7 and 13.4.

[0125] The solid dosage form of any of items 115 to 124, wherein the crystalline polymorph of enpatoran is characterized by PXRD peaks, expressed in degrees 20 ±0.2°, comprising peaks at 7.2, 9.7 and 13.4.

[0126] The solid dosage form of any of items 115 to 125, wherein the crystalline polymorph of enpatoran is characterized by PXRD peaks, expressed in degrees 20 ±0.2°, comprising peaks at 7.2, 9.7, 13.4 and 22.2.

[0127] The solid dosage form of any of items 114 to 126, wherein the crystalline polymorph of enpatoran is characterized by PXRD peaks, expressed in degrees 20 ±0.2°, comprising peaks at 7.2, 9.7, 13.4, 21.5 and 22.2.

[0128] The solid dosage form of any of items 115 to 127, wherein the crystalline polymorph of enpatoran is characterized by an orthorhombic space group P212121 with the lattice parameters a = 10.7499 ± 0.1 A, b = 16.4119 ± 0.1 A, c = 17.5927 ± 0.1 A, and a = y = P = 90°.

[0129] The solid dosage form of any of items 115 to 128, wherein the crystalline hemihydrate form H1 is characterized by one or more of items 121-128.

[0130] The solid dosage form of any of the preceding items, wherein the enpatoran comprises, or consists of, particles of a crystalline polymorph, preferably a hydrate or hemihydrate, more preferably a hemihydrate, even more preferably polymorphic form H1.

[0131] The solid dosage form of any of the preceding items, wherein the enpatoran comprises, or consists of, equant-shaped particles of a crystalline polymorph of enpatoran; wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate, more preferably polymorphic form H1.

[0132] The solid dosage form of any of the preceding items, wherein the enpatoran comprises, or consists of, particles of a crystalline polymorph of enpatoran, wherein the mean aspect ratio of the enpatoran particles in the solid dosage form is at least about 0.3, at least about 0.4, at least about 0.5, at least about 0.6, at least about 0.7, at least about 0.8 or at least about 0.9.

[0133] The solid dosage form of item 130 or 132, wherein the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a hydrate or hemihydrate, preferably a hemihydrate, more preferably polymorphic form H1.

[0134] The solid dosage form of item 130 or 133, wherein the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a crystalline hemihydrate polymorph characterized by one or more peaks from the powder X-ray diffraction (PXRD), wherein the peaks, expressed in degrees 26 ±0.2°, comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9.

[0135] The solid dosage form of any of items 130 to 134, wherein the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a crystalline hemihydrate polymorph characterized by one or more peaks from the powder X-ray diffraction (PXRD), wherein the peaks, expressed in degrees 26 ±0.2°, comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9 and further characterized by an orthorhombic space group P212121 with the lattice parameters a = 10.7499 ± 0.1 A, b = 16.4119 ± 0.1 A, c = 17.5927 ± 0.1 A, and a = y = P = 90°.

[0136] The solid dosage form of any of items 130 to 135, wherein the particles have a bulk density greater than about 0.3 g / cm3, greater than about 0.4 g / cm3, greater than about 0.5 g / cm3; greater than about 0.55 g / cm3; greater than about 0.6 g / cm3; greater than about 0.65 g / cm3; or greater than about 0.7 g / cm3.

[0137] The solid dosage form of any of items 130 to 136, wherein the particles have a bulk density less than about 0.95 g / cm3, less than about 0.9 g / cm3, less than about 0.85 g / cm3, or less than about 0.8 g / cm3.

[0138] The solid dosage form of any of items 130 to 137, wherein the solid dosage form has a bulk density from about 0.5 g / cm3to about 0.95 g / cm3, from about 0.55 g / cm3to about 0.9 g / cm3, from about 0.6 g / cm3to about 0.85 g / cm3, or from about 0.7 g / cm3to about 0.8 g / cm3.

[0139] The solid dosage form of any of items 130 to 138, wherein the particles have a flow function coefficient (ffc) greater than about 4, greater than about 5; greater than about 6; greater than about 7; or greater than about 8.

[0140] The solid dosage form of any of items 130 to 139, wherein the mean particle diameter d90 of the particles of enpatoran is less than about 600 pm, less than about 500 pm, or less than about 400 pm; and / or wherein the mean particle diameter d90 of the particles in the solid dosage form is from about 50 to about 500 pm, from about 100 to about 450 pm, or from about 150 to about 400 pm.

[0141] The solid dosage form of any of items 130 to 140, wherein the crystalline hemihydrate is polymorphic form H1.

[0142] The solid dosage form of item 130 or 147, wherein more than about 50%, more than about 60%, more than about 70%, more than about 75%, more than about 80%, more than about 85%, more than about 90%, or more than about 95% (e.g. by weight) of the enpatoran in the solid dosage form is of a crystalline hydrate or hemihydrate polymorph, preferably a crystalline hemihydrate polymorph, more preferably polymorphic form H1.

[0143] The solid dosage form of item 130 or 142, wherein more than about 50%, more than about 60%, more than about 70%, more than about 75%, more than about 80%, more than about 85%, more than about 90% or more than about 95% of the enpatoran particles in the solid dosage form are of a crystalline hydrate or hemihydrate polymorph, preferably a crystalline hemihydrate polymorph, more preferably polymorphic form H1.

[0144] The solid dosage form of any of items 130 to 143, wherein the particles of enpatoran are prepared by a process comprising the steps:i. preparing a suspension of enpatoran in a solvent comprising one or more organic solvents and water;ii. optionally heating the suspension to a recrystallization temperature;iii. stirring the suspension for a period of time at ambient temperature or at the recrystallization temperature;iv. optionally wet milling the suspension;v. optionally cooling the suspension; andvi. separating the particles of enpatoran from the solvent.

[0145] The process of item 144, wherein the particles enpatoran are a crystalline hemihydrate.

[0146] The process of item 145, wherein the crystalline hemihydrate is polymorphic form H1.

[0147] The process according to any one of items 144 to 146, wherein the heating of step (ii) comprises heating the suspension to a recrystallization temperature above at or above 35 °C, or at or above 40 °C, or at or above 45 °C, or at or above 50 °C.

[0148] The process according to any one of items 144 to 147, wherein step (iii) comprises stirring the suspension for a period of time from 30 minutes to about 24 hours, from 1 hour to 24 hours, or from 2 hours to 24 hours.

[0149] The process according to any one of items 144 to 148, wherein step (iv) comprises cooling the suspension to a temperature from below room temperature to 0 °C, from 0 °C to 10 °C, or from 0 °C to 5 °C.

[0150] The process according to 149, wherein the cooling temperature is achieved by cooling the suspension at a rate of 1 °C / minute or less, at a rate of 0.5 °C / minute or less, at a rate of 0.4 °C / minute less, at a rate of 0.3 °C / minute less, or at a rate of 0.2 °C / minute less.

[0151] The process according to any one of items 144 to 150, wherein the suspension may be held at the cooling temperature for from 10 minutes to 4 hours, from 20 minutes to 2 hours, or from 30 minutes to 1.5 hours.

[0152] The process according to any one of items 144 to 151 , wherein the solvent comprises one or more organic solvents and water.

[0153] The process of 152, wherein the one or more organic solvents and water may comprise from 80 to 99.9 % (v / v) of the one or more organic solvents and from 0.1 to 20 % (v / v) water; or from 85 to 99.9 % (v / v) of the one or more organic solvents and from 0.1 to 15 % (v / v) water; or from 90 to 99.9 % (v / v) of the one or more organic solvents and from 0.1 to 10 % (v / v) water; or from 98 to 99.9 % (v / v) of the one or more organic solvents and from 0.1 to 2 % (v / v) water; or from 99 to 99.8 % (v / v) of the one or more organic solvents and from 0.5 to 1.5 % (v / v) water.

[0154] The process according to item 152 or 153, wherein the one or more organic solvents are selected from an ester, ether, alcohol, ketone, or combination thereof.

[0155] The process according to any one of items 143 to 154, wherein more than 50%, more than 60%, more than 70%, more than 75%, more than 80%, more than 85%, more than 90% or more than 95% of the particles are equant-shaped.

[0156] The process according to any one of items 143 to 155, wherein the mean aspect ratio of the particles is at least about 0.3, at least about 0.4, at least about 0.5, at least about 0.6, at least about 0.7, at least about 0.8 or at least about 0.9.

[0157] The process according to any one of items 144 to 156, wherein the bulk density of the resulting particles is greater than about 0.3 g / cm3, greater than about 0.4 g / cm3, greater than about 0.5 g / cm3; greater than about 0.55 g / cm3; greater than about 0.6 g / cm3; greater than about 0.65 g / cm3; or greater than about 0.7 g / cm3.

[0158] The process according to any one of items 144 to 157, wherein the bulk density of the resulting particles is less than about 0.95 g / cm3, less than about 0.9 g / cm3, less than about 0.85 g / cm3, or less than about 0.8 g / cm3.

[0159] The process according to any one of items 144 to 158, wherein the flow function coefficient (ffc) of the resulting particles is greater than about 4; or greater than about 5; or greater than about 6; or greater than about 7; or greater than about 8.

[0160] The method of any of items 144 to 159 having the characteristics of the particle according to any one of items 1 to 143.

[0161] Solid dosage form as described in any of the items above, comprising particles of enpatoran obtainable by the process according to any one of 144 to 160.

[0162] A powder mixture useful in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form after compression, preferably direct compression, and optional coating with an immediate release coating, is characterized by one or more of items 1-143.

[0163] A powder mixture useful in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form after compression, preferably direct compression, and optional coating with an immediate release coating, is a solid dosage form as defined in one or more of items 1-143.

[0164] Use of a powder mixture in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form (after compression, preferably direct compression, and optional coating with an immediate release coating) is characterized by one or more of items 1-143.

[0165] Use of a powder mixture in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form (after compression, preferably direct compression, and optional coating with an immediate release coating) is a solid dosage form as defined in one or more of items 1-143.

[0166] The solid dosage form according to any of items 1 to 143, for use in treating or preventing a TLR7 / 8-related autoimmune disease, the solid dosage form preferably comprising a crystalline polymorph according to any one of items 115 to 143.

[0167] The solid dosage form of item 166 , wherein the TLR7 / 8-related autoimmune disease is selected from the group consisting of rheumatoid arthritis, autoimmune pancreatitis, lupus, lupus with active mucocutaneous manifestation, lupus with active cutaneous manifestation systemic lupus erythematosus, cutaneous lupus erythematosus, lupus nephritis, type I diabetes mellitus, multiple sclerosis, antiphospholipid syndrome, sclerosing cholangitis, systemic onset arthritis, irritable bowel disease, scleroderma, Sjogren's disease, vitiligo, myositis, dermatomyositis, polymyositis, pemphigus vulgaris, pemphigus foliaceus, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, hypopituitarism, graft-versus-host disease, autoimmune skin diseases, uveitis, pernicious anemia, and hypoparathyroidism.

[0168] A method for treatment or prevention of a TLR7 / 8-related autoimmune disease, comprising administering to a patient in need thereof a pharmaceutically effective amount of the solid dosage form of any one of items 1 to 143.

[0169] The method of item 168 , wherein the TLR7 / 8-related autoimmune disease is selected from the group consisting of rheumatoid arthritis, autoimmune pancreatitis, lupus, lupus with active mucocutaneous manifestation, lupus with active cutaneous manifestation, systemic lupus erythematosus, cutaneous lupus erythematosus, lupus nephritis, type I diabetes mellitus, multiple sclerosis, antiphospholipid syndrome, sclerosing cholangitis, systemic onset arthritis, irritable bowel disease, scleroderma, Sjogren's disease, vitiligo, myositis, dermatomyositis, polymyositis, pemphigus vulgaris, pemphigus foliaceus, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, hypopituitarism, graft- versus-host disease, autoimmune skin diseases, uveitis, pernicious anemia, and hypoparathyroidism.

[0170] Method for preparing a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a binder; a filler; and / or a disintegrant and optionally one more additional pharmaceutically acceptable excipients; comprising the steps ofa) providing a powder blend comprising, or consisting of, all ingredients of the core (1) as a homogenous mixture;b) compressing the powder blend, preferably by direct compression, into a core (1), preferably at a force of between 50 to 150 N; and optionallyc) coating the core (1) of step b) with an immediate release coating liquid, preferably using spray coating, wherein the immediate release coating liquid preferably comprises polyvinyl alcohol and / or hypromellose in water; andd) drying the wet coated core to obtain the solid dosage form;optionally wherein the core (1) comprises a binder selected from microcrystalline cellulose, powdered cellulose, copovidone, and combinations thereof.

[0171] Method for preparing a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof; and optionally one more additional pharmaceutically acceptable excipients; comprising the steps ofa) providing a powder blend comprising, or consisting of, all ingredients of the core (1) as a homogenous mixture;b) compressing the powder blend of step a), preferably by direct compression, into a core (1); and optionallyc) coating the core (1) of step b) with an immediate release coating liquid, preferably using spray coating, wherein the immediate release coating liquid preferably comprises polyvinyl alcohol and / or hypromellose in water; andd) drying the wet coated core of step c) to obtain the solid dosage form.

[0172] The method of item 170 or 171 , wherein the core (1 ) further comprises a glidant and / or a lubricant.

[0173] The method of any of items 170 to 172, wherein the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose sodium; and optionally a glidant, preferably silicon dioxide and / or a lubricant, preferably magnesium stearate.

[0174] The method of any of items 170 to 173, wherein the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably silicon dioxide, a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipients.

[0175] The method of any of items 170 to 174, wherein the active ingredient is enpatoran, preferably enpatoran H1, the binder is microcrystalline cellulose, the filler is mannitol, the disintegrant is selected from crospovidone, carboxy starch glycolate, carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose sodium, the lubricant is selected from magnesium stearate, calcium stearate, stearic acid, glycerol fatty acid esters and sodium stearyl fumarate and / or the glidant is selected from silicon dioxide and derivatives thereof.

[0176] The method of any of items 170 to 175, wherein the binder, the filler, the powdered cellulose, the disintegrant, the glidant, and the lubricant are as defined in any of items 9 to 95.

[0177] The method of any of items 170 to 176, wherein the binder, the filler, the powdered cellulose, the disintegrant, the glidant, and the lubricant are characterized by any of items 9 to 95.

[0178] The method of any of items 170 to 177, wherein the amount of binder, filler, powdered cellulose, disintegrant, glidant, and lubricant are as defined in any of items 30 to 95.

[0179] The method of any of items 170 to 178, wherein the copovidone, the microcrystalline cellulose, the mannitol, the crospovidone, the croscarmellose or pharmaceutically acceptable salt thereof, the powdered cellulose, the silicon dioxide, the stearic acid or pharmaceutical acceptable salt thereof is as defined in any of items 9 to 95.

[0180] The method of any of items 170 to 179, wherein the copovidone, the microcrystalline cellulose, the mannitol, the crospovidone, the croscarmellose or pharmaceutically acceptable salt thereof, the powdered cellulose, the silicon dioxide, the stearic acid or pharmaceutical acceptable salt thereof is characterized by any of items 9 to 95.

[0181] The method of any of items 170 to 180, wherein the active ingredient is enpatoran, preferably enpatoran H1.

[0182] The method of any of items 170 to 181, wherein the active ingredient is enpatoran, is a crystalline hemihydrate as defined in any of items 114 to 142.

[0183] The method of any of items 170 to 182, wherein the active ingredient is enpatoran, and wherein the enpatoran comprises, or consists of, particles of a crystalline polymorph of enpatoran, preferably H1, as defined in any of items 130 to 143.

[0184] The method of any of items 170 to 183, wherein the active ingredient is enpatoran, preferably enpatoran H1, the binder is microcrystalline cellulose, the filler is mannitol, the disintegrant is croscarmellose sodium, the lubricant is magnesium stearate and / or the glidant is highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide.

[0185] The method of any of items 170 to 184, wherein the immediate release coating is a film coating suitable for immediate release of the active ingredient.

[0186] The method of any of items 170 to 185, wherein the immediate release coating is a cosmetic coating and / or wherein the immediate release coating provides color, protection (e.g. light, environmental and moisture protection) and / or taste-masking for the core (1).

[0187] The method of any of items 170 to 186, wherein immediate release coating (2) is applied to the core (1) by applying an immediate release coating liquid using spray coating, preferably fluidized-bed spray coating, and drying the wet coated solid dosage form, simultaneously or concomitantly, preferably using a fluidized bed or an oven.

[0188] The method of any of items 170 to 187, wherein the immediate release coating liquid comprising, or consisting of, polyvinyl alcohol, macrogol, talcum, titanium dioxide, glycerol monocaprylocaprat, and iron oxide yellow; or polyvinyl alcohol (e.g. part, hydr.), calcium carbonate, talcum, hypromellose, glycerin-monocaprylocaprat, and iron oxide-yellow / red and black.

[0189] The method of any of items 170 to 188, wherein step a) comprises active sieving all ingredients of the core (1) (i.e all excipients and the active ingredient through a round hole sieve, e.g. 0.5-2 mm (or 0.7-1.5 mm, or a 0.8-1.7 mm, or a 1.0.9 to 1 ,9mm or a 1.0 mm) round whole sieve.

[0190] The method of any of items 170 to 189, wherein the ingredients of core (1) are sieved and filled into a container; optionally wherein the ingredients are added in a specific order preferably starting with the binder, followed by the active ingredient, followed by the filler, followed by the powdered cellulose, followed by the disintegrant, followed by the glidant, and finally followed by the lubricant; optionally wherein all ingredients except the lubricant are added and mixed, e.g. for 10 min, after which the lubricant is added, and the mixing is continued, e.g. for 5 min; to then compress the resulting powder mix in step b) into a (tablet) core (1).

[0191] The method of any of items 170 to 190, wherein in step b) for compression of the tablet a main compression force of 4-14 kn, or 4.5 to 12 kN, or 5 to 10 kN is used, optionally wherein the target hardness of the core (1) is 50-150 N, or 70-130, or about 80 N.

[0192] The method of any of items 170 to 191, wherein the immediate release coating is characterized by any of items 100 to 106.

[0193] The method according to any of items 170 to 192 wherein the final oral dosage form is as defined in any of items 1 to 143 above.

[0194] The method according to any of items 170 to 193 wherein the final oral dosage form is characterized by any of items 1 to 143 above.

[0195] Solid dosage form according to any of items 1 to 143 for use in the treatment of a patient suffering from an autoimmune disease.

[0196] Use of the solid dosage form according to any of items 1 to 143 in the manufacture of a medicament for the treatment of a patient suffering from an autoimmune disease.

[0197] Method for treating a TLR7 / 8-related autoimmune disease in a patient in need thereof, the method comprising administering to said patient the solid dosage form according to any of items 1 to 143.BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 : Process flow of a manufacturing process for enpatoran tablets as used in the examples.

[0018] Figure 2: Tablet hardness vs. main compression force for the preliminary identified prototype formulation TestFormulationl.

[0019] Figure 3: Disintegration time vs. tablet hardness of tablets (cores) of TestFormulationl.

[0020] Figure 4: Tablet hardness vs. main compression force for TestFormulation2 (black full line), TestFormulation3 (grey full line), TestFormulation4 (grey dashed line) and TestFormulation5 (black dashed line).

[0021] Figure 5: Tablet hardness vs. disintegration time for TestFormulation2 (black full line), TestFormulation3 (grey full line), TestFormulation4 (grey dashed line) and TestFormulation5 (black dashed line).

[0022] Figure 6: Disintegration of tablets at 80 N target hardness for TestFormulation2, TestFormulation3, TestFormulation4 and TestFormulation5.

[0023] Figure 7: Dissolution profiles of tablet (core) prototypes TestFormulation2 (full line) & TestFormulation4 (dashed line). Data represent mean ±SD, n = 6 (0.1 N HCL; 500mL).DETAILED DESCRIPTION

[0024] Each of the embodiments described herein can be combined with any other embodiment described herein not inconsistent with the embodiment with which it is combined. Furthermore, unless incompatible in a given context, wherever a compound (e.g. an active ingredient or excipient) is mentioned which is capable of ionization (e.g., protonation or deprotonation), the definition of said compound includes any pharmaceutically acceptable salts thereof. Accordingly, the phrase “or a pharmaceutically acceptable salt thereof’ is implicit in the description of all compounds described herein.

[0025] The present invention may be understood more readily by reference to the detailed description above and below of the particular and preferred embodiments of the invention andthe examples included herein. It is to be understood that the terminology used herein is for the purpose of describing specific embodiments only and is not intended to be limiting. It is further to be understood that unless specifically defined herein, the terminology used herein is to be given its traditional meaning as known in the relevant art. So that the invention may be more readily understood, certain technical and scientific terms are specifically defined below. Unless specifically defined elsewhere in this document, all other technical and scientific terms used herein have the meaning commonly understood by one of ordinary skill in the art to which this invention belongs.

[0026] “A”, “an”, and “the” include plural referents unless the context clearly dictates otherwise. As such, the terms “a” (or “an”), “one or more”, and “at least one” are used interchangeably herein.

[0027] As used herein, the term “about” when used in relationship to a value, e.g., the upper or lower limit of a range or a reference value, refers to any value that is reasonably close to the value referred to, for instance, any value that is less than 10% (or 5% or 3%, or 1%) below or above the value referred to. The term “about” also includes the exact value.

[0028] The term “patient” or “subject”, as used herein, means an animal, preferably a mammal, and most preferably a human.

[0029] “Pharmaceutically acceptable” indicates that the substance or composition must be compatible chemically and / or toxicologically, with the other ingredients comprising a formulation, and / or the mammal being treated therewith. Where herein it is referred to “salts”, “derivatives”, ’’excipient” and the like, it is to be understood that these are “pharmaceutically acceptable” “salts”, “derivatives”, ’’excipient” and the like, which means any “salt”, “derivative*, ’’excipient” etc. that is non-toxic and does not destroy the pharmacological activity.

[0030] As used herein, “%” or “percent” shall mean percent by weight (% (w / w)), unless specified otherwise herein.

[0031] The term "solid dosage form", as used herein, refers to a three-dimensional solid pharmaceutical preparation comprising an active ingredient (that is an active pharmaceutical ingredient or API) and at least one pharmaceutically acceptable excipient. Preferably the solid dosage form is a compressed mixture of enpatoran and one or more pharmaceutically acceptable excipients.

[0032] The term “enpatoran” as referred to herein is the INN of the compound with the IIIPAC name 5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile; and, as used herein, the terms “enpatoran” and “5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile” are interchangeable.

[0033] For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th Ed. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry”, 5th Ed., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001Solid dosage form

[0034] In a first aspect, present invention is directed to a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is preferably prepared by compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a (e.g. one, or two, etc.) binder; a filler; and / or a disintegrant, and optionally one or more further pharmaceutically acceptable excipients. The core is preferably prepared by direct compression.

[0035] According to one embodiment the solid dosage form comprises, or consists of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is prepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a binder; a filler; and a disintegrant; and optionally one or more further pharmaceutically acceptable excipients.

[0036] The term “active ingredient” is not particularly limited. Preferably the active ingredient is enpatoran (i.e. 5-[(3R,5S)-3-amino-5-(trifluoromethyl)piperidin-1-yl]quinoline-8-carbonitrile), more preferably a crystalline polymorph, in particular a hydrate, or hemihydrate such as form H1, as described in more details below.

[0037] The solid dosage form, in the core (1), comprises a binder. That is the solid dosage form, in the core (1), may comprise one, two, or more binder.

[0038] The term "binder", as used herein, refers to an agent that provides cohesion and strength to a solid dosage form. This facilitates the tablet formation during the compression process and ensures that the tablets remain intact after the compression. Binders which can be employed in the present invention are, for example, copovidone (e.g., Kollidon VA64) or acellulose derivative, such as hydroxypropyl methylcellulose, hydroxypropyl cellulose, microcrystalline cellulose (MCC), and powdered cellulose. According to one embodiment, the core (1) comprises a binder selected from microcrystalline cellulose, powdered cellulose, copovidone, and combinations thereof.

[0039] In any embodiment herein which mentions comprising “powdered cellulose” and a “binder”, it is to be understood that the “binder” refers to a binder other than powdered cellulose, preferably microcrystalline cellulose and / or copovidone, more preferably microcrystalline cellulose. Similarly, in any embodiment herein, which mentions comprising a certain wt.-% of “powdered cellulose” and a certain wt.-% of “binder”, it is to be understood that the wt.-% of “binder” refers to an amount of binder not including any powdered cellulose.

[0040] A commercially available copovidone is Kollidon VA64. A suitable copovidone may for example be characterized by one or more of the following: particle size of < 45 % is <50 pm and < 15 % is > 250 pm, preferably < 40 % is <50 pm and < 10 % is > 250 pm, more preferably < 35 % is <50 pm and < 7 % is > 250 pm; and / or a bulk density of 0.03-0.23 g / ml, preferably 0.05-0.18 g / ml, more preferably 0.08-015 g / ml; and / or a molecular weight (Mw) of 55,000 -80,000, preferably 50,000 - 75,000, more preferably 45,000 - 70,000.

[0041] Suitable microcrystalline cellulose grades may include microcrystalline cellulose grade 101, grade 102, grade 200, grade 301, grade 302, and a combination thereof. A preferred grade is microcrystalline cellulose grade 102 (microcrystalline cellulose type 102).

[0042] According to one embodiment, the core (1) of the solid dosage form comprises as a binder microcrystalline cellulose, preferably microcrystalline cellulose grade 102.

[0043] A suitable microcrystalline cellulose may be for example characterized by one or both of the following: average particle size (e.g. laser diffraction) of 80-180 pm, preferably 100-160 pm, more preferably 120-140 pm, even more preferably 125-135 pm, e.g. about 130 pm; and / or a bulk density of 0.24-0.37 g / ml, preferably 0.26-0.35 g / ml, more preferably 0.28-0.33 g / ml.

[0044] A commercial example of a suitable microcrystalline cellulose (MCC) grade 102 is for example Vivapur® 10 Premium.

[0045] Binder can be present in the solid dosage form according to the invention in a proportion of for example 1 to 75 wt.-%, relative to the total weight of the core, or relative to the total weight of the solid dosage form.

[0046] According to one embodiment, the core (1) comprises 1-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, even more preferably 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35-42 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, e.g. about 38.63 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0047] According to another embodiment, the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 20 wt.-%, or at least 25 wt.-%, or at least 30 wt.-%, or at least 33 wt.-%, or at least 35 wt.-%, or at least 35.6 wt.-%, or at least 37.6 wt.-%, or at least 38.1 wt.-%, or at least 38.3 wt.-%., binder, preferably microcrystalline cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0048] According to yet another embodiment, the core (1) comprises less than 75 wt.-%, preferably less than 70 wt.-%, more preferably less than 65 wt.-%, even more preferably less than 60 wt.-%, or less than 55 wt.-%, or less than 50 wt.-%, or less than 45 wt.-%, or less than 43 wt.-%, or less than 42 wt.-%, or less than 41.6 wt.-%, or less than 40.6 wt.-%, or less than 39.6 wt.-%, or less than 39.1 wt.-%, or less than 38.9 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0049] According to yet another embodiment, the core (1) comprises 1-75 wt.-%, preferably 2-72 wt.-%, more preferably 5-70 wt.-%, even more preferably 10-65 wt.-%, or 15-62 wt.-%, or 20-60 wt.-%, or 25-59 wt.-%, or 30-58 wt.-%, or 35-57 wt.-%, or 38-56 wt.-%, or 41-55 wt.-%, or 42-54 wt.-%, or 44-53 wt.-%, or 45-52 wt.-%, or 46-51 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0050] The solid dosage form, in the core (1), comprises a filler. That is the solid dosage form, in the core (1), may comprise one, two, or more filler.

[0051] The term “filler” as used herein is an agent increasing the bulk of the pharmaceutical preparation by providing the quantity of material which is needed to form a solid dosage form. A filler also serves to create desired flow properties and compression characteristics in the preparation of the solid dosage form as well as of solid pharmaceutical preparations such as tablets and capsule fillers. Fillers usable in the present invention may be for example a sugar alcohol such as mannitol, or sorbitol, or dulcitol, xylitol or ribitol (preferably mannitol or sorbitol, particular preferably mannitol), or a sugar such as glucose, fructose, mannose, lactose, saccharose or maltose.

[0052] According to one embodiment of the present invention, the core (1) of the solid dosage form comprises a filler selected from the group consisting of mannitol, sucrose, maltose, lactose, trehalose, glycerol, maltitol, isomalt, sorbitol, xylitol, and combinations thereof, preferably mannitol. According to a preferred embodiment the core (1) comprises mannitol as a filler. According to a particular embodiment, the core (1) comprises one filler, which is mannitol.

[0053] Mannitol suitable for the present invention may for example be characterized by one or more of the following: particle size of < 25 % is < 53 pm and < 25 % is > 500 pm, preferably < 20 % is < 53 pm and < 20 % is > 500 pm, more preferably < 15 % is < 53 pm and < 15 % is > 500 pm; and / or a pH value (10 % in water) of 4.2 - 81 , preferably, 4.3 - 7.8, more preferably 4.5 - 7.5; and / or loss on drying of <2 %, preferably, <1 %, more preferably <0.5 %. A commercial example of mannitol is Parteck® M200.

[0054] Filler can be present in the solid dosage form according to the invention for example in a proportion of 1-50 wt.-%, preferably 2-48 wt.-%, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core). According to one embodiment, the core (1) comprises 1-50 wt.-%, preferably 2-48 wt.-%, more preferably 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23-28 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25-26.5 wt.-%, or 25.25-26.25 wt.-%, or 25.55-25.95 wt.-%, e.g. about 25.76 wt.-%, filler, preferably mannitol, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0055] According to another embodiment, the core (1) comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.-%, or at least 21 wt.-%, or at least 22 wt.-%, or at least 23 wt.-%, or at least 23.75 wt.-%, or at least 24.75 wt.-%, or at least 25 wt-%, or at least 25.25 wt.-%, or at least 25.55 wt.-%, filler, preferably mannitol, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core). According to yet another embodiment, the core (1) comprises less than 55 wt.-%, preferably less than 50 wt.-%, more preferably less than 45 wt.-%, even more preferably less than 40 wt.-%, or less than 35 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.75 wt.-%, or less than 26.75 wt.-%, or less than 26.5 wt.-%, or less than 26.25 wt.-%, or less than 25.95 wt.-%, filler, preferably mannitol, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0056] According to yet another embodiment, the core (1) comprises 1-55 wt.-%, or 2-50 wt.-%, or 5-48 wt.-%, or 10-45 wt.-%, or 15-42 wt.-%, or 20-40 wt.-%, or 24-39 wt.-%, or 26-38 wt.-%, or 28-36 wt.-%, or 30-34 wt.-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt.-%, or 31-31.5 wt.-%, filler, preferably mannitol, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0057] The solid dosage form may further comprise a disintegrant. The term "disintegrant", as used herein, refers to a compound that expands and / or dissolves when wet, to cause disintegration of tablets or granulates to break apart and release the active ingredient. The disintegrant also functions to ensure that the active ingredient, e.g. enpatoran, is in contact with the solvent, such as water. Disintegrants serve to disintegrate tablets or granules etc. and thus enhance dissolution of the solid dosage form upon contact with the liquid dissolution medium. Suitable disintegrants include crospovidone (cross-linked polyvinyl N-pyrrolidone), carboxymethylcellulose and salts and derivatives thereof, such as crosslinked derivatives, for instance croscarmellose sodium (cross-linked polymer of carboxymethylcellulose sodium) sodium carboxymethyl glycolate, and starch (e.g. carboxy starch glycolate, or partially pregelatinized maize starch). Crospovidone and croscarmellose sodium are preferred. Croscarmellose sodium is particularly preferred. As used herein, the terms "croscarmellose sodium" and "croscarmellose-sodium" are interchangeable.

[0058] According to one embodiment, the core (1) of the solid dosage form comprises a disintegrant, which is selected from carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose or a pharmaceutically acceptable salt thereof (e.g. croscarmellose sodium); crospovidone, and starch (e.g. carboxy starch glycolate, or partially pregelatinized maize starch), and combinations thereof, preferably croscarmellose or a pharmaceutically acceptable salt thereof and / or crospovidone.

[0059] A suitable crospovidone may be for example characterized by one or more of the following: a bulk density of 0.10 to 0.40 g / ml, preferably 0.15 to 0.31 g / ml, more preferably 0.18 to 0.28 g / ml; and / or a specific surface area (N2-BET) of 1-5 m2 / g, preferably 2-4 m2 / g, more preferably 2.5-3.5 m2 / g about 3 m2 / g; and / or a particle size of < 60 % is > 50 pm and < 25 % is > 100 pm, preferably < 40 % is > 50 pm and < 15 % is > 100 pm, more preferably < 30 % is > 50 pm and < 10 % is > 100 pm; and / or a content of water-soluble material of <15 %, preferably, <12 %, more preferably <10 %; and / or a hydration capacity of 3-10 g water / g polymer, preferably 6.5-9 g water / g polymer, more preferably 7-8.5 g water / g polymer. A commercially available crospovidone is Kollidon® CL-SF.

[0060] According to a preferred embodiment, the disintegrant is croscarmellose or a pharmaceutically acceptable salt thereof, preferably croscarmellose sodium. The croscarmellose sodium is not particularly limited. A suitable croscarmellose or a pharmaceutically acceptable salt is for example characterized by one or more of the following: a degree of substitution (on dried basis) of 0.50-0.95 preferably, 0.55-0.90, more preferably 0.60-0.85, e.g. about 0.7; and / or a content of water-soluble material of <15 %, preferably, <12 %, more preferably <10 %; and / or a settling volume (The settling volume can be determined modified according to the monograph of CCS in the Ph. Eur. 1.5 g of CCS is dispersed in 100 mL of demineralized water in graduated 100 mL cylinders. The dispersions are shaken and allowed to settle for e.g. 24 h. Afterwards, the settling volume is determined) of 5-40 ml, preferably 8-35 ml, more preferably 10-30 ml; and / or a pH value (1 % in water) of 4.6 - 7.4, preferably, 4.8 -7.2, more preferably 5-7; and / or loss on drying (according to Ph. Eur., 2.2.32, no 99) of <15 %, preferably, <12 %, more preferably <10 %. A commercially available croscarmellose sodium is for example Ac-Di-Sol® SD-711.

[0061] Disintegrants are present in the pharmaceutical preparation (solid dosage form) according to the invention in a proportion of for example as defined below.

[0062] According to one embodiment, the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.25-3 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.-%, or 0.5-1.5 wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, e.g. about 1 wt.-%, disintegrant, preferably croscarmellose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0063] According to another embodiment, the core (1) comprises at least 0.01 wt.-%, preferably at least 0.05 wt.-%, more preferably at least 0.1 wt.-%, even more preferably atleast 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.7 wt.-%, or at least 0.75 wt.-%, or at least 0.80 wt.-%, or at least 0.85 wt.-%, or at least 0.90 wt.-%, or at least 0.95 wt.-%; disintegrant, preferably croscarmellose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core). According to yet another embodiment, the core (1) comprises less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, even more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.6 wt.-%, or less than 1.5 wt.-%, or less than 1.4 wt.-%, or less than 1.3 wt.-%, or less than 1.2 wt.-%, or less than 1.1 wt.-%, or less than 1.05wt.-%; disintegrant, preferably croscarmellose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0064] According to a particular embodiment, the solid dosage form comprises, or consists of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is prepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof. According to another particular embodiment, the solid dosage form comprises, or consists of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is preferably prepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient which is enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof.

[0065] According to another particular embodiment, the solid dosage form comprises, or consists of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) is prepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient which is enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof. According to another particular embodiment, the solid dosage form comprises, or consists of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) isprepared by compression, preferably direct compression; wherein the core (1) comprises, or consists of, an active ingredient which is enpatoran; powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof.

[0066] According to a preferred embodiment, the core (1) of the solid dosage form comprises powdered cellulose. The present inventors surprisingly found that the addition of powdered cellulose (e.g. 5%), when used in combination with other preferred excipients in accordance with the present invention as described herein (e.g. with a binder, such as MCC; a filler, such as Mannitol; a disintegrant, such as croscarmellose sodium; and an active ingredient, such as enpatoran H 1), can lead to the desired effect of a reasonable prolongation of the disintegration time, resulting in tablets that disintegrate e.g. in more than 1 minute but still disintegrate rapidly (<5 min) (without impairing the very rapid dissolution). This is unexpected, since cellulose powder has disintegrant-like properties, due to its fluid uptake and swelling characteristics; and since the addition of another binder (copovidone), or omitting the disintegrant did not lead to the desired effect of such a moderate prolongation of the disintegration time.

[0067] The powdered cellulose is not particularly limited. A powdered cellulose is for example characterized by a particle size distribution (e.g. retained on air jet sieve): up to 65 %, preferably up to 55 %, more preferably up to 50 %, or up to 48 %, or up to 47 %, or up to 46 %, e.g. about 45 %, particles with >32 pm (450 mesh); and / or up to 35 % preferably up to 25 %, more preferably up to 20 %, or up to 18 %, or up to 16 %, or up to 15 %, e.g. about 14 %, particles with > 63 pm (230 mesh); and / or up to 2 % particles, preferably up to 1 %, more preferably up to 0.5 %, or up to 0.2 %, or up to 0.1 %, or up to 0.05 %, e.g. 0 %, with >125 pm (120 mesh). According to another embodiment, in a suitable powdered cellulose > 95 %, or > 97 %, or > 99 % of particles may have a particle size of less than 250 pm. A suitable powdered cellulose for example may additionally or alternatively be characterized by a bulk density of 80 to 400 g / L, preferably 100 to 300 g / L, more preferably 140 to 280 g / L, 160 to 260 g / L, 180 to 240 g / L. A commercial example of a powdered cellulose is Elcema® F150.

[0068] According to one embodiment, the core (1) comprises 0.1-40 wt.-%, preferably 0.2-25 wt.-%, more preferably 0.5-15 wt.-%, even more preferably 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 3.5-6.5 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7-5.3 wt.-%, or 4.75-5.25 wt.-%, or 4.8-5.2 wt.-%, or 4.85-5.15 wt.-%, or 4.9-5.1 wt.-%, or 4.95-5.05 wt.-%, e.g. about 5 wt.-%, powdered cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0069] According to another embodiment, the core (1) comprises at least 0.05 wt.-%, preferably at least 0.1 wt.-%, more preferably at least 0.2 wt.-%, even more preferably at least 0.5 wt.-%, or at least 1 wt.-%, or at least 2 wt.-%, or at least 3 wt.-%, or at least 3.5 wt.-%, or at least 4 wt.-%, or at least 4.5 wt.-%, or at least 4.7 wt.-%, or at least 4.75 wt.-%, or at least 4.8 wt.-%, or at least 4.85 wt.-%, or at least 4.9 wt.-%, or at least 4.95 wt.-%; powdered cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core). According to another embodiment, the core (1) comprises less than 50 wt.-%, preferably less than 40 wt.-%, more preferably less than 25 wt.-%, even more preferably less than 15 wt.-%, or less than 10 wt.-%, or less than 8 wt.-%, or less than 7 wt.-%, or less than 6.5 wt.-%, or less than 6 wt.-%, or less than 5.5 wt.-%, or less than 5.3 wt.-%, or less than 5.25 wt.-%, or less than 5.2 wt.-%, or less than 5.15 wt.-%, or less than 5.1 wt.-%, or less than 5.05 wt.-%, powdered cellulose, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0070] According to one embodiment, the core (1) of the solid dosage form further comprises a glidant and / or a lubricant.

[0071] The solid dosage form may further comprise a glidant. The term "glidant", as used herein, refers to an inactive ingredient used as a flow aid that improves the flow characteristics of particulates such as powders or granules. Nonlimiting examples of glidants for use in the present invention include silicon dioxide (silica), talc, or tribasic calcium phosphate, and combinations thereof. Preferred as a glidant is silicon dioxide, such as highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide.

[0072] A suitable silicon dioxide is for example characterized by one or more of the following: specific surface area (BET method) of 100-300 m2 / g, preferably 150-250 m2 / g, more preferably 175-225 m2 / g, e.g. about 200 m2 / g; and / or a tamped density of 30-70 g / l, preferably 40-60 g / l, more preferably 45-55 g / l, e.g. about 50 g / l; and / or a SiC>2 content of >99 %, preferably >99.5 %, more preferably >99.8 %; a pH value of 3.4 - 4.8, preferably, 3.6 - 4.6, more preferably 3.7 - 4.5; and / or loss on drying of <3 %, preferably, <2 %, more preferably <1.5 %. A commercially available example of a highly dispersed silicon dioxide is Aerosil® 200.

[0073] Glidants are present in the pharmaceutical preparation (solid dosage form) according to the invention for example as defined below.

[0074] According to one embodiment, the core (1) comprises 0.01-15 wt.-%, preferably 0.05-10 wt.-%, more preferably 0.1-8 wt.-%, even more preferably 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.8 wt.-%, or 0.45-1.65 wt.-%, or 0.55-1.55 wt.-%, or 0.65-1.45 wt.-%, or 0.75-1.35 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.-%, or 1.0-1.1 wt.-%, e.g. about 1.05 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed silicon dioxide), relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0075] According to yet another embodiment, the core (1) comprises at least 0.01 wt.-%, preferably at least 0.05 wt.-%, more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.25 wt.-%, or at least 0.3 wt.-%, or at least 0.35 wt.-%, or at least 0.4 wt.-%, or at least 0.45 wt.-%, or at least 0.55 wt.-%, or at least 0.65 wt.-%, or at least 0.75 wt.-%, or at least 0.85 wt.-%, or at least 0.95 wt.-%, or at least 1.0 wt.-%, glidant, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core). According to yet another embodiment, the core (1) comprises less than 10 wt.-%, preferably less than 8 wt.-%, more preferably less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2 wt.-%, or less than 1.8 wt.-%, or less than 1.65 wt.-%, or less than 1.55 wt.-%, or less than 1.45 wt.-%, or less than 1.35 wt.-%, or less than 1.25 wt.-%, or less than 1.15wt.-%, or less than 1.1 wt.-%; glidant, preferably silicon dioxide (e.g. highly dispersed silicon dioxide), relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0076] The solid dosage form may further comprise a lubricant. The term “lubricant”, as used herein, refers to an inactive ingredient used to prevent sticking of ingredients to one another (when e.g. compressed to tablets, and e.g. reducing friction at the interface of the powder and wall during compression). A lubricant reduces powder sticking to the roll surface of roller compactors and sliding friction of the tableting material and punches in the die during the tableting operation and prevents sticking to the tablet punches.

[0077] Suitable lubricants include for example alkaline-earth metal salts of fatty acids, such as magnesium stearate or calcium stearate; fatty acids, such as stearic acid; glycerol fatty acid esters; and sodium stearyl fumarate. Preferred lubricants are stearic acid or a pharmaceutical acceptable salt thereof, preferably magnesium stearate (Mg stearate), calcium stearate (Ca-stearate), or stearic acid. A particularly preferred lubricant is magnesium stearate. As used herein, the terms "magnesium stearate" and "magnesium-stearate" are interchangeable.

[0078] According to one embodiment, the lubricant is stearic acid or a pharmaceutical acceptable salt thereof, preferably magnesium stearate (Mg stearate), calcium stearate (Ca stearate), or stearic acid, more preferably magnesium stearate (e.g. magnesium stearate vs).

[0079] A suitable magnesium stearate is for example characterized by one or more of the following: a specific surface area of 3-13 m2 / g, preferably 5-11 m2 / g, more preferably 6-10 m2 / g; and / or a median particle size (D50) of 4-14 pm, preferably 6-12 pm, more preferably 7-11 pm; and / or loss on drying (Ph.Eur. 2.2.32, no 99) of <10 %, preferably, <8 %, more preferably <6%. A commercially available example of a magnesium stearate is LIGAMED MF-2-V-MB.

[0080] Lubricants can be present in the solid dosage form according to the invention for example in a proportion as defined below.

[0081] According to an embodiment, the core (1) comprises 0.01-18 wt.-%, preferably 0. OS-15 wt.-%, more preferably 0.1-10 wt.-%, even more preferably 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt.-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, or 1.47-1.53 wt.-%, e.g. about 1.5 wt.-%, lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0082] According to yet another embodiment, the core (1) comprises at least 0.01 wt.-%, preferably at least 0.05 wt.-%, more preferably at least 0.1 wt.-%, or at least 0.2 wt.-%, or at least 0.3 wt.-%, or at least 0.4 wt.-%, or at least 0.5 wt.-%, or at least 0.6 wt.-%, or at least 0.8 wt.-%, or at least 1.0 wt.-%, or at least 1.2 wt.-%, or at least 1.3 wt.-%, or at least 1.4 wt.-%, or at least 1.45 wt.-%, or at least 1.47 wt.-%, lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0083] According to yet another embodiment, the core (1) comprises less than 15 wt.-%, preferably less than 10 wt.-%, more preferably less than 8 wt.-%, or less than 7 wt.-%, or less than 6 wt.-%, or less than 4 wt.-%, or less than 3 wt.-%, or less than 2.4 wt.-%, or less than 2.2 wt.-%, or less than 2.0 wt.-%, or less than 1.8 wt.-%, or less than 1.7 wt.-%, or less than 1.6 wt.-%, or less than 1.55 wt.-%, or less than 1.53 wt.-%, lubricant, preferably stearic acid or a pharmaceutical acceptable salt thereof (e.g. magnesium stearate), relative to the totalweight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0084] According to a particular embodiment, the core (1) of the solid dosage form comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose sodium; and optionally a glidant, preferably silicon dioxide and / or a lubricant, preferably magnesium stearate.

[0085] According to another particular embodiment, the core (1) of the solid dosage form comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably silicon dioxide, a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipient.

[0086] According to yet another particular embodiment, the solid dosage form comprises, or consists of, a core (1) comprising, or consisting of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably silicon dioxide, a lubricant, preferably magnesium stearate; optionally one more additional pharmaceutically acceptable excipients; and an optional immediate release coating (2) covering the core (1).

[0087] According to a specific embodiment of the present invention, the active ingredient is enpatoran, preferably enpatoran H1; the binder is microcrystalline cellulose; the filler is mannitol; the disintegrant is selected from crospovidone, carboxy starch glycolate, carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose sodium; the glidant is selected from silicon dioxide and derivatives thereof; and / or the lubricant is selected from magnesium stearate, calcium stearate, stearic acid, glycerol fatty acid esters and sodium stearyl fumarate. According to a specific embodiment of the present invention, the active ingredient is enpatoran, preferably enpatoran H1; the binder is microcrystalline cellulose; the filler is mannitol; the disintegrant is croscarmellose sodium; the glidant is highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide; and / or the lubricant is magnesium stearate.

[0088] The amount of active ingredient, preferably enpatoran, in the solid dosage form, that is, the dosage per solid dosage form, is not particularly limited. According to a generalembodiment, the solid dosage form, that is, the core (1) of the solid dosage form, comprises 0.1-200 mg, preferably 1-150 mg, more preferably 2-100 mg, even more preferably 5-60 mg, or 6-55 mg, or 7-54 mg, 8-53 mg, or 9-52 mg, active ingredient, preferably enpatoran. According to a specific embodiment, the solid dosage form (that is, the core (1) of the solid dosage form) comprises 15-75 mg, preferably 40-65 mg, or 40-60 mg, 45-55 mg, or 47-53 mg, or 48-52 mg, or 49-51 mg, active ingredient, preferably enpatoran. According to another specific embodiment, the solid dosage form (that is, the core (1) of the solid dosage form) comprises 5-45 mg, preferably 10-40 mg, or 15-35 mg, or 20-30 mg, or 22-28 mg, or 23-27 mg, or 24-26 mg, or 24.5-25.5 mg, active ingredient, preferably enpatoran, relative to the total weight of the core. According to yet another specific embodiment, the solid dosage form (that is, the core (1) of the solid dosage form) comprises 2-30 mg, preferably 3-20 mg, or 4-17 mg, or 5-15 mg, 6-14 mg, or 7-13 mg, or 8-12 mg, or 9-11 mg, or 9.5-10.5 mg, or 9.7-10.3 mg, active ingredient, preferably enpatoran.

[0089] According one embodiment, the core (1) of the solid dosage form comprises 0.1-60 wt.-%, preferably 0.5-55 wt.-%, more preferably 1-50 wt.-%, even more preferably 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 18-36 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.5-27.5 wt.-%, or 26.75-27.35 wt-%, or 26.85-27.25 wt.-%, or 26.95-27.15 wt.-%, or 27.0-27.1 wt.-%, e.g. about 27.05 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0090] According to another embodiment, the core (1) of the solid dosage form comprises at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 5 wt.-%, even more preferably at least 10 wt.-%, or at least 15 wt.-%, or at least 18 wt.-%, or at least 20 wt.-%, or at least 22 wt.-%, or at least 24 wt.-%, or at least 25 wt.-%, or at least 26 wt.-%, or at least 26.5 wt.-%, or at least 26.75 wt.-%, or at least 26.85 wt.-%, or at least 26.95 wt.-%, or at least 27 wt.-%; .-%, active ingredient, preferably enpatoran, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0091] According to yet another embodiment, the core (1) comprises less than 60 wt.-%, preferably less than 55 wt.-%, more preferably less than 50 wt.-%, even more preferably less than 45 wt.-%, or less than 40 wt.-%, or less than 36 wt.-%, or less than 34 wt.-%, or less than 32 wt.-%, or less than 30 wt.-%, or less than 29 wt.-%, or less than 28 wt.-%, or less than 27.5 wt.-%, or less than 27.35 wt.-%, or less than 27.25 wt.-%, or less than 27.15 wt.-%, or less than 27.1 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0092] According to yet another embodiment of the invention, the core (1) of the solid dosage form comprises 0.1-45 wt.-%, preferably 0.5-30 wt.-%, more preferably 1-25 wt.-%, even more preferably 2-20 wt.-%, or 5-15 wt-%, or 6-14 wt.-%, or 7-13 wt.-%, or 8-12 wt.-%, or 8.5-11.5 wt.-%, or 9-11 wt.-%, or 9.5-10.5 wt-%, or 9.6-10.4 wt.-%, or 9.7-10.3 wt.-%, or 9.8-10.2 wt.- %, or 9.9-10.1 wt.-%, or 9.95-10.05 wt.-%, e.g. about 10.0 wt.-%, active ingredient, preferably enpatoran, relative to the total weight of the core (or alternatively relative to the total weight of the final powder blend used to prepare the core).

[0093] According to a general embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 23-31 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, or 26.85-27.25 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6- 39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, or 38.4-38.8 wt.-%, binder, preferably microcrystalline cellulose; and / or1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt-%, or 25.25-26.25 wt- %, or 25.55-25.95 wt.-%, filler, preferably mannitol; and / or0.05-10 wt.-%, or 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.-%, or 0.5-1.5wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7-5.3 wt.-%, or 4.8-5.2 wt.-%, or 4.9-5.1 wt.-%, or 4.95-5.05 wt.- %, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.8 wt.-%, or 0.45-1.65 wt.-%, orO.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0094] According to another general embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 22-32 wt.-%, or 23-31 wt.-%, or 24-30 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, or 26.85-27.25 wt.-%, active ingredient, preferably enpatoran;1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 20-55 wt.-%, or 27-50 wt.-%, or 32-45 wt.-%, or 34-43 wt.-%, or 35.6-41.6 wt.-%, or 36.6-40.6 wt.-%, or 37.6- 39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.3-38.9 wt.-%, or 38.4-38.8 wt.-%, binder, preferably microcrystalline cellulose;1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 21-30 wt.-%, or 22-29 wt.-%, or 23.75-27.75 wt.-%, or 24.75-26.75 wt-%, or 25.25-26.25 wt- %, or 25.55-25.95 wt.-%, filler, preferably mannitol;0.05-10 wt.-%, or 0.15-6 wt.-%, or 0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.35-1.8 wt.-%, or 0.4-1.6 wt.-%, or 0.5-1.5wt.-%, or 0.6-1.4 wt.-%, or 0.7-1.3 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; 0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, or 4.7-5.3 wt.-%, or 4.8-5.2 wt.-%, or 4.9-5.1 wt.-%, or 4.95-5.05 wt.- %, powdered cellulose;0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.8 wt.-%, or 0.45-1.65 wt.-%, orO.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.4 wt.-%, or 0.8-2.2 wt-%, 1.0-2.0 wt.-%, or 1.2-1.8 wt.-%, or 1.3-1.7 wt-%, or 1.4-1.6 wt.-%, or 1.45-1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0095] According to a preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,23-31 wt.-%, or 25-29 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, or 26.85-27.25 wt.- %, active ingredient, preferably enpatoran; and- 34-43 wt-%, or 36.6-40.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, or 38.4-38.8 wt.-%, binder, preferably microcrystalline cellulose; and- 22-29 wt-%, or 23.75-27.75 wt-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.-%, or 25.55-25.95 wt.-%, filler, preferably mannitol; and0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and0.5-15 wt.-%, or 1-10wt.-%, or3-7wt.-%, or4-6wt.-%, or 4.5-5.5 wt.-%, or 4.8-5.2 wt.- %, or 4.9-5.1 wt.-%, powdered cellulose; and0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.3-5 wt.-%, or 0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45- 1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0096] According to another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,24-30 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, active ingredient, preferably enpatoran; and35.6-41.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, binder, preferably microcrystalline cellulose; and- 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.-%, filler, preferably mannitol; and0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.9-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and1-10 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, powdered cellulose; and0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.95-1.15 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.4-1.6 wt.-%, lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0097] According to another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,2-20 wt.-%, or 5-15 wt.-%, or 9-11 wt.-%, or 9.5-10.5 wt.-%, or 9.8-10.2 wt.-%, or 9.9- 10.1 wt.-%, active ingredient, preferably enpatoran; and41-55 wt.-%, or 45-52 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, or 48-48.6 wt.-%, binder, preferably microcrystalline cellulose; and- 26-38 wt-%, or 30-34 wt-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt-%, or 32-32.5 wt.-%, filler, preferably mannitol; and0.2-4 wt.-%, or 0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.8-1.2 wt.-%, or 0.9-1.1 wt.-%, or 0.95-1.05 wt.-%, disintegrant, preferably croscarmellose sodium; and0.5-15 wt.-%, or 1-10wt.-%, or3-7wt.-%, or4-6wt.-%, or 4.5-5.5 wt.-%, or 4.8-5.2 wt.- %, or 4.9-5.1 wt.-%, powdered cellulose; and0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.85-1.25 wt.-%, or 0.95-1.15 wt.- %, or 1.0-1.1 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.3-5 wt.-%, or 0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.3-1.7 wt.-%, or 1.4-1.6 wt.-%, or 1.45- 1.55 wt.-%, lubricant, preferably magnesium stearate,relative to the total weight of the core (1).

[0098] According to yet another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of,5-15 wt.-%, or 8-12 wt.-%, or 9.5-10.5 wt.-%, active ingredient, preferably enpatoran; and44-53 wt.-%, or 47-50.6 wt.-%, or 47.8-48.8 wt.-%, binder, preferably microcrystalline cellulose; and28-36 wt.-%, or 31.25-33.25 wt.-%, or 31.75-32.75 wt.-%, filler, preferably mannitol; and0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.9-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.8-5.2 wt.-%, powdered cellulose; and 0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.95-1.15 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.4-1.6 wt.-%, lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0099] According to yet another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of, 2-55 wt.-% active ingredient, preferably enpatoran, 5-70 wt.-% binder, 5-45 wt.-% filler, preferably mannitol; 0.15-6 wt.-%, disintegrant, preferably croscarmellose sodium; 0.5-15 wt.-% powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0100] According to yet another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of, 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder, 18-34 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0101] According to yet another preferred embodiment of the invention, the core (1) of the solid dosage form of the present invention comprises, or consists of, 1-20 wt.-% activeingredient, preferably enpatoran, 40-57 wt.-% binder, 24-40 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.2-7 wt.-%, wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the core (1).

[0102] According to other alternatives of the above embodiments, instead of relative to the total weight of the core (1), the indicated weight percentages (wt.-%) are relative to the total weight of the final powder blend used to prepare the core. According to yet other alternatives of the above embodiments, instead of relative to the total weight of the core (1), the indicated weight percentages (wt.-%) are relative to the total weight of the solid dosage form.

[0103] According to one embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 21-32 wt.-%, or 22-31 wt.-%, or 23-29 wt.-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and / or1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 19-54 wt.-%, or 26-49 wt.-%, or 31-44 wt.-%, or 33-42 wt.-%, or 34.5-40.5 wt.-%, or 35.5-39.5 wt.-%, or 36.5- 38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.-%, or 37.3-37.7 wt.-%, binder, preferably microcrystalline cellulose; and / or1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 20.5- 29.5wt.-%, or 21.5-28.5 wt.-%, or 22-28 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5- 25.5 wt.-%, or 24.7-25.3 wt.-%, or 24.8-25.2 wt.-%, filler, preferably mannitol; and / or 0.05-10 wt.-%, or 0.1-6 wt.-%, or 0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.25-1.8 wt.-%, or 0.3-1.6 wt.-%, or 0.4-1.5wt.-%, or 0.5-1.4 wt.-%, or 0.6-1.3 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.6-5.1 wt.-%, or 4.75-4.95 wt.-%, or 4.8-4.9 wt.-%, powdered cellulose; and / or0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.7 wt.-%, or 0.45-1.6 wt.-%, or 0.62-1.42 wt.-%, or 0.82-1.22 wt.-%, or 0.92-1.12 wt- %, or 0.97-1.07 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.0-1.9 wt.-%, or 1.1 -1.8 wt.-%, or 1.25-1.7 wt.-%, or 1.35- 1.55 wt.-%, or 1.40-1.50 wt.-%, lubricant, preferably magnesium stearate; and / or0.1-35 wt.-%, or 0.2-15 wt.-%, or 0.3-10 wt.-%, or 0.5-8 wt.-%, or 0.7-7 wt.-%, or 0.9-6 wt.-%, or 1.4-4.4 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3.0 wt.-%, or 2.85-2.95 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0104] According to another embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,0.5-55 wt.-%, or 2-45 wt.-%, or 5-40 wt.-%, or 15-38 wt.-%, or 20-34 wt.-%, or 21-32 wt.-%, or 22-31 wt.-%, or 23-29 wt.-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and1-75 wt.-%, or 5-70 wt.-%, or 10-65 wt.-%, or 15-60 wt.-%, or 19-54 wt.-%, or 26-49 wt.-%, or 31-44 wt.-%, or 33-42 wt.-%, or 34.5-40.5 wt.-%, or 35.5-39.5 wt.-%, or 36.5- 38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.-%, or 37.3-37.7 wt.-%, binder, preferably microcrystalline cellulose; and1-50 wt.-%, or 5-45 wt.-%, or 10-40 wt.-%, or 15-35 wt.-%, or 18-32 wt.-%, or 20.5- 29.5wt.-%, or 21.5-28.5 wt.-%, or 22-28 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5- 25.5 wt.-%, or 24.7-25.3 wt.-%, or 24.8-25.2 wt.-%, filler, preferably mannitol; and 0.05-10 wt.-%, or 0.1-6 wt.-%, or 0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.25-1.8 wt.-%, or 0.3-1.6 wt.-%, or 0.4-1.5wt.-%, or 0.5-1.4 wt.-%, or 0.6-1.3 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and 0.2-25 wt.-%, or 0.5-15 wt.-%, or 1-10 wt.-%, or 2-8 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.6-5.1 wt.-%, or 4.75-4.95 wt.-%, or 4.8-4.9 wt.-%, powdered cellulose; and0.05-10 wt.-%, or 0.2-6 wt.-%, or 0.25-4 wt.-%, or 0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4- 1.7 wt.-%, or 0.45-1.6 wt.-%, or 0.62-1.42 wt.-%, or 0.82-1.22 wt.-%, or 0.92-1.12 wt- %, or 0.97-1.07 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.1-10 wt.-%, or 0.2-7 wt.-%, or 0.3-5 wt.-%, or 0.4-4 wt.-%, or 0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.0-1.9 wt.-%, or 1.1 -1.8 wt.-%, or 1.25-1.7 wt.-%, or 1.35- 1.55 wt.-%, or 1.40-1.50 wt.-%, lubricant, preferably magnesium stearate; and optionally0.1-35 wt.-%, or 0.2-15 wt.-%, or 0.3-10 wt.-%, or 0.5-8 wt.-%, or 0.7-7 wt.-%, or 0.9-6 wt.-%, or 1.4-4.4 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3.0 wt.-%, or 2.85-2.95 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0105] According to yet another embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,- 22-31 wt-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and / or33-42 wt.-%, or 35.5-39.5 wt.-%, or 36.5-38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.- %, binder, preferably microcrystalline cellulose; and / or20.5-29.5 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, or 24.7-25.3 wt.- %, filler, preferably mannitol; and / or0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.4-1.5 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and / or0.5-15 wt.-%, or 1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and / or0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.- %, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or0.4-4 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and / or0.3-10 wt.-%, or 0.7-7 wt.-%, or 1.4-4.4 wt.-%, or 2.4-3.4 wt.-%, 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0106] According to yet another embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,- 22-31 wt-%, or 24-28 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, or 26-26.5 wt.-%, active ingredient, preferably enpatoran; and33-42 wt.-%, or 35.5-39.5 wt.-%, or 36.5-38.5 wt.-%, or 37-38 wt.-%, or 37.2-37.8 wt.- %, binder, preferably microcrystalline cellulose; and20.5-29.5 wt.-%, or 23-27 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, or 24.7-25.3 wt.- %, filler, preferably mannitol; and0.15-4 wt.-%, or 0.2-2 wt.-%, or 0.4-1.5 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.92-1.02 wt.-%, disintegrant, preferably croscarmellose sodium; and0.5-15 wt.-%, or 1-10 wt.-%, or 3-7 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and0.25-4 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.- %, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.4-4 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and optionally0.3-10 wt.-%, or 0.7-7 wt.-%, or 1.4-4.4 wt.-%, or 2.4-3.4 wt.-%, 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0107] According to yet another embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,or 23-29 wt.-%, or 25-27 wt.-%, or 25.75-26.75 wt.-%, active ingredient, preferably enpatoran; and34.5-40.5 wt.-%, or 36.5-38.5 wt.-%, or 37-38 wt.-%, binder, preferably microcrystalline cellulose; and21.5-28.5 wt.-%, or 24-26 wt.-%, or 24.5-25.5 wt.-%, filler, preferably mannitol; and 0.2-2 wt.-%, or 0.6-1.3 wt.-%, 0.8-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and1-10 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, powdered cellulose; and0.35-2 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.5-3 wt.-%, or 1.0-1.9 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and optionally0.5-8 wt.-%, or 0.9-6 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0108] According to a further embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,3-20wt.-%, 6-15wt.-%, or8-13wt.-%, or 8.5-12 wt.-%, or 9-11 wt.-%, active ingredient, preferably enpatoran; and / or35-56 wt.-%, or 40-54 wt.-%, or 43-51 wt.-%, or 44-50 wt.-%, or 45-49 wt.-%, or 46-48 wt.-%, binder, preferably microcrystalline cellulose; and / or23-40 wt.-%, or 25-38 wt.-%, or 27-36 wt.-%, or 29-34 wt.-%, or 29.5-33.5 wt.-%, or 30.5-32.5 wt.-%, filler, preferably mannitol; and / or0.2-2 wt.-%, or 0.3-1.6 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and / or2-8 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and / or0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and / or0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and / or0.5-8 wt.-%, or 0.9-6 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0109] According to a yet further embodiment of the invention, the solid dosage form of the present invention comprises, or consists of,3-20wt.-%, 6-15wt.-%, or8-13wt.-%, or 8.5-12 wt.-%, or 9-11 wt.-%, active ingredient, preferably enpatoran; and35-56 wt.-%, or 40-54 wt.-%, or 43-51 wt.-%, or 44-50 wt.-%, or 45-49 wt.-%, or 46-48 wt.-%, binder, preferably microcrystalline cellulose; and23-40 wt.-%, or 25-38 wt.-%, or 27-36 wt.-%, or 29-34 wt.-%, or 29.5-33.5 wt.-%, or 30.5-32.5 wt.-%, filler, preferably mannitol; and0.2-2 wt.-%, or 0.3-1.6 wt.-%, or 0.5-1.4 wt.-%, or 0.7-1.2 wt.-%, or 0.8-1.1 wt.-%, disintegrant, preferably croscarmellose sodium; and2-8 wt.-%, or 4-6 wt.-%, or 4.35-5.35 wt.-%, or 4.5-5.2 wt.-%, or 4.75-4.95 wt.-%, powdered cellulose; and0.3-3 wt.-%, or 0.35-2 wt.-%, or 0.4-1.7 wt.-%, or 0.62-1.42 wt.-%, or 0.92-1.12 wt.-%, glidant, preferably silicon dioxide (e.g. highly dispersed); and0.5-3 wt.-%, or 0.6-2.3 wt.-%, or 0.8-2.1 wt.-%, or 1.1-1.8 wt.-%, or 1.35-1.55 wt.-%, lubricant, preferably magnesium stearate; and optionally0.5-8 wt.-%, or 0.9-6 wt.-%, or 1.9-3.9 wt.-%, or 2.4-3.4 wt.-%, or 2.8-3.0 wt.-%, immediate release coating;relative to the total weight of the solid dosage form.

[0110] According to a general embodiments, the core (1) comprises, or consists of, 2-45 wt-% active ingredient, preferably enpatoran, 1-70 wt.-% binder, 1-45 wt.-% filler, preferably mannitol; 0.05-10 wt.-%, disintegrant, preferably croscarmellose sodium; 0.2-25 wt.-%, powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the solid dosage form. According to a general embodiments, the core (1) comprises, or consists of, 2-45 wt.-% active ingredient, preferably enpatoran, 1-70 wt.-% binder, 1-45 wt.-% filler, preferably mannitol; 0.05-10 wt.-%, disintegrant, preferably croscarmellose sodium; 0.2-25 wt.-%, powdered cellulose, 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highlydispersed); and 0.2-7 wt.-% lubricant, preferably magnesium stearate, relative to the total weight of the solid dosage form

[0111] In a specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 2-45 wt.-% active ingredient, preferably enpatoran, 5-70 wt.-% binder, 5-45 wt.-% filler, preferably mannitol; 0.15-6 wt.-%, disintegrant, preferably croscarmellose sodium; 0.5-15 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0112] In another specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder, 18-34 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form. In another specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder, 18-34 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0113] In yet another specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 23-29 wt.-% active ingredient, preferably enpatoran, 34.5-40.5 wt.-% binder, 22-28 wt.-% filler, preferably mannitol; 0.3-1.6 wt.-% disintegrant, preferably croscarmellose sodium; 3-7 wt.-% powdered cellulose; 0.4-1.7 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.8-2.1 wt.-% lubricant, preferably magnesium stearate; and optionally 1.9-3.9 wt.-% immediate release coating; relative to the total weight of the solid dosage form. In yet another specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 23-29 wt-% active ingredient, preferably enpatoran, 34.5-40.5 wt.-% binder, 22-28 wt.-% filler, preferably mannitol; 0.3-1.6 wt.-% disintegrant, preferably croscarmellose sodium; 3-7 wt.-% powdered cellulose; 0.4-1.7 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); 0.8-2.1 wt.-% lubricant, preferably magnesium stearate; and optionally 1.9-3.9 wt.-% immediate release coating; relative to the total weight of the solid dosage form

[0114] In yet another specific embodiment of the invention, the solid dosage form of the present invention comprises, or consists of, 1-20 wt.-% active ingredient, preferably enpatoran, 38-55 wt.-% binder, 23-40 wt.-% filler, preferably mannitol; 0.2-4 wt.-%, disintegrant, preferably croscarmellose sodium; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant, preferably silicon dioxide (e.g. highly dispersed); and / or 0.2-7 wt.-% lubricant, preferably magnesium stearate; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

[0115] The method for preparing the solid dosage form of the present invention is not particularly limited as long as it allows for the inclusion of the above-mentioned ingredients, while ensuring consistent results. For example, the solid dosage form of the present invention may be prepared by compression, e.g. by dry granulation / compression or direct compression, that is, the core (1) of the solid dosage form of the present invention may be prepared for example by dry granulation / compression or direct compression. Methods for preparing a tablet by compression, e.g. by dry granulation / compression or direct compression are well known in the art. A method for preparing the solid dosage form of the present invention by direct compression is described below. Thus, the solid dosage form of the present invention may for example be prepared using compression, particularly using direct compression. According to a preferred embodiment, the core of the solid dosage form is prepared by direct compression. That is the solid dosage form for example the core (1) may be prepared by compression, e.g. direct compression. According to a preferred embodiment, the core (1) is prepared by direct compression.

[0116] Preferably, the solid dosage form of the present invention is an immediate release solid dosage form, particularly an immediate release tablet. The term “immediate release” is to be construed in the way commonly used in the field. According to one embodiment, an immediate release dosage form is a dosage form, wherein in a standardized dissolution analysis (e.g. in accordance with Eur. Ph. A.), e.g. in .1 N HCI, the solid dosage form or the core (1) has a dissolution profile of >85% within 15 minutes e.g., 0.1 N HCI, that is a target release rate of >85% within 15 minutes. The solid dosage form of the present invention preferably has a disintegration time of greater than 1 min (60 s) but less than 5 min. Thus, according to a specific embodiment, the solid dosage form of the present invention (e.g. a core not (yet) comprising an immediate release coating) has a disintegration time (e.g. measured according to Eur. Ph. A.) of greater than 1 min (60 s) but less than 5 min.

[0117] According to one embodiment, tablet hardness, friability, disintegration time, and / or dissolution is to be determined according to Eur. Ph. A.

[0118] According to a general embodiment, the solid dosage form comprises an immediate release coating (2), which preferably is based on polyvinyl alcohol and / or hypromellose. According to a specific embodiment, the immediate release coating is a film coating suitable for immediate release of the active ingredient.

[0119] The immediate release coating may be a cosmetic coating. In particular, the immediate release coating may provide color, protection (e.g. light, environmental and moisture protection) and / or taste-masking for the core (1).

[0120] According to certain embodiments, the immediate release coating (2) is applied to the core (1) by applying an immediate release coating liquid using spray coating, e.g. fluidized-bed spray coating, and drying the wet coated solid dosage form, simultaneously or concomitantly, e.g. using a fluidized bed or an oven. According to a specific embodiment, the solid dosage form comprises an immediate release coating (2), comprising, or consisting of, polyvinyl alcohol, macrogol, talcum, titanium dioxide, glycerol monocaprylocaprat, and / or iron oxide yellow; or polyvinyl alcohol (e.g. part, hydr.), calcium carbonate, talcum, hypromellose, glycerin-monocaprylocaprat, and / or iron oxide-yellow / red and black.

[0121] In a specific embodiment of the invention, the solid dosage form comprises 0.1-20 wt.-%, preferably 0.5-15 wt.-%, more preferably 1-10 wt.-%, even more preferably 1.5-5 wt.-%, or 1.6-4.8 wt.-%, or 1.8-4.6 wt.-%, or 2-3.8 wt.-%, or 2.2-3.6 wt.-%, or 2.4-3.4 wt.-%, or 2.6-3.2 wt.-%, or 2.8-3 wt.-%, immediate release coating (2), relative to the total weight of the solid dosage form.

[0122] According to one embodiment of the invention, the solid dosage form comprises less than 5 wt.- %, preferably less than 2 wt.-%, more preferably less than 1 wt.- %, water, relative to the total weight of the solid dosage form.

[0123] According to another embodiment of the invention, the core (1) is a pellet or tablet with a particle size distribution such that at least 85 % of the dosage forms have a particle size of 2-10 mm, preferably 3-7 mm.

[0124] According to a preferred embodiment of the invention, the solid dosage form is an oral dosage form. According to another preferred embodiment of the invention, the solid dosage form is a tablet or mini-tablet, a pellet, or a granule, preferably a tablet.

[0125] The active ingredient used in the solid dosage form preferably is a TLR 7 / 8 inhibitor, preferably wherein the TLR 7 / 8 inhibitor is a TLR7 and / or TLR8 small molecule inhibitor. Suitable is a TLR 7 / 8 inhibitor may be found for example in WO2017 / 106607, WO2024100139, WO2018031434A1, or WO2019018354.

[0126] In a preferred embodiment, the TLR 7 / 8 inhibitor is enpatoran. That is, in a preferred embodiment the active ingredient of the solid dosage form of the present invention is enpatoran. According to a preferred embodiment, enpatoran is present in the core (1) as a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0127] In another preferred embodiment the active ingredient of the solid dosage form, the core (1) comprises a crystalline polymorph of enpatoran, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0128] In yet another preferred embodiment of the solid dosage form, the active ingredient is a crystalline polymorph of enpatoran, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0129] In another preferred embodiment of the solid dosage form, the active ingredient is enpatoran, which comprises, or consists of, a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0130] According to a specific embodiment, the active ingredient of the solid dosage form at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 % by weight, of the enpatoran is a crystalline polymorph, and wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate.

[0131] Preferably the crystalline hemihydrate of enpatoran is polymorphic form H1. That is, preferably the active ingredient of the solid dosage form preferably is enpatoran, the polymorphic form H1. Preferably the crystalline hemihydrate form H1 is characterized by one or more of the above or below.

[0132] As used herein, the term “polymorph” or “polymorphic form” refer to a crystallographically distinct form of a substance. The practical physical characteristics of a polymorphic form are influenced by the conformation and orientation of molecules in the unit cell, which defines a particular polymorphic form of a substance. Different polymorphs of the same compound may have different physical, chemical, biological and / or spectroscopic properties. For example, and without limitation, different polymorphic forms may have different stability properties. A particular polymorphic form may be more sensitive to relative humidity, heat and / or light. In some cases, differences in stability result from changes in chemical reactivity, such as and without limitation, differential oxidation. Such properties may provide for more suitable product qualities such as a dosage form that is more resistant to discoloration when comprised of a particular polymorph. Alternatively or additionally, a particular polymorphic form may have a different dissolution rate thereby providing, for example, a more desirable bioavailability. Polymorphs can be detected, identified, classified and characterized using well-known techniques such as, but not limited to, powder X-ray diffractometry (PXRD), single crystal X-ray diffractometry, differential scanning calorimetry (DSC), thermogravimetry (TGA), vibrational spectroscopy, solution calorimetry, solid state nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, Raman spectroscopy, hot stage optical microscopy, scanning electron microscopy (SEM), electron crystallography, quantitative analysis, solubility, and rate of dissolution.

[0133] In embodiments, the crystalline form of the enpatoran is the crystalline hemihydrate in polymorphic form H1, as described herein and in PCT / EP2024 / 072511.

[0134] Enpatoran hemihydrate form H1 may be characterized by one or more peaks from the powder X-ray diffraction (PXRD) (Cu-Ka1 radiation), presented in degrees 20 ±0.2°, wherein the peaks comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9. A powder X-Ray diffraction pattern may be obtained by standard techniques as described in the European Pharmacopeia 6th Edition chapter 2.9.33 and (may be) characterized by the X-ray powder diffractogram of Figure 4 (of PCT / EP2024 / 072516) (monochromatic Cu-Ka1 radiation, A = 1.5406 A, Stoe StadiP 611 KL transmission diffractometer).

[0135] Single crystal X-Ray structure data may be obtained on form H1 form (Oxford Diffraction Supernova Single Crystal X-ray Diffractometer with Graphite monochromator and CCD Detector) at 298 K. Hemihydrate form H1 crystallises in the orthorhombic space group P212121 with the lattice parameters a = 10.7499 ± 0.1 A, b = 16.4119 ± 0.1 A, c = 17.5927 ±0.1 A, and a = y = p = 90°. As can be seen from the single crystal structure of Figure 5 (of PCT / EP2024 / 072516), form H1 represents a hemi-hydrate form.

[0136] Form H1 is characterised by the following physical properties. Thermal behaviour shows dehydration <100 °C, followed by melting of anhydrous form A1 at -165 °C. TGA shows weight loss of -2.9 % (w / w) up to 130 °C which can be assigned to degradation of 0.5 mol water. The DSC scan of Form H1 was acquired on a Mettler-Toledo DSC1 with a heating rate of 5 K / min, using nitrogen purge gas at 50 mL / min. The TGA scan of Form H1 was acquired on a Mettler-Toledo TGA 851 with a heating rate of 5 K / min, using nitrogen purge gas at 50 mL / min.

[0137] Water Vapour Sorption behaviour reveals water uptake levels -0.5 % (w / w) in the full relative humidity (RH) range 0-98% RH. Hemi-hydrate form H1 can be classified as non-hygroscopic according to Ph. Eur. Criteria (section 5.11.). Water Vapour Sorption isotherm was acquired on a DVS Intrinsic system from SMS.

[0138] The crystalline polymorph enpatoran hemihydrate form H1 may be characterized by two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, or each of the PXRD peaks 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9. All PXRD peaks provided herein are measured with Cu-Ka1 radiation in degrees 20 and include ±0.2 degrees.

[0139] The crystalline polymorph of enpatoran hemihydrate form H1 may be characterized by PXRD peaks comprising a peak at 13.4.

[0140] The crystalline polymorph of enpatoran hemihydrate form H1 may be characterized by PXRD peaks comprising peaks at 9.7 and 13.4.

[0141] The crystalline polymorph of enpatoran hemihydrate form H1 may be characterized by PXRD peaks comprising peaks at 7.2, 9.7 and 13.4.

[0142] The crystalline polymorph of enpatoran hemihydrate form H1 may be characterized by PXRD peaks comprising peaks at 7.2, 9.7, 13.4 and 22.2.

[0143] The crystalline polymorph of enpatoran hemihydrate form H1 may be characterized by PXRD peaks comprising peaks at 7.2, 9.7, 13.4, 21.5 and 22.2.

[0144] In some embodiments, the crystalline form of the enpatoran of the particle is the crystalline hemihydrate in polymorphic form H1, as described herein and in PCT / EP2024 / 072511.

[0145] The particles of enpatoran described hereinabove (and below) may comprise one or more crystalline polymorphic forms of the compound. In embodiments, the polymorphic form may be an anhydrous form of the compound. Preferably, the crystalline polymorphic form of the compound is a hydrate or hemihydrate, and most preferably is a hemihydrate. In embodiments, the particles comprise different crystalline polymorphic forms of the compound. In some embodiments, the crystalline form enpatoran in the majority of particles is a hemihydrate, such as the Form H1 referred to below. In some embodiments, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, or at least about 95% of the particles have enpatoran in the hemihydrate form, such as the form H1.

[0146] According to preferred embodiments, the enpatoran comprises, or consists of, particles of a crystalline polymorph, preferably a hydrate or hemihydrate, more preferably a hemihydrate, even more preferably polymorphic form H1.

[0147] According to other preferred embodiments, the enpatoran comprises, or consists of, equant-shaped particles of a crystalline polymorph of enpatoran; wherein the crystalline polymorph is a hydrate or hemihydrate, preferably a hemihydrate, more preferably polymorphic form H1. Equant particles have roughly similar length, width and height, including both cubical particle, spherical particles, and other shapes.

[0148] The particles of enpatoran having polymorphic hemihydrate form H1, as described hereinabove, provide improved physical stability and high chemical stability. For example, at ambient conditions the particles of form H1 provide improved stability as compared to the enantiotropic behavior of certain anhydrous polymorphic forms. Based on the high physical stability, no protective packaging material may be necessary for the pharmaceutical formulations of enpatoran of the polymorphic hemihydrate form H1.

[0149] According to some embodiments, the enpatoran comprises, or consists of, particles of a crystalline polymorph of enpatoran, wherein the mean aspect ratio of the enpatoran particlesin the solid dosage form is at least about 0.3, at least about 0.4, at least about 0.5, at least about 0.6, at least about 0.7, at least about 0.8 or at least about 0.9. Aspect ratio is a parameter that describes the sizes of the particle in different dimensions. In some embodiments, the aspect ratio is the ratio of the width to the length of a particle. In some embodiments, the length is the maximum Feret diameter and the width is the minimum Feret diameter. In some embodiments, the length is the maximum distance between any two points on the perimeter of the particle parallel to the major axis and the width is the maximum distance between any two points on the perimeter of the particle parallel to the minor axis. The major axis passes through the center of mass of the object at an orientation corresponding to the minimum rotational energy of the shape. The minor axis passes through the center of mass at right angles to the major axis.

[0150] In some embodiments, the aspect ratio is determined from a two-dimensional representation of the particle. In other embodiments, the aspect ratio is determined from a three-dimensional representation of the particle. Preferably, the aspect ratio is determined from a two-dimensional representation of the particle(s) and corresponds to the ratio of the minimum Feret diameter to the maximum Feret diameter. The three-dimensional shape of particles can be determined, e.g., by using X-ray microtomography (see Yin et al., Sci Rep.2016 Apr 21:6:24763) and other 3D imaging systems such as dynamic image analysis using two cameras (see Liu et al., Chem. Eng. J., 438 (2022) and Rajagopalan et al., Volume 321, November 2017, Pages 479-493). The two-dimensional shape of particles can be determined, e.g., by optical microscopy. The dimensions and morphology of the particles may also be determined by, e.g., optical microscopy as described in USP, Method 776.

[0151] According to specific embodiments, the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a hydrate or hemihydrate, preferably a hemihydrate, more preferably polymorphic form H1.

[0152] According to other specific embodiments, the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a crystalline hemihydrate polymorph characterized by one or more peaks from the powder X-ray diffraction (PXRD), wherein the peaks, expressed in degrees 20 ±0.2°, comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9.

[0153] According to yet other specific embodiments, the crystalline polymorph of the majority (e.g. at least 60 %, or at least 70 %, or at least 80 %, or at least 90 %, or at least 95 %, or at least 97 %, or at least 98 %, or at least 99 %, or at least 99.5 %, or at least 99.7 %, or at least 99.8 %, or at least 99.9 %, or 100 %) of particles is a crystalline hemihydrate polymorph characterized by one or more peaks from the powder X-ray diffraction (PXRD), wherein the peaks, expressed in degrees 20 ±0.2°, comprise 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9 and further characterized by an orthorhombic space group P212121 with the lattice parameters a = 10.7499 ± 0.1 A, b = 16.4119 ± 0.1 A, c = 17.5927 ± 0.1 A, and a = y = 0 = 90°.

[0154] The enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles described hereinabove show improved bulk properties with markedly improved manufacturability. The enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles may have one or more of higher bulk density, higher flowability and improved manufacturing properties for tableting. The processing or handling of the active pharmaceutical ingredient during the formulation and manufacturing process may be greatly improved by using the enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles described hereinabove. The enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles can thus provide desirable processing properties. They can be easier to handle during manufacturing of the solid dosage forms allowing for improved active ingredient consistency in the dosage form. The enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles disclosed hereinabove may show good tableting behavior, including one or more of (i) low tendency to stick to manufacturing equipment, such as the punches of the tableting press, and / or (ii) have good flowability, allowing for a smooth and reproducible tableting of the drug.

[0155] The bulk density of the compositions may be determined as the ratio of the mass of an untapped powder sample and its volume including the contribution of the inter- particulate void volume. Accordingly, the bulk density depends on both the density of particles and the spatial arrangement of particles in the sample. According to some embodiments, the enpatoran particles have a bulk density greater than about 0.3 g / cm3, greater than about 0.4 g / cm3, greater than about 0.5 g / cm3; greater than about 0.55 g / cm3; greater than about 0.6 g / cm3; greater than about 0.65 g / cm3; or greater than about 0.7 g / cm3. According to further embodiments, the enpatoran particles have a bulk density less than about 0.95 g / cm3, less than about 0.9 g / cm3, less than about 0.85 g / cm3, or less than about 0.8 g / cm3.

[0156] According to yet further embodiments, the enpatoran or the enpatoran particles has a bulk density from about 0.5 g / cm3 to about 0.95 g / cm3, from about 0.55 g / cm3 to about 0.9 g / cm3, from about 0.6 g / cm3 to about 0.85 g / cm3, or from about 0.7 g / cm3 to about 0.8 g / cm3.

[0157] The enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles described hereinabove may additionally have a flow function coefficient (ffc) greater than about 4; greater than about 5; greater than about 6; greater than about 7; or greater than about 8. Powder flow is important during tableting to ensure uniformity of the API powder flow and distribution into the tablet dies. This ensures tablet weight uniformity and production of tablets with consistent and reproducible properties. Powder flow is important during tableting to ensure uniformity of both the active ingredient powder flow and the distribution into the tablet dies. This ensures tablet weight uniformity and production of tablets with consistent and reproducible properties.

[0158] How to carry out the flow function coefficient (ffc) tests is described in PCT / EP2024 / 072516 and it is referred thereto for further details.

[0159] In further embodiments, the mean (or mode or median) particle diameter d90 of the enpatoran crystalline polymorph (in particular the hemihydrate) and / or particles described hereinabove, is less than about 600 pm, less than about 500 pm, less than about 450 pm, or less than about 400 pm. In further embodiments, the mean, mode or median particle diameter d90 of the particles of 5-((3R,5S)-3-amino-5-trifluoromethyl-piperidin-1-yl)-quinoline-8-carbonitrile of the compositions described herein is greater than about 1 pm, greater than about 10 pm, greater than about 50 pm; or greater than about 100 pm. In further embodiments, the mean, mode or median particle diameter d90 of the particles of enpatoran (5-((3R,5S)-3-amino-5-trifluoromethyl-piperidin-1-yl)-quinoline-8-carbonitrile) of the compositions described herein is from about 1 to about 600 pm, from about 10 to about 500 pm, from about 50 to about 450 pm, or from about 100 to about 400 pm.

[0160] According to specific embodiments, more than about 50%, more than about 60%, more than about 70%, more than about 75%, more than about 80%, more than about 85%, more than about 90%, or more than about 95% (e.g. by weight) of the enpatoran in the solid dosage form is of a crystalline hydrate or hemihydrate polymorph, preferably a crystalline hemihydrate polymorph, more preferably polymorphic form H1. In further specific embodiments, more than about 50%, more than about 60%, more than about 70%, more than about 75%, more than about 80%, more than about 85%, more than about 90% or more than about 95% of the enpatoran particles in the solid dosage form are of a crystalline hydrate or hemihydratepolymorph, preferably a crystalline hemihydrate polymorph, more preferably polymorphic form H1.

[0161] Processes for preparing the enpatoran H1 and the H1 particles are described in PCT / EP2024 / 072511 and PCT / EP2024 / 072516 (which are disclosed herein by reference) and are also described hereinbelow. Details of a process for the preparation of enpatoran particles are provided below. Further details can be found in items 144 to 160 above and in PCT / EP2024 / 072516.

[0162] Suspension or crystallization in water, or mixtures of organic solvents with water, were found to be useful to produce more isotropic, equant particles (PCT / EP2024 / 072516). The solubility of the enpatoran in water is poor, and thus a crystallization from water is not efficient and control of the particle size distribution from an aqueous suspension was low. In contrast, the usage of organic solvents in mixtures with water for the suspension or crystallization of the enpatoran provides improved control of the particles size and provides the preferred particle shapes.

[0163] A process for preparing the enpatoran particles involves the dissolution and / or suspension of enpatoran in a solvent as described below, optionally wet milling the suspension / solution, optionally heating and cooling the suspension / solution, and separating the particles of enpatoran from the solvent.

[0164] Heating the suspension may facilitate partially or fully dissolving the enpatoran in the solvent. The optional heating may be at a temperature from room temperature (for example, 25 °C) to the boiling temperature of the solvent. In embodiments, the suspension is heated to a temperature at or above 35 °C, at or above 35 °C, at or above, 40 °C, at or above 45 °C, or at or above 50 °C. Preferably, stirring or other mixing is applied to the suspension during the heating. The suspension is stirred at the selected recrystallization temperature for a period of time from 30 minutes to a day or more. In embodiments, the suspension is stirred for a period of time from 30 minutes to about 24 hours, from 1 hour to 24 hours, or from 2 hours to 24 hours.

[0165] The suspension is optionally cooled to a temperature of room temperature or below. In embodiments, the suspension is cooled to a final temperature of room temperature to 0 °C, to 0 °C to 10 °C, or to 0 °C to 5 °C. Preferably the cooling temperature is achieved slowly, i.e. , by cooling the suspension at a rate of 1 °C / minute or less, at a rate of 0.5 °C / minute or less, at a rate of 0.4 °C / minute less or at a rate of 0.3 °C / minute less, or at a rate of 0.2 °C / minuteless. Preferably, stirring or other mixing is applied to the suspension during the cooling. The suspension may be held at the cooling temperature for a period of time prior to the separation of the particles of enpatoran from the solvent. The suspension may be held at the cooling temperature for from 10 minutes to 4 hours, from 20 minutes to 2 hours, or from 30 minutes to 1.5 hours.

[0166] The particles of enpatoran may be separated from the solvent by any means known in the art, including for example, filtration or centrifugation.

[0167] The solvent for producing the particles is water, preferably in combination with one or more organic solvents. The organic solvent may be an ester, ether, alcohol, ketone, or combination thereof. Further details regarding suitable solvent can be found in PCT / EP2024 / 072516.

[0168] A preferred solvent for the preparation of the particles of enpatoran is a mixture comprising isopropyl acetate and water. The water may be present in the isopropyl acetate at a concentration of between 0.1 % to 2 % (v / v); from 0.5 % to 2 % (v / v); or from 0.5 % to 1.5 % (v / v). In an embodiment, the solvent is isopropyl acetate with 1 % water (v / v).

[0169] Wet milling may be used control or reduce the size of the particles of enpatoran and / or to ensure a more uniform particle size distribution. In the wet milling process the particles are suspended in a liquid and passed through the wet mill. The mixture may be recirculated through the wet mill until the desired properties, such as particle size and / or uniformity, are obtained. The liquid for the wet milling is a solvent as described herein.

[0170] Wet milling may be performed using techniques, apparatus and conditions that are known in the art, including, for example, using a planetary mill, colloid mill, media mill, ball mills, disc mills, and conical mills. The skilled person appreciates that various aspects of the milling process, such as the milling time, milling speed (rotation speed), temperature, etc. may be varied in order to achieve the desired particle size and / or uniformity. Further details regarding wet milling can be found in PCT / EP2024 / 072516.Tableting powder mixture and use thereof

[0171] The present invention in a second aspect relates to a powder mixture useful in the preparation of a solid dosage form, in particular tablets and its use in the preparation of a solid dosage form of the invention.

[0172] In particular the present invention further relates to a powder mixture useful in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form after compression, preferably direct compression, and optional coating with an immediate release coating, is characterized by any feature disclosed hereinabove in the context of the solid dosage form, e.g. characterized by one or more of above items 1-143.

[0173] Additionally, the present invention further relates to a powder mixture useful in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form after compression, preferably direct compression, and optional coating with an immediate release coating, is a solid dosage form as defined in any of the embodiments above, including one or more of items 1-143 above.

[0174] Furthermore, the present invention relates to the use of a powder mixture in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form (after compression, preferably direct compression, and optional coating with an immediate release coating) is characterized by any feature disclosed hereinabove in the context of the solid dosage form, e.g. characterized by one or more of above items 1-143.

[0175] Additionally, the present invention further relates to a powder mixture in the preparation of a solid dosage form, preferably a tablet, wherein the solid dosage form (after compression, preferably direct compression, and optional coating with an immediate release coating) is a solid dosage form as defined in any of the embodiments above, including one or more of items 1-143 above.Uses of Solid Dosage Form

[0176] The present invention in a third aspect furthermore relates to the solid dosage form according to any of the embodiments describe above (including items 1 to 143 described above), for use in treating or preventing a TLR7 / 8-related autoimmune disease, the solid dosage form preferably comprising a crystalline polymorph according to any one of items 115 to 143.

[0177] According to some embodiments, the TLR7 / 8-related autoimmune disease is selected from the group consisting of rheumatoid arthritis, autoimmune pancreatitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, lupus nephritis, type I diabetes mellitus, multiple sclerosis, antiphospholipid syndrome, sclerosing cholangitis, systemiconset arthritis, irritable bowel disease, scleroderma, Sjogren's disease, vitiligo, myositis, dermatomyositis, polymyositis, pemphigus vulgaris, pemphigus foliaceus, inflammatory boweldisease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, hypopituitarism, graft-versus-host disease, autoimmune skin diseases, uveitis, pernicious anemia, and hypoparathyroidism.

[0178] Additionally disclosed herein is a method treatment or prevention of a TLR7 / 8-related autoimmune disease, comprising administering to a patient in need thereof a pharmaceutically effective amount of the solid dosage form described in any of the embodiments herein above (including items 1 to 143 described above); optionally, wherein the TLR7 / 8-related autoimmune disease is selected from the group consisting of rheumatoid arthritis, autoimmune pancreatitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, lupus nephritis, type I diabetes mellitus, multiple sclerosis, antiphospholipid syndrome, sclerosing cholangitis, systemic onset arthritis, irritable bowel disease, scleroderma, Sjogren's disease, vitiligo, myositis, dermatomyositis, polymyositis, pemphigus vulgaris, pemphigus foliaceus, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, hypopituitarism, graft-versus-host disease, autoimmune skin diseases, uveitis, pernicious anemia, and hypoparathyroidism.Method of preparation of the pharmaceutical composition

[0179] The present invention in a further aspect relates method of preparation of the pharmaceutical composition (solid dosage form) described in any of the embodiments herein above (including items 1 to 143 described above).

[0180] That is, the present invention further relates to a method for preparing a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; a binder; a filler; and / or a disintegrant and optionally one more additional pharmaceutically acceptable excipients, comprising the steps ofa) providing a powder blend comprising, or consisting of, all ingredients of the core (1) as a homogenous mixture;b) compressing the powder blend, preferably by direct compression, into a core (1), preferably at a force of between 50 to 150 N; and optionallyc) coating the core (1) of step b) with an immediate release coating liquid, wherein the immediate release coating liquid preferably comprises polyvinyl alcohol and / or Hypromellose in water; andd) drying the wet coated core to obtain the solid dosage form,optionally wherein the core (1) comprises a binder selected from microcrystalline cellulose, powdered cellulose, copovidone, and combinations thereof.

[0181] Moreover, the present invention further relates to method for preparing a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof; and optionally one more additional pharmaceutically acceptable excipients; comprising the steps ofa) providing a powder blend comprising, or consisting of, all ingredients of the core (1) as a homogenous mixture;b) compressing the powder blend of step a), preferably by direct compression, into a core (1); and optionallyc) coating the core (1) of step b) with an immediate release coating liquid, preferably using spray coating, wherein the immediate release coating liquid preferably comprises polyvinyl alcohol and / or Hypromellose in water; andd) drying the wet coated core of step c) to obtain the solid dosage form;e) to provide a dried solid dosage form;(optionally wherein the core (1) comprises a binder selected from microcrystalline cellulose, powdered cellulose, copovidone, and combinations thereof).

[0182] According to one embodiment of the above methods, the core (1) further comprises a glidant and / or a lubricant.

[0183] According to a preferred embodiment of the above methods, the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose sodium; and optionally a glidant, preferably silicon dioxide and / or a lubricant, preferably magnesium stearate.

[0184] According to another preferred embodiment of the above methods, the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably silicon dioxide, a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipients.

[0185] According to yet another preferred embodiment of the above methods, the active ingredient is enpatoran, preferably enpatoran H1, the binder is microcrystalline cellulose, the filler is mannitol, the disintegrant is selected from crospovidone, carboxy starch glycolate, carboxymethylcellulose and salts and derivatives thereof, especially croscarmellose sodium, the lubricant is selected from magnesium stearate, calcium stearate, stearic acid, glycerol fatty acid esters and sodium stearyl fumarate and / or the glidant is selected from silicon dioxide and derivatives thereof.

[0186] According to specific embodiments of the above methods, the binder, the filler, the powdered cellulose, the disintegrant, the glidant, and / or the lubricant are as defined in any of the embodiments relating to the above-described solid dosage form (first aspect), including above-described items 9 to 95.

[0187] According to other specific embodiments of the above methods, the binder, the filler, the powdered cellulose, the disintegrant, the glidant, and / or the lubricant are characterized by any of the embodiments relating to the solid dosage form described above (first aspect), including above-described items 9 to 95.

[0188] According to further specific embodiments of the above methods, the amount of binder, filler, powdered cellulose, disintegrant, glidant, and / or lubricant are as defined in any of the embodiments relating to the above-described solid dosage form (first aspect), including above-described items 30 to 95.

[0189] According yet further specific embodiments of the above methods, the copovidone, the microcrystalline cellulose, the mannitol, the crospovidone, the croscarmellose or pharmaceutically acceptable salt thereof, the powdered cellulose, the silicon dioxide, and / or the stearic acid or pharmaceutical acceptable salt thereof is as defined in any of the embodiments relating to the above-described solid dosage form (first aspect), including above-described items 9 to 95.

[0190] According to yet further specific embodiments of the above methods, the mannitol, the crospovidone, the croscarmellose or pharmaceutically acceptable salt thereof, the powdered cellulose, and / or the silicon dioxide, the stearic acid or pharmaceutical acceptable salt thereof is are characterized by any of the embodiments relating to the solid dosage form described above (first aspect), including above described items 9 to 95.

[0191] According to a preferred embodiment, the active ingredient is enpatoran, preferably enpatoran H1.

[0192] According to further preferred embodiment of the above methods, the active ingredient is enpatoran, is a crystalline hemihydrate as defined in any of the embodiments relating to the above-described solid dosage form (first aspect) and in particular to crystalline hemihydrates, including above-described items 114 to 142.

[0193] According to yet further preferred embodiment of the above methods, the active ingredient is enpatoran and wherein the enpatoran comprises, or consists of, particles of a crystalline polymorph of enpatoran, preferably H1, as defined in any of the embodiments relating to the above-described crystalline hemihydrate particles, including above-described items 130 to 143.

[0194] According to a particular embodiment of the above methods, the active ingredient is enpatoran, preferably enpatoran H1, the binder is microcrystalline cellulose, the filler is mannitol, the disintegrant is croscarmellose sodium, the lubricant is magnesium stearate and / or the glidant is highly dispersed silicon dioxide, e.g. hydrophilic fumed silicon dioxide.

[0195] According to another particular embodiment of the above methods, the immediate release coating is a film coating suitable for immediate release of the active ingredient.

[0196] According to a specific embodiment of the above methods, the immediate release coating is a cosmetic coating and / or wherein the immediate release coating provides color, protection (e.g. light, environmental and moisture protection) and / or taste-masking for the core (1).

[0197] According to another specific embodiment, the immediate release coating (2) is applied to the core (1) by applying an immediate release coating liquid using spray coating, e.g. a fluidized-bed spray coating, and drying the wet coated solid dosage form, simultaneously or concomitantly, e.g. using a fluidized bed or an oven.

[0198] According to further specific embodiments of the above methods, the immediate release coating liquid comprises, or consists of, polyvinyl alcohol, macrogol, talcum, titanium dioxide, glycerol monocaprylocaprat, and iron oxide yellow; or polyvinyl alcohol (e.g. part, hydr.), calcium carbonate, talcum, hypromellose, glycerin-monocaprylocaprat, and iron oxide-yellow / red and black.

[0199] According to one embodiment, wherein step a) comprises and sieving all ingredients of the core (1) (i.e all excipients and the active ingredient through a round hole sieve, e.g. 0.5-2 mm (or 0.7-1.5 mm, or a 0.8-1.7 mm, or a 1.0.9 to 1 ,9mm or a 1.0 mm) round whole sieve.

[0200] According to another embodiment of the above methods, the ingredients of core (1) are sieved and filled into a container; optionally wherein the ingredients are added in a specific order preferably starting with the binder, followed by the active ingredient, followed by the filler, followed by the powdered cellulose, followed by the disintegrant, followed by the glidant, and finally followed by the lubricant; optionally wherein all ingredients except the lubricant are added and mixed, e.g. for 10 min, after which the lubricant is added, and the mixing is continued, e.g. for 5 min; to then compress the resulting powder mix in step b) into a (tablet) core (1).

[0201] According to yet another embodiment, in step b) for compression of the tablet a main compression force of 4-14 kN, or 4.5 to 12 kN, or 5 to 10 kN is used, optionally wherein the target hardness of the core (1) is 50-150 N, or 70-130 N, or about 80 N.

[0202] According to further embodiments of the above methods, the immediate release coating is characterized by any of the embodiments relating to the above-described solid dosage form (first aspect) and in particular the immediate release coating, including abovedescribed items 100 to 106.

[0203] According to yet further embodiments of the above methods, the final oral dosage form is as defined in any of the embodiments relating to the above-described solid dosage form (first aspect), including above-described items 1 to 143 above.

[0204] According to yet further embodiments of the above methods, the final oral dosage form is characterized by any of the embodiments relating to the solid dosage form described above (first aspect), including above described items 1 to 143 above.

[0205] All references cited herein are incorporated by reference in the disclosure of the invention hereby.

[0206] Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable examples are described below. The examples are particularly to be construed such that they are not limited to the explicitly demonstrated combinations of features, but the exemplified features may be unrestrictedly combined again provided that the technical problem of the invention is solved. Similarly, the features of any claim can be combined with the features of one or more other claims. The present invention having been described in summary and in detail, is illustrated and not limited by the following examples.EXAMPLES

[0207] Enpatoran is a small molecule inhibitor of the Toll-Like-Receptor 7 and 8. The inhibition of Toll-Like-Receptors is linked to various autoimmune diseases, e.g. lupus, such as systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE), and multiple sclerosis.

[0208] The enpatoran formulations used in previous clinical trials were to be optimized towards a higher drug load to obtain a tablet with an acceptable size and weight. Furthermore, a specific polymorph was chosen, to avoid any forms of enpatoran that potentially may be unstable and characterized by unfavorable particle characteristics.Methods

[0209] As depicted in the examples below, in certain exemplary embodiments, formulations are prepared according to the following general procedures. It will be appreciated that, although the general methods depict the preparations of certain solid dosage forms of the present invention, the following general methods can be applied to prepare the solid dosage forms, as described herein. Hardness, friability, disintegration time, and dissolution can be measured according to Eur. Ph. A. The symbols and conventions used in the following are consistent with those used in the contemporary scientific literature. Unless otherwise indicated, all temperatures are expressed in °C (degrees Centigrade).

[0210] Styl'One tabletting press and a Glatt GC2 coater were used for tableting and coating, respectively.

[0211] Tablet dissolution was measured as follows. The tablet core prototypes were subjected to dissolution analysis in 0.1 N HCI. The target release rate was set at >85% within 15 minutes.Disolution tester Sotax AT Xtend 7X, with CP 7-35 piston pump for automated sampling; UV spectrometer: Analytik Jena Specord 200 plus. Tablet hardness was measured using Tablet tester Sotax ST50. Disintegration time was measured using disintegration tester Sotax DisiTest 50.

[0212] Enpatoran active ingredient and some excipients of the embodiments below were manufactured by a direct compression process step (c.f. Figure 1). All excipients (microcrystalline cellulose type 102; Parteck M 200; cellulose powdered; croscarmellose sodium; silicon dioxide, highly dispersed; and magnesium stearate VS) and the active ingredient (enpatoran H1) are weighed, sieved through a 1.0 mm round hole sieve, and filled into a container in a specific order. The first step is to sieve the microcrystalline cellulose into the container. This is followed by the addition of the active ingredient (enpatoran H 1 ), then Parteck M 200, cellulose powdered, croscarmellose sodium, and silicon dioxide, highly dispersed, which are mixed for 10 minutes. The final step is to add magnesium stearate VS to the mixed powder and mix for five minutes. The resulting mixture is then compressed into tablet cores using a 7.7 mm embossed round punch (6 mm for 25 mg tablets). Opadry Yellow is weighed and suspended in purified water, and the tablet cores are coated with the suspension.Identification of preliminarily prototype formulation

[0213] Enpatoran is a development compound aimed at the treatment of systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (OLE). It was shown that the engineered hemihydrate H1 polymorph of enpatoran is much more conducive to tablet preparation by compression than other polymorphic forms. In particular, it was found that the H1 polymorph of enpatoran, due to its favorable and more controllable properties (e.g., monomodal and tight particle size distribution, high bulk density, equant particle shape) was found to be particularly suitable for direct compression, a preparation process, which would not have been considered with other polymorphic forms of enpatoran. This, together with the high drug load requirement, was taken as an initiative to develop a tablet formulation for direct compression.

[0214] The objective was to develop an immediate-release film-coated tablet with a very rapid dissolution profile (>85% within 15 minutes e.g., 0.1N HCL). A formulation for the direct compression process was developed for this purpose and excipients that are suitable for direct tableting process were used.

[0215] In order to implement a process for direct compression, a certain number of points must be considered. The formulation should have good compressibility, which can be a challenge, if the active ingredient has poor compressibility. Furthermore, the required homogeneity of the final blend must be guaranteed by the mixing process and also be maintained during the tableting process. Otherwise, the various components may segregate, which can lead to an uneven distribution of the tablet components in the press and in an insufficient content uniformity. Furthermore, the consistency of the tablets produced cannot be guaranteed from batch to batch, since segregation phenomena might differ between batches.

[0216] One of the principal risk factors for segregation is a wide particle size distribution in direct compression formulations, in which active ingredients tend to be at the fine end of the range. When there is a wide range of particle sizes, there is an increased likelihood of sifting, where the smaller particles 'slip through' the bigger ones. Other bulk powder properties are also important for successful tabletting, such as good flowability and sufficient bulk density, and all of these factors combine to place a high requirement on the excipients used for direct compression.

[0217] Therefore, a more careful selection of excipients in comparison to granulation processes is required because the raw materials must demonstrate good flowability and compressibility. In order to master these challenges, the excipients were tested and selected carefully and are described below.Different formulations based on the technology of direct compression were evaluated based on their tabletability (tensile strength vs. compression pressure) and tablet qualities (hardness, friability, disintegration time and dissolution). The preliminarily identified prototype formulation showed a good tabletability with an increase of tablet hardness overall evaluated compression force levels (c.f. Figure 1 and 2 & Table 1).Table 1: Composition of the preliminarily identified prototype formulation [TestFormulationl (TabletFormulationl)].However, the tablets (cores) of the highest hardness level still showed relatively fast disintegration of about 30 s, which prove their feasibility for immediate release formulations (c.f. Figure 2 and 3). Nevertheless, the fast disintegration indicates a potential sensitivity of the tablets surface towards humidity. As the next process step involves coating of these tablets with an aqeuous suspension, a distinct prolongation of the disintegration to for example more than 60 s would be desirable. That is, the aim was to adapt the formulation to achieve a suitable disintegration time without impairing the very rapid dissolution.Prolongation of the disintegration

[0218] The strategy was to adapt the formulation, in particular with respect to the disintegrant or further binding agents. Therefore, a range of variations for the tablet formulation were tested (c.f. table 2 below, which lists some of them).

[0219] One approach was to change something about the disintegrant or binding agent. For example, the disintegrant was omitted (TestFormulation2), replaced by another one (Starch 1500; TestFormulation5) and another binding agent was added (cellulose powder (TestFormulation4); Kollidon VA64 (TestFormulation3)).Table 2: Composition of the different variations in the formulation

[0220] Reaching the target hardness level of 80 N was feasible with all formulations evaluated in this study except for TestFormulation5, where the high amount of starch 1500 replacing MCC as dry binder and Mannitol as filler, both with good dry binding properties led to a significant decrease in tablet hardness. Consequently, it was not possible to reach higher hardness values even by further increasing the compression force (cf. Figure 4).

[0221] Implementing powdered cellulose (e.g. 5%) (TestFormulation4) led to a slight increase in the required main compression force to obtain tablets with a hardness of approximately 80 and 100 N compared to the corresponding original formulation without disintegrant (TestFormulation2). Nevertheless, since the overall profile is still increasing at higher main compression force levels, the overall compression properties of these formulations are still good.

[0222] Surprisingly the addition of powdered cellulose (e.g. 5%) led to the desired effect of a reasonable prolongation of the disintegration time and resulted in tablets that disintegrate in more than 1 minute but still disintegrate rapidly (<5 min). This was not to be expected since the addition of another binder (Kollidon VA64; TestFormulation3) and omitting the disintegrant (TestFormulation2) did not lead to the desired effect. In addition, cellulose powder has disintegrant-like properties, due to its fluid uptake and swelling characteristics. This is also in contradiction to the extended disintegration time. Using starch 1500 as a replacement for croscarmellose sodium as disintegrant leads to far longer disintegration times than it was aimed for (TestFormulation5), despite the decreased overall tablet hardness.

[0223] Putting the focus on the target tablet hardness of 80 N and taking the aim of an average disintegration time of more than 1 min and a reasonable disintegration time (< 5 min) into account, formulation TestFormulation4 could be identified as most suitable candidate. The formulation TestFormulation2 had also nearly fulfilled the required disintegration time of min.1 min. Also, the target hardness of 80 N can be confirmed, as the stability of the tablets confirmed by the friability data (c.f.Table 3) is sufficient and the disintegration time values are in the target area.Table 3: Friability of the different variations in the formulation at a certain tablet hardness

[0224] The tablet core prototypes TestFormulation2 and TestFormulation4 were subjected to dissolution analysis in 0.1N HCI (cf. Figure 7, full line is TestFormulation2 and dashed line is TestFormulation4). TestFormulation4 achieved the target release rate (at >85% within 15 minutes in 0.1 N HCI) in contrast to the formulation omitting the disintegrant (TestFormulation2). Thus, TestFormulation4 had a desirable dissolution profile, while TestFormulation2 despite faster disintegration compared to the formulation with powdered cellulose (Figure 6) had a slower release rate than the target release rate (Figure 7).

[0225] In summary, an immediate-release film-coated tablet with a very rapid dissolution was developed for enpatoran with an appropriate disintegration time (>1 min and < 5 min) of the tablet core, which ensures further processing of the cores in the coating process.

[0226] Solid oral formulation consisting of enpatoran and one or more excipients is described below

[0227] Fillers: mannitol[02281 Binders: microcrystalline cellulose (MCC), powdered cellulose, Copovidone (e.g., Kollidon VA64)[02291 Disintegrants: crospovidone (e.g., Kollidon CL-SF), croscarmellose and its pharmaceutical acceptable salts, powdered cellulose

[0230] Lubricants: e.g. stearic acid and its pharmaceutical acceptable salts (e.g. Mg stearate).

[0231] Glidant: silicon dioxide, highly dispersed[02321 Coating agent: ready to use mixture containing polyvinylalkohol, macrogol, talcum, titanium dioxide, glycerol monocaprylocaprat, iron oxide yellow (Opadry QX321A220017 yellow), ready to use mixture containing polyvinyl alcohol part, hydr., calcium carbonate, talcum, hypromellose, glycerin-monocaprylocaprat, iron oxide-yellow / red & black (Opadry TF 271ZA220000-CN yellow) or other immediate release coating agents based on polyvinyl alcohol or hypromellose.

[0233] The following table contains an optimized exemplary formulation, which is a product of the above described insights.Table 4: Composition of optimized exemplary enpatoran formulation

[0234] In the following a more detailed description of the ingredients in the exemplary final formulation is provided:

[0235] Mannitol (Parteck® M200)

[0236] Mannitol is included (e.g. with 25.01% or 25.3%) in the formulation and acts as filler. Mannitol can be used to increase the compression bulk to a size practical for compression. For solid oral dosage forms it is widely used as diluent, plasticizer and sweetening agent. As diluent in tablet formulations it is often used, as it is not hygroscopic and can consequently be used with moisture sensitive active ingredients. Mannitol may be used for direct compression as well as for granulation. The functionality-related characteristics PSD and powder flow (characterized by e.g. flow through an orifice, hausner ratio, compressibility index, angle of repose) may impact the compression process.

[0237] Microcrystalline cellulose type 102 (MCC) (Vivapur® 102 Premium)

[0238] MCC is included (e.g. with 37.51%) in the formulation. MCC can act as a binder to impart cohesive qualities to the material. This facilitates the tablet formation during the compression process and ensures that the tablets remain intact after the compression. It is also often used as a as filler.

[0239] The functionality of MCC is inter alia based on its plasticity. During compression MCC plastically deforms and therefore, maximizes the area of interparticle bonding. Because of the broad PSD and its relatively low bulk density, small amounts of MCC are able to efficiently bind other materials. The broad PSD range provides optimum packaging density and coverage of other materials.

[0240] The flowability can be improved through the use of quality grade having larger particle size distribution. These coarser fractions, accounting for a large volume / mass fraction but a low number fraction, enable improved flow. This enhances the required die filling during the compression process and allows for a higher compression speed.

[0241] Cellulose, powdered (Elcema® F150)

[0242] Powdered cellulose is included (e.g. with 4.85%) in the formulation. It can act as binder and disintegrant. The functionality of powdered cellulose as disintegrant is related to its fluid uptake and swellability characteristics. The function-related properties PSD affects the swelling properties and therefore the disintegration.

[0243] Silicon dioxide, highly dispersed (Aerosil® 200)

[0244] Silica, colloidal anhydrous is included (e.g. with 1.02%) in the formulation. It can act as glidant to improve the flow characteristics of the powder by reducing the inter- particle friction and cohesion. Its small particle size and large specific surface area give it desirable flow characteristics that are exploited to improve the flow properties of dry powders in a number of processes such as tableting and capsule filling. Colloidal silicon dioxide is hygroscopic but adsorbs large quantities of water without liquefying. Aerosil 200 has a specific surface area of 200 m2 / g.

[0245] Croscarmellose sodium (Ac-Di-Sol® SD-711)

[0246] Croscarmellose sodium (CCS) is included in the formulation (e.g. 0.97% based on the entire formulation). It acts as disintegrant in order to facilitate the disintegration after oral administration.

[0247] Croscarmellose sodium (CCS) is cross-linked carboxymethylcellulose sodium and used as a superdisintegrant. The functionality of CCS as a superdisintegrant is related to its fluid uptake and swellability characteristics. It is known from literature [Pharmaceutical Excipients- Properties, Functionality, an Applications in Research and Industry; Edited by Otilia M.Y.Koo; Wiley; The influence of product brand-to-brand variability on Superdisintegrant Performance. A case study with Croscarmellose Sodium; Na Zhao & L.L. Augsburger; Pharmaceutical Development and Technology 11:179-185 (2006)] that the function-related properties PSD and degree of substitution (including the ratio of acidic to basic substituents) are the major factors influencing the swelling of CCS. Because swelling of CCS is attributed to the hydration of the carboxymethyl group, the carboxymethyl substitution increases the swelling ability of CCS. Compared to the acidic substituent, the basic substituent (its sodium salt) is more hydrophilic and tends to swell more extensively. Therefore, CCS show with basic substituents a better tendency to swell than with acidic substituents. The swelling ability of CCS is also adversely impacted at lower pH due to conversion of carboxymethyl sodium to it less hydrophilic free form [Pharmaceutical Excipients- Properties, Functionality, an Applications in Research and Industry; Edited by Otilia M.Y.Koo; Wiley],

[0248] Magnesium stearate VS (LIGAMED MF-2-V-MB)

[0249] Mg stearate is included (e.g. with 1.46%) in the formulation. It acts as lubricant / glidant in order to reduce friction at the interface of the powder and wall during compression. In addition, it improves the flow characteristics by reducing the particle- particle friction. Magnesium stearate is a boundary layer lubricant and the functionality is based on minimization of any irregular surfaces of the excipients by film formation on their surface. This reduces interparticle contact points, decreases friction and cohesive forces. Finally, the flowability of the powder blend is improved and the compression process is facilitated.

[0250] Qpadry® QX321A220017 yellow

[0251] An immediate release coating is applied for cosmetic purposes. Therefore, the coating uniformity and coating process efficiency have no impact on dissolution. However, the appearance and therefore the patient compliance may be impacted. For the coating process, fully formulated dry blend systems for the aqueous film coating of pharmaceutical oral solid dosage forms were used. Opadry® QX321A220017 yellow is based on the polymer polyvinyl alcohol (PVA).

Claims

CLAIMS1. A solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) preferably is prepared by compression; wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; and a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler; and a disintegrant.

2. The solid dosage form of claim 1, wherein the core (1) further comprises a glidant and / or a lubricant3. The solid dosage form of claim 1 or 2, wherein the core (1) comprises, or consists of, an active ingredient, which is enpatoran; powdered cellulose; a binder, preferably microcrystalline cellulose; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose sodium; and optionally a glidant, preferably silicon dioxide and / or a lubricant, preferably magnesium stearate.

4. The solid dosage form of any of the preceding claims, wherein the core (1) comprisesi. enpatoran, preferably enpatoran H1;ii. a binder selected from microcrystalline cellulose, copovidone, and a combination thereof, preferably microcrystalline cellulose;iii. a filler selected from the group consisting of mannitol, sucrose, maltose, lactose, trehalose, glycerol, maltitol, isomalt, sorbitol, xylitol, and combinations thereof, preferably mannitol;iv. a disintegrant, selected from crospovidone, carboxy starch glycolate, carboxymethylcellulose and salts and derivatives thereof, and combinations thereof, preferably croscarmellose or a pharmaceutically acceptable salt thereof, more preferably croscarmellose sodium; andv. powdered cellulose; and optionallyvi. a glidant, which is selected from silicon dioxide (silica), talc, and tribasic calcium phosphate, or a combination thereof, preferably highly dispersed silicon dioxide; and / orvii. a lubricant, which is selected from stearic acid or a pharmaceutical acceptable salt thereof, glycerol fatty acid esters and sodium stearyl fumarate, preferably stearic acidor a pharmaceutical acceptable salt thereof, or a combination thereof, preferably magnesium stearate, calcium stearate, or stearic acid, glycerol fatty acid esters and sodium stearyl fumarate.

5. The solid dosage form of any of the preceding claims, wherein the solid dosage form comprises, or consists of, a core (1) comprising, or consisting of, an active ingredient, which is enpatoran H1; powdered cellulose; a binder, preferably microcrystalline cellulose grade 102; a filler, preferably mannitol; a disintegrant, preferably croscarmellose sodium; a glidant, preferably highly dispersed silicon dioxide, a lubricant, preferably magnesium stearate; and optionally one more additional pharmaceutically acceptable excipients; and an optional immediate release coating (2) covering the core (1).

6. The solid dosage form of any of the preceding claims, wherein the core (1) comprises, or consists of, 2-55 wt.-% active ingredient, preferably enpatoran; 5-70 wt.-% binder; 5-45 wt.-% filler; 0.15-6 wt.-%; disintegrant; 0.5-15 wt.-% powdered cellulose; 0.2-6 wt.-% glidant; and / or 0.2-7 wt.-%, wt.-% lubricant, relative to the total weight of the core (1).

7. The solid dosage form of any of the preceding claims, wherein the core (1) comprises, or consists of,24-30 wt.-%, or 26-28 wt.-%, or 26.55-27.55 wt.-%, active ingredient, preferably enpatoran; and / or35.6-41.6 wt.-%, or 37.6-39.6 wt.-%, or 38.1-39.1 wt.-%, binder; and / or- 23.75-27.75 wt.-%, or 24.75-26.75 wt.-%, or 25.25-26.25 wt.-%, filler; and / or0.3-2 wt.-%, or 0.6-1.4 wt.-%, or 0.9-1.1 wt.-%, disintegrant; and / or1-10 wt.-%, or 4-6 wt.-%, or 4.5-5.5 wt.-%, powdered cellulose; and / or0.35-2 wt.-%, or 0.65-1.45 wt.-%, or 0.95-1.15 wt.-%, glidant; and / or0.5-3 wt.-%, 1.0-2.0 wt.-%, or 1.4-1.6 wt.-%, lubricant,relative to the total weight of the core (1).

8. The solid dosage form of any of the preceding claims, wherein solid dosage form comprises, or consists of, 2-45 wt.-% active ingredient; 5-70 wt.-% binder; 5-45 wt.-% filler; 0.15-6 wt.-%, disintegrant; 0.5-15 wt.-% powdered cellulose; 0.2-6 wt.-% glidant; and / or 0.2-7wt.-% lubricant; and optionally 0.3-10 wt.-% immediate release coating; relative to the total weight of the solid dosage form.

9. The solid dosage form of any of the preceding claims, wherein the core (1) comprises, or consists of,i. 5-35 wt.-% active ingredient, preferably enpatoran, 30-47 wt.-% binder; 18-34 wt.-% filler; 0.2-4 wt.-%, disintegrant; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant; and / or 0.2-7 wt.-% lubricant; and optionally 0.3-10 wt.-% immediate release coating;orii. 23-29 wt.-% active ingredient, preferably enpatoran, 34.5-40.5 wt.-% binder; 22-28 wt.- % filler; 0.3-1.6 wt.-% disintegrant; 3-7 wt.-% powdered cellulose; 0.4-1.7 wt.-% glidant; and / or 0.8-2.1 wt.-% lubricant; and optionally 1.9-3.9 wt.-% immediate release coating;oriii. 1-20 wt.-% active ingredient, preferably enpatoran, 38-55 wt.-% binder, 23-40 wt.-% filler; 0.2-4 wt.-% disintegrant; 1-10 wt.-% powdered cellulose; 0.2-6 wt.-% glidant; and / or 0.2-7 wt.-% lubricant; and optionally 0.3-10 wt.-% immediate release coating;relative to the total weight of the solid dosage form.

10. The solid dosage form of any of the preceding claims, wherein the core (1) is prepared by compression, preferably direct compression.

11. The solid dosage form of any of the preceding claims, wherein the active ingredient is enpatoran, which comprises, or consists of, a crystalline hemihydrate, preferably form H1, preferably wherein the crystalline hemihydrate form H1 is characterized by one, or more, two or more, three or more, four or more, five or more, six or more, seven or more, eight or more, nine or more, ten or more, eleven or more, twelve or more, thirteen or more, fourteen or more, fifteen or more, sixteen or more, seventeen or more, eighteen or more, nineteen or more, or each of the PXRD peaks, expressed in degrees 26 ±0.2°, 7.2, 9.7, 13.4, 14.3, 17.0, 17.8, 19.9, 20.6, 21.5, 21.9, 22.2, 22.6, 23.0, 23.5, 24.1, 25.1, 25.5, 25.8, 26.4 and 26.9.

12. The solid dosage form according to any one of the preceding claims, wherein the solid dosage form is an oral dosage form; preferably wherein the solid dosage form is a tablet or mini-tablet, a pellet, or a granule, preferably a tablet.

13. The solid dosage form according to any of the preceding claims, for use in treating or preventing a TLR7 / 8-related autoimmune disease, the solid dosage form preferably comprising a crystalline polymorph according to any one of claims 1 to 12; optionally wherein the TLR7 / 8-related autoimmune disease is selected from the group consisting of rheumatoid arthritis, autoimmune pancreatitis, lupus, systemic lupus erythematosus, cutaneous lupus erythematosus, lupus nephritis, type I diabetes mellitus, multiple sclerosis, antiphospholipid syndrome, sclerosing cholangitis, systemic onset arthritis, irritable bowel disease, scleroderma, Sjogren's disease, vitiligo, myositis, dermatomyositis, polymyositis, pemphigus vulgaris, pemphigus foliaceus, inflammatory bowel disease, Crohn's disease, ulcerative colitis, autoimmune hepatitis, hypopituitarism, graft-versus-host disease, autoimmune skin diseases, uveitis, pernicious anemia, and hypoparathyroidism.

14. Method for preparing a solid dosage form comprising, or consisting of, i) a core (1); and optionally ii) an immediate release coating (2) covering the core (1); wherein the core (1) comprises, or consists of, an active ingredient, preferably enpatoran; optionally powdered cellulose; a binder, preferably selected from microcrystalline cellulose, copovidone, and a combination thereof; a filler, preferably mannitol; and a disintegrant, preferably croscarmellose or a pharmaceutically acceptable salt thereof; and optionally one more additional pharmaceutically acceptable excipients; comprising the steps ofa) providing a powder blend comprising, or consisting of, all ingredients of the core (1) as a homogenous mixture;b) compressing the powder blend of step a), preferably by direct compression, into a core (1); and optionallyc) coating the core (1) of step b) with an immediate release coating liquid, preferably using spray coating, wherein the immediate release coating liquid preferably comprises polyvinyl alcohol and / or Hypromellose in water; andd) drying the wet coated core of step c) to obtain the solid dosage form.

15. The method according to claim 14, wherein the final oral dosage form is as defined in any of claims 1 to 12.

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