Pharmaceutical composition comprising rusotinib

Abstract

The present invention relates to a solid oral pharmaceutical composition comprising rusotinib or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient wherein the composition comprises less than 2.0% by weight of povidone. In addition, the present invention relates to a process for the preparation of the pharmaceutical composition according to the present invention.

Description

Technical Field

[0001] This invention relates to a solid oral pharmaceutical composition comprising ruxolitinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient. Background Technology

[0002] Ruxotinib is the International Nonproprietary Name (INN) of the drug molecule with the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropionitrile. Ruxotinib itself, in its free base form, has the following chemical structure: Ruxotinib is a selective inhibitor of Janus-associated kinases (JAK1) and JAK2, which mediate the signaling of various cytokines and growth factors important for hematopoiesis and immune function. Ruxotinib inhibits JAK-STAT signaling and cell proliferation in a cytokine-dependent cell model of hematologic malignancies, which plays a role in regulating the development, proliferation, and activation of various immune cell types important for the pathogenesis of graft-versus-host disease.

[0003] In Europe, ruxolitinib is marketed under the brand name Jakavi®. Jakavi® is used to treat myelofibrosis, polycythemia vera, and graft-versus-host disease.

[0004] According to its product characteristics overview, Jakavi® is formulated as a film-free tablet containing 5 mg, 10 mg, 15 mg, or 20 mg of ruxotinib phosphate (calculated as ruxotinib free base), and consists of additional components including microcrystalline cellulose, magnesium stearate, colloidal anhydrous silica, sodium glycolate starch, povidone, hydroxypropyl cellulose (low substitution), and lactose monohydrate. Studies show that, based on the total weight of the Jakavi® formulation, Jakavi® contains 2% by weight of povidone.

[0005] As described above, Jakavi® comprises the drug molecule ruxotinib in phosphate form. Ruxotinib phosphate is disclosed in EP 2 173 752 A2, which also discloses ruxotinib maleate and sulfate. EP 2 173 752 A2 states that the ruxotinib salt exhibits superior water solubility, dissolution rate, and chemical stability compared to the free base form of ruxotinib.

[0006] However, there is still a need to provide solid oral pharmaceutical compositions containing ruxolitinib that are chemically stable relative to ruxolitinib, for example, to provide relatively long high product quality, relatively long shelf life and / or allow for more flexible storage conditions. Summary of the Invention

[0007] Therefore, the object of the present invention is to provide a solid oral pharmaceutical composition comprising ruxotinib or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient, wherein the composition is relatively stable in terms of the chemical stability of ruxotinib.

[0008] This objective has been achieved by a solid oral pharmaceutical composition comprising ruxolitinib or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient, wherein the composition comprises less than 2.0% by weight of povidone relative to the total weight of the pharmaceutical composition.

[0009] Surprisingly, it has been found that the lower the povidone content in the pharmaceutical composition according to the invention, the higher the chemical stability of the pharmaceutical composition relative to ruxolitinib.

[0010] It can even be shown that the solid oral pharmaceutical composition according to the invention is more stable in terms of the chemical stability of ruxotinib compared to the Jakavi® composition.

[0011] Furthermore, it has been found that the pharmaceutical compositions according to the invention exhibit sufficient solubility and dissolution rate to allow for effective oral bioavailability.

[0012] Furthermore, it has been found that the pharmaceutical compositions according to the invention can be formulated in a manner bioequivalent to Jakavi® products.

[0013] As mentioned above, the solid oral pharmaceutical composition is relatively stable in terms of the chemical stability of ruxolitinib.

[0014] In this context, the term "stability" is understood to refer to the stability caused by... Arbeitsgemeinschaft für pharmazeutische Verfahrenstechnik According to the definition established by the Applied Pharmaceutical Product Safety Commission (APV), "stability" refers to the quality of a drug that meets specifications up to the end of its shelf life as determined by the manufacturer. Therefore, the quality of a drug is determined by the content and purity of the active ingredient, sensory properties, physicochemical properties, and microbiological properties, wherein the content of the active ingredient should not be less than 90% of the declared value at the end of the shelf life.

[0015] Preferably, the pharmaceutical composition according to the invention is tested at a temperature of 30°C ± 2°C and a relative humidity of 65% ± 5% RH (see [reference needed]). Patent Drug Committee (CPMP) "Stability Testing Guidelines: Stability Testing of Existing Active Substances and Related Finished Products", CPMP / QWP / 122 / 02, 1st revised errata, December 17, 2003), having a stability or shelf life of at least 1 year, preferably at least 2 years, more preferably at least 3 years, more preferably at least 3.5 years, more preferably at least 4 years, more preferably at least 4.5 years, and even more preferably at least 5 years.

[0016] Furthermore, preferably, the pharmaceutical composition according to the invention is tested at a temperature of 30°C ± 2°C and a relative humidity of 65% ± 5% RH (see [reference needed]). Patent Drug Committee (CPMP) "Stability Testing Guidelines: Stability Testing of Existing Active Substances and Related Finished Products", CPMP / QWP / 122 / 02, 1st revised errata, December 17, 2003), has a stability or shelf life of up to 1 year, preferably up to 2 years, more preferably up to 3 years, more preferably up to 3.5 years, more preferably up to 4 years, more preferably up to 4.5 years, and even more preferably up to 5 years.

[0017] As described above, the present invention relates to solid oral pharmaceutical compositions comprising ruxolitinib or a pharmaceutically acceptable salt thereof as an active pharmaceutical ingredient, wherein the composition comprises less than 2.0% by weight of povidone relative to the total weight of the pharmaceutical composition.

[0018] According to a preferred embodiment of the pharmaceutical composition of the present invention, the composition comprises less than 1.5% by weight, preferably less than 1.0% by weight, more preferably less than 0.75% by weight, more preferably less than 0.50% by weight, and even more preferably less than 0.25% by weight, based on the total weight of the pharmaceutical composition. It has been found that the lower the povidone content in the pharmaceutical composition according to the present invention, the higher the chemical stability of the pharmaceutical composition relative to ruxolitinib.

[0019] In another preferred embodiment of the pharmaceutical composition according to the invention, the composition is free of povidone.

[0020] In another preferred embodiment of the pharmaceutical composition of the present invention, the composition comprises less than 0.50% by weight, preferably less than 0.45% by weight, more preferably less than 0.40% by weight, more preferably less than 0.35% by weight, and even more preferably less than 0.30% by weight of a lubricant. Surprisingly, it has been found that the lower the lubricant content, particularly the magnesium stearate content, of the pharmaceutical composition according to the present invention, the higher the chemical stability of the pharmaceutical composition relative to ruxolitinib.

[0021] In another preferred embodiment of the pharmaceutical composition according to the invention, the lubricant is magnesium stearate. In particular, magnesium stearate adversely affects the chemical stability of ruxolitinib.

[0022] In addition to ruxotinib free base or a pharmaceutically acceptable salt thereof, the pharmaceutical compositions according to the invention may contain one or more other active pharmaceutical ingredients. However, according to another preferred embodiment of the invention, ruxotinib or a pharmaceutically acceptable salt thereof is the only active pharmaceutical ingredient contained in the composition.

[0023] According to another preferred embodiment of the pharmaceutical composition of the present invention, the active pharmaceutical ingredient contained in the composition is ruxotinib in its free base form. The free base of ruxotinib is disclosed in EP 1 966 202 A1.

[0024] According to another preferred embodiment of the invention, the active pharmaceutical ingredient included in the composition is ruxotinib in a pharmaceutically acceptable salt form. In particular, povidone adversely affects the chemical stability of ruxotinib with respect to ruxotinib salts.

[0025] In another preferred embodiment of the pharmaceutical composition according to the invention, a pharmaceutically acceptable salt of ruxotinib is selected from ruxotinib phosphate, ruxotinib maleate, ruxotinib sulfate, and ruxotinib oxalate. Ruxotinib phosphate, ruxotinib maleate, and ruxotinib sulfate are disclosed in EP 2 173752 A2, wherein the salt is described as a 1:1 salt between ruxotinib and an acid. Ruxotinib oxalate is disclosed in EP 3 183 252 A1.

[0026] In another preferred embodiment of the pharmaceutical composition of the present invention, a pharmaceutically acceptable salt of ruxolitinib is ruxolitinib phosphate.

[0027] The pharmaceutical compositions according to the present invention can be formulated for immediate-release, modified-release, controlled-release, sustained-release, prolonged-release, extended-release, or delayed-release of ruxotinib. However, according to a preferred embodiment of the present invention, the pharmaceutical composition is an immediate-release composition. Pharmaceutical compositions with immediate-release, modified-release, controlled-release, sustained-release, prolonged-release, extended-release, or delayed-release properties and their preparation are well known in the prior art and are common knowledge to those skilled in the art.

[0028] The pharmaceutical composition according to the invention is a solid and can therefore be in the form of, for example, tablets, capsules, pills, granules, powders, etc. However, according to a preferred embodiment of the invention, the pharmaceutical composition is a tablet, particularly a film-free tablet.

[0029] According to another preferred embodiment of the pharmaceutical composition of the present invention, the pharmaceutical composition comprises ruxotinib or a pharmaceutically acceptable salt thereof, calculated as a free base, in the range of 2 mg to 50 mg. Specifically, the pharmaceutical composition of the present invention comprises 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxotinib free base or a pharmaceutically acceptable salt thereof, calculated as a free base.

[0030] According to another preferred embodiment of the pharmaceutical composition of the present invention, the pharmaceutical composition is free of acid-reactive pharmaceutical excipients. It has been found that the lower the content of the pharmaceutical composition according to the present invention relative to acid-reactive pharmaceutical excipients, the higher the chemical stability of the pharmaceutical composition relative to ruxotinib. Acid-reactive pharmaceutical excipients are known in the art and can be determined by measuring the pH of a solution or suspension of the excipient in water, for example by measuring the pH of a solution or suspension of 10 mg of the excipient in 1 ml of water at room temperature.

[0031] According to another preferred embodiment of the pharmaceutical composition of the invention, the composition is prepared by a method including a wet granulation step, preferably using water as the granulation liquid, wherein the active pharmaceutical ingredient is preferably granulated, optionally mixed with at least one pharmaceutically acceptable excipient.

[0032] The pharmaceutical compositions of the present invention prepared by the method described herein ensure a sufficient dissolution rate of the active pharmaceutical ingredient from the pharmaceutical composition and sufficient mechanical strength of the composition.

[0033] In another preferred embodiment of the pharmaceutical composition of the present invention, the composition is free of cellulose ester derivatives, nitrogen-containing polymers, and polymers having unsaturated bonds. These polymers may adversely affect the chemical stability of ruxolitinib and its dissolution.

[0034] According to another preferred embodiment of the invention, the pharmaceutical composition further comprises a diluent, a disintegrant, a binder, and optionally a lubricant and a flow aid.

[0035] Diluents are fillers used to increase the volume of a pharmaceutical composition. By combining diluents with the active pharmaceutical ingredient, sufficient weight and size are given to the final product to aid in production and handling.

[0036] According to a preferred embodiment of the invention, the amount of diluent used is 15% to 95% by weight, preferably 50% to 90% by weight, based on the total weight of the composition. Suitable examples of diluents used according to the invention include microcrystalline cellulose and lactose monohydrate.

[0037] The pharmaceutical compositions of the present invention may further comprise a binder. The binder ensures that a pharmaceutical composition with desired or required mechanical strength can be formed. Suitable binders for the present invention include hydroxypropyl cellulose, hydroxypropyl methylcellulose, and sodium carboxymethyl cellulose. In view of the present invention, the amount of binder used is preferably from 1% to 20% by weight, based on the total weight of the composition.

[0038] The pharmaceutical compositions of the present invention may further comprise a disintegrant. Adding a disintegrant to the pharmaceutical composition promotes the breakdown of the composition into smaller fragments in an aqueous environment, thereby increasing the usable surface area and promoting faster release of the active pharmaceutical ingredient. Suitable examples of disintegrants used according to the present invention include crospovidone, sodium glycolate starch, sodium crospovidone carboxymethyl cellulose, and mixtures of any of the foregoing substances. Within the framework of the present invention, the amount of disintegrant used is preferably from 1% to 25% by weight based on the total weight of the composition. In the context of the present invention, a preferred disintegrant is sodium glycolate starch, preferably in an amount of 1% to 5% by weight based on the total weight of the composition.

[0039] The pharmaceutical compositions of the present invention may also contain lubricants. Lubricants are generally used to reduce sliding friction. In particular, they are used to reduce friction at the interface between the blend to be packaged / compressed and the metering device of the packaging / compressing machine. Suitable lubricants to be used according to the present invention include magnesium stearate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, talc, and glyceryl fumarate. Magnesium stearate is a preferred lubricant within the framework of the present invention. Based on the total weight of the composition, the amount of lubricant is preferably from 0.01% to 0.5% by weight, more preferably from 0.01% to 0.4% by weight.

[0040] The pharmaceutical compositions of the present invention may further comprise a flow aid. The flow aid enhances product flow by reducing interparticle friction. Suitable examples of flow aids are colloidal silica. Based on the total weight of the composition, the amount of flow aid is preferably from 0.01% to 5% by weight, more preferably from 0.01% to 3% by weight.

[0041] The typical pharmaceutical compositions provided by this invention are solid oral pharmaceutical compositions in tablet form, preferably in the form of film-free tablets, wherein the compositions do not contain povidone, and wherein the compositions contain... - Ruxotinib or a pharmaceutically acceptable salt thereof, preferably a pharmaceutically acceptable salt of ruxotinib, more preferably ruxotinib phosphate, as the active pharmaceutical ingredient, preferably in an amount of 2% to 15% by weight based on the total weight of the composition; - At least one diluent, preferably selected from microcrystalline cellulose and lactose monohydrate, preferably in an amount of 70% to 95% by weight based on the total weight of the composition; - A disintegrant, preferably sodium glycolate starch, preferably in an amount of 1% to 10% by weight based on the total weight of the composition; - The binder, preferably hydroxypropyl cellulose, is preferably in an amount of 1% to 10% by weight based on the total weight of the composition. - An optional lubricant, preferably magnesium stearate, is preferably used in an amount of 0.01% to 0.4% by weight based on the total weight of the composition. - Optional flow aid, preferably colloidal silica, in an amount preferably from 0.01% to 3.0% by weight based on the total weight of the composition.

[0042] The present invention also relates to a method for preparing a pharmaceutical composition according to the present invention, comprising the following steps: a) Provide ruxolitinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient; b) Mix the active pharmaceutical ingredient with a pharmaceutically acceptable excipient to obtain a mixture; c) Wet granulating the mixture to obtain wet granules; and d) Optionally, the wet particles are dried.

[0043] In a preferred embodiment of the method of the present invention, the method includes the following steps: a) Provides ruxotinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient, preferably a pharmaceutically acceptable salt of ruxotinib, and more preferably ruxotinib phosphate; b) The active pharmaceutical ingredient is mixed with a diluent, a disintegrant, and optionally a binder as a pharmaceutically acceptable excipient to obtain a mixture; c) The mixture is wet-granulated with a granulation liquid, preferably water, to obtain wet granules, wherein the granulation liquid optionally contains a binder; d) Dry the wet particles to obtain dry wet particles; e) Optionally, the dried wet granules are mixed with at least a flow aid and / or lubricant to obtain a granulation mixture; and f) Compress the dried wet granules or optional granulation mixture into tablets. Detailed Implementation

[0044] Comparative Example 1 As a comparative example, commercially available Jakavi® 5mg, 10mg, 15mg and 20mg tablets were analyzed.

[0045] According to the Jakavi® product characteristics overview, the tablets contain ruxotinib in the form of phosphate, along with microcrystalline cellulose, magnesium stearate, anhydrous colloidal silica, sodium glycolate starch, povidone, hydroxypropyl cellulose, and lactose monohydrate as pharmaceutical excipients. The amounts of 5 mg, 10 mg, 15 mg, and 20 mg of ruxotinib shown in Jakavi® tablets are calculated based on the free base of ruxotinib.

[0046] Analytical methods determined that the commercially available Jakavi® 5mg, 10mg, 15mg and 20mg tablets consist of 4.125 wt% ruxotinib phosphate, 44.66 wt% microcrystalline cellulose, 0.5 wt% magnesium stearate, 1.0 wt% anhydrous colloidal silica, 3.0 wt% sodium glycolate starch, 2.0 wt% povidone, 2.0 wt% hydroxypropyl cellulose (low-substituted) and 42.715 wt% lactose monohydrate.

[0047] Furthermore, the average hardness of the commercially available Jakavi® 5mg, 10mg, 15mg, and 20mg tablets is determined according to the specifications in the European Pharmacopoeia (European Pharmacopoeia, 8th edition, Chapter 2.9.8 "Tablet Hardness", page 412 (German version)). The 5mg tablets are round and exhibit an average hardness of 51N, the 10mg tablets are round and exhibit an average hardness of 73N, the 15mg tablets are oval and exhibit an average hardness of 102N, and the 20mg tablets are capsule-shaped and exhibit an average hardness of 105N.

[0048] According to the European Pharmacopoeia (European Pharmacopoeia, 8th edition, 7th supplement, Chapter 2.9.3 "Dissolution test of solid oral dosage forms", pp. 7367-7375 (German version)), the ruxolitinib content of the tablets was analyzed by paddle method (apparatus 2) at 50 rpm in 900 ml buffer solutions at 37°C and pH values ​​of 1.2 (hydrochloric acid solution), 4.5 (acetic acid-sodium acetate buffer), and 6.8 (phosphate buffer). in vitro Dissolution rate.

[0049] The results of the dissolution test are shown in the table below, where infinity data corresponds to stirring at 150 rpm for 15 minutes after the 45-minute time point.

[0050] Table 1: Average dissolution of Jakavi® 5mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 2: Average dissolution of Jakavi® 10mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 3: Average dissolution of Jakavi® 15mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 4: Average dissolution of Jakavi® 20mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 5: Average dissolution of Jakavi® 20mg + 5mg tablets (one Jakavi® 20mg tablet and one Jakavi® 5mg tablet) at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablet pairs); values ​​in parentheses are RSD [%] (relative standard deviation)) In addition, the chemical stability of Jakavi® 20 mg tablets was investigated, including initial values ​​after purchase and values ​​after storage in aluminum-aluminum packaging under accelerated conditions of 40°C / 75% RH / 15 days or 60°C / 75% RH / 15 days. The results of the stability studies are shown in Table 6 below.

[0051] Table 6: Stability of Jakavi® 20mg tablets The data in Table 6 were determined by high-performance liquid chromatography (HPLC) and evaluated using an area normalization method. HPLC was performed using the following parameters: High performance liquid chromatography, chromatographic conditions: Column: Zorbax Eclipse XDB C18, 3.5μm (150×4.6mm); Mobile phase: A. Water, B. Acetonitrile, linear elution (as shown below) Detection wavelength: 220nm; Flow rate: 1.0 ml / min Column temperature: 30℃; Test solvent: acetonitrile-water (1:1); Test concentration: 250 μg / ml.

[0052] Example 1 Ruxotinib phosphate tablets containing 5 mg, 10 mg, 15 mg, and 20 mg (calculated as ruxotinib free base) of ruxotinib phosphate were prepared by wet granulation technology, and have the following composition: In the first stage of the wet granulation step, ruxolitinib phosphate and microcrystalline cellulose (dry) are mixed for 10 minutes (stirring at 150 RPM, then at 2000 RPM). Water (used for the first granulation step) is then added and the mixture is granulated for 5 minutes.

[0053] In the second stage of the wet granulation step, the excipients HPC-L, lactose monohydrate, and sodium glycolate starch are added to the wetted granulation mixture, and the resulting mixture is stirred and mixed (stirred at 150 RPM, then 2000 RPM) for 10 minutes. The remaining water (for the second granulation step) is added, and granulation continues for 5 minutes.

[0054] The obtained particles were wet-milled and sieved (1.5 mm mesh, 4.0 mm gasket, 800 rpm), and then dried at 40°C to a LOD of 2.3%.

[0055] The dried granules are mixed with colloidal silica, sieved, lubricated with magnesium stearate, and compressed into tablets.

[0056] The 5mg tablets are round and exhibit an average hardness of 61N; the 10mg tablets are round and have an average hardness of 95N; the 15mg tablets are oval and have an average hardness of 99N; and the 20mg tablets are capsule-shaped and have an average hardness of 141N. The tablet hardness was determined as described in "Comparative Example 1" above.

[0057] The results of the dissolution test of the tablets of Example 1 (as described in “Comparative Example 1”) are shown in the table below, where infinite data correspond to stirring at 150 rpm for 15 minutes after the 45-minute time point.

[0058] Table 7: Average dissolution of 5mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 8: Average dissolution of 20mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablets); values ​​in parentheses are RSD [%] (relative standard deviation)) Table 9: Average dissolution of 25mg tablets at different pH values ​​(volume 900ml; 50rpm; N=3 (number of tablet pairs); values ​​in parentheses are RSD [%] (relative standard deviation)) Furthermore, regarding the chemical stability of ruxolitinib, the stability of the tablets according to the present invention was investigated, namely, the initial values ​​after tablet preparation, and the values ​​after storage in aluminum-aluminum packaging under accelerated conditions of 40°C / 75% RH / 15 days or 60°C / 75% RH / 15 days. The results of the stability studies are shown in Table 10 below: Table 10: Stability of ruxolitinib phosphate 20 mg tablets The data in Table 10 have been determined and evaluated using the method described in “Comparative Example 1” above.

[0059] The comparison of stability data from Comparative Example 1 with that from Example 1 clearly demonstrates that ruxolitinib exhibits significantly higher stability in the compositions of the present invention. This comparison is also shown in Table 11 below.

[0060] Table 11: Comparison of stability data Furthermore, a comparison of the dissolution data of Comparative Example 1 with the dissolution data of this embodiment according to the present invention shows that the dissolution rates are comparable.

Claims

1. A solid oral pharmaceutical composition comprising ruxolitinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient, wherein, The composition contains less than 2.0% by weight of povidone.

2. The pharmaceutical composition according to claim 1, characterized in that, The composition contains less than 1.5% by weight, preferably less than 1.0% by weight, more preferably less than 0.75% by weight, more preferably less than 0.50% by weight, and even more preferably less than 0.25% by weight of povidone.

3. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The pharmaceutical composition does not contain povidone.

4. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition contains less than 0.50% by weight, preferably less than 0.45% by weight, more preferably less than 0.40% by weight, more preferably less than 0.35% by weight, and even more preferably less than 0.30% by weight of lubricant.

5. The pharmaceutical composition according to claim 4, characterized in that, The lubricant is magnesium stearate.

6. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The active pharmaceutical ingredient, ruxotinib or a pharmaceutically acceptable salt thereof, is the only active pharmaceutical ingredient contained in the composition.

7. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The active pharmaceutical ingredient contained in the composition is ruxotinib in its free base form.

8. The pharmaceutical composition according to any one of claims 1 to 6, characterized in that, The active pharmaceutical ingredient contained in the composition is ruxolitinib in a pharmaceutically acceptable salt form.

9. The pharmaceutical composition according to claim 8, characterized in that, The pharmaceutically acceptable salts of ruxolitinib are selected from ruxolitinib phosphate, ruxolitinib maleate, ruxolitinib sulfate, and ruxolitinib oxalate.

10. The pharmaceutical composition according to claim 9, characterized in that, The pharmaceutically acceptable salt of ruxolitinib is ruxolitinib phosphate.

11. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition is an immediate-release composition.

12. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The pharmaceutical composition is a tablet.

13. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition comprises the active pharmaceutical ingredient ruxolitinib or a pharmaceutically acceptable salt thereof in the range of 2 mg to 50 mg, calculated as a free base.

14. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition comprises 5 mg, 10 mg, 15 mg, 20 mg or 25 mg of ruxolitinib or a pharmaceutically acceptable salt thereof, calculated as free base.

15. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The pharmaceutical composition does not contain acidic pharmaceutical excipients.

16. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition is prepared by a method including a wet granulation step, wherein the active pharmaceutical ingredient is preferably granulated and optionally mixed with at least one pharmaceutically acceptable excipient.

17. The pharmaceutical composition according to any one of the preceding claims, characterized in that, The composition further comprises a diluent, a disintegrant, a binder, and optionally a lubricant and / or a flow aid.

18. A method for preparing a pharmaceutical composition according to any one of the preceding claims, comprising the following steps: a) Provide ruxolitinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient; b) Mix the active pharmaceutical ingredient with a pharmaceutically acceptable excipient to obtain a mixture; c) The mixture is wet-granulated to obtain wet granules; and d) Optionally, the wet particles are dried.

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