Baricitinib tablet and preparation method thereof

Abstract

The application relates to the technical field of medicines, and particularly discloses a baricitinib tablet and a preparation method thereof. The baricitinib tablet comprises a tablet core and a coating film, the tablet core is obtained by tabletting core materials, the coating film is formed by solidifying a coating liquid, and the components of the coating liquid comprise hydroxypropyl methyl cellulose, medical-grade polyacrylic acid resin, egg white protein and water. Compared with a single-component hydroxypropyl methyl cellulose coating film, the coating film can make a greater contribution to the hardness of the baricitinib tablet, and is helpful to overcome the adverse effect of microcrystalline cellulose on the hardness of the baricitinib tablet. By adopting the technical scheme, a tablet product with relatively high hardness can be produced by using relatively poor microcrystalline cellulose, the requirement of a tablet production process on raw materials is reduced, and full use of the microcrystalline cellulose is facilitated.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical technology, and more specifically, to a baricitinib tablet and a method for preparing the same. Background Technology

[0002] Baricitinib is a small molecule compound that selectively inhibits JAK1 and JAK2, and is commonly used to treat autoimmune diseases such as rheumatoid arthritis (RA), atopic dermatitis, and systemic lupus erythematosus. Currently, baricitinib is often marketed as tablets, and to reduce the contact between the active ingredient and the external environment, the tablet cores containing baricitinib are usually coated, with hydroxypropyl methylcellulose being a commonly used coating material.

[0003] Chinese patent CN107334738B discloses a pharmaceutical composition containing baricitinib (i.e., baricitinib tablets, hereinafter the same). This pharmaceutical composition can be prepared into coated tablets, with a weight gain of 2-5% after coating. The patent also discloses that its tablet core may include the following components by weight percentage: 1% baricitinib, 55% microcrystalline cellulose, 40% mannitol, 3% croscarmellose sodium, and 1% magnesium stearate.

[0004] Regarding the aforementioned technologies, the inventors believe that microcrystalline cellulose is the most important component of the tablet core, and its physical properties have a significant impact on the hardness of baricitinib tablets. However, the sources of microcrystalline cellulose are complex, and baricitinib tablets prepared using microcrystalline cellulose from different sources often exhibit significant differences in tablet hardness, resulting in some baricitinib tablet products failing to possess good hardness performance. Summary of the Invention

[0005] In related technologies, baricitinib tablets prepared using microcrystalline cellulose from different sources often exhibit significant differences in tablet hardness, resulting in some baricitinib tablet products failing to achieve satisfactory hardness performance. To improve this deficiency, this application provides a baricitinib tablet and its preparation method.

[0006] In a first aspect, this application provides a baricitinib tablet, which adopts the following technical solution:

[0007] A baricitinib tablet, comprising a tablet core and a coating film covering the surface of the tablet core, wherein the tablet core is obtained by tableting a core material containing baricitinib technical and microcrystalline cellulose, and the coating film is formed by curing a coating solution under hot air blowing at 85-95°C, wherein the weight gain of the tablet core after loading the coating film is 4-10%, and the coating solution comprises the following components in parts by weight: 10-14 parts hydroxypropyl methylcellulose, 8-12 parts medical grade polyacrylic acid resin, 4-16 parts egg white protein, and 240-260 parts water.

[0008] By adopting the above technical solution, this application defines the formulation components of the coating solution. By using the coating solution of this application to coat the tablet core, hydroxypropyl methylcellulose, polyacrylic acid resin, and egg white protein can be loaded onto the tablet surface. The carboxyl groups in the polyacrylic acid resin can combine with the amino groups in the egg white protein, and hydrogen bonds can be formed between hydroxypropyl methylcellulose, polyacrylic acid resin, and egg white protein. Furthermore, the egg white protein coagulates upon heating during the coating process, thus forming a relatively dense coating film with good mechanical properties on the tablet core surface. Compared with a single-component hydroxypropyl methylcellulose coating film, the coating film of this application contributes more to the hardness of baricitinib tablets, helping to overcome the adverse effects of poor physical properties of microcrystalline cellulose on tablet hardness, resulting in baricitinib tablets with good hardness. By adopting the technical solution of this application, tablets with relatively high hardness can be produced even using relatively low-quality microcrystalline cellulose, reducing the requirements for raw materials in the tablet manufacturing process and facilitating the full utilization of microcrystalline cellulose.

[0009] Preferably, the coating solution comprises the following components in parts by weight: 12-14 parts hydroxypropyl methylcellulose, 10-12 parts medical-grade polyacrylic acid resin, 10-16 parts egg white protein, and 250-260 parts water.

[0010] By adopting the above technical solution, the raw material ratio of the coating solution was optimized, which helps to overcome the adverse effects of microcrystalline cellulose on the hardness of baricitinib tablets and improves the hardness of baricitinib tablets even when the performance of microcrystalline cellulose is poor.

[0011] Preferably, the weight gain of the core after loading with the coating film is 8-10%.

[0012] By adopting the above technical solution, the weight gain rate of the tablet core was optimized, which helps to overcome the adverse effects of microcrystalline cellulose on the hardness of baricitinib tablets and improves the hardness of baricitinib tablets even when the performance of microcrystalline cellulose is poor.

[0013] Preferably, the coating solution further comprises 0.8-4.8 parts by weight of a filler, wherein the filler comprises hydroxyapatite.

[0014] By adopting the above technical solution, hydroxyapatite itself has good hardness, and the calcium ions on the surface of hydroxyapatite particles can easily adsorb the carboxyl groups in polyacrylic resin and the free carboxyl groups in egg white protein, so that polyacrylic resin and egg white protein can be indirectly bound through hydroxyapatite particles. Therefore, the addition of hydroxyapatite helps to improve the hardness of baricitinib tablets.

[0015] Preferably, the filler is nano-sized hydroxyapatite.

[0016] By adopting the above technical solution, nano-sized hydroxyapatite is preferred as the filler. Compared with micron-sized hydroxyapatite, nano-sized hydroxyapatite has a relatively small particle size, so it can more fully adsorb with polyacrylic acid resin and egg white protein, and improve the hardness of baricitinib tablets.

[0017] Preferably, the filler is modified hydroxyapatite, which is prepared as follows: calcium nitrate, sodium phosphate, and sodium citrate are weighed in a molar ratio of 6:3.6:(1-4) and prepared into solutions respectively. Then, the calcium nitrate solution is added dropwise to the sodium citrate solution, and after stirring, the sodium phosphate solution is added and stirring is continued to obtain a precursor solution. The precursor solution is subjected to hydrothermal treatment and then centrifuged for purification to obtain an intermediate. The intermediate is dried to obtain modified hydroxyapatite.

[0018] By adopting the above technical solution, this application preferably uses modified hydroxyapatite as the filler. Sodium citrate is added during the preparation of modified hydroxyapatite, allowing a portion of the sodium citrate to be adsorbed onto the surface of the hydroxyapatite. Sodium citrate can introduce a certain amount of carboxyl groups onto the surface of the hydroxyapatite, which, when used in appropriate amounts, can improve the filler's ability to form hydrogen bonds and enhance the binding effect between the filler and components such as hydroxypropyl methylcellulose, polyacrylic acid resin, and egg white protein, thereby increasing the hardness of baricitinib tablets.

[0019] Preferably, the molar ratio of calcium nitrate to sodium citrate is 6:(2-3).

[0020] While adding sodium citrate can enhance the filler's ability to form hydrogen bonds, the adsorption of sodium citrate also occupies adsorption sites on the hydroxyapatite surface, hindering the adsorption and binding between carboxyl groups and calcium ions. Therefore, this application optimizes the molar ratio of calcium nitrate to sodium citrate, which helps to significantly improve the hardness of baricitinib tablets.

[0021] Preferably, the core material also includes hydroxyapatite whiskers, the amount of which is 3-15% of the weight of the microcrystalline cellulose.

[0022] By adopting the above technical solution, after adding hydroxyapatite whiskers to the core material, the hydroxyapatite whiskers can play a certain reinforcing role for the tablet core, and some of the hydroxyapatite whiskers will be distributed on the surface of the tablet core. The modified hydroxyapatite and polyacrylic acid resin in the coating solution can both be adsorbed onto the hydroxyapatite whiskers on the surface of the tablet core through carboxyl groups, thereby improving the bonding between the coating film and the tablet core, reducing the possibility of the coating film falling off and breaking under external force, and helping to improve the hardness of baricitinib tablets.

[0023] Preferably, the amount of hydroxyapatite whiskers used is 9-15% of the weight of microcrystalline cellulose.

[0024] By adopting the above technical solution, the amount of hydroxyapatite whiskers was optimized, which helps to fully improve the hardness of baricitinib tablets.

[0025] Secondly, this application provides a method for preparing baricitinib tablets, which adopts the following technical solution.

[0026] A method for preparing baricitinib tablets includes the following steps:

[0027] (1) Prepare a core material containing baricitinib technical and microcrystalline cellulose, and then compress the core material to obtain a tablet core for later use; prepare any of the above-mentioned coating solutions for later use.

[0028] (2) Add the tablet core to the coating equipment and coat the tablet core with the coating solution prepared in step (1) under hot air blowing at 85-95℃, so that the weight gain rate of the tablet core after loading the coating film reaches 4-10%, and obtain baricitinib tablets.

[0029] By adopting the above technical solution, the method of this application first prepares the tablet core and the coating liquid, then the coating liquid is solidified on the surface of the tablet core through coating treatment, the coating film is loaded onto the surface of the tablet core, and then the egg white protein is fully heated and coagulated by baking to obtain baricitinib tablets.

[0030] In summary, this application has the following beneficial effects:

[0031] 1. Compared with single-component hydroxypropyl methylcellulose coating films, the coating film of this application can contribute more to the hardness of baricitinib tablets, helping to overcome the adverse effects of microcrystalline cellulose on the hardness of baricitinib tablets. By adopting the technical solution of this application, tablet products with relatively high hardness can be produced even using relatively low-quality microcrystalline cellulose, reducing the requirements of the tablet manufacturing process on raw materials and helping to fully utilize microcrystalline cellulose.

[0032] 2. In this application, modified hydroxyapatite is preferred as the filler. Sodium citrate introduces a certain amount of carboxyl groups on the surface of modified hydroxyapatite. When the dosage is appropriate, it can improve the filler's ability to form hydrogen bonds and improve the binding effect between the filler and components such as hydroxypropyl methylcellulose, polyacrylic acid resin, and egg white protein, thereby improving the hardness of baricitinib tablets. Detailed Implementation

[0033] The present application will be further described in detail below with reference to the embodiments, preparation examples and comparative examples. The raw materials involved in the present application can all be obtained commercially.

[0034] Preparation example of modified hydroxyapatite

[0035] The following explanation uses Preparation Example 1 as an example.

[0036] Preparation Example 1

[0037] In this preparation example, the modified hydroxyapatite was prepared according to the following method:

[0038] Calcium nitrate, sodium phosphate, and sodium citrate were weighed in a molar ratio of 6:3.6:1 and prepared into solutions. The calcium nitrate solution was then added dropwise to the sodium citrate solution. After stirring magnetically for 5 minutes, the sodium phosphate solution was added and the magnetic stirring was continued for 10 minutes to obtain the precursor solution. The precursor solution was subjected to hydrothermal treatment at 180℃ for 6 hours, followed by centrifugation purification to obtain the intermediate. The intermediate was dried at 80℃ to obtain modified hydroxyapatite.

[0039] In this embodiment, the calcium nitrate solution is prepared by mixing 1 mol of calcium nitrate with 0.75 L of deionized water. If the amount of water used to prepare the calcium nitrate solution (in L) is recorded as x, then the amount of water used to prepare the sodium phosphate solution is 2x, and the amount of water used to prepare the sodium citrate solution is x.

[0040] As shown in Table 1, the difference between preparation examples 1-5 lies in the amount of sodium citrate used.

[0041] Table 1. Molar ratio of calcium nitrate, sodium phosphate, and sodium citrate

[0042] sample Calcium nitrate Sodium phosphate Sodium citrate Preparation Example 1 6 3.6 1 Preparation Example 2 6 3.6 2 Preparation Example 3 6 3.6 2.5 Preparation Example 4 6 3.6 3 Preparation Example 5 6 3.6 4

[0043] Example

[0044] Examples 1-5

[0045] The following description uses Example 1 as an example.

[0046] Example 1

[0047] In this embodiment, the baricitinib tablet comprises a tablet core and a coating film covering the surface of the tablet core. The tablet core is obtained by compressing core material in a DP30A single-punch tablet press. The coating film is formed by curing a coating solution onto the surface of the tablet core. The weight gain of the tablet core after loading the coating film is 4%. The loading of the coating film is carried out in a coating pan with an inlet air temperature of 85°C. The coating solution comprises the following components: 10 kg of hydroxypropyl methylcellulose, 8 kg of medical-grade polyacrylic acid resin, 4 kg of egg white protein, and 240 kg of water.

[0048] In this embodiment, microcrystalline cellulose is prepared by hydrolyzing cotton pulp with a degree of polymerization of 1274.2. The degree of polymerization of microcrystalline cellulose is 214.1, and the bulk density is 0.392 g / mL.

[0049] This embodiment also provides a method for preparing baricitinib tablets, including the following steps:

[0050] (1) Weigh 55 kg of microcrystalline cellulose, 40 kg of mannitol and 3 kg of disintegrant (specifically, sodium croscarmellose), mix them to obtain mixed excipients; disperse 1 kg of baricitinib technical in 20 kg of pure water to obtain granulation solution, spray the granulation solution into the excipients, mix evenly and dry to constant weight; then dry granulate the mixed materials, granulate the obtained granules and add 1 kg of lubricant (magnesium stearate) to mix to obtain core material, compress the core material to obtain tablet core, and set aside; weigh 10 kg of hydroxypropyl methylcellulose, 8 kg of medical grade polyacrylic acid resin, 4 kg of egg white protein and 240 kg of water, mix them to obtain coating solution, and set aside.

[0051] (2) Add the tablet core to the coating equipment and use the coating solution prepared in step (1) to coat the tablet core so that the weight gain of the tablet core after being loaded with the coating film is 4%. Then bake the tablet core loaded with the coating film at 70°C to obtain baricitinib tablets.

[0052] As shown in Table 2, the main differences between Examples 1-5 are the raw material ratio of the coating solution and the air inlet temperature of the coating pan.

[0053] Table 2 Raw material ratio of coating solution

[0054]

[0055] Examples 6-9

[0056] As shown in Table 3, the difference between Examples 6-9 and Example 5 is that the weight gain rate after loading the core with the coating film is different.

[0057] Table 3 Weight gain rate of the core after coating

[0058] sample Example 5 Example 6 Example 7 Example 8 Example 9 Weight gain rate / % 4 6 8 9 10

[0059] Example 10

[0060] The difference between this embodiment and Embodiment 9 is that the coating solution also includes a filler, and the amount of filler used is 0.8 kg.

[0061] The filler in this embodiment is hydroxyapatite with an average particle size of 2.4 μm.

[0062] Example 11

[0063] The difference between this embodiment and Embodiment 10 is that the filler used is nano-sized hydroxyapatite with an average particle size of 50 nm.

[0064] Example 12

[0065] The difference between this embodiment and Example 11 is that the filler used is the modified hydroxyapatite from Preparation Example 1.

[0066] As shown in Table 4, the difference between Examples 12-16 is that the preparation methods of hydroxyapatite are different.

[0067] Table 4 Examples of hydroxyapatite preparation

[0068] sample Example 12 Example 13 Example 14 Example 15 Example 16 Preparation Example Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5

[0069] Examples 17-20

[0070] As shown in Table 5, the difference between Examples 17-20 and Example 14 is that the amount of filler used is different.

[0071] Table 5 Filler Dosage

[0072] sample Example 14 Example 17 Example 18 Example 19 Example 20 Filler / kg 0.8 1.8 2.8 3.8 4.8

[0073] Example 21

[0074] The difference between this embodiment and embodiment 20 is that the core material also includes hydroxyapatite whiskers. The hydroxyapatite whiskers are mixed together with the other raw materials when preparing the mixed excipients. The amount of hydroxyapatite whiskers is 3% of the weight of microcrystalline cellulose.

[0075] As shown in Table 6, the difference between Examples 21-25 is that the percentage of hydroxyapatite used to the weight of microcrystalline cellulose (hereinafter referred to as whisker percentage) is different.

[0076] Table 6. Percentage of Whiskers

[0077] sample Example 21 Example 22 Example 23 Example 24 Example 25 Whiskers percentage 3 6 9 12 15

[0078] Comparative Example

[0079] Comparative Example 1

[0080] A baricitinib tablet is assembled from a tablet core and a coating film. The tablet core is prepared according to Example 1 of Chinese Patent Publication No. CN107334738B, wherein the microcrystalline cellulose used is prepared by hydrolyzing leaf pulp with a degree of polymerization of 560.4. The degree of polymerization of the microcrystalline cellulose is 153.8, and the bulk density is 0.493 g / mL. The coating film is formed by curing a coating solution on the surface of the tablet core. The specific processing is carried out in a coating pan. The hot air temperature entering the coating pan is 85°C. The coating solution is a hydroxypropyl methylcellulose dispersion with a solid content of 20%. The weight gain of the tablet core after loading the coating film is 2%.

[0081] Comparative Example 2

[0082] The difference between this comparative example and comparative example 1 is that the microcrystalline cellulose used in comparative example 1 is replaced with the microcrystalline cellulose of example 1.

[0083] Comparative Example 3

[0084] The difference between this comparative example and Comparative Example 1 is that the weight gain rate after loading the core with the coating film was adjusted to 5%.

[0085] Comparative Example 4

[0086] The difference between this comparative example and Example 1 is that egg white protein was replaced with an equal mass of hydroxypropyl methylcellulose.

[0087] Comparative Example 5

[0088] The difference between this comparative example and Example 1 is that the medical-grade polyacrylic acid resin is replaced with an equal mass of hydroxypropyl methylcellulose.

[0089] Performance testing methods

[0090] Following the method described in the appendix of the Pharmacopoeia of the People's Republic of China, the tablet hardness measured in Examples 1-25 and Comparative Examples 1-5 was tested using a tablet hardness tester. Then, the ratio between the tablet hardness measured in Examples 1-25 and Comparative Examples 1-5 and the tablet hardness measured in Comparative Example 1 was calculated, and this ratio was recorded as the relative hardness. The results are shown in Table 7.

[0091] Table 7 Relative Hardness

[0092]

[0093]

[0094] Combining Examples 1-5 and Comparative Examples 1-2 with Table 7, it can be seen that the relative hardness measured in Comparative Example 2 is much higher than that in Comparative Example 1, indicating that the microcrystalline cellulose used in Comparative Example 1 and the examples of this application is of poor quality, which has a significant impact on tablet hardness. However, the relative hardness measured in Examples 1-5 is all greater than that in Comparative Example 1, indicating that by adopting the technical solution of this application, even microcrystalline cellulose of relatively poor quality can produce tablet products with relatively high hardness (compared to Comparative Example 1), reducing the requirements of the tablet manufacturing process on raw materials and helping to fully utilize microcrystalline cellulose.

[0095] Based on Example 1, Comparative Example 1 and Comparative Example 3, and in conjunction with Table 7, it can be seen that even when the weight gain rate of the tablet core is increased from 2% to 5% based on Comparative Document 1, the increase in hardness performance is relatively limited, indicating that the coating film formed by using hydroxypropyl methylcellulose alone contributes little to the hardness of the tablet.

[0096] Combining Example 1 and Comparative Examples 4-5 with Table 7, it can be seen that the relative hardness measured in Example 1 is greater than that in Comparative Examples 4-5, indicating that when egg white protein and polyacrylic resin are not used together, the coating film is unlikely to contribute sufficiently to the overall hardness of the tablet.

[0097] As can be seen from Examples 5-9 and Table 7, the hardness performance of baricitinib tablets is improved to a certain extent as the core weight gain rate increases, indicating that the coating film of this application makes a significant contribution to the overall hardness of baricitinib tablets.

[0098] Based on Examples 9 and 10-12 and Table 7, it can be seen that the hardness measured in Examples 10-12 is higher than that in Example 9, indicating that the addition of filler helps improve the hardness performance of baricitinib tablets. The hardness performance of Examples 10-12 gradually increases, indicating that under the condition of 0.8 parts, nano-sized hydroxyapatite contributes more to the hardness performance than micron-sized hydroxyapatite, while the modified hydroxyapatite in Preparation Example 1 contributes more to the hardness performance than nano-sized hydroxyapatite.

[0099] Referring to Examples 12-16 and Table 7, it can be seen that under the condition of 0.8 parts, as the amount of sodium citrate added during the preparation of modified hydroxyapatite increases, the hardness performance first increases and then decreases. This indicates that when too much sodium citrate is added, it hinders the further improvement of the hardness of baricitinib tablets. It can be speculated that this is because sodium citrate occupies too many adsorption sites on the surface of hydroxyapatite, hindering the adsorption and binding between the carboxyl groups of polyacrylic acid resin and calcium ions. However, when the molar ratio of calcium nitrate to sodium citrate is 6:(2-3), it helps to fully improve the hardness of baricitinib tablets.

[0100] Based on Examples 14, Comparative Example 2, Examples 17-20, and Table 7, it can be seen that, with the modified hydroxyapatite of Preparation Example 3 as the preferred filler, the hardness performance of baricitinib tablets gradually improves with the increase of filler content, and is close to that of Comparative Example 2 at a content of 4.8 parts.

[0101] Based on Examples 20, Comparative Example 2, Examples 21-25, and Table 7, it can be seen that after adding hydroxyapatite whiskers to Examples 21-25 based on Example 20, the hardness performance of baricitinib tablets is higher than that of Comparative Example 2. Moreover, when the amount of hydroxyapatite whiskers is 9-15% of the weight of microcrystalline cellulose, the hardness performance of baricitinib tablets is better, which gives baricitinib tablets superior hardness performance even when the quality of microcrystalline cellulose is relatively poor.

[0102] This specific embodiment is merely an explanation of this application and is not intended to limit it. After reading this specification, those skilled in the art can make modifications to this embodiment without contributing any inventive step, but such modifications are protected by patent law as long as they fall within the scope of the claims of this application.

Claims

1. A baricitinib tablet, characterized in that, The baricitinib tablet comprises a tablet core and a coating film covering the surface of the tablet core. The tablet core is obtained by compression processing of a core material containing baricitinib technical and microcrystalline cellulose. The coating film is formed by curing a coating solution under hot air blowing at 85-95°C. The weight gain of the tablet core after loading the coating film is 4-10%. The coating solution comprises the following components in parts by weight: 10-14 parts hydroxypropyl methylcellulose, 8-12 parts medical-grade polyacrylic acid resin, 4-16 parts egg white protein, and 240-260 parts water; the coating solution also includes 0.8-4.8 parts... The filler is selected by weight, wherein the filler is modified hydroxyapatite or nano-sized hydroxyapatite with an average particle size of 50 nm. The modified hydroxyapatite is prepared by the following method: calcium nitrate, sodium phosphate and sodium citrate are weighed according to a molar ratio of 6:3.6:(1-4) and respectively prepared into solutions. Then, the calcium nitrate solution is added dropwise to the sodium citrate solution. After stirring, the sodium phosphate solution is added and stirring is continued to obtain a precursor solution. The precursor solution is subjected to hydrothermal treatment and then centrifuged and purified to obtain an intermediate. The intermediate is dried to obtain modified hydroxyapatite.

2. The baricitinib tablets according to claim 1, characterized in that, The coating solution comprises the following components in parts by weight: 12-14 parts hydroxypropyl methylcellulose, 10-12 parts medical-grade polyacrylic acid resin, 10-16 parts egg white protein, and 250-260 parts water.

3. The baricitinib tablets according to claim 2, characterized in that, The weight gain of the core after loading with the coating film is 8-10%.

4. The baricitinib tablets according to claim 1, characterized in that, The molar ratio of calcium nitrate to sodium citrate is 6:(2-3).

5. The baricitinib tablets according to claim 4, characterized in that, The core material also includes hydroxyapatite whiskers, the amount of which is 3-15% of the weight of the microcrystalline cellulose.

6. The baricitinib tablets according to claim 5, characterized in that, The amount of hydroxyapatite whiskers used is 9-15% of the weight of microcrystalline cellulose.

7. A method for preparing baricitinib tablets, characterized in that, Includes the following steps: (1) Prepare a core material containing baricitinib technical and microcrystalline cellulose, and then compress the core material to obtain a tablet core for later use; prepare the coating solution according to any one of claims 1-6 for later use; (2) Add the tablet core to the coating equipment and coat the tablet core with the coating solution prepared in step (1) under hot air blowing at 85-95℃, so that the weight gain rate of the tablet core after loading the coating film reaches 4-10%, and obtain baricitinib tablets.

Images