Brivaracetam sustained-release tablets and a preparation method thereof

Abstract

This invention discloses a briceceran sustained-release tablet and its preparation method, belonging to the field of pharmaceutical formulations. This invention aims to solve the problems of food effect, release instability, and processability issues associated with briceceran sustained-release tablets. Technical solution: A tablet-within-a-tablet structure is adopted, with the sustained-release core containing a composite hydroxypropyl methylcellulose (high / medium viscosity mixture) and micronized ethyl cellulose, and the immediate-release outer layer containing a disintegrant; the preparation includes ethanol granulation and compression steps. Technical effects: Achieves stable drug release over 24 hours, with a postprandial / fasting release difference of <3%, avoiding dose dumping, while improving flowability and hardness by 53%, suitable for industrial production.

Description

Technical Field

[0001] This invention belongs to the field of pharmaceutical preparations, specifically relating to a brucetam sustained-release tablet and its preparation method. Background Technology

[0002] Epilepsy is a common chronic neurological disorder characterized by abnormal and excessive synchronized discharge of brain neurons. Beriracetam is a new generation of highly selective, high-affinity synaptic vesicle protein 2A (SV2A) ligand that can effectively control epileptic seizures. Currently, all briciracetam available globally are immediate-release tablets, taken twice daily.

[0003] This twice-daily dosing regimen has inherent drawbacks: First, patients experience significant peak-and-trough fluctuations in blood drug concentrations. Peak concentrations can easily trigger adverse reactions such as dizziness and drowsiness, while trough concentrations may increase the risk of breakthrough seizures due to levels below the effective therapeutic window. Second, multiple daily doses reduce patient adherence, especially for epilepsy patients requiring long-term treatment. Therefore, developing a once-daily extended-release formulation of brucetam has significant clinical value.

[0004] In the development of sustained-release formulations, hydrophilic gel matrix technology, such as the use of high-viscosity hydroxypropyl methylcellulose (HPMC) alone, is a common approach. However, the drug release behavior of such single-matrix formulations is highly susceptible to interference from the gastrointestinal environment (such as pH and peristalsis) and food. In particular, a high-fat diet can significantly alter the physiological state of the gastrointestinal tract, potentially leading to a large release of the drug in a short period, known as "dose dumping," which poses a serious safety risk for antiepileptic drugs with a narrow therapeutic window.

[0005] To address this issue, some technicians have attempted to simply blend hydrophobic matrix materials (such as ethyl cellulose, EC) with HPMC. However, this simple physical mixing often fails to form a uniform and stable matrix structure. The differences in properties between the two materials can lead to localized aggregation or delamination during granulation or tableting, resulting in uneven internal tablet structure. This, in turn, causes significant differences in drug release behavior between tablets and batches, making it difficult to guarantee product quality uniformity. Furthermore, when the drug loading and total matrix material content are high, new technical problems arise, namely poor powder flowability and compressibility. This leads to phenomena such as sticking, cracking, and loosening of tablets during compression, making it difficult to meet the required physical properties of tablets, such as hardness and brittleness, posing a challenge to large-scale industrial production.

[0006] In summary, there is an urgent need in this field for a novel brucetam extended-release formulation that can not only achieve stable drug release over 24 hours and overcome food effects, but also possess excellent formulation formability and stable batch-to-batch quality to meet clinical needs and industrial production requirements. Summary of the Invention

[0007] The purpose of this invention is to overcome the shortcomings of existing technologies and provide a bricetam sustained-release tablet and its preparation method. This invention, through the creative selection and combination of hydrophilic gel matrix materials and hydrophobic inert matrix materials, constructs a "biphase-regulated microporous composite matrix system" with synergistic effects. This system not only endows the tablets with excellent in vitro release stability and resistance to food effects, but also significantly improves the physical and mechanical properties and production reproducibility of the formulation.

[0008] The objective of this invention can be achieved through the following technical solutions:

[0009] A bricetan sustained-release tablet, wherein the bricetan sustained-release tablet has a tablet-within-a-tablet structure, comprising a sustained-release core and an immediate-release outer layer covering the sustained-release core;

[0010] The sustained-release core is made from the following raw materials in parts by weight:

[0011] Bricitan: 40–100 doses;

[0012] Composite hydrophilic gel framework material: 30-80 parts;

[0013] Micronized hydrophobic inert framework material: 10-50 parts;

[0014] Filler: 20-60 parts;

[0015] Lubricant: 0.5–2 parts;

[0016] The composite hydrophilic gel framework material is composed of high-viscosity hydroxypropyl methylcellulose and medium-viscosity hydroxypropyl methylcellulose mixed in a mass ratio of (3-5):1.

[0017] The micronized hydrophobic inert framework material is ethyl cellulose with an average particle size of less than 20 μm.

[0018] The immediate-release outer layer is made from the following raw materials in parts by weight:

[0019] Bricitan: 10–25 doses;

[0020] Filler: 30-90 parts;

[0021] Disintegrant: 2-10 parts;

[0022] Adhesive: 1 to 5 parts;

[0023] Lubricant: 0.5 to 2 parts.

[0024] Furthermore, the high-viscosity hydroxypropyl methylcellulose has a viscosity of 80,000-120,000 mPa·s; the medium-viscosity hydroxypropyl methylcellulose has a viscosity of 10,000-20,000 mPa·s.

[0025] Furthermore, the filler in the sustained-release core and the immediate-release outer layer is selected from one or more of microcrystalline cellulose, lactose, and dicalcium phosphate.

[0026] Furthermore, the disintegrant in the immediate-release outer layer is selected from one or more of croscarmellose sodium, croscarmellose, and low-substituted hydroxypropyl cellulose.

[0027] Furthermore, the adhesive in the immediate-release outer layer is selected from one of povidone K30 and hydroxypropyl cellulose.

[0028] Furthermore, the lubricant in the slow-release core and the quick-release outer layer is selected from one or two of magnesium stearate and silicon dioxide.

[0029] Furthermore, the present invention also provides a method for preparing the above-mentioned bricetrastane sustained-release tablets, comprising the following steps:

[0030] (1) Preparation of sustained-release core: The prescribed amount of high-viscosity hydroxypropyl methylcellulose and medium-viscosity hydroxypropyl methylcellulose are premixed evenly to obtain a composite hydrophilic gel skeleton material. Then, the prescribed amount of bricetan, the composite hydrophilic gel skeleton material, the micronized hydrophobic inert skeleton material and the filler are mixed to obtain a dry mixture. Then, 75% ethanol aqueous solution is added to the dry mixture for granulation. The mixture is passed through a 20-mesh sieve to obtain wet particles. The wet particles are then dried in a fluidized bed at 50-60℃, and the particle weight loss is controlled to be less than 2.0%. The dried particles are then granulated through an 18-24 mesh sieve. The prescribed amount of lubricant is added, and the mixture is mixed in a three-dimensional mixer for 5-10 minutes to obtain sustained-release core particles. The sustained-release core particles are then pre-compressed into sustained-release cores using a tablet press.

[0031] (2) Preparation of immediate-release outer layer powder: Mix the prescribed amount of bricetan, filler, disintegrant and binder, then add lubricant and mix to obtain immediate-release outer layer powder;

[0032] (3) Compressing into tablets: Place the sustained-release core in the center of half of the total amount of immediate-release outer layer powder, then fill in the remaining immediate-release outer layer powder, and compress to obtain the bricetan sustained-release tablet.

[0033] Furthermore, the amount of the 75% ethanol aqueous solution used is 35% to 45% of the total weight of the dry mixture.

[0034] The beneficial effects of this invention are:

[0035] (1) Advantages of industrial production: This invention solves the process problem of high drug loading by combining HPMC and micronized EC (flowability ↑32%, compressibility ↑44%), improves tablet hardness by 53% (compared to the worst comparative example), and reduces brittleness by 83%, meeting the requirements of large-scale production.

[0036] (2) Breakthrough in quality controllability: The micronized EC of this invention ensures the uniformity of the skeleton structure and releases batch-to-batch differences that are significantly lower than those of the prior art (the fluctuation range of 2 / 3 of the comparative examples is >25%).

[0037] (3) Enhanced clinical safety: The invention’s unique “biphasic-regulated microporous composite framework” completely overcomes the food effect (postprandial / fasting release difference <3%), avoids the risk of dose dumping, and provides a safety guarantee for antiepileptic drugs with narrow therapeutic windows.

[0038] In summary, this invention, through disruptive innovations in material selection (composite HPMC + micronized EC) and structural design (tablet within a tablet), simultaneously overcomes three major bottlenecks in existing technologies: poor process performance, uncontrollable release behavior, and food effects, thus possessing significant value for both industrialization and clinical application. Detailed Implementation

[0039] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention. Meanwhile, unless otherwise specified, the raw materials, reagents, or devices used in the following embodiments can be obtained from conventional commercial channels. The specifications and sources of some main raw materials are as follows:

[0040] (1) Buricertan: Purity >99.5%, Zhejiang Huahai Pharmaceutical Co., Ltd.

[0041] (2) Hydroxypropyl methylcellulose K100M (HPMC K100M): Dow Chemical Company, USA, viscosity 100000 mPa·s.

[0042] (3) Hydroxypropyl methylcellulose K15M (HPMC K15M): Dow Chemical Company, USA, viscosity 15000 mPa·s.

[0043] (4) Ethyl cellulose (EC, Ethocel) TM 10 FP Premium): Dow Chemical Company, USA, micronized grade, D 90 <20μm.

[0044] (5) Ethyl cellulose (EC, Ethocel)TM 10 Premium): Dow Chemical Company, USA, standard particle size.

[0045] (6) Microcrystalline cellulose (MCC, Avicel® PH102): FMC Corporation, USA.

[0046] (7) Crosslinked sodium carboxymethyl cellulose (Ac-Di-Sol®): FMC Corporation, USA.

[0047] (8) Povidone K30 (PVP K30): BASF, Germany.

[0048] (9) Magnesium stearate: Commercially available.

[0049] Example 1

[0050] This embodiment provides a 100mg / tablet brucetam extended-release tablet, each tablet containing 100mg brucetam (20mg immediate-release layer and 80mg extended-release core). 1000 tablets are prepared.

[0051] 1. Preparation of sustained-release core:

[0052] (1) Prescription: Buriceran 80g, HPMC K100M 45g, HPMC K15M 15g, micronized ethyl cellulose (Ethocel) TM 10 FP Premium) 25g, Microcrystalline cellulose 35g, Magnesium stearate 2g.

[0053] (2) Preparation steps:

[0054] a. Place 45g HPMC K100M and 15g HPMC K15M in a mixer and premix for 10 minutes.

[0055] b. Add 80g bricetan, 25g micronized ethyl cellulose and 35g microcrystalline cellulose, and dry mix in a high-efficiency wet granulation machine for 10 minutes.

[0056] c. Slowly add 80g of 75% ethanol aqueous solution as a wetting agent and stir at low speed to form a soft material.

[0057] d. Granulate the soft material through a 20-mesh sieve and dry it in a fluidized bed at 60°C until the LOD of the particles is less than 2.0%.

[0058] e. Use a granulator to granulate through a 24-mesh sieve.

[0059] f. Add 2g of magnesium stearate and mix in a three-dimensional mixer for 5 minutes.

[0060] g. Using an 8mm round shallow concave punch, press the above particles into a sustained-release core weighing approximately 202mg and with a hardness of 40-60N.

[0061] 2. Preparation of the immediate-release outer layer:

[0062] (1) Prescription: Brucetan 20g, lactose 70g, croscarmellose sodium 6g, povidone K30 4g, magnesium stearate 2g.

[0063] (2) Preparation steps:

[0064] a. Place 20g bricetan, 70g lactose, 6g croscarmellose sodium, and 4g povidone K30 in a mixer and mix for 15 minutes.

[0065] b. Add 2g of magnesium stearate and continue mixing for 5 minutes to obtain the immediate-release outer layer powder.

[0066] 3. Compress into tablets:

[0067] Use the ZP-19 tablet press with a 12mm round shallow concave punch.

[0068] First, fill about 51g of the immediate-release outer layer powder (1 / 2 of the total amount) into the mold hole, place the sustained-release core prepared in step 1g in the center, and then fill in the remaining 51g of the immediate-release outer layer powder.

[0069] By controlling the pressure, bricetam extended-release tablets were obtained.

[0070] Comparative Example 1

[0071] Comparative Example 1 served as the control group for Example 1. Compared to Example 1, in the formulation of the sustained-release core, 45g of HPMCK100M and 15g of HPMC K15M were replaced with an equal amount of a single high-viscosity HPMC, namely 60g of HPMC K100M. All other raw materials, dosages, and preparation processes were exactly the same as in Example 1, ultimately yielding bricetam sustained-release tablets.

[0072] Comparative Example 2

[0073] Comparative Example 2 served as the control group for Example 1. Compared to Example 1, the sustained-release core formulation contained 25g of micronized ethyl cellulose (Ethocel). TM Replace 10 FP Premium with an equal amount of 25g standard granular ethyl cellulose (Ethocel). TM (10 Premium). All other raw materials, dosages, and preparation processes were exactly the same as in Example 1, ultimately yielding bricetrast extended-release tablets.

[0074] Comparative Example 3

[0075] Comparative Example 3 served as the control group for Example 1. Compared to Example 1, the sustained-release core formulation was modified by replacing "45g HPMCK100M + 15g HPMC K15M" with "60g HPMC K100M" and "25g micronized EC" with "25g standard particle-grade EC". All other raw materials, dosages, and preparation processes were identical to those in Example 1, ultimately yielding bricetam sustained-release tablets.

[0076] Comparative Example 4

[0077] Comparative Example 4 served as the control group for Example 1. Compared to Example 1, 25g of micronized ethyl cellulose was removed from the sustained-release core formulation and replaced with an equal amount of filler (25g of microcrystalline cellulose) to maintain a substantially unchanged core weight. Specifically, the sustained-release core formulation was adjusted to: 80g bricetam, 45g HPMC K100M, 15g HPMC K15M, 60g microcrystalline cellulose (35g + 25g), and 2g magnesium stearate. All other preparation processes remained identical to those in Example 1, ultimately yielding bricetam sustained-release tablets.

[0078] Test Example 1

[0079] The bricetam sustained-release tablets prepared in Example 1 and Comparative Examples 1 to 4 were subjected to particle properties (angle of repose and compressibility index). The test procedure is as follows, and the test results are shown in Table 1:

[0080] (1) Angle of repose determination: The fixed funnel method was used. An appropriate amount of bricetam sustained-release tablets was taken and allowed to fall freely from the funnel, forming a conical accumulation on a horizontal plate. The height (h) and the radius (r) of the base of the accumulation were measured, and the angle of repose α was calculated using the formula tan(α) = h / r. The measurement was repeated 3 times, and the average value was taken.

[0081] (2) Compression index determination: Take a certain amount (m) of bricetam sustained-release tablets and gently place them into a 100mL graduated cylinder. Record the volume (V0) at its loose density. Then, vibrate the graduated cylinder on a tapped density meter at a specified frequency and amplitude until the volume no longer changes. Record the volume (V0) at the tapped density. f Compression index (%) is calculated using the formula: [(V0 - V...]]. f Calculate using [(V0)]×100%. Repeat the measurement 3 times and take the average value.

[0082] Table 1. Results of particle property tests

[0083]

[0084] Analysis of the data in Table 1:

[0085] (1) Superiority of Example 1: The angle of repose (29.5°) and compressibility index (12.6%) of Example 1 were the lowest among all groups, indicating that its particles have excellent flowability and compressibility. This is entirely attributed to its unique technical solution: the synergistic effect of the composite hydrophilic gel framework material (high viscosity HPMC K100M + medium viscosity HPMC K15M) and the micronized hydrophobic inert framework material (micronized EC).

[0086] (2) Comparative Analysis with Comparative Example 1: Comparative Example 1 simply replaced the composite HPMC in Example 1 with a single high-viscosity HPMC K100M. The results showed that its angle of repose (35.2°) and compressibility index (18.1%) were significantly worse than those of Example 1. This directly proves that the introduction of medium-viscosity HPMC K15M is not a simple material replacement, but a key improvement to the particle processing performance. According to the description in the Summary of the Invention, HPMC K15M acts as a "plasticizer" and "binder" here, thereby significantly improving the flowability and compressibility of the particles.

[0087] (3) Comparative Analysis with Comparative Example 2: Comparative Example 2 simply replaced the micronized EC in Example 1 with standard particle-grade EC. The results showed that its angle of repose (37.8°) and compressibility index (20.5%) were worse than those of Comparative Example 1. This strongly demonstrates that the "micronization" of the hydrophobic framework material is another key factor in achieving excellent processing performance. Micronized EC can be more uniformly dispersed and filled in the voids between HPMC framework particles, reducing friction and porosity, thereby improving the overall flowability and compressibility of the powder, while standard particle-grade EC cannot effectively achieve this effect.

[0088] (4) Comparative Analysis with Comparative Example 3: Comparative Example 3 used both high-viscosity HPMC and standard particle-grade EC, representing a superposition of problems. Its angle of repose (41.3°) and compressibility index (25.4%) were the worst among all groups, indicating that its flowability and compressibility were very unsatisfactory. This result perfectly matches the technical problem of "poor powder flowability and poor compressibility" described in the background art, thus proving that the technical solution of Example 1 (composite HPMC + micronized EC) is an effective solution to this problem.

[0089] (5) Comparative Analysis with Comparative Example 4: Comparative Example 4, based on the composite HPMC of Example 1, removed the micronized EC. Its angle of repose (31.8°) and compressibility index (15.5%) were superior to Comparative Examples 1, 2, and 3, but still inferior to Example 1. This reveals two important pieces of information:

[0090] A. The composite HPMC system itself can significantly improve particle properties.

[0091] B. The addition of micronized EC further enhances the performance of the composite HPMC system, achieving optimal results. This demonstrates the synergistic effect between composite HPMC and micronized EC.

[0092] Test Example 2

[0093] The brisaectatine sustained-release tablets prepared in Example 1 and Comparative Examples 1 to 4 were tested for their tablet physical properties (hardness and friability). The test procedures are as follows, and the test results are shown in Table 2.

[0094] (1) Hardness test: Randomly select 10 finished tablets and use a tablet hardness tester to measure the radial crushing pressure (N). Record the value of each tablet and calculate the average value.

[0095] (2) Friability determination: Accurately weigh a certain weight (W0, about 6.5g) of tablets and place them in a friability tester, rotating it 100 times at a speed of 25 rpm. After removing it, use a soft brush to remove the floating powder and weigh it accurately again (W). Calculate the friability using the formula: Friability (%) = [(W0-W) / W0] × 100%.

[0096] Table 2 Results of physical properties of tablets

[0097]

[0098] Analysis of the data in Table 2:

[0099] (1) Advantages of Example 1: The tablets of Example 1 have the highest hardness (115N) and the lowest brittleness (0.15%), and their physical properties are excellent, fully meeting the requirements of commercial production and distribution.

[0100] (2) Correlation with Table 1 data: The results in Table 2 show a completely positive correlation with the results in Table 1. The better the compressibility of the granules (the lower the compressibility index), the higher the hardness and the lower the brittleness of the compressed tablets.

[0101] A. The hardness of Comparative Examples 1, 2, and 3 decreased sequentially (90N→80N→75N), while their brittleness increased sequentially (0.42%→0.64%→0.90%), which corresponds perfectly to their gradually deteriorating particle properties in Table 1.

[0102] B. In particular, Comparative Example 3 showed a friability of 0.90%, which is close to the upper limit of 1.0% in the conventional pharmacopoeia, indicating a clear quality risk.

[0103] C. The physical properties of Comparative Example 4 (hardness 105N, brittleness 0.28%) are also better than those of Comparative Examples 1, 2 and 3, but not as good as those of Example 1, which once again confirms the necessity of the combination of composite HPMC and micronized EC for obtaining the best formability.

[0104] Test Example 3

[0105] The in vitro dissolution tests were performed on the brisaectam sustained-release tablets prepared in Example 1 and Comparative Examples 1 to 4. The test procedures are as follows, and the test results are shown in Table 3:

[0106] (1) Test items: In vitro cumulative release under simulated fasting and postprandial conditions.

[0107] (2) Testing process:

[0108] a. Apparatus: Paddle plate method (Chinese Pharmacopoeia / USP Dissolution Determination Method II).

[0109] b. Dissolution medium:

[0110] Fasted conditions: First, rotate in 900 mL of hydrochloric acid solution at pH 1.2 for 2 hours, then replace the medium with 900 mL of phosphate buffer at pH 6.8 at the end of the second hour, and continue dissolution for 24 hours; Fed conditions: Dissolve directly in 900 mL of phosphate buffer (pH 5.0, containing an appropriate amount of surfactant such as sodium dodecyl sulfate to simulate bile salts) simulating a postprandial state for 24 hours.

[0111] c. Parameters: Rotation speed 50 rpm, temperature 37±0.5℃.

[0112] d. Sampling: Samples were taken at 1h, 2h, 4h, 8h, 12h, and 24h, and an equal volume of dissolution medium at the same temperature was added. After filtration through a 0.45μm filter membrane, the concentration of bricetam was determined by high-performance liquid chromatography (HPLC), and the cumulative release rate was calculated. Six tablets were measured in each group, and the average value was calculated.

[0113] Table 3. Results of in vitro dissolution test (cumulative release rate %)

[0114]

[0115] Analysis of the data in Table 3:

[0116] (1) Example 1: Successfully achieving stable sustained release and overcoming food effects:

[0117] A. Stable release: According to the data from Example 1 (fasting), the drug was released stably within 24 hours, with 27.8% released in 1 hour (rapid onset of action in the immediate-release layer), and the rate gradually slowed down thereafter, reaching about 81.4% by 12 hours and complete release in 24 hours, showing an ideal sustained-release curve.

[0118] B. Overcoming the food effect: Comparing the "fasting" and "postprandial" curves of Example 1, the cumulative release rates at each time point are almost identical (e.g., 45.2% vs 46.8% at 4h; 65.8% vs 68.1% at 8h). This strongly demonstrates that the "dual-phase regulated microporous composite framework system" constructed in this invention has extremely high structural stability, effectively resists interference from the simulated postprandial environment, fundamentally avoids the risk of "dose dumping," and achieves a technological breakthrough.

[0119] (2) Comparative analysis with Comparative Example 1: The release rate of Comparative Example 1 (single high-viscosity HPMC) was significantly faster than that of Example 1 (e.g., 82.3% released after 8 hours, compared to 65.8% in Example 1). This indicates that the composite HPMC framework in Example 1 forms a stronger and more uniform gel layer than the single HPMC framework, resulting in stronger and more sustained control over drug release. The addition of medium-viscosity HPMCK15M optimized the structural integrity of the gel layer.

[0120] (3) Comparative Analysis with Comparative Examples 2 and 3: The results of Comparative Examples 2 and 3 revealed the critical issue of "large batch-to-batch variation." This indicates that standard particle-grade EC cannot form a uniform and stable composite framework with HPMC. During granulation and tableting, EC and HPMC may separate or be unevenly distributed, resulting in inconsistent internal structures in each tablet or even each batch of product, making drug release behavior unpredictable and uncontrollable. This is precisely the drawback of simple physical mixing as pointed out in the background art. Example 1, by using micronized EC, ensured a highly uniform dispersion of the hydrophobic framework in the hydrophilic gel network, thereby guaranteeing high reproducibility of release behavior and uniformity of product quality.

[0121] (4) Comparative Analysis with Comparative Example 4: Comparative Example 4 (containing only compound HPMC, without EC) was tested under simulated postprandial (Fed) conditions, and the results were decisive. This tablet released over 52.3% within 1 hour and over 91.5% within 4 hours, exhibiting a typical "dose dumping" phenomenon. This result contrasts sharply with the stable release observed in Example 1 under the same postprandial conditions, irrefutably demonstrating that the hydrophobic, inert microporous framework constructed by micronized EC is indispensable for resisting changes in the postprandial gastrointestinal environment and preventing drug burst release, and is key to solving the food effect problem.

[0122] It should be noted that, in this document, terms such as “comprising,” “including,” or any other variations thereof are intended to cover non-exclusive inclusion, such that a process, method, article, or apparatus that comprises a list of elements includes not only those elements but also other elements not expressly listed, or elements inherent to such process, method, article, or apparatus.

[0123] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A brucetam extended-release tablet, characterized in that, The bricetan sustained-release tablet has a tablet-within-a-tablet structure, including a sustained-release core and an immediate-release outer layer covering the sustained-release core; The sustained-release core is made from the following raw materials in parts by weight: Bricitan: 40–100 doses; Composite hydrophilic gel framework material: 30-80 parts; Micronized hydrophobic inert framework material: 10-50 parts; Filler: 20-60 parts; Lubricant: 0.5–2 parts; The composite hydrophilic gel framework material is composed of high-viscosity hydroxypropyl methylcellulose and medium-viscosity hydroxypropyl methylcellulose mixed in a mass ratio of (3-5):

1. The micronized hydrophobic inert framework material is ethyl cellulose with an average particle size of less than 20 μm. The immediate-release outer layer is made from the following raw materials in parts by weight: Bricitan: 10–25 doses; Filler: 30-90 parts; Disintegrant: 2-10 parts; Adhesive: 1 to 5 parts; Lubricant: 0.5–2 parts; The high-viscosity hydroxypropyl methylcellulose has a viscosity of 80,000-120,000 mPa·s; the medium-viscosity hydroxypropyl methylcellulose has a viscosity of 10,000-20,000 mPa·s.

2. The brivaracetam sustained release tablet according to claim 1, wherein The fillers in the sustained-release core and the immediate-release outer layer are selected from one or more of microcrystalline cellulose, lactose, and dicalcium phosphate.

3. The brucetam sustained-release tablet according to claim 1, characterized in that, The disintegrant in the immediate-release outer layer is selected from one or more of croscarmellose sodium, croscarmellose, and low-substituted hydroxypropyl cellulose.

4. The brivaracetam sustained release tablet according to claim 1, wherein the tablet is a tablet having a weight of 100 mg. The adhesive in the immediate-release outer layer is selected from either povidone K30 or hydroxypropyl cellulose.

5. A brucetam sustained-release tablet according to claim 1, characterized in that, The lubricant in the slow-release core and the quick-release outer layer is selected from one or two of magnesium stearate and silicon dioxide.

6. The method of claim 1 to 5, wherein the method is characterized in that, Includes the following steps: (1) Preparation of sustained-release core: The prescribed amount of high-viscosity hydroxypropyl methylcellulose and medium-viscosity hydroxypropyl methylcellulose are premixed evenly to obtain a composite hydrophilic gel skeleton material. Then, the prescribed amount of bricetan, the composite hydrophilic gel skeleton material, the micronized hydrophobic inert skeleton material and the filler are mixed to obtain a dry mixture. Then, 75% ethanol aqueous solution is added to the dry mixture for granulation. The mixture is passed through a 20-mesh sieve to obtain wet particles. The wet particles are then dried in a fluidized bed at 50-60℃, and the particle weight loss is controlled to be less than 2.0%. The dried particles are then granulated through an 18-24 mesh sieve. The prescribed amount of lubricant is added, and the mixture is mixed in a three-dimensional mixer for 5-10 minutes to obtain sustained-release core particles. The sustained-release core particles are then pre-compressed into sustained-release cores using a tablet press. (2) Preparation of immediate-release outer layer powder: Mix the prescribed amount of bricetan, filler, disintegrant and binder, then add lubricant and mix to obtain immediate-release outer layer powder; (3) Compressing into tablets: Place the sustained-release core in the center of half of the total amount of immediate-release outer layer powder, then fill in the remaining immediate-release outer layer powder, and compress to obtain the bricetan sustained-release tablet.

7. The method of claim 6, wherein the brivaracetam sustained release tablet is prepared by the steps of, The amount of the 75% ethanol aqueous solution used is 35% to 45% of the total weight of the dry mixture.

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