Briracetam sustained release preparation and preparation method thereof

Abstract

The invention belongs to the field of pharmaceutical preparations, and relates to a briracetam sustained release preparation and a preparation method thereof. The sustained-release tablet is a sustained-release micro-tablet and comprises a tablet core layer, and the tablet core layer comprises an active component, a sustained-release framework material and a tablet core auxiliary material; the active component is briracetam or pharmaceutically acceptable salt, complex or hydrate of briracetam; the slow-release framework material is composed of a corrosion framework material and an insoluble framework material. The briracetam sustained-release preparation provided by the invention is a sustained-release micro-tablet which is easy to swallow; the administration dosage can be flexibly and accurately adjusted; good slow release performance is achieved, and the medicine taking frequency of a patient can be reduced; meanwhile, the problem that the briracetam is poor in taste is solved; the compliance of a patient is greatly improved, and the clinical value is higher.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of pharmaceutical preparations, and relates to a sustained-release brivaracetam preparation and a preparation method thereof. BACKGROUND

[0002] The information disclosed in this Background section is for the purpose of increasing the understanding of the background of the application without admitting that such information forms prior art.

[0003] Brivaracetam is a new antiepileptic drug for the treatment or adjunctive treatment of partial-onset seizures in patients over 1 month. The common oral dosage forms of brivaracetam are oral solution and tablets, both of which belong to immediate-release preparations. The defects of these existing dosage forms are as follows: 1. Tablets are not divisible, and dose adjustment is not flexible, which makes it difficult to meet the individualized (such as light, severe cases, and age and weight differences) dosing needs; 2. Due to the extremely bitter taste of brivaracetam, the oral solution is difficult to accept, and the patient compliance is poor; 3. The dosing frequency of the immediate-release preparation is high, generally twice a day, the blood drug concentration fluctuates greatly, and the adverse risk is high. In order to improve the drug experience, it is urgent to develop a new dosage form with sustained release, adjustable dose, easy to swallow and taste masking. Ordinary sustained-release preparations such as sustained-release tablets and sustained-release capsules usually have a large volume, which is difficult for some special patients (such as children, the elderly, etc.) to swallow, increasing the difficulty of taking medicine.

[0004] Microtablets are flat or concave microtablets with a diameter of 1.0-3.0 mm, and the ratio of diameter to thickness is usually 1. Compared with ordinary tablets, microtablets have a smaller volume and a higher drug loading capacity, which are very suitable for the administration of patients with difficulty in swallowing, and the dose can be accurately and flexibly adjusted. Microtablets can be coated with different functional excipients to achieve taste masking, enteric coating or sustained release; therefore, the film-controlled sustained release of microtablets can be achieved by coating. However, it is found that the sustained-release coating usually has high requirements for coating equipment and long process time, and the process reproducibility is poor, which is not conducive to industrial production. In addition, the sustained-release technology that can be used for microtablets also includes matrix sustained release. However, it is extremely challenging to develop a matrix sustained-release microtablet, especially for brivaracetam which is a highly water-soluble drug, it is difficult to form a robust matrix to achieve long-term slow release. Therefore, the existing technology lacks a long-acting sustained-release microtablet with simple process, high safety and suitable for highly water-soluble drugs, which cannot meet the clinical needs of children, the elderly and other patients with difficulty in swallowing. It is of urgent clinical value to develop a brivaracetam microtablet preparation with sustained-release performance, dose flexibility and excellent compliance. SUMMARY

[0005] In order to solve the problems in the prior art, the present application provides a brivaracetam sustained-release preparation and a preparation method thereof, the brivaracetam sustained-release preparation provided by the present application is a sustained-release microtablet, which is easy to swallow, can flexibly and accurately adjust the dosage, has good sustained-release performance, can reduce the frequency of taking medicine for patients, solves the problem of poor taste of brivaracetam, greatly improves the compliance of patients and has great clinical value.

[0006] In order to achieve the above-mentioned purpose, the technical scheme of the present application is as follows: In a first aspect, the present application provides a brivaracetam sustained-release preparation, which is a sustained-release microtablet, comprising a tablet core layer, wherein the tablet core layer comprises an active ingredient, a sustained-release matrix material and tablet core excipients; the active ingredient is brivaracetam or a pharmaceutically acceptable salt, complex or hydrate thereof; the sustained-release matrix material is composed of a dissolvable matrix material and an insoluble matrix material; the dissolvable matrix material is selected from one or more of glyceryl behenate, carnauba wax, hydrogenated vegetable oil and microcrystalline wax; the insoluble matrix material is selected from one or more of quaternary ammonium methacrylate copolymer type B (Eudragit RS PO), quaternary ammonium methacrylate copolymer type A (Eudragit RL PO), ethyl cellulose and a mixture of polyvinyl acetate povidone (Kollidon SR); and the tablet core excipients are pharmaceutical excipients used for the preparation of the microtablet.

[0007] The present application uses a sustained-release matrix material to control the release of the brivaracetam microtablet to the active ingredient of brivaracetam by using a matrix sustained-release technology. The research of the present application shows that when only the dissolvable matrix material is used, a lower amount cannot achieve long-term sustained release, and a higher amount cannot be normally tabletted due to serious sticking and sticking, which is caused by the low melting point of brivaracetam and the dissolvable matrix material. When only the insoluble matrix material is used, a higher amount cannot achieve complete dissolution at the end point (24 hours), and a lower amount has a risk of burst release in the early stage, which has a safety risk. The present application accidentally found that when the dissolvable matrix material and the insoluble matrix material are simultaneously added, not only can the good sustained-release effect be ensured, the risk of burst release be reduced and complete dissolution at the end point (24 hours) be achieved, but also the tabletting can be successfully performed without sticking and sticking, and different sustained-release effects can be achieved by adjusting the ratio of the two.

[0008] Further, a coating layer is further coated on the surface of the tablet core layer. The taste-masking coating is performed by the coating layer to avoid the problem of poor compliance of patients caused by the extremely bitter taste of brivaracetam.

[0009] In a second aspect, the present application provides a preparation method of the brivaracetam sustained-release preparation, comprising the following steps: Mixing the active ingredient, the sustained-release matrix material and the tablet core excipients to obtain a mixture; The mixture is tabletted into a tablet core layer by using a powder direct compression process.

[0010] Further, the method further comprises the following steps: The tablet core layer is subjected to taste-masking coating, so that the tablet core layer is coated with a coating layer.

[0011] The present application has the following advantages: (1) The present application uses a combination of insoluble and erodible matrix materials to prepare sustained-release microtablets, which can not only avoid burst release in the early release stage, but also ensure that the active ingredients are completely dissolved at the end of dissolution, and can be smoothly tableted without sticking and colliding. In addition, the proportion of the two can be adjusted to achieve different sustained-release effects from 12 hours to 24 hours. The present application uses a sustained-release matrix material to prepare a sustained-release microtablet of the highly water-soluble drug brivaracetam, filling the blank of similar technology and avoiding the shortcomings of film-controlled sustained-release technology, such as complex process, high requirement for coating equipment, long process time, and poor process reproducibility.

[0012] (2) The brivaracetam sustained-release preparation provided by the present application has a small diameter (1.5-2.5 mm) and a low tablet weight (4-10 mg), which is easier to swallow and more acceptable to children and other patients with swallowing difficulties. In addition, the dosage can be flexibly and accurately adjusted, and the preparation is convenient to carry and transport.

[0013] (3) Compared with the brivaracetam immediate-release preparation, the brivaracetam sustained-release preparation provided by the present application only needs to be administered once a day, which can reduce blood drug concentration fluctuations, reduce adverse reactions, and improve patient compliance. Compared with the brivaracetam oral solution, the brivaracetam sustained-release preparation provided by the present application is taste-friendly and more acceptable to patients.

[0014] (4) The preparation method of the brivaracetam sustained-release preparation provided by the present application is simple, uses a powder direct compression process, is easy to scale up, and is conducive to industrialized production. BRIEF DESCRIPTION OF DRAWINGS

[0015] The accompanying drawings, which form a part of the present application, are used to provide further understanding of the present application, and the schematic embodiments of the present application and their descriptions are used to explain the present application, and do not constitute an improper limitation on the present application.

[0016] Figure 1 The dissolution curves of the brivaracetam sustained-release preparations prepared by the embodiments and the comparative embodiments of the present application. DETAILED DESCRIPTION

[0017] It should be noted that the following detailed description is exemplary and is intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as generally understood by those skilled in the art to which the present application belongs.

[0018] It is to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of example embodiments in accordance with the present application. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "comprises" and / or "comprising," when used in this specification, specify the presence of stated features, steps, operations, elements, components, and / or groups thereof, but do not preclude the presence or addition of one or more other features, steps, operations, elements, components, and / or groups thereof.

[0019] In view of the fact that it is difficult to make a sustained-release preparation of brivaracetam micro-tablets by using a simple process, the present application provides a sustained-release preparation of brivaracetam and a preparation method thereof.

[0020] In one typical embodiment of the present application, a sustained-release preparation of brivaracetam is provided, which is a sustained-release micro-tablet comprising a tablet core layer, the tablet core layer comprising an active ingredient, a sustained-release matrix material, and tablet core excipients; the active ingredient is brivaracetam or a pharmaceutically acceptable salt, complex or hydrate thereof; the sustained-release matrix material is composed of a dissolvable matrix material and an insoluble matrix material; the dissolvable matrix material is selected from one or more of glyceryl behenate, carnauba wax, hydrogenated vegetable oil, and microcrystalline wax; the insoluble matrix material is selected from one or more of quaternary ammonium methacrylate copolymer type B (Eudragit RS PO), quaternary ammonium methacrylate copolymer type A (Eudragit RL PO), ethyl cellulose, and a mixture of polyvinyl acetate povidone (Kollidon SR); and the tablet core excipients are pharmaceutical excipients used to form the micro-tablet preparation.

[0021] The matrix material of the bioerodible matrix tablet is a water-insoluble but erodible waxy material, a gastric or enteric material, etc. This kind of matrix tablet controls drug release through diffusion and erosion control of the pore as the solid fat or wax gradually erodes.

[0022] In some embodiments, the content of the active ingredient in the tablet core layer is 5wt% to 25wt%, preferably 10wt% to 20wt%; the content of the sustained-release matrix material is 50wt% to 90wt%, preferably 55wt% to 85wt%, and further preferably 60wt% to 80wt%; and the balance is the tablet core excipients.

[0023] Specifically, the content of the dissolvable matrix material is 5wt% to 40wt%, preferably 10wt% to 35wt%, and further preferably 15wt% to 30wt%.

[0024] Specifically, the content of the insoluble matrix material is 20wt% to 65wt%, preferably 25wt% to 60wt%, and further preferably 30wt% to 55wt%.

[0025] In some embodiments, the erodible matrix material is glyceryl behenate or hydrogenated vegetable oil. Studies have shown that the erodible matrix material, especially glyceryl behenate, works better with the insoluble matrix material.

[0026] In some embodiments, the insoluble matrix material comprises a polyvinyl acetate povidone mixture. Preferably, the insoluble matrix material further comprises quaternary ammonium-based methacrylate copolymer type B and / or ethyl cellulose.

[0027] In some embodiments, the tablet core excipient comprises a filler.

[0028] Specifically, the filler is one or more of anhydrous dibasic calcium phosphate, microcrystalline cellulose, starch, etc. Studies have shown that the filler, especially anhydrous dibasic calcium phosphate, works better under the buffering formulation system.

[0029] Specifically, in the tablet core layer, the content of the filler is 1wt% to 40wt%, preferably 5wt% to 35wt%, further preferably 10wt% to 30wt%, and more preferably 10wt% to 20wt%.

[0030] In some embodiments, the tablet core excipient comprises a glidant.

[0031] Specifically, the glidant is one or more of hydrophobic colloidal silicon dioxide, talc, silicon dioxide, etc. Studies have shown that the glidant, especially hydrophobic colloidal silicon dioxide, works better under the buffering formulation system.

[0032] Specifically, in the tablet core layer, the content of the glidant is 0.5wt% to 4wt%, preferably 1wt% to 3.5wt%, and further preferably 1.5wt% to 3wt%.

[0033] In some embodiments, the tablet core excipient comprises a lubricant.

[0034] Specifically, the lubricant is one or more of magnesium stearate, stearic acid, sodium stearyl fumarate, etc. Studies have shown that the lubricant, especially magnesium stearate, works better under the buffering formulation system.

[0035] Specifically, in the tablet core layer, the content of the lubricant is 0.5wt% to 4wt%, preferably 1wt% to 3.5wt%, and further preferably 1.5wt% to 3wt%.

[0036] In some embodiments, the hardness of the tablet core layer is 5 to 20N.

[0037] In some embodiments, a coating layer is further included, which is coated on the surface of the tablet core layer.

[0038] Specifically, the material of the coating layer is a taste-masking coating material, which is one or more of methacrylic acid amino alkyl ester copolymer type E (Eudragit E PO), a gastric soluble film coating premix (Opadry), ethyl cellulose, and the like, and preferably Eudragit E PO.

[0039] In some embodiments, the diameter of the sustained-release microtablet is 1.5-2.5 mm, and the ratio of the diameter to the thickness is 0.7-1.3. Specifically, the diameter of the sustained-release microtablet is 1.7-2.3 mm, and the ratio of the diameter to the thickness is 0.8-1.2.

[0040] In some embodiments, the weight of the sustained-release microtablet is 4-10 mg, and preferably 5-9 mg.

[0041] In another embodiment of the present application, a preparation method of the above-mentioned brivaracetam sustained-release preparation is provided, which comprises the following steps: Mixing the active ingredient, the sustained-release matrix material, and the tablet core auxiliary materials to obtain a mixture; Using a powder direct compression process to compress the mixture into a tablet core layer.

[0042] In some embodiments, the active ingredient, the sustained-release matrix material, and the tablet core auxiliary materials except the lubricant are mixed, and then the lubricant is added and mixed to obtain a mixture. This mixing method can better perform compression.

[0043] In some embodiments, the method further comprises the following steps: Coating the tablet core layer with a taste-masking coating to coat the surface of the tablet core layer with a coating layer, thereby obtaining the brivaracetam sustained-release preparation.

[0044] In a third embodiment of the present application, a method for treating epilepsy is provided, which comprises administering to a subject or patient a therapeutically effective amount of a brivaracetam sustained-release preparation, wherein the in-vitro dissolution rate of the brivaracetam sustained-release preparation is as follows: the dissolution rate at 1 hour is not more than 40%, the dissolution rate at 4 hours is between 45% and 75%, and the dissolution rate at 24 hours is more than 85%; wherein the dissolution rate is detected by the second method (paddle method) of the Chinese Pharmacopoeia, at a rotation speed of 50 rpm and a temperature of 37℃±0.5℃, and the dissolution medium is 900 ml of pH 6.8 phosphate buffer.

[0045] The treatment according to the present application refers to a method implemented in order to obtain a beneficial or desired clinical result. For the purposes of the present application, a beneficial or desired clinical result includes, but is not limited to, alleviating symptoms, reducing the extent of disease, stabilizing (i.e., not worsening) the state of disease, delaying or slowing the development of disease, improving or remitting the state of disease, and relieving symptoms (whether partially or completely), whether detectable or undetectable. In addition, "treatment" can also refer to prolonging the survival period compared with the expected survival period if no treatment is received.

[0046] The therapeutically effective amount according to the present application means the amount of active compound or pharmaceutical agent, including the compound according to the present application, which can cause the biological or medical response that is being sought in the tissue system, animal or human by the researcher, veterinarian, medical doctor or other medical person, which includes alleviation or partial alleviation of the symptoms of the disease, syndrome, condition, or disorder being treated.

[0047] In some embodiments, the brivaracetam sustained release preparation is the brivaracetam sustained release preparation described above.

[0048] In some embodiments, the subject or patient is a human or a non-human mammal. The non-human mammal can be a mouse, a rat, a dog, a rabbit, a pig, etc.

[0049] In order to enable persons skilled in the art to more clearly understand the technical solutions of the present application, the technical solutions of the present application will be described in detail below with specific examples and comparative examples.

[0050] The raw materials used in the examples are all conventional raw materials, and the equipment used is all conventional equipment, which can be commercially purchased.

[0051] Examples 1-3 A brivaracetam sustained release microtablet was prepared using one insoluble matrix material and one erodible matrix material, and the prescription composition and tabletting are shown in Table 1.

[0052] Table 1 Prescription composition and evaluation of Examples 1-3

[0053] Preparation process: Pre-treatment of raw and auxiliary materials: pass the raw and auxiliary materials through a 50-mesh sieve, respectively, for standby.

[0054] Mixing: weigh the prescription amount of the sieved raw and auxiliary materials, mix the magnesium stearate and other raw and auxiliary materials for 15 min, then add the prescription amount of magnesium stearate, and continue mixing for 5 min to obtain the total mixed powder.

[0055] Tableting: take the total mixed powder for tabletting, and the punch model is Φ2mm 10-head punch needle circular shallow concave micro punch mold. Tablet according to the theoretical tablet weight, and the hardness is 5-20N.

[0056] The tabletting shows that when a brivaracetam sustained release microtablet is prepared using one insoluble matrix material and one erodible matrix material at the same time, tabletting can be successfully performed without sticking phenomenon.

[0057] Examples 4-6 A brivaracetam sustained release microtablet was prepared using two insoluble matrix materials and one erodible matrix material, and the prescription composition and tabletting are shown in Table 2.

[0058] Table 2 Prescription composition and evaluation of Examples 4-6

[0059] Preparation process: Raw material pretreatment: The raw materials were sieved through a 50 mesh sieve and prepared for use.

[0060] Mixing: The prescribed amount of raw materials after sieving was weighed, and magnesium stearate was added to the other raw materials, mixed for 15 min, then the prescribed amount of magnesium stearate was added, and mixing was continued for 5 min to obtain the total mixed powder.

[0061] Tabletting: The total mixed powder was taken for tabletting, and the punch type was Φ2mm 10-head punch needle circular shallow concave micro punch mold. The tablets were pressed according to the theoretical tablet weight, and the hardness was 5-20N.

[0062] The tabletting results showed that when two insoluble matrix materials and one erodible matrix material were used to prepare brivaracetam sustained-release microtablets, tabletting could also be successfully performed without sticking.

[0063] Examples 7-12 Flavor masking coating of brivaracetam sustained-release microtablets.

[0064] The tablet cores of Examples 1-6 were subjected to flavor masking coating, as shown in Table 3.

[0065] Table 3 Coating weight gain of Examples 7-12

[0066] Preparation process: (1) Eudragit EPO premixed powder or Opadry was dispersed in purified water to prepare a coating solution.

[0067] (2) High-efficiency coating machine and coating pan were used for coating, with air intake of 150 m 3 / h, air intake temperature of 50-70℃, pan rotation speed of 5-10 rpm, pan negative pressure of -30 Pa, atomization pressure of 0.3 bar, spray angle pressure of 0.5 bar, and peristaltic pump rotation speed of 5-10 rpm.

[0068] Example 8 Pharmacokinetic study of brivaracetam sustained-release microtablets in beagle dogs: Drug information: T1: Example 1, specification: 100mg; T2: Example 5, specification: 100mg; R: control preparation (brivaracetam tablets, specification: 50mg, manufacturer: UCB). Dosing method: Examples 1 and 5 once a day, dosing for one day, 4 samples each; control preparation twice a day, dosing for one day, 4 samples. Pharmacokinetic experiments were conducted on Examples 1, 5 and the control preparation to evaluate their effectiveness. The results are shown in Table 4.

[0069] Table 4 In vivo pharmacokinetics of brivaracetam sustained-release microtablets

[0070] Comparative Example 1-2 The sustained-release brivaracetam microtablets were prepared using only the erodible matrix material. The prescription composition and tableting are shown in Table 5.

[0071] Table 5 Prescription composition and evaluation of Comparative Example 1-2

[0072] Preparation process: Pre-treatment of raw and auxiliary materials: pass the raw and auxiliary materials through a 50-mesh sieve, respectively, and reserve.

[0073] Mixing: weigh the prescribed amount of sieved raw and auxiliary materials, mix the magnesium stearate and other raw materials for 15 min, then add the prescribed amount of magnesium stearate and continue mixing for 5 min to obtain the total mixed powder.

[0074] Tableting: take the total mixed powder for tableting, punch type: Φ2mm 10-head punch needle circular shallow concave micro punch mold. Tableting according to the theoretical tablet weight, hardness 5-20N.

[0075] Aging: age the tableted microtablets at 60℃ for 24 hours.

[0076] Comparative Example 3-4 The sustained-release brivaracetam microtablets were prepared using only the insoluble matrix material. The prescription composition and tableting are shown in Table 6.

[0077] Table 6 Prescription composition and evaluation of Comparative Example 3-4

[0078] Preparation process: Pre-treatment of raw and auxiliary materials: pass the raw and auxiliary materials through a 50-mesh sieve, respectively, and reserve.

[0079] Mixing: weigh the prescribed amount of sieved raw and auxiliary materials, mix the magnesium stearate and other raw materials for 15 min, then add the prescribed amount of magnesium stearate and continue mixing for 5 min to obtain the total mixed powder.

[0080] Tableting: take the total mixed powder for tableting, punch type: Φ2mm 10-head punch needle circular shallow concave micro punch mold. Tableting according to the theoretical tablet weight, hardness 5-20N.

[0081] Test Example 1: Dissolution curve determination The second method (paddle method) of Chinese Pharmacopoeia 2020 Edition General 0931 was used, the analysis method was HPLC, the dissolution medium was water, the dissolution volume was 900mL, the rotation speed was 50rpm, and the temperature was 37±0.5℃. The test results are shown in Table 7 andFigure 1 as shown.

[0082] Table 7 Brivaracetam sustained-release microtablets dissolution curve determination

[0083] Figure 1 The results of Table 7 show that in Comparative Example 1, a lower amount of glyceryl behenate is used alone, and the dissolution rate is 49% at 1 hour and the dissolution is basically complete at 6 hours, indicating that when a lower amount of erodible matrix material (especially a lower amount of glyceryl behenate alone) is used alone, the drug release rate is faster and the sustained-release effect is poorer. In Comparative Example 2, there is also a problem of a faster drug release rate. In Comparative Example 3, a higher amount of Kollidon® SR is used alone, and the dissolution rate is less than 80% at 24 hours, indicating that when a higher amount of insoluble matrix material (a higher amount of Kollidon® SR alone) is used alone, the brivaracetam cannot be completely dissolved within 24 hours, which can lead to incomplete release of the active ingredient in the body, thereby affecting the efficacy. In Comparative Example 4, a lower amount of Kollidon® SR is used alone, and the dissolution rate thereof is 51% at 2 hours, and there is a burst release phenomenon, which has a risk of burst release. The brivaracetam sustained-release microtablets prepared in Examples 1-6 can ensure good sustained-release effect, reduce the risk of burst release, and achieve complete dissolution at the end point. Among them, glyceryl behenate is combined with Kollidon SR, or further adding ethyl cellulose, which is more conducive to complete dissolution at the end point.

[0084] Test Example 2: Evaluation of taste masking effect of brivaracetam sustained-release microtablets of Examples 1-12.

[0085] Examples 1-12 (1 bag, 100 mg specification) were placed in a syringe, 2 ml of purified water was added, filtered after 30 s, the brivaracetam content in the filtrate was determined, and the taste masking effect was evaluated.

[0086] Table 8 Evaluation of taste masking effect of brivaracetam sustained-release microtablets

[0087] Note: The brivaracetam content in the filtrate is the brivaracetam concentration in the filtrate * 2.5 ml / 100 mg * 100%.

[0088] The results show that the brivaracetam content in the filtrate of the sustained-release microtablets prepared in Examples 7-12 is lower than that of the sustained-release microtablets prepared in Examples 1-6, indicating that the taste masking coating effect of the present application is good, which can effectively avoid the bitter taste caused by the dissolution of brivaracetam in the oral cavity.

[0089] The above merely provides the preferred embodiments of the present application, and is not used to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the principles and technical scope of the present application shall fall into the scope of the present application.

Claims

1. A sustained-release preparation of brivaracetam, characterized in that: It is a sustained-release microtablet, comprising a core layer, wherein the core layer comprises an active ingredient, a sustained-release matrix material and a core excipient; the active ingredient is brivaracetam or a pharmaceutically acceptable salt, complex or hydrate thereof; the sustained-release matrix material is composed of an erodible matrix material and an insoluble matrix material; the erodible matrix material is selected from one or more of glyceryl behenate, carnauba wax, hydrogenated vegetable oil and microcrystalline wax; the insoluble matrix material is selected from one or more of quaternary ammonium methacrylate copolymer type B, quaternary ammonium methacrylate copolymer type A, ethyl cellulose and a polyvinyl acetate-povidone mixture; the core excipient is a pharmaceutical excipient used to constitute a microtablet preparation.

2. The brivaracetam sustained-release preparation according to claim 1, wherein In the tablet core layer, the content of the active ingredient is 5wt% to 25wt%, or 10wt% to 20wt%; the content of the sustained-release matrix material is 50wt% to 90wt%, or 55wt% to 85wt%, or 60wt% to 80wt%; the balance is tablet core excipients; Alternatively, the content of the erodible skeleton material is 5wt% to 40wt%, or 10wt% to 35wt%, or 15wt% to 30wt%; Alternatively, the content of the insoluble skeleton material is 20 wt% to 65 wt%, or 25 wt% to 60 wt%, or 30 wt% to 55 wt%.

3. The brivaracetam sustained-release preparation according to claim 1, wherein The soluble skeleton material is glyceryl behenate or hydrogenated vegetable oil; Alternatively, the insoluble skeleton material comprises a polyvinyl acetate-povidone mixture; or, the insoluble skeleton material further comprises a quaternary ammonium methacrylate copolymer type B and / or ethyl cellulose.

4. The brivaracetam sustained-release preparation according to claim 1, wherein The tablet excipients include fillers; Or, the filler is one or more of anhydrous calcium hydrogen phosphate, microcrystalline cellulose, starch, etc.; Alternatively, in the core layer, the content of the filler is 1 wt% to 40 wt%, or 5 wt% to 35 wt%, or 10 wt% to 30 wt%, or 10 wt% to 20 wt%.

5. The brivaracetam sustained-release preparation according to claim 1, wherein The core excipients include glidants Or, the glidant is one or more of hydrophobic colloidal silicon dioxide, talc, silicon dioxide, etc.; Alternatively, in the core layer, the content of the glidant is 0.5 wt% to 4 wt%, or 1 wt% to 3.5 wt%, or 1.5 wt% to 3 wt%.

6. The brivaracetam sustained-release preparation according to claim 1, wherein: The tablet core excipients include lubricants; Or, the lubricant is one or more of magnesium stearate, stearic acid, sodium stearyl fumarate, etc.; Alternatively, in the core layer, the content of the lubricant is 0.5 wt % to 4 wt %, or 1 wt % to 3.5 wt %, or 1.5 wt % to 3 wt %.

7. The brivaracetam sustained-release preparation according to claim 1, wherein: It also includes a coating layer coated on the surface of the core layer; Alternatively, the coating layer is made of a taste-masking coating material, and the taste-masking coating material is one or more of aminoalkyl methacrylate copolymer type E, gastric-soluble film coating premix, ethyl cellulose, and the like.

8. The brivaracetam sustained-release preparation according to claim 1, wherein The hardness of the core layer is 5~20N; Alternatively, the diameter of the sustained-release microtablet is 1.5 to 2.5 mm, and the diameter-to-thickness ratio is 0.7 to 1.3; or, the diameter of the sustained-release microtablet is 1.7 to 2.3 mm, and the diameter-to-thickness ratio is 0.8 to 1.2; Alternatively, the sustained-release microtablet has a tablet weight of 4 to 10 mg, or 5 to 9 mg.

9. A method for preparing the brivaracetam sustained-release preparation according to claim 1, characterized in that: The steps include: mixing the active ingredient, the sustained-release matrix material, and the tablet core excipients to obtain a mixed material; The mixed material is compressed into a tablet core layer by adopting a powder direct tableting process.

10. The preparation method according to claim 9, characterized in that: The active ingredient, the sustained-release matrix material, and the tablet core excipients except the lubricant are mixed, and then the lubricant is added and mixed to obtain a mixed material; Or, further comprising the following steps: The core layer is subjected to taste masking coating so that the surface of the core layer is covered with the coating layer.

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