Upatinib sustained release tablet and preparation method thereof

Abstract

The invention relates to the technical field of oral non-biological medicine preparations, in particular to an upatinib sustained release tablet and a preparation method thereof. The invention discloses a preparation method of an upatinib sustained-release tablet, and aims to solve the problem that the dissolution rate of the upatinib sustained-release tablet is unstable, namely, the upatinib sustained-release tablet can stably control the release of upatinib in different gastrointestinal tract environments through the synergistic cooperation of all the components of the upatinib sustained-release tablet, and the preparation method of the upatinib sustained-release tablet is relatively low in cost and easy to operate. The large-scale production is facilitated; the upatinib sustained release tablet comprises the following components in percentage by weight: 3.0%-3.5% of upatinib, 18%-19.50% of a pH regulator, 50%-55% of a filler, 17%-22% of an adhesive, 0.1%-1% of a flow aid, 1%-2% of a lubricant and 0.01%-10.9% of a coating material.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of oral non-biological drug preparations, and particularly relates to a ulaplicitide sustained-release tablet and a preparation method thereof. BACKGROUND

[0002] Ulaplicitide is a targeted drug for treating rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis, etc., and is mainly a selective JAK inhibitor, thereby reducing symptoms such as arthritis. Ulaplicitide is a new type of oral small molecule drug developed by the American AbbVie company, which can selectively inhibit JAK1.

[0003] Ulaplicitide sustained-release tablets were approved for marketing in the United States by the FDA on August 16, 2019. On December 17, 2019, they were approved for marketing in the European Union by the EMA, under the trade name RINVOQ, in a specification of 15 mg. On January 23, 2020, the PMDA approved ulaplicitide sustained-release tablets for marketing in Japan, under the trade name RINVOQ, in specifications of 7.5 mg and 15 mg. On February 18, 2022, ulaplicitide was approved by the NMPA in China and officially entered the Chinese market. Import of 15 mg and 30 mg ulaplicitide sustained-release tablets was approved for marketing. On February 14, 2023, 45 mg ulaplicitide sustained-release tablets were approved for marketing. Ulaplicitide has a relatively fast absorption speed and belongs to a small molecule targeted drug, is gradually released and absorbed in the gastrointestinal tract, and the drug concentration can reach the peak within 1-2 hours, and the metabolic half-life is 10-14 hours. Therefore, the impression of JAK inhibitors is that they have a very fast onset of action and are very fast-acting in relieving itching, and they also have fast drug metabolism.

[0004] However, in some implementations, the drug dissolution and release rate of ulaplicitide sustained-release tablets is unstable in gastrointestinal environments with different pH values, which affects the therapeutic effect of the drug and the medication compliance of patients. SUMMARY

[0005] To solve the technical problems existing in the prior art, the application provides a ulaplicitide sustained-release tablet and a preparation method thereof.

[0006] In a first aspect, the application provides a ulaplicitide sustained-release tablet, which adopts the following technical scheme: A ulaplicitide sustained-release tablet, by weight percentage, ulaplicitide 3.0%-3.5%, pH adjusting agent 18%-19.50%, filler 50%-55%, adhesive 17%-22%, glidant 0.1%-1%, lubricant 1%-2%, and coating material 0.01%-10.9%.

[0007] By adopting the above technical scheme, upatin is the core component of the upatin sustained-release tablet. The filler provides the basic weight and volume of the upatin sustained-release tablet, so that the upatin sustained-release tablet reaches a suitable weight and volume, meeting the production and taking requirements. Moreover, the filler can be mixed with the upatin sustained-release tablet to improve the flowability and compression formability of the overall material, avoid tight combination during tabletting, and reduce the looseness and fragility of tabletting. The pH regulator can improve the solubility and effectiveness of the upatin sustained-release tablet by preventing the upatin from hydrolysis, oxidation and other degradation reactions due to inappropriate pH. The glidant can improve the flowability of the material, facilitate the mixing and tabletting during the preparation process of the upatin sustained-release tablet, and ensure the quality uniformity of the upatin sustained-release tablet. The lubricant has a certain glidant effect and can cooperate with the glidant to improve the flow efficiency of the material, further ensuring the tabletting quality. The coating material is a film or sugar coating component on the outer surface of the upatin sustained-release tablet, which can protect the upatin sustained-release tablet, improve the taking property, and regulate the drug release.

[0008] Therefore, through the synergistic effect of 3.0%-3.5% upatin, 18%-19.50% pH regulator, 50%-55% filler, 17%-22% binder, 0.1%-1% glidant, 1%-2% lubricant, and 0.01%-10.9% coating material, the upatin sustained-release tablet can be ensured to be released stably.

[0009] Further, the upatin sustained-release tablet includes, by weight percentage, 3.04% upatin, 19.13% pH regulator, 53.55% filler, 19.53% binder, 0.19% glidant, 1.46% lubricant, and 3.1% coating material.

[0010] By adopting the above technical scheme, the synergistic effect of 3.04% upatin, 19.13% pH regulator, 53.55% filler, 19.53% binder, 0.19% glidant, 1.46% lubricant, and 3.1% coating material can further make the upatin sustained-release tablet be released stably.

[0011] Further, the pH regulator is selected from at least one of tartaric acid, malic acid, and ascorbic acid.

[0012] By adopting the above technical scheme, the upatin can be more stable in the case of inappropriate pH, the upatin sustained-release tablet can be released more stably, and the effectiveness of the upatin sustained-release tablet can be improved.

[0013] Further, the filler is selected from at least one of microcrystalline cellulose, mannitol, lactose, starch, pregelatinized starch, dextrin, glucose, and calcium hydrogen phosphate.

[0014] By adopting the above technical solution, the filler can assist in the dispersion of utpatinib, making the distribution of utpatinib more uniform in the utpatinib sustained-release tablets, which is conducive to the stable dissolution and release of utpatinib.

[0015] Furthermore, the filler includes a mixture of microcrystalline cellulose and mannitol.

[0016] By adopting the above technical solutions, on the one hand, microcrystalline cellulose, with its strong water absorption and good compressibility, can effectively prevent excessive wetting during the wet granulation process, thus widening the range of process endpoints for utpatinib sustained-release tablets and facilitating large-scale production. Mannitol provides low hygroscopicity and good compressibility; the combination of the two optimizes the flowability and formability of the material, ensuring the hardness and content uniformity of utpatinib sustained-release tablets. On the other hand, mannitol does not undergo Maillard reactions with amino compounds, avoiding the risk of active pharmaceutical ingredient degradation due to reducing sugars (such as lactose), while microcrystalline cellulose, through its low hygroscopicity, reduces the impact of moisture on the stability of utpatinib. The synergistic effect of the two enhances the stability of utpatinib.

[0017] Furthermore, the adhesive is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl cellulose, sodium carboxymethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose phthalate, and cellulose acetate phthalate. Hydroxypropyl methylcellulose is preferred.

[0018] By employing the above-mentioned technical solutions, the adhesive can effectively prevent utpatinib from undergoing chemical degradation such as oxidation and hydrolysis during storage, thus extending the shelf life of the drug. The adhesive (such as dextrin) also has a sustained-release function, allowing for the regulation of drug release rates and achieving timed and rated release. By binding the drug powder together, the adhesive ensures that the tablets maintain their structural integrity during production and transportation, preventing breakage, while also providing a physical basis for subsequent disintegration and dissolution.

[0019] Furthermore, the flow aid is selected from at least one of colloidal silica and talc.

[0020] By adopting the above technical solution, the flowability of utpatinib sustained-release tablets can be improved, the problem of poor material flow during the preparation of utpatinib sustained-release tablets can be solved, and the content uniformity of utpatinib sustained-release tablets can be improved.

[0021] Furthermore, the lubricant is selected from at least one of magnesium stearate, calcium stearate, sodium stearate, and glyceryl monostearate and glyceryl distearate. Magnesium stearate is preferred.

[0022] By adopting the technical scheme, material and equipment, internal friction or adhesion of the material in the preparation process of the ulipristal slow-release tablet can be reduced, the smooth forming and demolding of the ulipristal slow-release tablet in the tabletting process can be ensured, and the loss in the production process can be reduced, and the quality of the ulipristal slow-release tablet can be stabilized.

[0023] In a second aspect, the application provides a preparation method of the ulipristal slow-release tablet, including: mixing the ulipristal, the binder, the pH regulator, the glidant, the filler and the lubricant to obtain a mixture; tabletting the mixture to obtain initial ulipristal slow-release tablets; and coating the initial ulipristal slow-release tablets with the coating material to obtain the ulipristal slow-release tablet.

[0024] Understandably, the preparation method of the ulipristal slow-release tablet provided by the application has the same beneficial effects as the ulipristal slow-release tablet prepared by any of the above, which will not be repeated here. In addition, the preparation method of the ulipristal slow-release tablet provided by the application can select various conventional granulation methods such as wet granulation and fluidized bed granulation, and the steps are relatively simple, the equipment requirement is not high, and it is beneficial to industrial production, that is, the process is relatively simple, the production cost is relatively low, and it is beneficial to large-scale production.

[0025] Further, the mixing of the ulipristal, the binder, the pH regulator, the glidant, the filler and the lubricant to obtain the mixture includes: mixing the ulipristal and the binder to form a first mixture. Mixing part of the pH regulator and the glidant to form a second mixture. Mixing the filler, the lubricant, the first mixture, the second mixture and the remaining pH regulator to obtain the mixture.

[0026] By adopting the technical scheme, by forming the first mixture, forming the second mixture and then mixing the filler, the lubricant and the remaining pH regulator to form the mixture, the uneven dispersion and content fluctuation in the preparation process of the ulipristal slow-release tablet are solved by using the physical property difference of each component of the ulipristal slow-release tablet, and the content uniformity and dissolution stability of the ulipristal slow-release tablet are improved.

[0027] In summary, the application includes at least one of the following beneficial technical effects: 1. The synergistic effect of 3.0%-3.5% ulipristal, 18%-19.50% pH regulator, 50%-55% filler, 17%-22% binder, 0.1%-1% glidant, 1%-2% lubricant and 0.01%-10.9% coating material in the application can ensure the stable release of the ulipristal slow-release tablet. 2. The filler of the present application comprises a mixture of microcrystalline cellulose and mannitol. On the one hand, microcrystalline cellulose has strong water absorption and good compressibility, which can effectively prevent excessive wetting during the wet granulation process, making the preparation process endpoint range of upatinib sustained-release tablets wider and facilitating large-scale production. Mannitol provides low hygroscopicity and good compressibility, and the combination of the two can optimize the flowability and formability of the material, ensuring the hardness and content uniformity of upatinib sustained-release tablets. On the other hand, mannitol does not undergo Maillard reaction with amino compounds, avoiding the risk of degradation of the main drug caused by reducing sugars (such as lactose), and microcrystalline cellulose reduces the influence of moisture on the stability of upatinib through its low hygroscopicity. The combination of the two can enhance the stability of upatinib; 3. The present application uses specific PH regulators and other components of upatinib sustained-release tablets in combination to stably control drug release in different gastrointestinal environments; 4. In the preparation method of the upatinib sustained-release tablets of the present application, by forming a first mixture, forming a second mixture, and then mixing the filler, lubricant, and the remaining PH regulator to form a mixture, this step-by-step mixing method takes advantage of the physical property differences of the components of the upatinib sustained-release tablets to solve the problems of uneven distribution and content fluctuation during the preparation process of the upatinib sustained-release tablets, improving the content uniformity and stability of the upatinib sustained-release tablets; 5. The preparation method of the upatinib sustained-release tablets of the present application is relatively simple, has low production cost, and is suitable for large-scale production. BRIEF DESCRIPTION OF DRAWINGS

[0028] In order to more clearly illustrate the technical solutions in the present disclosure, the following will briefly introduce the drawings needed to be used in some embodiments of the present application. Obviously, the drawings described below are only some of the drawings of the present application, and other drawings can also be obtained by those skilled in the art based on these drawings.

[0029] Figure 1 Figure 1 is a graph showing the dissolution of upatinib sustained-release tablets in different dissolution media according to embodiment 1; Figure 2 Figure 2 is a graph showing the release rate of upatinib sustained-release tablets in pH 1.2 hydrochloric acid solution according to some embodiments; Figure 3 Figure 3 is a graph showing the release rate of upatinib sustained-release tablets in pH 4.5 acetate buffer solution according to some embodiments; Figure 4 Figure 4 is a graph showing the release rate of upatinib sustained-release tablets in pH 6.8 phosphate buffer solution according to some embodiments. DETAILED DESCRIPTION

[0030] The technical solutions in the embodiments of the present application are clearly and completely described below in combination with specific embodiments. Obviously, the described embodiments are only some of the embodiments of the present application, but not all the embodiments. Based on the embodiments provided by the present application, all other embodiments obtained by a person of ordinary skill in the art belong to the scope of protection of the present application.

[0031] Unless otherwise required by context, the term "comprises" in the specification and claims is to be construed as open, inclusive, meaning "including but not limited to". In the description of the specification, the terms "one embodiment", "some embodiments", "exemplary embodiment", "exemplary", or "some examples" are intended to mean that the particular feature, structure, material, or characteristic being described in connection with the embodiment or example includes at least one embodiment or example of the present application. The illustrative representations of the above terms do not necessarily refer to the same embodiment or example. In addition, a particular feature, material, or characteristic can be included in any suitable manner in any one or more embodiments or examples.

[0032] Hereinafter, the terms "first" and "second" are used only for descriptive purposes and should not be construed as indicating or implying relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined with "first" and "second" can explicitly or implicitly include one or more of the features.

[0033] Unless otherwise defined, all technical terms used herein have the same meaning as commonly understood by a person of ordinary skill in the art. In the present application, "at least one" means one or more, and "multiple" means two or more. "At least one of the following" or the like means any combination of the items, including a single item or any combination of multiple items. For example, at least one of a, b or c can mean a, b, c, a and b, a and c, b and c, or a, b and c, where a, b and c can be single or multiple.

[0034] The following raw materials in the present application are all commercially available products, and the disclosure of the raw materials in the present application should not be understood as limiting the source of the raw materials.

[0035] Example 1

[0036] Example 1 provides a sustained-release upatin tablet, and the preparation method of the sustained-release upatin tablet comprises the following operation steps: S1: mixing upatin and a binder to form a first mixture. The binder is selected from hydroxypropyl methyl cellulose.

[0037] S2: mixing part of the PH regulator and the flow aid to form a second mixture. The PH regulator is tartaric acid, and the flow aid is colloidal silicon dioxide.

[0038] S3: mixing the filler, the lubricant, the first mixture, the second mixture and the rest of the PH regulator to form a mixture. The filler is a mixture of microcrystalline cellulose and mannitol, and the lubricant is magnesium stearate.

[0039] S4: tabletting the mixture obtained in S2 to obtain initial upatinib sustained-release tablets.

[0040] S5: coating the initial upatinib sustained-release tablets with a coating material to obtain upatinib sustained-release tablets. The coating material is film-coating premix (gastroresistant type).

[0041] The amounts of the above components are 3.04% of upatinib, 19.53% of hydroxypropylmethyl cellulose, 32.69% of microcrystalline cellulose, 20.86% of mannitol, 19.13% of L (+) -tartaric acid, 0.19% of colloidal silicon dioxide, 1.46% of magnesium stearate, and 3.1% of film-coating premix (gastroresistant type).

[0042] Example 2

[0043] Example 2 provides a method for preparing upatinib sustained-release tablets, which is the same as that of Example 1, except that the PH regulator, the filler, the binder, the flow aid and the lubricant are respectively hydroxypropyl cellulose 19.25%, lactose 32.29%, starch 20.96%, malic acid 18.43%, colloidal silicon dioxide 0.49%, hard sodium fumarate 1.36%, and the rest of upatinib and the coating material are the same as those of Example 1.

[0044] Example 3

[0045] Example 3 provides a method for preparing upatinib sustained-release tablets, which is the same as that of Example 1, except that the PH regulator, the filler, the binder, the flow aid and the lubricant are respectively hydroxyethyl cellulose 18.83%, dextrin 31.79%, pregelatinized starch 22.47%, ascorbic acid 18.93%, talc 0.59%, calcium stearate 1.16%, and the rest of upatinib and the coating material are the same as those of Example 1.

[0046] Example 4

[0047] Example 4 provides a ulipristal sustained-release tablet, the preparation method of which is the same as that of Example 1, except that the pH adjuster, the filler, the binder, the glidant and the lubricant are carboxymethyl cellulose 20.23%, dextrin 31.92%, starch 20.52%, malic acid 19.43%, talc 0.59%, glycerol monostearate 1.17%, and the rest of ulipristal and coating materials are the same as those of Example 1.

[0048] Example 5

[0049] Example 5 provides a ulipristal sustained-release tablet, the preparation method of which is the same as that of Example 1, except that the pH adjuster, the filler, the binder, the glidant and the lubricant are sodium carboxymethyl cellulose 18.10%, microcrystalline cellulose 31.46%, pregelatinized starch 21.70%, tartaric acid 19.39%, colloidal silicon dioxide 0.42%, magnesium stearate 1.35%, and the rest of ulipristal and coating materials are the same as those of Example 1.

[0050] Example 6

[0051] Example 6 provides a ulipristal sustained-release tablet, the preparation method of which is the same as that of Example 1, except that the pH adjuster, the filler, the binder, the glidant and the lubricant are hydroxyethyl methyl cellulose 20.21%, microcrystalline cellulose 30.91%, glucose 20.93%, tartaric acid 20.14%, colloidal silicon dioxide 0.35%, magnesium stearate 1.32%, and the rest of ulipristal and coating materials are the same as those of Example 1.

[0052] Example 7

[0053] Example 7 provides a ulipristal sustained-release tablet, the preparation method of which is the same as that of Example 1, except that the pH adjuster, the filler, the binder, the glidant and the lubricant are hydroxypropyl methyl cellulose phthalate 13.83%, calcium hydrogen phosphate 32.15%, mannitol 22.64%, tartaric acid 23.23%, colloidal silicon dioxide 0.53%, magnesium stearate 1.48%, and the rest of ulipristal and coating materials are the same as those of Example 1.

[0054] Example 8

[0055] Example 8 provides a ulipristal sustained-release tablet, the preparation method of which is the same as that of Example 1, except that the pH adjuster, the filler, the binder, the glidant and the lubricant are cellulose acetate phthalate 19.26%, microcrystalline cellulose 32.16%, mannitol 21.52%, tartaric acid 19.14%, colloidal silicon dioxide 0.47%, magnesium stearate 1.31%, and the rest of ulipristal and coating materials are the same as those of Example 1.

[0056] Example 9

[0057] Example 9 provides a sustained-release upatinib tablet, which is prepared by the same method as that of Example 1, except that the pH regulator, the filler, the binder, the glidant and the lubricant are respectively: hydroxypropyl methyl cellulose 20.13%, calcium hydrogen phosphate 32.26%, mannitol 20.78%, L(+) - tartaric acid 18.93%, colloidal silicon dioxide 0.41%, magnesium stearate 1.35%, and the rest of upatinib and coating materials are the same as those of Example 1.

[0058] Example 10

[0059] Example 10 provides a sustained-release upatinib tablet, which is prepared by the same method as that of Example 1, except that the pH regulator, the filler, the binder, the glidant and the lubricant are respectively: sodium carboxymethyl cellulose 19.25%, microcrystalline cellulose 30.41%, pre-gelatinized starch 22.16%, tartaric acid 20.26%, colloidal silicon dioxide 0.41%, glycerol monostearate 1.37%, and the rest of upatinib and coating materials are the same as those of Example 1.

[0060] Example 11

[0061] Example 11 provides a sustained-release upatinib tablet, which is prepared by the same method as that of Example 1, except that the pH regulator, the filler, the binder, the glidant and the lubricant are respectively: carboxymethyl cellulose 21.11%, pre-gelatinized starch 31.37%, starch 20.61%, malic acid 18.93%, talc 0.45%, glycerol monostearate 1.39%, and the rest of upatinib and coating materials are the same as those of Example 1.

[0062] Performance test The upatinib sustained-release tablets obtained in the above examples and comparative examples are subjected to release rate determination.

[0063] The specific test method is as follows: the paddle method is used, 900 mL of pH 1.2 hydrochloric acid solution, pH 4.5 acetate buffer solution, and pH 6.8 phosphate buffer solution are used as the dissolution medium, the temperature is 37 ± 0.5 ℃, and the rotation speed is 100 r / min.

[0064] The upatinib sustained-release tablets prepared in Examples 1-11 are respectively subjected to dissolution rate test according to the above conditions, samples are taken at different time points, the concentration of upatinib in the samples is determined by high performance liquid chromatography, the cumulative release rate of the drug is calculated, and the results are shown in Figures 1-4 , the horizontal axis is time, in hours, and the vertical axis is release rate; wherein, as shown in Figure 1 , the horizontal axis is time, in hours, and the vertical axis is release rate; wherein, as shown in Figure 1A release rate graph of the upatinib sustained-release tablets of the embodiment 1 in different dissolution media shows that the release time of upatinib is relatively fast, and the dissolution rate of upatinib in different dissolution media is relatively close, and the stability is good.

[0065] Figure 2 A release rate graph of the upatinib sustained-release tablets of the embodiment in the pH 1.2 hydrochloric acid solution; Figure 3 A release rate graph of the upatinib sustained-release tablets of the embodiment in the pH 4.5 acetate buffer solution; Figure 4 A release rate graph of the upatinib sustained-release tablets of the embodiment in the pH 6.8 phosphate buffer solution. By comparing the release stability of the upatinib sustained-release tablets of the embodiments in different dissolution media, the release stability of the upatinib sustained-release tablets of the embodiment 1 is better, and the upatinib sustained-release tablets can be completely dissolved within 12 hours, and the solubility release degree basically reaches 100%, and the release degree of the upatinib sustained-release tablets of the other embodiments is basically below 90% within 12 hours.

[0066] Among the upatinib sustained-release tablets of the embodiments 1-11 in different dissolution media, only the release rate of the embodiment 1 is more stable. Therefore, the joint action of the specific pH adjuster and other components makes the release rate of the upatinib sustained-release tablets more stable under different dissolution conditions, which indicates that the prepared sustained-release tablets improve the sustained-release performance of the upatinib sustained-release tablets, and prolong the effective time of the upatinib, that is, the number of medication of the patient is reduced, and the medication cost of the patient is reduced.

[0067] The specific embodiments are only an explanation of the present application, and are not a limitation of the present application, and the person skilled in the art can make a modification of the present embodiments without creative contribution according to the needs after reading the present specification, but as long as the present application is within the scope of the claims, it is protected by the patent law.

Claims

1. An upadacitinib sustained release tablet, characterized in that, by weight percentage, comprising: upatinib 3.0%-3.5%, pH regulator 18%-19.50%, filler 50%-55%, binder 17%-22%, glidant 0.1%-1%, lubricant 1%-2%, coating material 0.01%-10.9%.

2. The ulpristin sustained release tablet according to claim 1, characterized by, by weight percentage, comprising: upatinib 3.04%, pH regulator 19.13%, filler 53.55%, binder 19.53%, glidant 0.19%, lubricant 1.46%, coating material 3.1%.

3. The ulpratene sustained release tablet according to claim 1, characterized by, The pH regulator is selected from at least one of at least one of tartaric acid, malic acid and ascorbic acid.

4. The ulpristin sustained release tablet according to claim 1, characterized by, The filler is selected from at least one of microcrystalline cellulose, mannitol, lactose, starch, pregelatinized starch, dextrin, glucose and calcium hydrogen phosphate.

5. The ulpristin sustained release tablet according to claim 4, characterized in that, The filler comprises a mixture of microcrystalline cellulose and mannitol.

6. The ulpristin sustained release tablet according to claim 1, characterized by, The binder is selected from at least one of hydroxypropyl methylcellulose, hydroxypropyl cellulose, hydroxyethyl cellulose, carboxymethyl fiber, sodium carboxymethyl cellulose, hydroxyethyl methyl cellulose, hydroxypropyl methyl cellulose phthalate and cellulose acetate phthalate.

7. The ulpratene sustained release tablet according to claim 1, characterized by, The glidant is selected from at least one of colloidal silicon dioxide and talc powder.

8. The ulpratene sustained release tablet according to claim 1, characterized by, The lubricant is selected from at least one of magnesium stearate, calcium stearate, sodium hard fumarate and glycerol mono-diestearate.

9. A method of preparing the sustained-release upadacitinib tablet according to any one of claims 1-8, characterized by, comprising: mixing the upatinib, the binder, the pH regulator, the glidant, the filler and the lubricant to obtain a mixture; tabletting the mixture to obtain initial upatinib sustained-release tablets; coating the initial upatinib sustained-release tablets with the coating material to obtain the upatinib sustained-release tablets.

10. The method of preparing the sustained-release upadacitinib tablet according to claim 8, characterized by, The mixing the upatinib, the binder, the pH regulator, the glidant, the filler and the lubricant to obtain a mixture comprises: mixing the upatinib and the binder to form a first mixture; mixing part of the pH regulator and the glidant to form a second mixture; mixing the filler, the lubricant, the first mixture, the second mixture and the remaining pH regulator to obtain a mixture.

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