Pharmaceutical composition containing ruxolitinib

Abstract

The present invention relates to a solid oral pharmaceutical composition containing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutically active ingredient, wherein the composition contains less than 2.0% by weight of povidone relative to the total weight of the composition. The present invention also relates to a method for producing the pharmaceutical composition.

Description

Technical Field

[0001] The present invention relates to a solid oral pharmaceutical composition containing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutical active ingredient.

Background Art

[0002] Ruxolitinib is a low molecular weight compound represented by the chemical name (R)-3-(4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl)-3-cyclopentylpropanenitrile, and the international non-proprietary name (INN) "ruxolitinib" is assigned to it.

[0003] The free base form of ruxolitinib is known and its chemical structure is shown. TIFF2026513027000001.tif2546

[0004] Ruxolitinib is a selective inhibitor of JAK1 and JAK2. These kinases are involved in the signal transduction of multiple cytokines and growth factors important for hematopoiesis and immune function. Ruxolitinib inhibits the cell proliferation of JAK-STAT signal transduction and cytokine-dependent hematopoietic malignant cell models, and also shows the effect of regulating the development, proliferation and activation of immune cells related to graft-versus-host disease (GVHD).

[0005] In Europe, ruxolitinib is sold under the trade name Jakavi (registered trademark), and Jakavi is used for the treatment of myelofibrosis, polycythaemia vera and graft-versus-host disease.

[0006] Jakavi is a non-film-coated tablet containing 5 mg, 10 mg, 15 mg, and 20 mg of ruxolitinibulinate (as free base equivalent), and also contains microcrystalline cellulose, magnesium stearate, anhydrous colloidal silica, cross-linked sodium starch glycolate, povidone, low-substituted hydroxypropyl cellulose, and lactose monohydrate. It has been confirmed that Jakavi contains 2 wt% povidone of the total formulation.

[0007] The phosphate form of ruxolitinib is disclosed in Patent Document 1, which also discloses the fumarate and sulfate forms, and states that these salt forms have superior water solubility, dissolution rate, and chemical stability compared to the free base form.

[0008] However, in order to enable longer-term quality retention, long-term storage, and flexible storage conditions for solid oral formulations containing ruxolitinib, there is a need to provide a chemically stable formulation of ruxolitinib. [Prior art documents] [Patent Documents]

[0009] [Patent Document 1] European Patent EP2173752A2 [Patent Document 2] European Patent EP1966202A1 [Patent Document 3] European Patent EP3183252A1 [Overview of the project] [Problems that the invention aims to solve]

[0010] Therefore, an object of the present invention is to provide a solid oral pharmaceutical composition containing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutically active ingredient, wherein the composition is relatively stable with respect to the chemical stability of ruxolitinib. [Means for solving the problem]

[0011] The object of the present invention is achieved by a solid oral pharmaceutical composition containing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutically active ingredient, and containing less than 2.0% by weight of povidone based on the total weight of the composition. [Effects of the Invention]

[0012] Surprisingly, it was found that the lower the povidone content in the pharmaceutical composition according to the present invention, the higher the stability of the pharmaceutical composition with respect to the chemical stability of ruxolitinib.

[0013] Furthermore, it was shown that the solid oral pharmaceutical composition according to the present invention exhibits higher stability with respect to the chemical stability of ruxolitinib compared to the Jakavi composition.

[0014] In addition, it was found that the pharmaceutical composition according to the present invention exhibits sufficient solubility and dissolution rate to enable effective oral bioavailability.

[0015] Furthermore, it was found that the pharmaceutical composition according to the present invention can be formulated to have bioequivalence with Jakavi products.

[0016] As mentioned above, the solid oral pharmaceutical composition is relatively stable with respect to the chemical stability of ruxolitinib. [Modes for carrying out the invention]

[0017] In this specification, the term “stability” is understood in accordance with the definition created by the Arbeitsgemeinschaft for pharmazeutische Verfahrenstechnik (APV), namely, “stability” means that the pharmaceutical product maintains its quality in accordance with the specifications until the end of the expiration date set by the manufacturer. Therefore, the quality of a pharmaceutical product is determined by the active ingredient content and purity, sensory perceptible properties, physicochemical properties, and microbiological properties, where the active ingredient content is required not to fall below 90% of the stated value until the end of the expiration date.

[0018] It is preferable that the pharmaceutical composition according to the present invention has a stability or shelf life of at least 1 year, preferably at least 2 years, more preferably at least 3 years, even more preferably at least 3.5 years, even more preferably at least 4 years, even more preferably at least 4.5 years, and even more preferably at least 5 years under conditions of 30℃±2℃ and relative humidity of 65%±5% (see Committee for Proprietary Medicinal Products (CPMP), “Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished Products”, CPMP / QWP / 122 / 02, rev 1 corr of December 17, 2003).

[0019] Furthermore, it is preferable that the pharmaceutical composition according to the present invention has a stability or shelf life of up to 1 year, preferably up to 2 years, more preferably up to 3 years, even more preferably up to 3.5 years, even more preferably up to 4 years, even more preferably up to 4.5 years, and even more preferably up to 5 years, under conditions of 30℃±2℃ and relative humidity of 65%±5% (see Committee for Proprietary Medicinal Products (CPMP), “Guideline on Stability Testing: Stability Testing of Existing Active Substances and Related Finished Products”, CPMP / QWP / 122 / 02, rev 1 corr of December 17, 2003).

[0020] As already described above, the present invention relates to a solid oral pharmaceutical composition containing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutical active ingredient and containing less than 2.0% by weight of povidone based on the total weight of the composition.

[0021] In a preferred embodiment of the pharmaceutical composition according to the present invention, the composition contains less than 1.5% by weight, preferably less than 1.0% by weight, more preferably less than 0.75% by weight, still more preferably less than 0.50% by weight, and even more preferably less than 0.25% by weight of povidone based on the total weight of the composition. It has been found that the lower the povidone content in the pharmaceutical composition according to the present invention, the higher the stability of the pharmaceutical composition with respect to the chemical stability of ruxolitinib.

[0022] In another preferred embodiment of the pharmaceutical composition according to the present invention, the composition does not contain povidone.

[0023] In another preferred embodiment of the pharmaceutical composition according to the present invention, the composition contains less than 0.50% by weight, preferably less than 0.45% by weight, more preferably less than 0.40% by weight, still more preferably less than 0.35% by weight, and even more preferably less than 0.30% by weight of a lubricant based on the total weight of the composition. Surprisingly, it has been found that the lower the lubricant content, particularly the magnesium stearate content, in the pharmaceutical composition according to the present invention, the higher the stability of the pharmaceutical composition with respect to the chemical stability of ruxolitinib.

[0024] In another preferred embodiment of the pharmaceutical composition according to the present invention, the lubricant is magnesium stearate. In particular, magnesium stearate has an adverse effect on the chemical stability of ruxolitinib.

[0025] In addition to ruxolitinib free base or a pharmaceutically acceptable salt thereof, the pharmaceutical composition according to the present invention may contain one or more additional pharmaceutical active ingredients. However, in another preferred embodiment of the present invention, ruxolitinib or a pharmaceutically acceptable salt thereof is the only pharmaceutical active ingredient contained in the composition.

[0026] In another preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutically active ingredient contained in the composition is ruxolitinib in free base form. Ruxolitinib free base is disclosed in EP1966202A1 (Patent Document 2).

[0027] In another preferred embodiment of the present invention, the pharmaceutically active ingredient contained in the composition is ruxolitinib in a pharmaceutically acceptable salt form. In particular with respect to ruxolitinib salts, povidone adversely affects the chemical stability of ruxolitinib.

[0028] According to another preferred embodiment of the pharmaceutical composition according to the present invention, pharmaceutically acceptable salts of ruxolitinib are selected from the group consisting of ruxolitinib phosphate, ruxolitinib maleate, ruxolitinib sulfate, and ruxolitinib oxalate. Ruxolitinib phosphate, ruxolitinib maleate, and ruxolitinib sulfate are disclosed in Patent Document 1 (EP2173752A2), where these salts are described as 1:1 salts of ruxolitinib and the acid. Ruxolitinib oxalate is disclosed in Patent Document 3 (EP3183252A1).

[0029] In another preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutically acceptable salt of ruxolitinib is ruxolitinibulinate.

[0030] The pharmaceutical compositions according to the present invention can be formulated for immediate release, modified release, controlled release, sustained release, extended release, delayed release, or delayed-initiated release of ruxolitinib. However, in preferred embodiments of the present invention, the pharmaceutical composition is an immediate-release composition. Immediate-release, modified-release, controlled-release, sustained-release, extended-release, or delayed-release pharmaceutical compositions and methods for producing the same are well known in the art and are in the general knowledge of those skilled in the art.

[0031] The pharmaceutical composition according to the present invention is a solid and therefore can be in the form of, for example, tablets, capsules, pills, granules, powders, etc.

[0032] However, in a preferred embodiment of the present invention, the pharmaceutical composition is a tablet, and more particularly, a non-film tablet.

[0033] In another preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutical composition contains 2 mg to 50 mg of ruxolitinib or a pharmaceutically acceptable salt thereof, calculated as free base. In particular, the pharmaceutical composition according to the present invention contains 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxolitinib free base or a pharmaceutically acceptable salt thereof (on a free base basis).

[0034] In another preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutical composition does not contain an acid-reactive pharmaceutical excipient. It has been found that the lower the content of the acid-reactive pharmaceutical excipient in the pharmaceutical composition according to the present invention, the greater the stability of the pharmaceutical composition with respect to the chemical stability of ruxolitinib. Acid-reactive pharmaceutical excipients are known in the art and can be determined, for example, by measuring the pH value of a solution or suspension obtained by dissolving or suspending 10 mg of the excipient in 1 mL of water at room temperature.

[0035] According to another preferred embodiment of the pharmaceutical composition according to the present invention, the pharmaceutical composition is prepared by a process including a wet granulation step, preferably using water as the granulation liquid, and preferably the pharmaceutically active ingredient is granulated by mixing it with at least one pharmaceutically acceptable excipient, which is optionally used.

[0036] The pharmaceutical composition of the present invention prepared using the above-described process ensures a sufficient dissolution rate of the active pharmaceutical ingredient and sufficient mechanical strength of the composition.

[0037] In another preferred embodiment of the pharmaceutical composition according to the present invention, the composition does not contain cellulose ester derivative-containing polymers, nitrogen-containing polymers, or polymers having unsaturated bonds. These polymers may adversely affect the chemical stability and dissolution of ruxolitinib.

[0038] In another preferred embodiment of the present invention, the pharmaceutical composition further comprises a diluent, a disintegrant, a binder, and optionally a lubricant and a fluidizing agent.

[0039] Diluents are fillers used to increase the volume of pharmaceutical compositions. By combining diluents with active pharmaceutical ingredients, the final product is given sufficient weight and size to facilitate manufacturing and handling.

[0040] In preferred embodiments of the present invention, the diluent is used in an amount of 15% to 95% by weight, preferably 50% to 90% by weight, based on the total weight of the composition. Examples of diluents suitable for use in accordance with the present invention include microcrystalline cellulose and lactose monohydrate.

[0041] The pharmaceutical composition of the present invention may further contain a binder. The binder ensures that the pharmaceutical composition can be formed in a form having the desired or required mechanical strength. Suitable binders for use in accordance with the present invention include hydroxypropyl cellulose, hydroxypropyl methylcellulose, and sodium carboxymethylcellulose. In view of the present invention, the binder is preferably used in an amount of 1% to 20% by weight based on the total weight of the composition.

[0042] The pharmaceutical composition of the present invention may further contain a disintegrant. The disintegrant is added to facilitate the breakdown of the pharmaceutical composition into smaller fragments in an aqueous environment, thereby increasing the available surface area and promoting a more rapid release of the active pharmaceutical ingredient.

[0043] Examples of disintegrants suitable for use in accordance with the present invention include crospovidone, cross-linked sodium starch glycolate, croscarmellose sodium, and any mixture thereof. Within the scope of the present invention, the disintegrant is preferably used in an amount of 1% to 25% by weight based on the total weight of the composition. A preferred disintegrant in the context of the present invention is cross-linked sodium starch glycolate, preferably in an amount of 1% to 5% by weight based on the total weight of the composition.

[0044] The pharmaceutical compositions of the present invention may further contain lubricants. Lubricants are generally used to reduce sliding friction. In particular, they are used to reduce friction at the interface between the mixture to be encapsulated / tableted and the filling section of the capsule filling machine / tablet press. Suitable lubricants for use according to the present invention include magnesium stearate, stearic acid, glyceryl behenate, hydrogenated vegetable oil, talc, and glyceryl fumarate. A preferred lubricant within the scope of the present invention is magnesium stearate. The lubricant is preferably used in an amount of 0.01% to 0.5% by weight, more preferably 0.01% to 0.4% by weight, based on the total weight of the composition.

[0045] The pharmaceutical composition of the present invention may further contain a fluidizing agent. The fluidizing agent improves the fluidity of the product by reducing interparticle friction. A suitable example of a fluidizing agent is anhydrous silicic acid colloid (colloidal silicon dioxide). The fluidizing agent is preferably used in an amount of 0.01% to 5% by weight, more preferably 0.01% to 3% by weight, based on the total weight of the composition.

[0046] A typical pharmaceutical composition provided by the present invention is a solid oral pharmaceutical composition in the form of a tablet, preferably a non-film tablet, the composition does not contain povidone, and the composition - The active pharmaceutical ingredient contains ruxolitinib or a pharmaceutically acceptable salt thereof, preferably a pharmaceutically acceptable salt of ruxolitinib, more preferably ruxolitinibulinate, preferably in an amount of 2% to 15% by weight based on the total weight of the composition; - Containing at least one diluent, preferably selected from the group consisting of microcrystalline cellulose and lactose monohydrate, and preferably in an amount of 70% to 95% by weight based on the total weight of the composition; - Contains a disintegrant, preferably cross-linked sodium starch glycolate, preferably in an amount of 1% to 10% by weight based on the total weight of the composition; - Contains a binder, preferably hydroxypropyl cellulose, preferably in an amount of 1% to 10% by weight based on the total weight of the composition; - Optionally, it may contain a lubricant, preferably magnesium stearate, preferably in an amount of 0.01% to 0.4% by weight based on the total weight of the composition; - The composition optionally contains a fluidizing agent, preferably colloidal silica, and preferably in an amount of 0.01% to 3.0% by weight based on the total weight of the composition.

[0047] The present invention also relates to a method for preparing a pharmaceutical composition according to the present invention, comprising the following steps: a) A step of providing ruxolitinib or a pharmaceutically acceptable salt thereof as a pharmaceutical active ingredient; b) A step of mixing the pharmaceutically active ingredient with a pharmaceutically acceptable excipient to obtain a mixture; c) A step of wet granulation of the mixture to obtain a wet granule; and d) A step of drying the wet granules as necessary.

[0048] In a preferred embodiment of the process of the present invention, the process includes the following steps: a) A step of providing ruxolitinib or a pharmaceutically acceptable salt thereof, preferably a pharmaceutically acceptable salt of ruxolitinib, more preferably ruxolitinibrate, as a pharmaceutically active ingredient; b) A step of mixing the pharmaceutically active ingredient with a diluent, a disintegrant, and optionally a binder and a pharmaceutically acceptable excipient to obtain a mixture; c) A step of obtaining a wet granule by wet granulation of the mixture with a granulation liquid, preferably water, wherein the granulation liquid optionally contains a binder; d) A step of drying the wet granules to obtain dried wet granules; e) a step of mixing the dry wet granules with at least a fluidizing agent and / or a lubricant, if necessary, to obtain a granulated mixture; and f) A step of manufacturing tablets by compressing the dry wet granules or any granular mixture.

[0049] [Comparative Example 1] Commercially available Jakavi 5 mg, 10 mg, 15 mg, and 20 mg tablets were analyzed as comparative examples.

[0050] According to the product characteristics summary for Jakavi, the tablets contain ruxolitinib in phosphate form and contain microcrystalline cellulose, magnesium stearate, anhydrous colloidal silica, cross-linked sodium starch glycolate, povidone, hydroxypropyl cellulose, and lactose monohydrate as pharmaceutical excipients. The ruxolitinib amounts in the 5 mg, 10 mg, 15 mg, and 20 mg Jakavi tablets are calculated based on the amount of free ruxolitinib.

[0051] Analytical methods revealed that the above-mentioned commercially available Jakavi 5 mg, 10 mg, 15 mg, and 20 mg tablets consist of 4.125% by weight ruxolitinibrinate, 44.66% by weight microcrystalline cellulose, 0.5% by weight magnesium stearate, 1.0% by weight anhydrous colloidal silica, 3.0% by weight cross-linked sodium starch glycolate, 2.0% by weight povidone, 2.0% by weight hydroxypropyl cellulose (low substitution), and 42.715% by weight lactose monohydrate.

[0052] Furthermore, the average hardness of the above-mentioned commercially available Jakavi 5 mg, 10 mg, 15 mg, and 20 mg tablets was determined according to Eur.Ph. (European Pharmacopoeia, 8th edition, 2.9.8 "Hardness of Tablets", p.412 [German version]). The 5 mg tablet was round and had an average hardness of 51 N, the 10 mg tablet was round and had an average hardness of 73 N, the 15 mg tablet was oval and had an average hardness of 102 N, and the 20 mg tablet was capsule-shaped and had an average hardness of 105 N.

[0053] The in vitro dissolution rate of ruxolitinib in the above tablets was analyzed using the paddle method (apparatus 2) at 50 rpm, 37°C, and 900 mL of buffer solution under the conditions of pH 1.2 (hydrochloric acid solution), pH 4.5 (acetic acid-sodium acetate buffer), and pH 6.8 (phosphate buffer), in accordance with the provisions of Eur.Ph. (European Pharmacopoeia, 8th edition, 7th supplement, 2.9.3 "Dissolution tests for solid oral preparations", pp. 7367-7375 [German version]).

[0054] The results of the dissolution test are shown in the table below, where the data with ∞ (infinity) corresponds to data obtained after stirring at 150 rpm for 15 minutes from the 45-minute mark onwards.

[0055] Table 1: Average dissolution values ​​of Jakavi 5 mg tablets at different pH values ​​(volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 1]

[0056] Table 2: Average dissolution values ​​of Jakavi 10 mg tablets at different pH values ​​(volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 2]

[0057] Table 3: Average dissolution values ​​of Jakavi 15 mg tablets at different pH values ​​(volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 3]

[0058] Table 4: Average dissolution values ​​of Jakavi 20 mg tablets at different pH values ​​(volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 4]

[0059] Table 5: Average dissolution values ​​of Jakavi 20 mg tablets + 5 mg tablets (one Jakavi 20 mg tablet and one Jakavi 5 mg tablet) at different pH values ​​(volume 900 mL, 50 rpm, N=3 [number of tablet pairs]; values ​​in parentheses are RSD [%] (coefficient of variation)). [Table 5]

[0060] Furthermore, the stability of Jakavi 20 mg tablets was investigated from the perspective of the chemical stability of ruxolitinib. Specifically, the initial values ​​immediately after purchase of the tablets were investigated, as well as the values ​​after storage in aluminum-aluminum packaging under accelerated conditions of 40°C / 75% relative humidity / 15 days or 60°C / 75% relative humidity / 15 days. The results of the stability tests are shown in Table 6 below.

[0061] Table 6: Stability of Jakavi 20 mg tablets [Table 6]

[0062] The data in Table 6 were measured by high-performance liquid chromatography and evaluated using the area percentage method. High-performance liquid chromatography was performed with the following parameters.

[0063] High-performance liquid chromatography, chromatography conditions: Column: Zorbax Eclipse XDB C18, 3.5 μm (150 × 4.6 mm); Mobile phase: A. Water, B. Acetonitrile, linear elution (see below) TIFF2026513027000008.tif64166 Detection wavelength: 220 nm; Flow rate: 1.0 mL / min; Column temperature: 30°C; Test solvent: Acetonitrile-water (1:1); Test concentration: 250 μg / mL.

[0064] [Example 1] Ruxolitinibulinate tablets (ruxolitinibulinate tablets containing 5 mg, 10 mg, 15 mg, and 20 mg of ruxolitinib free base) were prepared by wet granulation technology based on the following composition. TIFF2026513027000009.tif115166

[0065] In the first step of this wet granulation process, ruxolitinibulinate and microcrystalline cellulose are dry-mixed for 10 minutes (stirring at 150 RPM, knife at 2000 RPM). Then, water (water for the first granulation step) is added, and the mixture is granulated for 5 minutes.

[0066] In the second stage of this wet granulation process, the excipients HPC-L, lactose monohydrate, and sodium starch glycolate are added to the wet granulation mixture, and the resulting mixture is stirred and mixed for 10 minutes (stirring at 150 RPM, knife at 2000 RPM). The remaining water (water for the second granulation step) is added, and granulation is continued for 5 minutes.

[0067] The obtained granules are wet-milled and sieved (mesh 1.5 mm, gasket 4.0 mm, 800 rpm), and the resulting granules are dried at 40 °C to obtain a LOD (loss on drying) of 2.3%.

[0068] The dried granules are mixed with colloidal silica, sieved, lubricated with magnesium stearate, and compressed into tablets.

[0069] The 5 mg tablet is round and has an average hardness of 61 N, the 10 mg tablet is round and has an average hardness of 95 N, the 15 mg tablet is oval and has an average hardness of 99 N, and the 20 mg tablet is capsule-shaped and has an average hardness of 141 N. The tablet hardness is measured by the method described in the "Comparative Example 1" section above.

[0070] The results of the dissolution test for the tablet in Example 1 (conducted according to the method described in the "Comparative Example 1" section) are shown in the table below. Here, the infinity data corresponds to stirring at 150 rpm for 15 minutes after 45 minutes.

[0071] Table 7: Average dissolution values ​​of 5 mg tablets at different pH values ​​(Volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 7]

[0072] Table 8: Average dissolution values ​​of 20 mg tablets at different pH values ​​(Volume 900 mL, 50 rpm, N=3 [number of tablets]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 8]

[0073] Table 9: Average dissolution values ​​of 25 mg tablets at different pH values ​​(volume 900 mL, 50 rpm, N=3 [tablet logarithm]; values ​​in parentheses are RSD [%] (coefficient of variation)) [Table 9]

[0074] The stability of the tablets according to the present invention was investigated from the perspective of the chemical stability of ruxolitinib. Specifically, the initial values ​​immediately after tablet preparation and the values ​​after storage in aluminum-aluminum packaging under accelerated conditions of 40°C / 75% relative humidity / 15 days or 60°C / 75% relative humidity / 15 days were examined. The results of the stability tests are shown in Table 10 below.

[0075] Table 10: Stability of ruxolitinibrinate 20 mg tablets [Table 10]

[0076] The data in Table 10 were measured and evaluated using the method described in the "Comparative Example 1" section above.

[0077] Comparing the stability data of Comparative Example 1 with that of Example 1, it is clear that the stability of ruxolitinib is significantly higher in the composition of the present invention. This comparison is also shown in Table 11 below.

[0078] Table 11: Comparison of stability data [Table 11]

[0079] Comparing the elution data of Comparative Example 1 with the elution data of this embodiment according to the present invention, it became clear that the elution rates were equivalent.

Claims

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

2. The pharmaceutical composition according to claim 1, wherein the composition contains less than 1.5% by weight of povidone, preferably less than 1.0% by weight, more preferably less than 0.75% by weight, even more preferably less than 0.50% by weight, and even more preferably less than 0.25% by weight of povidone, based on the total weight of the composition.

3. The pharmaceutical composition according to claim 1 or 2, wherein the pharmaceutical composition does not contain povidone.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the composition contains a lubricant in an amount of less than 0.50% by weight, preferably less than 0.45% by weight, more preferably less than 0.40% by weight, even more preferably less than 0.35% by weight, and even more preferably less than 0.30% by weight, based on the total weight of the composition.

5. The pharmaceutical composition according to claim 4, wherein the lubricant is magnesium stearate.

6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the aforementioned pharmaceutical active ingredient is the only pharmaceutical active ingredient contained in the composition.

7. The pharmaceutical composition according to any one of claims 1 to 6, wherein the pharmaceutically active ingredient is ruxolitinib in its free base form.

8. The pharmaceutical composition according to any one of claims 1 to 6, wherein the pharmaceutically active ingredient is a pharmaceutically acceptable salt of ruxolitinib.

9. The pharmaceutical composition according to claim 8, wherein the pharmaceutically acceptable salt of ruxolitinib is a salt selected from the group consisting of ruxolitinib phosphate, ruxolitinib maleate, ruxolitinib sulfate, and ruxolitinib oxalate.

10. The pharmaceutical composition according to claim 9, wherein the pharmaceutically acceptable salt of ruxolitinib is ruxolitinibulinate.

11. The pharmaceutical composition according to any one of claims 1 to 10, wherein the pharmaceutical composition is an immediate-release composition.

12. The pharmaceutical composition according to any one of claims 1 to 11, wherein the pharmaceutical composition is a tablet.

13. The pharmaceutical composition according to any one of claims 1 to 12, wherein the pharmaceutical composition contains 2 mg to 50 mg of ruxolitinib or a pharmaceutically acceptable salt thereof as a free base.

14. The pharmaceutical composition according to any one of claims 1 to 13, wherein the pharmaceutical composition contains 5 mg, 10 mg, 15 mg, 20 mg, or 25 mg of ruxolitinib (as free base amount).

15. The pharmaceutical composition according to any one of claims 1 to 14, wherein the pharmaceutical composition does not contain an acid-reactive pharmaceutical additive.

16. The pharmaceutical composition according to any one of claims 1 to 15, wherein the pharmaceutical composition is prepared by a process including a wet granulation step.

17. The pharmaceutical composition according to any one of claims 1 to 16, wherein the pharmaceutical composition further comprises an excipient, a disintegrant, a binder, and optionally a lubricant and / or a fluidizing agent.

18. A method for preparing a pharmaceutical composition according to any one of claims 1 to 17, comprising the following steps: a) A step of preparing ruxolitinib or a pharmaceutically acceptable salt thereof as the active pharmaceutical ingredient; b) A step of mixing the pharmaceutical active ingredient with a pharmaceutical additive to obtain a mixture; c) A step of wet granulation of the mixture to obtain wet granules; and d) A step of drying the wet granules as necessary.

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