A kind of Zolpidem tartrate orally disintegrating sustained-release tablet and preparation method thereof

Abstract

The present invention belongs to the technical field of pharmaceutical preparations, and specifically relates to a zolpidem tartrate orally disintegrating sustained-release tablet and a preparation method thereof. The sustained-release tablet comprises zolpidem tartrate, a sustained-release material, benzyl benzoate or / and methyl cyclodextrin, a filler, a disintegrant, a colorant and a lubricant. The tablet has a certain sustained-release effect on the basis of maintaining rapid disintegration characteristics, does not cause drowsiness the next day, has good stability, and has a simple preparation process, and is suitable for commercial production.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to an orally disintegrating sustained-release zolpidem tartrate tablet and a preparation method thereof. Background Art

[0002] Insomnia is a common sleep disorder and physiological and psychological disease in clinical practice. With the acceleration of the pace of life and the increase of life pressure, the incidence of insomnia in my country has shown a significant upward trend year by year. Insomnia has become the second most common disease in neurology clinics, second only to headaches. The symptoms of insomnia generally include difficulty falling asleep, shallow sleep, difficulty maintaining sleep (easy to wake up, waking up early), and affecting daily work, study and life during the day.

[0003] Zolpidem tartrate is a non-benzodiazepine, γ-aminobutyric acid A-benzodiazepine receptor agonist that can selectively antagonize γ-aminobutyric acid A complex receptors and promote the action of GABA. It has a strong sedative and hypnotic effect and is mainly used for hypnosis in clinical practice. It takes effect 30 minutes after taking the medicine and has a half-life in the blood of about 2.5 hours. Compared with benzodiazepines, zolpidem has fewer sequelae, and long-term use is less likely to produce tolerance and dependence. It almost does not cause rebound insomnia and is the first choice for non-benzodiazepines to treat insomnia.

[0004] Zolpidem tartrate is a polymorphic drug with multiple crystal forms such as A, B, C, D, E, F, G, and H, and the polymorphic forms can be transformed in a certain process, such as changes in storage conditions; Zolpidem tartrate is almost insoluble in water and organic solvents, and is easily soluble in 0.1 mol / L hydrochloric acid solution.

[0005] At present, the common preparations of zolpidem tartrate that have been marketed include: common tablets, capsules, sublingual tablets, oral sprays and solutions. Common tablets and capsules are usually taken before going to bed and can take effect quickly, but the effect is short-lived, generally 2 to 6 hours. Patients with early awakening symptoms often need to get up in the middle of the night to take the medicine again, which seriously interferes with sleep quality. Zolpidem oral spray is used for short-term treatment of patients with difficulty falling asleep and insomnia; sublingual tablets are quickly absorbed through the oral mucosa and are used for short-term treatment of patients with difficulty falling asleep and insomnia, but patients also need to get up in the middle of the night to take the medicine again, which interferes with sleep quality and reduces compliance. The zolpidem sustained-release preparation developed by Sanofi-Aventis abroad can take effect quickly, but the drug release time is slow, and the blood drug concentration is maintained at a high level for a long time. Due to the large total amount of drug released, long-term use of the drug often causes drowsiness and dizziness the next day, and the incidence of anxiety reaches 6.3%, accompanied by headaches, gastrointestinal reactions and other serious adverse reactions.

[0006] CN1334729A discloses a controlled-release dosage form containing zolpidem or its salt, which can release zolpidem in a predetermined time according to a biphasic dissolution distribution; CN103230381B discloses a zolpidem tartrate timed pulse controlled-release micropill, which can be delayed for a certain period of time and then released rapidly. There are many other prior arts of controlled-release drug delivery systems or timed drug delivery systems similar to the above, which generally produce a drug release time lag effect through different material coating layers outside the micropill or tablet core, or multiple drug-containing layers to adjust the drug release rate. Such preparations often have the disadvantages of incomplete release of active drug ingredients, and also have the defect of strictly limiting the amount of drug in each drug layer, and the process operation is difficult.

[0007] The existing zolpidem tartrate pharmaceutical preparations still have the following problems: they have not considered the basic theories of biopharmaceutics to study the effects of dosage forms on the in vivo absorption and stability of polymorphic drug crystal forms, how to achieve transmembrane absorption of poorly soluble or poorly absorbed drugs in the gastrointestinal segment, and how to achieve rapid onset of action after taking the drug and maintain it for a certain period of time without causing adverse reactions such as drowsiness, dizziness, anxiety, etc. the next day. Summary of the invention

[0008] In view of the shortcomings of zolpidem tartrate preparations in the prior art, the present invention provides an orally disintegrating sustained-release tablet of zolpidem tartrate, which has a certain sustained-release effect on the basis of maintaining rapid disintegration characteristics and does not induce drowsiness the next day. The tablet has good stability and a simple preparation process, and is suitable for commercial production.

[0009] Conventional methods for controlling drug release rate include increasing the amount of binder, reducing the amount of disintegrant, extending the disintegration time, and coating the active ingredients. However, these methods are usually complicated in preparation process, high in cost, slow in effect, and the particles become larger after coating, which makes them feel gritty and affects the taste. In addition, the release rate of zolpidem tartrate from the preparation is easily affected by the external environment such as pH value, and it is difficult to maintain the sustained release effect throughout the entire period of medication.

[0010] The inventors found that after Zolpidem tartrate and a sustained-release material are mixed to obtain a sustained-release mixture, the sustained-release time is as long as 4 hours. Further adding benzyl benzoate and / or methyl cyclodextrin in different proportions can significantly extend the sustained-release time without affecting the disintegration time limit. By adding other commonly used pharmaceutical excipients, an orally disintegrating sustained-release tablet can be prepared.

[0011] Specifically, the purpose of the present invention is achieved through the following technical solutions:

[0012] A zolpidem tartrate orally disintegrating sustained-release tablet comprises zolpidem tartrate, a sustained-release material, benzyl benzoate and / or methyl cyclodextrin, a filler, a disintegrant, a colorant and a lubricant.

[0013] Preferably, in the sustained-release tablet, the sustained-release material is selected from one or more of: hydroxypropyl methylcellulose, behenyl glyceride, methylcellulose, glyceryl monostearate, carrageenan or zein.

[0014] Further preferably, in the sustained-release tablet, the sustained-release material is hypromellose, behenyl glyceride or methylcellulose.

[0015] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate to the sustained-release material is 1:3-8; further preferably, the weight ratio of zolpidem tartrate to the sustained-release material is 1:4-6.

[0016] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate: the total weight of benzyl benzoate or / and methylcyclodextrin is 1:0.5-3; the weight ratio of zolpidem tartrate: the total weight of benzyl benzoate or / and methylcyclodextrin is 1:1-2. That is, in the sustained-release tablet, benzyl benzoate and methylcyclodextrin can be selected alone, or a mixture of the two can be used.

[0017] Preferably, in the sustained-release tablet, the filler is selected from one or more of microcrystalline cellulose, maltitol, xylitol, glucose, sucrose, lactose, lactose monohydrate or sorbitol; further preferably, the filler is microcrystalline cellulose, maltitol or xylitol.

[0018] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate to the filler is 1:2-14, and more preferably, the weight ratio of zolpidem tartrate to the filler is 1:5-11.

[0019] Preferably, in the sustained-release tablet, the disintegrant is sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, sodium alginate or guar gum.

[0020] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate to disintegrant is 1:0.5-3, and more preferably, the weight ratio of zolpidem tartrate to disintegrant is 1:1.25-2.25.

[0021] Preferably, in the sustained-release tablet, the colorant is calcium carbonate, yellow iron oxide, black iron oxide or aluminum chelating agent.

[0022] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate to colorant is 1:0.005-0.02.

[0023] Preferably, in the sustained-release tablet, the lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate, calcium stearate, polyethylene glycol, sodium benzoate, sucrose fatty acid ester, talc or white beeswax.

[0024] Preferably, in the sustained-release tablet, the weight ratio of zolpidem tartrate to lubricant is 1:0.1-0.2.

[0025] Preferably, in the sustained-release tablet, zolpidem tartrate is zolpidem hemitartrate E crystal form.

[0026] The present invention provides a method for preparing zolpidem tartrate orally disintegrating sustained-release tablets:

[0027] The sustained-release material, benzyl benzoate and / or methyl cyclodextrin are dissolved in an aqueous solution of an organic solvent, zolpidem tartrate is added and stirred to dissolve, vacuum dried, and then crushed with a grinder to obtain particles, and then a filler and a disintegrant are added and mixed evenly, and then a colorant and a lubricant are added, mixed evenly, and tableted.

[0028] Preferably, in the method for preparing the sustained-release tablet, the aqueous solution of the organic solvent is an ethanol-water solution or an isopropanol-water solution with a volume ratio of 90 to 95%.

[0029] Compared with the prior art, the present invention has the following outstanding advantages:

[0030] 1. The orally disintegrating sustained-release tablet of the present invention has a short disintegration time in the oral cavity and has no sandy feeling. On the basis of ensuring rapid onset of effect, it can play a certain sustained-release effect without causing drowsiness the next day;

[0031] 2. The orally disintegrating sustained-release tablet of the present invention has good stability, and the crystal form does not change before and after preparation and after long-term storage;

[0032] 3. The orally disintegrating sustained-release tablet of the present invention has a simple preparation process and is suitable for commercial production. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Crystalline data of the orally disintegrating sustained-release zolpidem tartrate tablets obtained in Example 2 after being placed under accelerated experimental conditions for 6 months at 0 days DETAILED DESCRIPTION

[0034] The following specific embodiments are listed to further illustrate the present invention. Zolpidem hemi-tartrate E crystal form may be used, and other crystal forms may also be used. The scope of the present invention should not be limited in any way. Those skilled in the art can make various modifications or improvements based on the basic idea of ​​the present invention, but as long as they do not deviate from the basic idea of ​​the present invention, they are all within the scope of the present invention.

[0035] Example 1

[0036] 1) Prescription

[0037]

[0038] 2) Preparation process

[0039] The prescribed amount of hydroxypropyl methylcellulose and benzyl benzoate are dissolved in 200 mL of 95% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Microcrystalline cellulose and sodium carboxymethyl starch are then added and mixed evenly. Calcium carbonate and magnesium stearate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0040] Example 2

[0041] 1) Prescription

[0042]

[0043] 2) Preparation process

[0044] The prescribed amount of behenic acid glyceride and methyl cyclodextrin are dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0045] Example 3

[0046] 1) Prescription

[0047]

[0048] 2) Preparation process

[0049] The prescribed amount of methylcellulose, benzyl benzoate and methyl cyclodextrin are dissolved in 400 mL of a 90% by volume isopropanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Xylitol and sodium alginate are then added and mixed evenly. Black iron oxide and calcium stearate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0050] Example 4

[0051] 1) Prescription

[0052]

[0053] 2) Preparation process

[0054] Dissolve the prescribed amount of glyceryl monostearate and methyl cyclodextrin in 300 mL of 95% by volume isopropanol-water solution, then add zolpidem tartrate and stir to dissolve, dry in vacuum at room temperature to remove the solvent, and grind with a grinder with a sieve aperture of 50 mesh to obtain granules, then add lactose monohydrate, glucose, and cross-linked polyvinylpyrrolidone and mix evenly, then add yellow ferric oxide, polyethylene glycol, and white beeswax, mix evenly, and compress into tablets with a tableting pressure of 6.0 to 10.0 KN. The specification is 12.5 mg of zolpidem tartrate per tablet.

[0055] Example 5

[0056] 1) Prescription

[0057]

[0058] 2) Preparation process

[0059] The prescribed amount of carrageenan, zein and methyl cyclodextrin are dissolved in 500 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Lactose, sorbitol and guar gum are then added and mixed evenly. An aluminum chelating agent, sodium benzoate and talcum powder are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0060] Example 6

[0061] 1) Prescription

[0062]

[0063]

[0064] 2) Preparation process

[0065] The prescribed amount of behenic acid glyceride and methyl cyclodextrin are dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0066] Example 7

[0067] 1) Prescription

[0068]

[0069] 2) Preparation process

[0070] The prescribed amount of behenic acid glyceride and methyl cyclodextrin are dissolved in 500 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0071] Example 8

[0072] 1) Prescription

[0073]

[0074]

[0075] 2) Preparation process

[0076] The prescribed amount of behenic acid glyceride and methyl cyclodextrin are dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0077] Comparative Example 1

[0078] 1) Prescription

[0079]

[0080] 2) Preparation process

[0081] The prescribed amount of polyvinyl alcohol and methyl cyclodextrin are dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0082] Comparative Example 2

[0083] 1) Prescription

[0084]

[0085]

[0086] 2) Preparation process

[0087] The prescribed amount of behenic acid glyceryl and triethyl citrate are dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0088] Comparative Example 3

[0089] 1) Prescription

[0090]

[0091] 2) Preparation process

[0092] The prescribed amount of behenic acid glyceride is dissolved in 300 mL of 90% by volume ethanol-water solution, and then zolpidem tartrate is added and stirred to dissolve. After vacuum drying at room temperature to remove the solvent, the mixture is crushed using a grinder with a sieve aperture of 50 mesh to obtain granules. Maltitol and cross-linked polyvinylpyrrolidone are then added and mixed evenly. Yellow ferric oxide and sodium stearyl fumarate are then added and mixed evenly. The mixture is tableted at a tableting pressure of 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0093] Comparative Example 4

[0094] 1) Prescription

[0095]

[0096]

[0097] 2) Preparation process

[0098] Mix the prescribed amount of behenic acid glyceride, methyl cyclodextrin and zolpidem tartrate evenly, then add maltitol and cross-linked polyvinylpyrrolidone and mix evenly, then add yellow ferric oxide and sodium stearyl fumarate, mix evenly, and press into tablets. The tableting pressure is 6.0 to 10.0 KN. The specification is that each tablet contains 12.5 mg of zolpidem tartrate.

[0099] Comparative Example 5

[0100] 1) Prescription

[0101]

[0102] 2) Preparation method

[0103] The zolpidem tartrate, filler, disintegrant and binder in the immediate-release layer of the prescription are mixed, granulated with water, and then a lubricant and a glossing agent are added; the zolpidem tartrate, filler, sustained-release material and stabilizer in the sustained-release layer of the prescription are mixed, granulated with water, and then a lubricant and a glossing agent are added, and the amount of the active ingredient zolpidem tartrate in the immediate-release layer and the sustained-release layer must be strictly controlled during the preparation process; the above-mentioned sustained-release granules and immediate-release granules are tableted using a rotary tablet press with a tableting pressure of 6.0 to 10.0 KN, and the specification is 12.5 mg of zolpidem tartrate per tablet.

[0104] Verification Example

[0105] Experimental Example 1: Determination of disintegration time of the obtained preparations and comparison of dissolution behavior

[0106] Disintegration time determination: refer to the disintegration time inspection method of the fourth general rule 0921 of the 2020 edition of the Chinese Pharmacopoeia, adjust the position of the disintegrator basket so that when the basket is at the lowest position, it is about 25mm from the bottom of the cup, and inject purified water at about 37°C into the 1000ml beaker of the disintegrator so that the screen is about 15mm below the water surface. Set the water bath temperature to 37°C, and measure the water temperature with a calibrated thermometer. After the temperature reaches 37°C ± 1°C and is kept constant, take 6 tablets of each of the preparations of Examples 1-5, respectively, and place them in the glass tubes of the disintegrator baskets, add baffles (the "V" groove of the baffle is open upwards), and set the "preset time" to 5min, start the disintegrator for inspection, and record the disintegration time of each tablet. The disintegration time of the preparations obtained in each embodiment and comparative example is shown in Table 1.

[0107] Dissolution test: Take the tablets obtained in each embodiment and comparative example (6 tablets for measurement), refer to the test apparatus of the second method of the fourth part 0931 dissolution test method of the "Chinese Pharmacopoeia" 2020 edition, use 500mL of 0.01mol / L hydrochloric acid solution as the dissolution medium, the rotation speed is 100 revolutions per minute, and the dissolution amount is detected at 5, 30, 60, 240, 600, and 720min. The results are shown in Table 1.

[0108] Table 1 Disintegration time and dissolution test results of Examples 1 to 8 and Comparative Examples 1 to 5

[0109]

[0110] Note: “-” in the table means that the substance has been basically released at the previous time point, and the time point has not been measured.

[0111] As can be seen from Table 1, the dissolution rate of the tablets obtained in Examples 1 to 5 is moderate, which can make the patient take effect immediately after taking the medicine, and have a certain sustained release effect (sustained release time is about 12h), and will not cause drowsiness the next day; an excessive amount of disintegrant is added to the prescription of Example 6, so that the obtained tablet has a burst release phenomenon when it starts to release; Example 7 uses an excessive amount of methyl cyclodextrin, and Example 8 uses an excessive amount of behenic acid glyceride, both of which make the tablet release incomplete; Comparative Example 1 uses polyvinyl alcohol, and the sustained release effect may be reduced due to different copolymers and degradation characteristics; Comparative Example 2 uses triethyl citrate instead of benzyl benzoate or methyl cyclodextrin, and Comparative Example 3 does not use benzyl benzoate or methyl cyclodextrin, and no coordination effect of benzyl benzoate or methyl cyclodextrin and sustained release material is produced, and the sustained release time of the obtained tablet is shortened; Comparative Example 4 is prepared by direct tableting method, and no coordination effect of sustained release effect is produced; Comparative Example 5 uses the process in the prior art, and the obtained tablet has a fast release rate and has the defect of burst release, while the release time is maintained for a short time and the sustained release effect is slightly poor.

[0112] Experimental Example 2: Stability Study of the Prepared Preparation

[0113] The product was packaged in a sealed double-layer aluminum-plastic bag and placed under the conditions of temperature 40±2℃ and relative humidity 75±5% (accelerated) for 6 months. Samples were taken at the end of the 0th, 3rd and 6th month, and the related substances (total impurities, %) were determined.

[0114] Table 2 Stability test results of Examples 1 to 8 and Comparative Examples 1 to 5

[0115] Example 0 days (%) 3 months (%) 6 months (%) Example 1 0.008 0.011 0.015 Example 2 0.007 0.010 0.014 Example 3 0.008 0.013 0.016 Example 4 0.009 0.012 0.017 Example 5 0.008 0.011 0.019 Example 6 0.009 0.013 0.021 Example 7 0.011 0.018 0.027 Example 8 0.010 0.016 0.023 Comparative Example 1 0.011 0.029 0.075 Comparative Example 2 0.012 0.028 0.094 Comparative Example 3 0.013 0.042 0.116 Comparative Example 4 0.012 0.071 0.130 Comparative Example 5 0.013 0.352 0.495

[0116] As can be seen from Table 2, compared with the comparative example, the tablets obtained in each embodiment of the present invention have better stability, and the total impurity content changes less under accelerated conditions for 6 months. At the same time, the formulation and preparation method of the present invention are conducive to the maintenance of the crystal form of zolpidem tartrate, and no crystal form transformation occurs. It can be seen from the accompanying drawings that the orally disintegrating sustained-release tablets obtained in Example 2 of the present invention remain unchanged after being placed under accelerated conditions (temperature 40±2°C; relative humidity 75±5%) for 6 months.

Claims

1. A zolpidem tartrate orally disintegrating sustained-release tablet, characterized in that: The sustained-release tablet comprises zolpidem tartrate, a sustained-release material, benzyl benzoate or / and methyl cyclodextrin, a filler, a disintegrant, a colorant and a lubricant, wherein the sustained-release material is one or more of hydroxypropyl methylcellulose, behenyl glyceride, methylcellulose, glyceryl monostearate, carrageenan or zein, the weight ratio of zolpidem tartrate to the sustained-release material is 1:3-8, and the weight ratio of zolpidem tartrate to the total weight of benzyl benzoate or / and methyl cyclodextrin is 1:0.5-3. The disintegrant is sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, sodium alginate or guar gum, and the weight ratio of zolpidem tartrate to disintegrant is 1:0.5-3. The preparation method of the sustained-release tablet is as follows: dissolving the sustained-release material, benzyl benzoate and / or methyl cyclodextrin in an aqueous solution of an organic solvent, adding zolpidem tartrate and stirring to dissolve, vacuum drying, using a pulverizer to crush to obtain particles, then adding a filler and a disintegrant to mix evenly, then adding a colorant and a lubricant, mixing evenly, and tableting.

2. The sustained-release tablet according to claim 1, characterized in that In the sustained-release tablet, the weight ratio of zolpidem tartrate to the sustained-release material is 1:4-6.

3. The sustained-release tablet according to claim 1, characterized in that In the sustained-release tablet, the filler is selected from one or more of microcrystalline cellulose, maltitol, xylitol, glucose, sucrose, lactose, lactose monohydrate or sorbitol.

4. The sustained-release tablet according to claim 3, characterized in that In the sustained-release tablet, the filler is microcrystalline cellulose, maltitol or xylitol.

5. The sustained-release tablet according to claim 1, characterized in that In the sustained-release tablet, the colorant is calcium carbonate, yellow iron oxide, black iron oxide or aluminum chelating agent.

6. The sustained-release tablet according to claim 1, characterized in that In the sustained-release tablet, the lubricant is selected from one or more of magnesium stearate, sodium stearyl fumarate, calcium stearate, polyethylene glycol, sodium benzoate, sucrose fatty acid ester, talc or white beeswax.

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