Oral pharmaceutical dosage form providing immediate release of vidofludimus

Abstract

The invention relates to a pharmaceutical tablet for oral administration, which comprises or essentially consists of vidofludimus or a physiologically acceptable salt and / or solvate thereof; one or more fillers; one or more disintegrants; optionally, one or more lubricants; preferably, which comprises an intragranular phase and optionally an extragranular phase, wherein the intragranular phase is dry granulated; and wherein said pharmaceutical tablet under in vitro conditions in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 75 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet.

Description

Oral pharmaceutical dosage form providing immediate release of vidofludimus

[0001] Priority is claimed of European patent application no. 23 191 536.4 that was filed on August 15, 2023, and of European patent application no. 24 179 295.1 that was filed on May 31, 2024.FIELD OF THE INVENTION

[0002] The invention relates to a pharmaceutical tablet for oral administration, which comprises or essentially consists of vidofludimus or a physiologically acceptable salt and / or solvate thereof; one or more fillers; one or more disintegrants; optionally, one or more lubricants; preferably, which comprises an intragranular phase and optionally an extragranular phase, wherein the intragranular phase is dry granulated; and wherein said pharmaceutical tablet under in vitro conditions in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 75 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet.BACKGROUND ART

[0003] Vidofludimus calcium (IMU-838) is a selective and potent second-generation dihydroorotate dehydrogenase (DHODH) oral immunomodulator being developed for the treatment of several chronic inflammatory diseases, including relapsing -remitting Multiple Sclerosis (RRMS).

[0004] WO 2003 / 006424 and WO 2003 / 006425 relate to compounds as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

[0005] WO 2012 / 001148 relates to calcium salts of compound as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

[0006] WO 2012 / 001151 relates to salts as anti-inflammatory, immunomodulatory and anti-proliferatory agents.

[0007] WO 2016 / 200778 relates to methods for treatment of melanoma.

[0008] WO 2018 / 177151 relates to compounds modulating activity of famesoid x receptor and methods for the use thereof.

[0009] WO 2019 / 101888 relates to a dosage regimen of vidofludimus for use in the prevention or treatment of chronic inflammatory and / or autoimmune diseases.

[0010] WO 2019 / 175396 relates to calcium salt polymorphs as anti-inflammatory, immunomodulatory and anti-proliferatory agent.

[0011] WO 2021 / 214033 relates to vidofludimus for use in the treatment or prevention of viral diseases.

[0012] US 2023 / 051911 relates to methods of treating or ameliorating multiple sclerosis by the DHODH inhibitor vidofludimus or a pharmaceutically acceptable salt and / or a solvate, in particular a hydrate, thereof or a solvate, in particular a hydrate, of a pharmaceutically acceptable salt thereof, by administering to a human patient a therapeutically effective amount of the DHODH inhibitor, more specifically a daily dose of about 10 mg to about 45 mg.

[0013] J. Leban et al., Bioorg. Med. Chem. Lett. (2005), 15:4854 relates to SAR, species specificity, and cellular activity of cyclopentene dicarboxylic acid amides as DHODH inhibitors.

[0014] A. Muehler et al., Drugs in R&D (2019) 19:351, doi: 10.1007 / s40268-019-00286-z relates to the selective oral immunomodulator vidofludimus in patients with active rheumatoid arthritis: safety results from the COMPONENT study.

[0015] F. Hahn et al., Viruses (2020) 12: 1394, doi: 10.3390 / vl2121394 report that IMU-838, a developmental DHODH inhibitor in Phase II for autoimmune disease, shows anti-SARS-CoV-2 and broadspectrum antiviral efficacy in vitro.

[0016] Y. Zhu et al., Front. Pharmacol. (2020) 11:590, doi: 10.3389 / fphar.2020.00590 relates to repositioning an immunomodulatory drug vidofludimus as a famesoid X receptor modulator with therapeutic effects on NAFLD.

[0017] A. Muehler et al., Eur. J. Drug Metab. Pharmacokinet. (2020) 45:557, doi: 10.1007 / s 13318- 020-00623-7, relates to safety, tolerability and pharmacokinetics of vidofludimus calcium (IMU-838) after single and multiple ascending oral doses in healthy male subjects.

[0018] A. Muehler et al., Mult. Scler. Relat. Dis. (2020) 102129:43, doi: 10.1016 / j.msard.2020.102129 relates to vidofludimus calcium, a next generation DHODH inhibitor for the treatment of relapsingremitting multiple sclerosis.

[0019] K. Sharma et al., BMJ Open (2022) 12:e055205, doi: 10.1136 / bmjopen-2021-055205 relates to a prospective, randomized, parallel-group, open-label study to evaluate the effectiveness and safety of IMU-838, in combination with oseltamivir, in adults with CO VID-19: the IONIC trial protocol.

[0020] M.J.G.T. Vehreschild et al., Infect. Dis. Ther. (2022) 11:2159, doi: 10.1007 / s40121-022-00690- 0 relates to safety and efficacy of vidofludimus calcium in patients hospitalized with COVID- 19: a double-blind, randomized, placebo-controlled, phase 2 trial.

[0021] R.J. Fox et al., Ann. Clin. Transl. Neurol. (2022) 9:977 relates to a double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium relapsing-remitting multiple sclerosis.

[0022] E.J. Carey et al., Hepatol. Commun. (2022) 6: 1589 relates to a pilot study of vidofludimus calcium for treatment of primary sclerosing cholangitis.

[0023] There is a demand for oral pharmaceutical dosage forms of vidofludimus at different dose strength ranging from about 5 mg to about 50 mg, expressed as equivalent dose relative to the anhydrous non-salt form of vidofludimus.

[0024] It is an object of the invention to provide advantageous oral dosage forms of vidofludimus.SUMMARY OF THE INVENTION

[0025] This object has been achieved by the subject-matter of the patent claims.

[0026] It has been surprisingly found that oral dosage forms can be prepared that provide immediate release of vidofludimus and that are easy to manufacture. The oral dosage forms according to the invention require a minimum number of pharmaceutical excipients.

[0027] Further, it has been surprisingly found that oral dosage forms can be prepared from comparatively simple pharmaceutical compositions. These pharmaceutical compositions allow for preparing oral dosage forms having different dose strength of vidofludimus at the same total weight, wherein only the amount of a single excipient (filler) needs to be altered in order to compensate the different amount of vidofludimus (i.e. the different dose strength), whereas the content of all other excipients (e.g. disinte- grant and lubricant) can remain the same.

[0028] Still further, it has been surprisingly found that fast disintegrating tablets can be prepared that provide immediate release of vidofludimus in vitro. The solubility of the non-salt form of vidofludimus strongly depends on the pH value and it is practically insoluble in water. Nevertheless, with the oral dosage forms according to the invention dissolution profdes can be achieved where at least 75%, at least 90%, or even more of the vidofludimus that was originally contained in the dosage form have been released within 45 minutes at pH 7.5 (50 mM citrate buffer containing 2% SDS).

[0029] Y et further, it has been surprisingly found that when the vidofludimus formulation is granulated, preferably dry granulated, neither binder nor disintegrant is needed in the extragranular phase.

[0030] Furthermore, it has been surprisingly found that tablets containing vidofludimus can be advantageously prepared by dry granulation. The dry granulated tablets have several advantages compared to wet granulated tablets, especially with respect to disintegration time in accordance with Ph. Eur. 2.9. 1, resistance to crushing in accordance with Ph. Eur. 2.9.8, dissolution in accordance with Ph. Eur. 2.9.3, flowability in accordance with Ph. Eur. 2.9.16. and processability in high speed processes.

[0031] Moreover, it has been surprisingly found that vidofludimus is very well compatible with microcrystalline cellulose. Microcrystalline cellulose can be used as predominant excipient, i.e. the excipient having the greatest content of all excipients, e.g. 70 wt.-% and above. When the vidofludimusformulation containing microcrystalline cellulose is granulated, preferably dry granulated, no additional binder is needed, not even in the intragranular phase. Surprisingly, fast disintegrating tablets providing immediate release can be manufactured by dry granulation wherein the sum of the content of vidofludi- mus and the content of microcrystalline cellulose amounts to more than 90 wt.-% and even about 95 wt.-%.

[0032] It has been surprisingly found that vidofludimus, in particular vidofludimus calcium present as polymorph A, is particularly stable in tablets. Such tablets can be produced by dry or wet granulation. The color of vidofludimus calcium present as polymorph A is white to off-white (see e.g. WO 2019 / 175396). Therefore, tablets containing vidofludimus calcium present as polymorph A do not need a coating for blinding in clinical studies. In contrast, vidofludimus free acid in crystalline form is yellow (see e.g. WO 2012 / 001148).DETAILED DESCRIPTION OF THE INVENTION

[0033] A first aspect of the invention relates to a pharmaceutical tablet for oral administration, which comprises or essentially consists of- vidofludimus or a physiologically acceptable salt and / or solvate thereof;- one or more fillers;- one or more disintegrants;- optionally, one or more lubricants; preferably, which comprises an intragranular phase and optionally an extragranular phase, wherein the intragranular phase is dry granulated; and which under in vitro conditions in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 75 wt.- % of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet.

[0034] Preferably, the vidofludimus or a physiologically acceptable salt and / or solvate thereof is crystalline.

[0035] In preferred embodiments, the vidofludimus or a physiologically acceptable salt and / or solvate thereof is micronized.

[0036] Preferably, the vidofludimus or a physiologically acceptable salt and / or solvate thereof preferably has a particle size distribution such that the value for Dv50, determined by laser light diffraction in accordance with Ph. Eur. 2.9.31, is at most 70 pm, preferably at most 60 pm, more preferably at most50 pm, yet more preferably at most 40 pm, even more preferably at most 30 pm, most preferably at most 20 pm, and in particular at most 10 pm.

[0037] In other preferred embodiments the vidofludimus or a physiologically acceptable salt and / or solvate thereof is not micronized.

[0038] Preferably, the vidofludimus or a physiologically acceptable salt and / or solvate thereof preferably has a particle size distribution such that the value for Dv50, determined by laser light diffraction in accordance with Ph. Eur. 2.9.31, is at least 80 pm, preferably at least 90 pm, more preferably at least 100 pm, yet more preferably at least 110 pm, even more preferably at least 120 pm, most preferably at least 130 pm, and in particular at least 140 pm.

[0039] Preferably, the vidofludimus or a physiologically acceptable salt and / or solvate thereof is both, crystalline and micronized.

[0040] Preferably, vidofludimus is present as calcium salt, preferably as hemicalcium monohydrate:

[0041] Preferably, vidofludimus calcium is present as polymorph A in accordance with WO 2019 / 175396 (sometimes also referred to as "polymorph I"). For the purpose of the specification, vidofludimus calcium polymorph A is characterized by an X-ray powder diffraction pattern having characteristic peaks expressed in degrees 2theta at ±0.2 of the values 2 theta = 5.91°, 9.64°, 16.78°, 17.81°, 19.81°, and 25.41°.

[0042] Excipients such as fillers, disintegrants, lubricants and the like are known to the skilled person and have the generally acknowledged meaning. In this regard, reference is made to e.g. P.J. Sheskey et al., Handbook of Pharmaceutical Excipients, 9th ed., Pharmaceutical Press, 2020.

[0043] Definitions and properties of all excipients preferably comply with the corresponding monographs in Ph. Eur. 11.2th ed., 07 / 2023. Any reference to Ph. Eur. refers to this 11.2th ed., 07 / 2023.

[0044] Preferably, the total weight content of the one or more fillers is at least 25 wt.-%, relative to the total weight of the tablet.

[0045] Preferably, the total weight content of the one or more fillers is at least 30 wt.-%, preferably at least 35 wt.-%, more preferably at least 40 wt.-%, still more preferably at least 45 wt.-%, yet morepreferably at least 50 wt.-%, even more preferably at least 55 wt.-%, most preferably at least 60 wt.-%, and in particular at least 65 wt.-%, in each case relative to the total weight of the tablet.

[0046] Preferably, the one or more fillers comprise or essentially consist of a filler selected from microcrystalline cellulose, mannitol, starch (e.g. com starch), polyvinylpyrrolidone, tribasic calcium phosphate, lactose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methacrylic acid copolymer, and ammonio methacrylic acid copolymers or mixtures thereof.

[0047] More preferably, the one or more fillers comprise or essentially consist of a filler selected from microcrystalline cellulose, mannitol, starch, lactose, tribasic calcium phosphate, and polyvinylpyrrolidone.

[0048] More preferably, the one or more fillers comprise or essentially consist of a filler selected from microcrystalline cellulose, lactose, and polyvinylpyrrolidone.

[0049] Yet more preferably, the one or more fillers comprise or essentially consist of microcrystalline cellulose as the sole filler.

[0050] Preferably, the total weight content of the one or more disintegrants is at least 1.5 wt.-%, relative to the total weight of the tablet.

[0051] Preferably, the total weight content of the one or more disintegrants is at least 1.8 wt.-%, preferably at least 2.1 wt.-%, more preferably at least 2.4 wt.-%, still more preferably at least 2.7 wt.-%, yet more preferably at least 3.0 wt.-%, even more preferably at least 3.3 wt.-%, most preferably at least 3.6 wt.-%, and in particular at least 3.9 wt.-%, in each case relative to the total weight of the tablet.

[0052] Preferably, the one or more disintegrants comprise or essentially consist of a disintegrant selected from crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose sodium, sodium starch glycolate, and pregelatinized starch or mixtures thereof.

[0053] More preferably, the one or more disintegrants comprise or essentially consist of a disintegrant selected from crosslinked polyvinylpyrrolidone, and crosslinked carboxymethyl cellulose sodium.

[0054] Y et more preferably, the one or more disintegrants comprise or essentially consist of crosslinked polyvinylpyrrolidone as the sole disintegrant.

[0055] Preferably, the one or more lubricants comprise or essentially consist of magnesium stearate, calcium stearate, stearic acid, polyethylene glycol, and sodium stearyl fumarate. Mixtures are also contemplated.

[0056] More preferably, the one or more lubricants comprise or essentially consist of magnesium stearate, and sodium stearyl fumarate. Mixtures are also contemplated.

[0057] Yet more preferably, the one or more lubricants comprise or essentially consist of magnesium stearate as the sole lubricant.

[0058] In one embodiment, the one or more fillers comprise or essentially consist of a filler selected from microcrystalline cellulose, mannitol, starch, lactose, tribasic calcium phosphate, and polyvinylpyrrolidone, the one or more disintegrants comprise or essentially consist of a disintegrant selected from crosslinked polyvinylpyrrolidone, and crosslinked carboxymethyl cellulose sodium and the one or more lubricants comprise or essentially consist of magnesium stearate, and sodium stearyl fumarate. Mixtures are also contemplated.

[0059] In one embodiment, the one or more fdlers comprise or essentially consist of a fdler selected from microcrystalline cellulose, lactose, and polyvinylpyrrolidone, the one or more disintegrants comprise or essentially consist of a disintegrant selected from crosslinked polyvinylpyrrolidone, and crosslinked carboxymethyl cellulose sodium and the one or more lubricants comprise or essentially consist of magnesium stearate, and sodium stearyl fumarate. Mixtures are also contemplated.

[0060] Preferably, the total weight content of the one or more lubricants is at least 0.4 wt.-%, preferably at least 0.6 wt.-%, more preferably at least 0.8 wt.-%, still more preferably at least 1.0 wt.-%, yet more preferably at least 1.2 wt.-%, even more preferably at least 1.4 wt.-%, most preferably at least 1.6 wt.- %, and in particular at least 1.8 wt.-%, in each case relative to the total weight of the tablet.

[0061] Preferably, the total weight content of the one or more lubricants is at most 3.6 wt.-%, preferably at most 3.4 wt.-%, more preferably at most 3.2 wt.-%, still more preferably at most 3.0 wt.-%, yet more preferably at most 2.8 wt.-%, even more preferably at most 2.6 wt.-%, most preferably at most 2.4 wt.- %, and in particular at most 2.2 wt.-%, in each case relative to the total weight of the tablet.

[0062] In one embodiment, the total weight content of the one or more lubricants is in the range of from 0.4 wt.-% to 3.6 wt.-%, preferably in the range of from 0.6 wt.-% to 3.4 wt.-%, more preferably in the range of from 0.8 wt.-% to 3.2 wt.-%, yet more preferably in the range of from 1.0 wt.-% to 3.0 wt.-%, yet more preferably in the range of from 1.2 wt.-% to 2.8 wt.-%, yet more preferably in the range of from 1.4 wt.-% to 2.6 wt.-%, yet more preferably in the range of from 1.6 wt.-% to 2.4 wt.-%, most preferred in the range of 1.8 wt.-% to 2.2 wt.-%, in each case relative to the total weight of the tablet.

[0063] In one embodiment, the total weight content of the one or more disintegrants is in the range of from 1.8 wt.-% to 8.0 wt.-%, preferably in the range of from 2.1 wt.-% to 7.7 wt.-%, more preferably in the range of from 2.4 wt.-% to 7.4 wt.-%, yet more preferably in the range of from 2.7 wt.-% to 7.1 wt.- %, yet more preferably in the range of from 3.0 wt.-% to 6.8 wt.-%, yet more preferably in the range of from 3.3 wt.-% to 6.5 wt.-%, yet more preferably in the range of from 3.6 wt.-% to 6.2 wt.-%, most preferred in the range of 3.9 wt.-% to 5.9 wt.-%, in each case relative to the total weight of the tablet.

[0064] In one embodiment, the total weight content of the one or more fillers is in the range of from 65 wt.-% to 95 wt.-%, preferably in the range of from 67.5 wt.-% to 92.5 wt.-%, more preferably in the range of from 70 wt.-% to 90 wt.-%, yet more preferably in the range of from 72.5 wt.-% to 87.5 wt.- %, yet more preferably in the range of from 75 wt.-% to 85 wt.-%, yet more preferably in the range of from 77.5 wt.-% to 82.5 wt.-%, in each case relative to the total weight of the tablet.

[0065] In one embodiment, the pharmaceutical tablet comprises vidofludimus or a physiologically acceptable salt and / or solvate thereof, such as vidofludimus calcium, in the range of from 2.0 wt.-% to 25 wt.-%, one or more fillers in the range of from 65 wt.-% to 95 wt.-%, one or more lubricants in the range of from 0.4 wt.-% to 3.6 wt.-% and one or more disintegrants in the range of from 1.8 wt.-% to 8.0 wt.- 0 / / o.

[0066] Preferably, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is at least 1.0 wt.-%, relative to the total weight of the tablet.

[0067] Preferably, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is at least 1.5 wt.-%, preferably at least 2.0 wt.-%, more preferably at least 2.5 wt.-%, in each case relative to the total weight of the tablet.

[0068] In one embodiment, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is in the range of from 1.0 wt.-% to 26.0 wt.-%, preferably in the range of from 1.5 wt.-% to 25.5 wt.-%, more preferably in the range of from 2.0 wt.-% to 25.0 wt.-%, yet more preferably in the range of from 2.5 wt.-% to 24.5 wt.-%, in each case relative to the total weight of the tablet.

[0069] Preferably, the minimum weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof increases as the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof increases.

[0070] Preferably, the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is within the range of from 5.0 to 50 mg, relative to the equivalent weight of the free acid of vidofludimus. Preferred doses of the vidofludimus or a physiologically acceptable salt and / or solvate thereof include but are not limited to 5 mg, 10 mg, 15 mg, 20 mg, 22.5 mg, 30 mg, and 45 mg, in each case relative to the equivalent weight of the free acid of vidofludimus.

[0071] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 5 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 1.5 wt.- %, preferably at least 2.0 wt.-%, more preferably at least 2.5 wt.-%, in each case relative to the total weight of the tablet.

[0072] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 5 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 1.5 wt.-% to 5.0 wt.-%, more preferably in the range of from 2.0 wt.-% to 4.0 wt.-%, yet more preferably in the range of from 2.5 wt.-% to 3.0 wt.-%, in each case relative to the total weight of the tablet.

[0073] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 10 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 3.0 wt.- %, preferably at least 4.0 wt.-%, more preferably at least 5.0 wt.-%, still more preferably at least 5.5 wt.- %, in each case relative to the total weight of the tablet.

[0074] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 10 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 3.0 wt.-% to 8.0 wt.-%, more preferably in the range of from 4.0 wt.-% to 7.0 wt.-%, yet more preferably in the range of from 5.0 wt.-% to 6.0 wt.-%, in each case relative to the total weight of the tablet.

[0075] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 15 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 4.5 wt.- %, preferably at least 6.0 wt.-%, more preferably at least 7.5 wt.-%, in each case relative to the total weight of the tablet.

[0076] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 15 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 4.5 wt.-% to 10wt.-%, more preferably in the range of from 6.0 wt.-% to 9.0 wt.-%, yet more preferably in the range of from 7.5 wt.-% to 8.5 wt.-%, in each case relative to the total weight of the tablet.

[0077] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 20 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 6.0 wt.- %, preferably at least 8.0 wt.-%, more preferably at least 10 wt.-%, in each case relative to the total weight of the tablet.

[0078] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 20 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of thevidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 6.0 wt.-% to 12 wt.-%, more preferably in the range of from 8.0 wt.-% to 11 wt.-%, yet more preferably in the range of from 10 wt.-% to 11 wt.-%, in each case relative to the total weight of the tablet.

[0079] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 30 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 9.0 wt.- %, preferably at least 12 wt.-%, more preferably at least 15 wt.-%, in each case relative to the total weight of the tablet.

[0080] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 30 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 9.0 wt.-% to 20 wt.-%, more preferably in the range of from 12 wt.-% to 18 wt.-%, yet more preferably in the range of from 15 wt.-% to 16 wt.-%, in each case relative to the total weight of the tablet.

[0081] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 45 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably at least 18 wt.- %, preferably at least 20 wt.-%, more preferably at least 22 wt.-%, in each case relative to the total weight of the tablet.

[0082] When the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is 45 mg relative to the equivalent weight of the free acid of vidofludimus, the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is preferably in the range of from 18 wt.-% to 25 wt.-%, more preferably in the range of from 20 wt.-% to 24 wt.-%, yet more preferably in the range of from 22 wt.-% to 23 wt.-%, in each case relative to the total weight of the tablet.

[0083] In a preferred embodiment, the pharmaceutical tablet comprises vidofludimus or a physiologically acceptable salt and / or solvate thereof, such as vidofludimus calcium, in the range of from 2.0 wt.- % to 25 wt.-%, microcrystalline cellulose in the range of from 65 wt.-% to 95 wt.-% and crospovidone in the range of from 1.8 wt.-% to 8.0 wt.-%.

[0084] In a preferred embodiment, the pharmaceutical tablet comprises vidofludimus or a physiologically acceptable salt and / or solvate thereof, such as vidofludimus calcium, in the range of from 2.0 wt.- % to 25 wt.-%, microcrystalline cellulose in the range of from 65 wt.-% to 95 wt.-%, crospovidone in the range of from 1.8 wt.-% to 8.0 wt.-% and magnesium stearate in the range of from 0.4 wt.-% to 3.6 wt.-%.

[0085] In a preferred embodiment, the pharmaceutical tablet comprises vidofludimus or a physiologically acceptable salt and / or solvate thereof, such as vidofludimus calcium, in the range of from 2.0 wt.- % to 25 wt.-%, microcrystalline cellulose in the range of from 65 wt.-% to 95 wt.-%, crospovidone in the range of from 1.8 wt.-% to 8.0 wt.-%, magnesium stearate in the range of from 0.4 wt.-% to 3.6 wt.- % and povidone in the range of from 4.0 wt.-% to 10 wt.-%.

[0086] In a preferred embodiment, the pharmaceutical tablet comprises vidofludimus or a physiologically acceptable salt and / or solvate thereof, such as vidofludimus calcium, in the range of from 2.0 wt.- % to 25 wt.-%, microcrystalline cellulose in the range of from 65 wt.-% to 95 wt.-%, crospovidone in the range of from 1.8 wt.-% to 8.0 wt.-%, magnesium stearate in the range of from 0.4 wt.-% to 3.6 wt.- %, povidone in the range of from 4.0 wt.-% to 10 wt.-% and talc in the range of from 0.4 wt.-% to 3.6 wt.-%.

[0087] Preferably, the total weight of the tablet is at most 600 mg, preferably at most 550 mg, more preferably at most 500 mg, still more preferably at most 450 mg, yet more preferably at most 400 mg, even more preferably at most 350 mg, most preferably at most 300 mg, and in particular at most 250 mg.

[0088] Preferably, the total weight of the tablet is at least at least 40 mg, preferably at least at least 60 mg, more preferably at least at least 80 mg, still more preferably at least at least 100 mg, yet more preferably at least at least 120 mg, even more preferably at least at least 140 mg, most preferably at least at least 160 mg, and in particular at least 180 mg. In a preferred embodiment, the total weight of the tablet is about 200 mg.

[0089] Preferably, the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 37.5 wt.-%, preferably at least 40.0 wt.- %, more preferably at least 42.5 wt.-%, still more preferably at least 45.0 wt.-%, yet more preferably at least 47.5 wt.-%, even more preferably at least 50.0 wt.-%, most preferably at least 52.5 wt.-%, and in particular at least 55.0 wt.-%, in each case relative to the total weight of the tablet.

[0090] Preferably, the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 57.5 wt.-%, preferably at least 60.0 wt.- %, more preferably at least 62.5 wt.-%, still more preferably at least 65.0 wt.-%, yet more preferably at least 67.5 wt.-%, even more preferably at least 70.0 wt.-%, most preferably at least 72.5 wt.-%, and in particular at least 75.0 wt.-%, in each case relative to the total weight of the tablet.

[0091] Preferably, the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 77.5 wt.-%, preferably at least 80.0 wt.- %, more preferably at least 82.5 wt.-%, still more preferably at least 85.0 wt.-%, yet more preferably at least 87.5 wt.-%, even more preferably at least 90.0 wt.-%, most preferably at least 92.5 wt.-%, and in particular at least 95.0 wt.-%, in each case relative to the total weight of the tablet.

[0092] In one embodiment the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fillers is in the range of from 40.0 wt.-% to 99.0 wt.- %, preferably in the range of from 45.0 wt.-% to 99.0 wt.-%, more preferably in the range of from 50.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 55.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 60.0 wt.-%to 99.0 wt.-%, yet more preferably in the range of from 65.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 70.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 75.0 wt.-%to 99.0 wt.-%, yet more preferably in the range of from 80.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 85.0 wt.-% to 99.0 wt.-%, yet more preferably in the range of from 90.0 wt.-% to 99.0 wt.-%, most preferred in the range of 95.0 wt.-% to 99.0 wt.-%, in each case relative to the total weight of the tablet.

[0093] In preferred embodiments, the tablet according to the invention comprises a film coating.

[0094] In other preferred embodiments, the tablet according to the invention is uncoated.

[0095] Preferably, the tablet according to the invention has a circular cross section with a diameter within the range of from 6 mm to 10 mm, preferably 7 mm to 9 mm.

[0096] Preferably, the tablet according to the invention is granulated, preferably dry granulated. Preferably, the tablet according to the invention comprises an intragranular phase and optionally an extra- granular phase.

[0097] Preferably, the intragranular phase comprises essentially the total amount of the vidofludimus or the physiologically acceptable salt and / or solvate thereof.

[0098] Preferably, the intragranular phase comprises essentially the total amount of the one or more fdlers.

[0099] Preferably, the intragranular phase comprises essentially the total amount of the one or more disintegrants.

[0100] Preferably, the intragranular phase comprises a first portion of the one or more lubricants and the extragranular phase comprises a second portion of the one or more lubricants.

[0101] Preferably, the first portion of the one or more lubricants is greater than the second portion of the one or more lubricants.

[0102] As used herein, the term “essentially consists” means that specific further components can be present, namely those not materially affecting the essential characteristics of the compound or composition addressed.

[0103] Preferably, the intragranular phase essentially consists of the vidofludimus or the physiologically acceptable salt and / or solvate thereof, the one or more fillers, the one or more disintegrants, and optionally at least a portion of the one or more lubricants.

[0104] Preferably, the extragranular phase essentially consists of at least a portion of the one or more lubricants.

[0105] Preferably, the intragranular phase is dry granulated.

[0106] Preferably, the tablet according to the invention under in vitro conditions in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 77.5 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet, preferably at least 80 wt.-%, more preferably at least 82.5 wt.-%, still more preferably at least 85 wt.-%, yet more preferably at least 87.5 wt.- %, even more preferably at least 90 wt.-%, most preferably at least 92.5 wt.-%, and in particular at least 93 wt. -%.

[0107] Preferably, the tablet according to the invention under in vitro conditions in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 93.5 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet, preferably at least 94 wt.-%, more preferably at least 94.5 wt.-%, still more preferably at least 95 wt.-%, yet more preferably at least 95.5 wt.- %, even more preferably at least 96 wt.-%, most preferably at least 96.5 wt.-%, and in particular at least 97 wt. -%.

[0108] Preferably, the tablet according to the invention under in vitro conditions in accordance with Ph. Eur. 2.9.1. disintegrates within at most 4.5 minutes, preferably at most 4.0 minutes, more preferably at most 3.5 minutes, still more preferably at most 3.0 minutes, yet more preferably at most 2.5 minutes, even more preferably at most 2.0 minutes, most preferably at most 1.5 minutes, and in particular at most 1.0 minute.

[0109] Preferably, the tablet according to the invention in accordance with Ph. Eur. 2.9.8. has a resistance to crushing of at least 50 N, preferably at least 55 N, more preferably at least 60 N, still more preferably at least 65 N, yet more preferably at least 70 N, even more preferably at least 75 N, most preferably at least 80 N, and in particular at least 85 N.

[0110] Preferably, the tablet according to the invention in accordance with Ph. Eur. 2.9.8. has a resistance to crushing of at most 155 N, preferably at most 150 N, more preferably at most 145 N, still more preferably at most 140 N, yet more preferably at most 135 N, even more preferably at most 130 N, most preferably at most 125 N, and in particular at most 120 N.

[0111] Another aspect of the invention relates to a process for the preparation of a pharmaceutical tablet according to the invention as described above.

[0112] The process for the preparation of a pharmaceutical tablet according to the invention comprises the steps of(a) providing a mixture comprising or essentially consisting of vidofludimus or a physiologically acceptable salt and / or solvate thereof; one or more fdlers; one or more disintegrants; and optionally, one or more lubricants;(b) dry granulating the mixture provided in step (a); preferably by roller compaction; thereby obtaining a dry granulate;(c) optionally, blending the dry granulate obtained in step (b) with one or more additional excipients thereby obtaining a blend;(d) compressing the dry granulate obtained in step (b) or the blend obtained in step (c) to tablets; and(e) optionally, applying a fdm coating to the tablets obtained in step (d).

[0113] Another aspect of the invention related to a dry granulate that is obtained in step (b).

[0114] Another aspect of the invention relates to a packaging comprising one or more of the tablets according to the invention as described above.

[0115] Preferably, the packaging is a bottle having a closure and optionally containing a desiccant.

[0116] Preferably, the packaging is a blister.

[0117] Another aspect of the invention relates to a tablet according to any of the above embodiments for use in the prevention and / or treatment of a disease or a medical condition in a subject in need thereof, wherein said disease is selected from the group consisting of graft versus host and host versus graft reactions, rheumatoid arthritis, multiple sclerosis (including relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis), lupus erythematosus, inflammatory bowel disease (in particular ulcerative colitis and Crohn’s disease), long COVID syndrome, type 1 diabetes and psoriasis, preferably relapsing-remitting multiple sclerosis (RRMS).

[0118] Another aspect of the invention relates to a method of prevention and / or treatment of a disease or a medical condition in a subject in need thereof comprising administering a tablet according to any of the above embodiments to said subject, wherein said disease is selected from the group consisting of graft versus host and host versus graft reactions, rheumatoid arthritis, multiple sclerosis (including relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis), lupus erythematosus, inflammatory bowel disease (in particular ulcerative colitis and Crohn’s disease), long CO VID syndrome, type 1 diabetes and psoriasis, preferably relapsing-remitting multiple sclerosis (RRMS).

[0119] Another aspect of the invention relates to a use of a tablet according to any of the above embodiments in a method of prevention and / or treatment of a disease or a medical condition in a subject in need thereof, wherein said disease is selected from the group consisting of graft versus host and host versus graft reactions, rheumatoid arthritis, multiple sclerosis (including relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis), lupus erythematosus, inflammatory bowel disease(in particular ulcerative colitis and Crohn’s disease), long CO VID syndrome, type 1 diabetes and psoriasis, preferably relapsing -remitting multiple sclerosis (RRMS).

[0120] As used herein, the term “subject” refers to any member of the animal kingdom including humans. In some embodiments, “subject” refers mammals. In some embodiments, “subject” refers to humans, at any stage of development. In some embodiments, “subject” refers to a human patient.EXAMPLES

[0121] The following examples further illustrate the invention but are not to be construed as limiting its scope.Example 1 - wet granulation:

[0122] Tablets of different strength (expressed as equivalent doses relative to the anhydrous non-salt form of vidofludimus) having the following composition were manufactured by aqueous wet granulation:

[0123] Vidofludimus calcium was mixed with the intragranular portion of microcrystalline cellulose and then granulated with an aqueous solution of povidone. The wet granulate was sieved and dried. The dried granulate was blended, mixed with crospovidone, the extragranular portion of microcrystalline cellulose, and talc. Thereafter, the mixture was mixed with magnesium stearate, compressed into tablets and packaged. For each dose strength, 5000 tablets were prepared.

[0124] Disintegration time was determined in accordance with Ph. Eur. 2.9.1. Results are also contained in the above table.Example 2 - dry granulation:

[0125] Tablets of different strength having the following composition were manufactured by dry granulation (roller compaction):

[0126] Vidofludimus calcium was blended with the intragranular portion of microcrystalline cellulose and crospovidone. The intragranular portion of magnesium stearate was added and the mixture was dry granulated by roller compaction. The extragranular portions of magnesium stearate and microcrystalline cellulose were added and the resultant mixture was compressed into tablets and packaged.

[0127] Disintegration time was determined in accordance with Example 1. Bulk density, tapped density, Hausner ratio, loss on drying and friability were also determined in accordance with Ph. Eur. Results are also contained in the above table.

[0128] A comparison of wet granulation according to Example 1 with dry granulation according to Example 2 revealed certain advantages of dry granulation. The manufacture of the wet granulated tablets was affected by reproducibility issues. There were challenges with the release tests (dissolution and resistance to crushing) as well as galenic challenges (poor flowability despite granulation). The manufacture by dry granulation was much faster and a better processability during tableting could be achieved thereby resulting in an increase of output. In separate experiments (not shown), it was observed that at a dose strength of 20 mg and 22.5 mg, respectively, wet granulation allows for manufacturing 3,000 - 5,000 tablets / hour, whereas dry granulation allows for manufacturing 15,000 - 20,000 tablets / hour.

[0129] Further, the disintegration times of tablets made by dry granulation was significantly shorter than the disintegration times of tablets made by wet granulation.Example 3 - dry granulation:

[0130] In accordance with Example 2, tablets of different strength having the following composition were manufactured by dry granulation (roller compaction):

[0131] Disintegration time was determined in accordance with Examples 1 and 2.Example 4 - drv granulation vs. wet granulation:

[0132] In accordance with Examples 1 -3, tablets of different strength having the following composition were manufactured by dry granulation (roller compaction) or wet granulation, respectively:1(rating excellent: +++, very poor: — )

[0133] Dissolution and resistance to crushing are given in range where more than one batch was produced. Dissolution was determined in accordance with Ph. Eur. 2.9.3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm (500 mb for tablets having a strength below 15 mg, 750 mb for tablets having a strength of 15 mg, and 1000 mb for tablets having a strength greater than 15 mg). Resistance to crushing was determined in accordance with Ph. Eur. 2.9.8. Results are also contained in the above table.

[0134] As demonstrated by the above comparative date, the dry granulated tablets were better than the wet granulated tablets especially with respect to resistance to crushing and flowability. Another advantage of the dry granulated tablets was that they could be manufactured by a much faster process (no need for drying). Better processability during tableting resulted in an increase of output (tablets / hour).

Claims

Patent claims:

1. A pharmaceutical tablet for oral administration, which comprises or essentially consists of vidofludimus or a physiologically acceptable salt and / or solvate thereof;- one or more fdlers;- one or more disintegrants;- optionally, one or more lubricants; preferably, which comprises an intragranular phase and optionally an extragranular phase, wherein the intragranular phase is dry granulated; and which under in vitro conditions in accordance with Ph. Eur. 2.9.

3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 75 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet.

2. The tablet according to claim 1, wherein the vidofludimus or a physiologically acceptable salt and / or solvate thereof is crystalline.

3. The tablet according to claim 1 or 2, wherein vidofludimus is present as calcium salt, preferably as hemicalcium monohydrate.

4. The tablet according to claim 3, wherein vidofludimus calcium is present as polymorph A in accordance with WO 2019 / 175396.

5. The tablet according to any of the preceding claims, wherein the vidofludimus or a physiologically acceptable salt and / or solvate thereof is not micronized.

6. The tablet according to any of claims 1 to 4, wherein the vidofludimus or a physiologically acceptable salt and / or solvate thereof is micronized.

7. The tablet according to any of the preceding claims, wherein the total weight content of the one or more fdlers is at least 25 wt.-%, relative to the total weight of the tablet.

8. The tablet according to any of the preceding claims, wherein the total weight content of the one or more fdlers is at least 30 wt.-%, preferably at least 35 wt.-%, more preferably at least 40 wt.- %, still more preferably at least 45 wt.-%, yet more preferably at least 50 wt.-%, even morepreferably at least 55 wt.-%, most preferably at least 60 wt.-%, and in particular at least 65 wt.- %, in each case relative to the total weight of the tablet.

9. The tablet according to any of the preceding claims, wherein the one or more fdlers comprise or essentially consist of a filler selected from microcrystalline cellulose, mannitol, starch (e.g. com starch), polyvinylpyrrolidone, tribasic calcium phosphate, lactose, methyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methacrylic acid copolymer, and ammonio methacrylic acid copolymers.

10. The tablet according to any of the preceding claims, wherein the one or more fdlers comprise or essentially consist of microcrystalline cellulose.

11. The tablet according to any of the preceding claims, wherein the total weight content of the one or more disintegrants is at least 1.5 wt.-%, relative to the total weight of the tablet.

12. The tablet according to any of the preceding claims, wherein the total weight content of the one or more disintegrants is at least 1.8 wt.-%, preferably at least 2.1 wt.-%, more preferably at least 2.4 wt.-%, still more preferably at least 2.7 wt.-%, yet more preferably at least 3.0 wt.-%, even more preferably at least 3.3 wt.-%, most preferably at least 3.6 wt.-%, and in particular at least 3.9 wt.-%, in each case relative to the total weight of the tablet.

13. The tablet according to any of the preceding claims, wherein the one or more disintegrants comprise or essentially consist of a disintegrant selected from crosslinked polyvinylpyrrolidone, crosslinked carboxymethyl cellulose sodium, sodium starch glycolate, and pregelatinized starch.

14. The tablet according to any of the preceding claims, wherein the one or more disintegrants comprise or essentially consist of crosslinked polyvinylpyrrolidone.

15. The tablet according to any of the preceding claims, wherein the one or more lubricants comprise or essentially consist of magnesium stearate, calcium stearate, stearic acid, polyethylene glycol, and sodium stearyl fumarate.

16. The tablet according to any of the preceding claims, wherein the one or more lubricants comprise or essentially consist of magnesium stearate.

17. The tablet according to any of the preceding claims, wherein the total weight content of the one or more lubricants is at least 0.4 wt.-%, preferably at least 0.6 wt.-%, more preferably at least 0.8wt.-%, still more preferably at least 1.0 wt.-%, yet more preferably at least 1.2 wt.-%, even more preferably at least 1.4 wt.-%, most preferably at least 1.6 wt.-%, and in particular at least 1.8 wt.- %, in each case relative to the total weight of the tablet.

18. The tablet according to any of the preceding claims, wherein the total weight content of the one or more lubricants is at most 3.6 wt.-%, preferably at most 3.4 wt.-%, more preferably at most 3.2 wt.-%, still more preferably at most 3.0 wt.-%, yet more preferably at most 2.8 wt.-%, even more preferably at most 2.6 wt.-%, most preferably at most 2.4 wt.-%, and in particular at most 2.2 wt.- %, in each case relative to the total weight of the tablet.

19. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is at least 1.0 wt.-%, relative to the total weight of the tablet.

20. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 37.5 wt.-%, preferably at least 40.0 wt.-%, more preferably at least 42.5 wt.-%, still more preferably at least 45.0 wt.-%, yet more preferably at least 47.5 wt.-%, even more preferably at least 50.0 wt.-%, most preferably at least 52.5 wt.-%, and in particular at least 55.0 wt.- %, in each case relative to the total weight of the tablet.

21. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 57.5 wt.-%, preferably at least 60.0 wt.-%, more preferably at least 62.5 wt.-%, still more preferably at least 65.0 wt.-%, yet more preferably at least 67.5 wt.-%, even more preferably at least 70.0 wt.-%, most preferably at least 72.5 wt.-%, and in particular at least 75.0 wt.- %, in each case relative to the total weight of the tablet.

22. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 57.5 wt.-%, preferably at least 60.0 wt.-%, more preferably at least 62.5 wt.-%, still more preferably at least 65.0 wt.-%, yet more preferably at least 67.5 wt.-%, even more preferably at least 70.0 wt.-%, most preferably at least 72.5 wt.-%, and in particular at least 75.0 wt.- %, in each case relative to the total weight of the tablet.

23. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or the physiologically acceptable salt and / or solvate thereof is at least 1.5 wt.-%,preferably at least 2.0 wt.-%, more preferably at least 2.5 wt.-%, in each case relative to the total weight of the tablet.

24. The tablet according to any of the preceding claims, wherein the dose of the vidofludimus or a physiologically acceptable salt and / or solvate thereof is within the range of from 5.0 to 50 mg, relative to the equivalent weight of the free acid of vidofludimus.

25. The tablet according to any of the preceding claims, wherein the total weight of the tablet is at most 600 mg, preferably at most 550 mg, more preferably at most 500 mg, still more preferably at most 450 mg, yet more preferably at most 400 mg, even more preferably at most 350 mg, most preferably at most 300 mg, and in particular at most 250 mg.

26. The tablet according to any of the preceding claims, wherein the total weight of the tablet is at least at least 40 mg, preferably at least at least 60 mg, more preferably at least at least 80 mg, still more preferably at least at least 100 mg, yet more preferably at least at least 120 mg, even more preferably at least at least 140 mg, most preferably at least at least 160 mg, and in particular at least 180 mg.

27. The tablet according to any of the preceding claims, wherein the total weight content of the vidofludimus or a physiologically acceptable salt and / or solvate thereof and of the one or more fdlers is at least 77.5 wt.-%, preferably at least 80.0 wt.-%, more preferably at least 82.5 wt.-%, still more preferably at least 85.0 wt.-%, yet more preferably at least 87.5 wt.-%, even more preferably at least 90.0 wt.-%, most preferably at least 92.5 wt.-%, and in particular at least 95.0 wt.- %, in each case relative to the total weight of the tablet.

28. The tablet according to any of the preceding claims, which comprises a fdm coating.

29. The tablet according to any of the preceding claims, which is uncoated.

30. The tablet according to any of the preceding claims, which has a circular cross section with a diameter within the range of from 6 mm to 10 mm, preferably 7 mm to 9 mm.

31. The tablet according to any of the preceding claims, which comprises an intragranular phase and optionally an extragranular phase.

32. The tablet according to claim 31, wherein the intragranular phase comprises essentially the total amount of the vidofludimus or the physiologically acceptable salt and / or solvate thereof.

33. The tablet according to claim 31 or 32, wherein the intragranular phase comprises essentially the total amount of the one or more fillers.

34. The tablet according to any of claims 31 to 33, wherein the intragranular phase comprises essentially the total amount of the one or more disintegrants.

35. The tablet according to any of claims 31 to 34, wherein the intragranular phase comprises a first portion of the one or more lubricants and the extragranular phase comprises a second portion of the one or more lubricants.

36. The tablet according to claim 35, wherein the first portion is greater than the second portion.

37. The tablet according to any of claims 31 to 36, wherein the intragranular phase essentially consists of the vidofludimus or the physiologically acceptable salt and / or solvate thereof, the one or more fillers, the one or more disintegrants, and optionally at least a portion of the one or more lubricants.

38. The tablet according to any of claims 31 to 37, wherein the extragranular phase essentially consists of at least a portion of the one or more lubricants.

39. The tablet according to any of claims 31 to 38, wherein the intragranular phase is dry granulated.

40. The tablet according to the preceding claims, which under in vitro conditions in accordance with Ph. Eur. 2.9.

3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 77.5 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet, preferably at least 80 wt.-%, more preferably at least 82.5 wt.-%, still more preferably at least 85 wt.-%, yet more preferably at least 87.5 wt.-%, even more preferably at least 90 wt.-%, most preferably at least92.5 wt.-%, and in particular at least 93 wt.-%.

41. The tablet according to the preceding claims, which under in vitro conditions in accordance with Ph. Eur. 2.9.

3. using the paddle method in 50 mM citrate buffer pH 7.5 + 2% SDS at 37±1°C and at 100 rpm dissolves within 45 minutes at least 93.5 wt.-% of the vidofludimus or the physiologically acceptable salt and / or solvate thereof originally contained in the tablet, preferably at least 94 wt.-%, more preferably at least 94.5 wt.-%, still more preferably at least 95 wt.-%, yet more preferably at least 95.5 wt.-%, even more preferably at least 96 wt.-%, most preferably at least96.5 wt.-%, and in particular at least 97 wt.-%.

42. The tablet according to the preceding claims, which under in vitro conditions in accordance with Ph. Eur. 2.9.

1. disintegrates within at most 4.5 minutes, preferably at most 4.0 minutes, more preferably at most 3.5 minutes, still more preferably at most 3.0 minutes, yet more preferably at most 2.5 minutes, even more preferably at most 2.0 minutes, most preferably at most 1.5 minutes, and in particular at most 1.0 minute.

43. The tablet according to the preceding claims, which in accordance with Ph. Eur. 2.9.

8. has a resistance to crushing of at least 50 N, preferably at least 55 N, more preferably at least 60 N, still more preferably at least 65 N, yet more preferably at least 70 N, even more preferably at least 75 N, most preferably at least 80 N, and in particular at least 85 N.

44. The tablet according to the preceding claims, which in accordance with Ph. Eur. 2.9.

8. has a resistance to crushing of at most 155 N, preferably at most 150 N, more preferably at most 145 N, still more preferably at most 140 N, yet more preferably at most 135 N, even more preferably at most 130 N, most preferably at most 125 N, and in particular at most 120 N.

45. A process for the preparation of a pharmaceutical tablet according to any of the preceding claims comprising the steps of(a) providing a mixture comprising or essentially consisting of vidofludimus or a physiologically acceptable salt and / or solvate thereof; one or more fdlers; one or more disintegrants; and optionally, one or more lubricants;(b) dry granulating the mixture provided in step (a); preferably by roller compaction; thereby obtaining a dry granulate;(c) optionally, blending the dry granulate obtained in step (b) with one or more additional excipients thereby obtaining a blend;(d) compressing the dry granulate obtained in step (b) or the blend obtained in step (c) to tablets; and(e) optionally, applying a film coating to the tablets obtained in step (d).

46. A packaging comprising one or more of the tablets according to any of claims 1 to 44.

47. The packaging according to claim 46, which is a bottle having a closure and optionally containing a desiccant.

48. The packaging according to claim 46, which is a blister.

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