Trazodone sustained-release tablet and preparation method thereof

Abstract

The present invention provides a trazodone sustained-release tablet and a preparation method thereof. The sustained-release tablet contains trazodone hydrochloride, a waxy sustained-release matrix material, a porogen, a binder, and other pharmaceutical excipients. Trazodone, the waxy matrix sustained-release material, and other necessary excipients are formed into an erodible matrix sustained-release tablet. The preparation process is simple, production reproducibility is good, and the product release is slow and uniform without burst release, which is consistent with the release behavior of original foreign sustained-release preparations. The product of the present invention can be taken once daily, which not only improves patient compliance with treatment but also avoids or reduces large fluctuations in blood drug concentration, thereby reducing toxic side effects and greatly improving the safety and effectiveness of the drug.

Description

Technical Field

[0001] The present invention belongs to the field of pharmaceutical preparations, and in particular relates to a trazodone sustained-release tablet and a preparation method thereof. Background Art

[0002] Depression is a common mental illness characterized by low mood, decreased interest, pessimism, slowed thinking, lack of initiative, self-blame, poor diet and sleep, fear of various illnesses, and general discomfort. In severe cases, suicidal thoughts and behaviors may occur. The etiology of depression includes genetic, biochemical, and psychosocial factors. Biochemical factors primarily refer to the possibility that depression is associated with decreased concentrations of the neurotransmitters serotonin (5-HT) and norepinephrine (NE) in the brain's synaptic cleft.

[0003] Trazodone is a serotonin reuptake inhibitor and 5-HT2 receptor antagonist used for depression with or without anxiety. Unlike other psychotropics, trazodone has no contraindications for glaucoma or urinary disorders. Furthermore, because trazodone lacks anticholinergic activity and does not cause the typical cardiac effects of tricyclic antidepressants, it is more widely used.

[0004] Trazodone hydrochloride is a white to off-white crystalline powder that is soluble in water, poorly soluble in methanol, ethanol, chloroform, and acetonitrile, extremely poorly soluble in acetic anhydride, and practically insoluble in diethyl ether. Its chemical name is 2-{3-[4-(3-chlorophenyl)-1-piperazinyl]propyl}-1,2,4-triazolo[4,3-α]pyridin-3(2H)-one hydrochloride, and its structural formula is shown below:

[0005]

[0006] Conventional trazodone tablets are typically prescribed for twice-daily (BID) or three-times-daily (TID) dosing, which directly results in the drug not being stably maintained in the therapeutic window. High drug concentrations increase the risk of dose-related side effects, while low drug concentrations result in reduced efficacy. Therefore, there is a need for a once-daily trazodone formulation that can achieve and maintain stable effective concentrations for 24 hours or longer, thereby reducing the frequency and severity of side effects. Summary of the Invention

[0007] CN101252932A provides the formula and preparation process for trazodone hydrochloride sustained-release tablets (Oleptro), produced by ANGELINI and marketed in the United States. The tablets primarily utilize a cross-linked high-amylose starch called "CONTRAMID" to control drug release. However, this excipient is not available in China.

[0008] CN102935074A discloses a method for preparing trazodone hydrochloride osmotic pump controlled-release tablets, disclosed by Chengdu Kanghong Pharmaceutical Group Co., Ltd. The controlled-release tablets consist of a tablet core, a semipermeable membrane coating, and a drug-release aperture. This preparation process is complex, requires high equipment requirements, and requires the use of organic solvents, which is not conducive to production reproducibility and environmental friendliness.

[0009] CN105748421A provides a method for preparing a hydrophilic gel matrix tablet of trazodone hydrochloride disclosed by Shenzhen Pan-Gu Pharmaceutical Co., Ltd., which controls the release rate of the drug by adjusting the ratio of HPMC with different viscosities. However, the dosage of the skeleton material used in this solution must be above a certain content to achieve the purpose of controlling drug release. When the skeleton material content is low or the amount of drug is large, the gel layer formed on the surface of the tablet is discontinuous. At the same time, the release of water-soluble drugs leaves "holes" inside the skeleton, which can cause local expansion of the tablet and even act as a disintegrant, so that the drug is released rapidly, but the purpose of slow drug release is not achieved. The system is unstable and prone to sudden release problems. In addition, the wet granulation process uses 80% high-concentration ethanol, which has problems such as environmental protection and explosion-proof modification of workshops.

[0010] In view of the deficiencies in the prior art, the present invention provides a trazodone sustained-release tablet and a preparation method thereof.

[0011] The technical solutions of the present invention are as follows:

[0012] The present invention provides a trazodone sustained-release tablet, comprising components of trazodone or a pharmaceutically acceptable salt thereof, a waxy sustained-release matrix material, a pore-forming agent, a binder, and a lubricant, wherein the ratio of the waxy sustained-release matrix material to the pore-forming agent is 1:(2.5-4.5) w / w. Preferably, the ratio of the waxy sustained-release matrix material to the pore-forming agent is 1:(3-4) w / w.

[0013] Preferably, the sustained-release tablet is composed of the following ingredients by weight: 35% to 70% of trazodone or a pharmaceutically acceptable salt thereof, 6% to 15% of a waxy sustained-release matrix material, 25% to 35% of a porogen, 3% to 10% of a binder, and 0.5% to 2.5% of a lubricant.

[0014] Preferably, the sustained-release tablet is composed of the following ingredients by weight: 49.50% to 51.19% of trazodone hydrochloride, 6.83% to 13.65% of a waxy sustained-release matrix material, 27.30% to 34.13% of a porogen, 3.53% to 9.90% of a binder, and 0.99% to 1.06% of a lubricant.

[0015] Preferably, the waxy sustained-release matrix material is selected from any one or more of beeswax, hydrogenated vegetable oil, synthetic wax, carnauba wax, glyceryl stearate, propylene glycol stearate, and stearyl alcohol, preferably carnauba wax.

[0016] Preferably, the porogen is one or a combination of sucrose, D-mannitol, sorbitol, and xylitol, preferably sucrose.

[0017] Preferably, the binder is selected from one or more of hydroxypropyl cellulose, povidone, hypromellose, and sodium carboxymethyl cellulose; preferably povidone.

[0018] Preferably, the lubricant is selected from one or more combinations of magnesium stearate, talc, sodium stearyl fumarate, and micro-powdered silica gel; preferably magnesium stearate.

[0019] In some exemplary embodiments, the present invention provides a trazodone sustained-release tablet having the following weight ratio composition:

[0020] Trazodone hydrochloride 51.19%

[0021] Carnauba wax 10.24%

[0022] Sucrose 30.72%

[0023] Povidone K30 6.83%

[0024] Magnesium stearate 1.02%.

[0025] In some exemplary embodiments, the present invention provides the following trazodone sustained-release tablet, wherein the sustained-release tablet has the following composition:

[0026] Trazodone hydrochloride 75mg

[0027] Carnauba wax 15 mg

[0028] Sucrose 45 mg

[0029] Povidone K30 10 mg

[0030] Magnesium stearate 1.5 mg.

[0031] In some exemplary embodiments, the present invention provides the following trazodone sustained-release tablet, wherein the composition of the sustained-release tablet is as follows:

[0032] Trazodone hydrochloride 150mg

[0033] Carnauba wax 30 mg

[0034] Sucrose 90 mg

[0035] Povidone K30 20 mg

[0036] Magnesium stearate 3 mg.

[0037] On the other hand, the present invention also provides a method for preparing the trazodone sustained-release tablets, which adopts a fluidized bed melt granulation process and comprises the following steps:

[0038] 1) Grind the API, i.e., trazodone or its pharmaceutically acceptable salt, and pass it through a 60-mesh sieve; and pass the excipients through a 30-mesh sieve;

[0039] 2) Mix all the raw and auxiliary materials except lubricant thoroughly;

[0040] 3) Place the mixed material in 2) in a fluidized bed for boiling preheating, setting the inlet air temperature to 50-70°C and the fan frequency to 5-20Hz;

[0041] 4) Increase the inlet air temperature to 90-100°C and perform melt granulation until the outlet air temperature of the fluidized bed is greater than 80°C, then stop granulation; turn off the heating and quickly cool the granules to room temperature;

[0042] 5) Continue to boil the granules in 4) in the fluidized bed, set the inlet air temperature at 30-50°C and the fan frequency at 20-50 Hz, and spray purified water into the fluidized bed for secondary granulation. Stop granulation when the moisture content of the granules is 1-3%.

[0043] 6) The granules prepared in 5) are sized, and then a lubricant is added for overall mixing, and finally tableting is performed.

[0044] The present invention provides a trazodone sustained-release tablet and a preparation method thereof. Trazodone is combined with a waxy sustained-release matrix material and other necessary excipients to form an erodible matrix sustained-release tablet. The preparation process is simple, production reproducibility is good, and the product releases slowly and evenly without burst release, closely resembling the release behavior of original international sustained-release preparations. The product, taken once daily, not only improves patient compliance with treatment but also avoids or minimizes large fluctuations in blood drug concentrations, thereby reducing toxic side effects and significantly improving the drug's safety and effectiveness. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1-4 The in vitro cumulative release percentage-time curves of the trazodone sustained-release tablets and the original formulation (75 mg) in different media (the media were pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, pH 6.0 phosphate buffer, and pH 6.8 phosphate buffer, respectively);

[0046] Figure 5-8The in vitro cumulative release percentage-time curves of the trazodone sustained-release tablets and the original formulation (150 mg) in Example 2 in different media (the media were pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, pH 6.0 phosphate buffer, and pH 6.8 phosphate buffer, respectively);

[0047] Figure 9 This is the in vitro cumulative release percentage-time curve of the trazodone sustained-release tablets of Example 3-5;

[0048] Figure 10 This is the in vitro cumulative release percentage-time curve of the trazodone sustained-release tablets of Example 6-7;

[0049] Figure 11 This is the in vitro cumulative release percentage-time curve of the trazodone sustained-release tablets of Example 8-9;

[0050] Figure 12 This is the in vitro cumulative release percentage-time curve of the trazodone sustained-release tablets of Example 10-11;

[0051] Figure 13 The properties of the particles after melt granulation in Example 1;

[0052] Figure 14 This is the granule properties after wet granulation in Comparative Example 2. Implementation Method

[0053] The following examples may enable those skilled in the art to more fully understand the present invention, but the present invention is not limited to the scope of the examples. Example 1

[0054] (1) Prescription

[0055] Trazodone hydrochloride 75mg

[0056] Carnauba wax 15 mg

[0057] Sucrose 45 mg

[0058] Povidone K30 10 mg

[0059] Magnesium stearate 1.5 mg

[0060] (2) Preparation process of trazodone sustained-release tablets:

[0061] Crush the raw materials and pass them through a 60-mesh sieve, and pass the excipients through a 30-mesh sieve. Weigh the raw and excipients according to the prescribed amount, and mix them evenly except for magnesium stearate in equal amounts to obtain a premixed powder. Add the premixed powder to a fluidized bed, set the inlet air temperature to 90°C, the fan frequency to 15Hz, and melt granulate. When the outlet air temperature reaches above 80°C, stop heating and keep ventilation to gradually cool the material. When the material temperature drops below 60°C, add purified water by atomization and granulate, controlling the moisture content of the material to 1.0-3.0%. Pass the granules through a 0.8mm sieve, add the prescribed amount of lubricant, mix evenly, and press into tablets using a 12mm×4mm special-shaped die to control the hardness to 3-6kg.

[0062] (3) Determination of the release rate of trazodone sustained-release tablets:

[0063] According to the first method of dissolution and release determination method 0931 of the fourth part of the Chinese Pharmacopoeia 2020 edition, trazodone sustained-release tablets were placed in a dissolution cup, and 900 ml of degassed pH 1.2 hydrochloric acid medium, pH 4.5 acetate buffer, pH 6.0 phosphate buffer and pH 6.8 phosphate buffer were used as release media, respectively. The rotation speed was 100 rpm and the temperature was (37±0.5)°C. 10 ml of release medium was taken at 0.5 h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 16 h, 20 h, and 24 h, respectively. At the same time, an equal amount of fresh medium at the same temperature was supplemented, and the mixture was filtered through a 0.45 µm microporous filter membrane. The filtrate was diluted and detected by high performance liquid chromatography.

[0064] Accurately weigh an appropriate amount of reference substance and determine it in the same way. Calculate its cumulative release percentage using the external standard method.

[0065] HPLC chromatographic conditions are as follows:

[0066] Chromatographic column: C18 column (50*4.6mm, 5μm), column temperature 30℃;

[0067] Flow rate: 1.5 ml / min;

[0068] Detection wavelength: 254nm;

[0069] Mobile phase: pH 6.0 phosphate buffer-acetonitrile (50:50);

[0070] Injection volume: 10 μl;

[0071] Inspection time: 6 minutes.

[0072] Dissolution phenomenon: At the beginning, the tablets rotate at the bottom of the dissolution basket. After 8 hours, they gradually float up along the wall of the basket. At the end of dissolution, they float on the top of the dissolution basket. The appearance of the tablets remains intact without obvious defects, and the dissolution liquid is relatively clear.

[0073]

[0074]

[0075]

[0076] Example 2

[0077] (1) Prescription

[0078] Trazodone hydrochloride 150mg

[0079] Carnauba wax 30 mg

[0080] Sucrose 90 mg

[0081] Povidone K30 20 mg

[0082] Magnesium stearate 3 mg

[0083] (2) Preparation process of trazodone sustained-release tablets:

[0084] Crush the raw materials and pass them through a 60-mesh sieve, and pass the excipients through a 30-mesh sieve. Weigh the raw and excipients according to the prescribed amount, and mix them evenly except for magnesium stearate in equal amounts to obtain a premixed powder. Add the premixed powder to the fluidized bed, set the inlet temperature to 90°C, the fan frequency to 15Hz, and melt granulate. When the outlet temperature reaches above 80°C, stop heating and keep ventilation to gradually cool the material. When the material temperature drops below 60°C, add purified water by atomization and granulate, controlling the moisture content of the material to 1.0-3.0%. Pass the granules through a 0.8mm sieve, add the prescribed amount of lubricant, mix evenly, and press into tablets with a 14mm×6mm special-shaped die to control the hardness to 4-7kg.

[0085] Dissolution phenomenon: At the beginning, the tablets rotate at the bottom of the dissolution basket. After 8 hours, they gradually float up along the wall of the basket. At the end of dissolution, they float on the top of the dissolution basket. The appearance of the tablets remains intact without obvious defects, and the dissolution liquid is relatively clear.

[0086]

[0087]

[0088]

[0089]

[0090] The release rate of the trazodone sustained-release tablets of Example 1 is shown in Tables 1-4 and Figure 1-4(The media were pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, pH 6.0 phosphate buffer and pH 6.8 phosphate buffer, respectively). The release rate of the trazodone sustained-release tablets of Example 2 is shown in Tables 5-8 and Figure 5-8 (The media were, in order, pH 1.2 hydrochloric acid, pH 4.5 acetate buffer, pH 6.0 phosphate buffer, and pH 6.8 phosphate buffer.) Thus, for the homemade samples in Examples 1 and 2, namely, the carnauba wax and sucrose weight ratio was 1:3, the dissolution profiles of the homemade preparations and the original formulation (TRITTICO) in each medium were highly similar, indicating that the release profiles of both strengths of trazodone sustained-release tablets were consistent with those of the original formulation, and both achieved good in vitro sustained-release effects. Dissolution was faster in pH 1.2 hydrochloric acid and pH 4.5 acetate buffer, while dissolution was incomplete after 24 hours in pH 6.8 phosphate buffer. Therefore, pH 6.0 phosphate buffer was used as the key medium to compare the effects of different examples and comparative examples on product properties. Example 3

[0091] Trazodone hydrochloride 75 mg

[0092] Carnauba wax 20 mg

[0093] Sucrose 40 mg

[0094] Povidone K30 10 mg

[0095] Magnesium stearate 1.5 mg Example 4

[0096] Trazodone hydrochloride 75mg

[0097] Carnauba wax 12 mg

[0098] Sucrose 48 mg

[0099] Povidone K30 10 mg

[0100] Magnesium stearate 1.5 mg Example 5

[0101] Trazodone hydrochloride 75mg

[0102] Carnauba wax 10 mg

[0103] Sucrose 50 mg

[0104] Povidone K30 10 mg

[0105] Magnesium stearate 1.5 mg

[0106] The preparation method and dissolution determination method of the trazodone sustained-release tablets of Examples 3-5 are the same as those of Example 1.

[0107] The release rates of the trazodone sustained-release tablets of Examples 3-5 are shown in Table 9 and Figure 9 The release curves show that in Example 3, when the weight ratio of carnauba wax to sucrose was 1:2, drug release was slow, with only 79% released in 24 hours, indicating incomplete release. At the end of dissolution, the tablets still sank to the bottom of the dissolution basket. In Example 4, when the weight ratio of carnauba wax to sucrose was 1:4, drug dissolution was similar to that of the original formulation, with a slightly faster release rate and a similarity factor F2 greater than 50. In Example 5, when the weight ratio of carnauba wax to sucrose was 1:5, drug release was significantly faster, with more than 90% released in 8 hours. At the end of dissolution, there was a significant loss of tablets, and the similarity factor F2 value was less than 50, indicating a dissimilarity with the in vitro dissolution of the original formulation.

[0108] Example 6

[0109] Trazodone hydrochloride 75mg

[0110] Carnauba wax 15 mg

[0111] Sucrose 45 mg

[0112] Povidone K30 15 mg

[0113] Magnesium stearate 1.5 mg Example 7

[0114] Trazodone hydrochloride 75mg

[0115] Carnauba wax 15 mg

[0116] Sucrose 45 mg

[0117] Povidone K30 5 mg

[0118] Magnesium stearate 1.5 mg

[0119] The preparation method and dissolution determination method of the trazodone sustained-release tablets of Examples 6-7 are the same as those of Example 1.

[0120] The release rates of the trazodone sustained-release tablets of Examples 6 and 7 are shown in Table 10 and Figure 10 Comparison of the release curves shows that, in Example 6, increasing the amount of povidone K30 slowed the drug release; in Example 7, decreasing the amount of povidone K30 accelerated the drug release. However, the dissolution phenomenon and dissolution curve remained similar to those of the original formulation, indicating that povidone K30 had little effect on the release rate within this dosage range.

[0121] Example 8

[0122] (1) Prescription

[0123] Trazodone hydrochloride 75mg

[0124] Carnauba wax 15 mg

[0125] Sucrose 45 mg

[0126] Povidone K30 10 mg

[0127] Magnesium stearate 1.5 mg

[0128] (2) Preparation process of trazodone sustained-release tablets:

[0129] Micronize the API to a D90 value of <10μm. Pass the excipients through a 30-mesh sieve. Weigh the raw and excipients according to the prescribed amount and, except for magnesium stearate, mix them uniformly in equal increments to obtain a premixed powder. Add the premixed powder to a fluidized bed, set the inlet air temperature to 90°C and the fan frequency to 15Hz, and melt granulate. When the outlet air temperature reaches above 80°C, stop heating and maintain ventilation to gradually cool the material. When the material temperature drops below 60°C, atomize and add purified water for granulation, controlling the moisture content to 1.0-3.0%. Pass the granules through a 0.8mm sieve, add the prescribed amount of lubricant, mix uniformly, and compress into tablets using a 12mm x 4mm die with a hardness of 3-6 kg. Example 9

[0130] (1) Prescription

[0131] Trazodone hydrochloride 75mg

[0132] Carnauba wax 15 mg

[0133] Sucrose 45 mg

[0134] Povidone K30 10 mg

[0135] Magnesium stearate 1.5 mg

[0136] (2) Preparation process of trazodone sustained-release tablets:

[0137] Crush the API through a 60-mesh sieve and pass the excipients through a 30-mesh sieve. Weigh the raw and excipients according to the prescribed amount and, except for magnesium stearate, mix them uniformly in equal increments to obtain a premixed powder. Add the premixed powder to a fluidized bed, set the inlet air temperature to 90°C and the fan frequency to 15 Hz, and melt granulate. When the outlet air temperature reaches above 80°C, stop heating and maintain ventilation to gradually cool the material. When the material temperature drops below 60°C, remove the material, pass it through a 0.8 mm sieve, and granulate it. Add the prescribed amount of lubricant, mix uniformly, and compress it into tablets using a 12 mm x 4 mm die with a hardness of 3-6 kg.

[0138] The release rates of the trazodone sustained-release tablets of Examples 8 and 9 are shown in Table 11 and Figure 11 , the comparison of particle properties is shown in Table 12, and the comparison of tablet properties is shown in Table 13. From the comparison of release curves, it can be seen that: after the raw material of Example 8 is micronized, the drug release is slightly faster, but there is no obvious difference from the mechanically crushed raw material, indicating that this product is BCS Class I, and the particle size of the raw material has no obvious effect on the release of the preparation. Example 9 did not undergo secondary granulation with purified water, and there was more fine powder and poor particle uniformity. Although the average cumulative release curve did not change significantly, there were large differences between tablets. In addition, due to the high temperature of the melt granulation process and the low moisture content of the particles, the tablets had lower hardness and greater friability. The loss of manual tablet breaking was large, and the friability of the split tablets did not meet the requirements. The above shows that secondary granulation with purified water is a key step that affects the properties of the product.

[0139]

[0140]

[0141] Comparative Example 1

[0142] (1) Prescription

[0143] Trazodone hydrochloride 150mg

[0144] Hypromellose K100M 30 mg

[0145] Lactose 90 mg

[0146] Povidone K30 20 mg

[0147] Magnesium stearate 3 mg

[0148] (2) Preparation process of trazodone sustained-release tablets:

[0149] Weigh the prescribed amount of trazodone hydrochloride, hypromellose (K100M), and lactose and premix. Add 80% ethanol solution as a binder for wet granulation. Granulate the tablets using a 30-mesh wet granulation method. Dry at 55 ± 5°C and granulate the tablets again using a 30-mesh granulation method. Add magnesium stearate and mix thoroughly. Tablets are then compressed and coated. Comparative Example 2

[0150] (1) Prescription

[0151] Trazodone hydrochloride 150mg

[0152] Hypromellose K100M 240 mg

[0153] Lactose 90 mg

[0154] 80% ethanol solution

[0155] Silicon dioxide 3 mg

[0156] Magnesium stearate 8mg

[0157] (2) Preparation process of trazodone sustained-release tablets:

[0158] Weigh the prescribed amount of trazodone hydrochloride, hypromellose (K100M), and lactose and premix. Add 80% ethanol solution as a binder for wet granulation. Granulate the tablets using a 30-mesh wet granulation method. Dry at 55 ± 5°C and granulate the tablets again using a 30-mesh granulation method. Add silicon dioxide and magnesium stearate and mix thoroughly. Tablets are then compressed and coated.

[0159] The release rates of the trazodone sustained-release tablets of Comparative Examples 1 and 2 are shown in Table 14 and Figure 12 . From the comparison of the release curves, it can be seen that in Comparative Example 1, the sustained-release matrix and pore-forming agent were replaced with high-viscosity hypromellose and lactose in equal amounts, resulting in the preparation of trazodone hydrochloride tablets with no sustained-release effect. In Comparative Example 2, the amount of sustained-release matrix (hydroxypropyl methylcellulose K100M) was increased to 48.9% of the weight of the whole tablet to achieve a similar sustained-release effect to the original formulation. However, due to the high viscosity of hypromellose K100M, the uniformity of the prepared particles was still poor even with the use of high-concentration ethanol (see the comparison of the properties of particles prepared by different formulation processes). Figure 13 、 14 ).

[0160]

Claims

1. A trazodone sustained-release tablet, characterized in that: The sustained-release tablet is composed of the following ingredients by weight: 35% to 70% of trazodone or a pharmaceutically acceptable salt thereof, 6% to 15% of a waxy sustained-release matrix material, 25% to 35% of a porogen, 3% to 10% of a binder, and 0.5% to 2.5% of a lubricant; the ratio of the waxy sustained-release matrix material to the porogen is 1:3 w / w; The method for preparing the trazodone sustained-release tablets adopts a fluidized bed melt granulation process, comprising the following steps: 1) Grind the raw material through a 60-mesh sieve and the excipients through a 30-mesh sieve; 2) Mix all the raw and auxiliary materials except lubricant thoroughly; 3) The mixed material in 2) is placed in a fluidized bed for boiling preheating, with the inlet air temperature set at 50-70°C and the fan frequency at 5-20 Hz; 4) Raise the inlet air temperature to 90-100°C and perform melt granulation until the outlet air temperature of the fluidized bed is greater than 80°C, then stop granulation; turn off the heating and quickly cool the granules to room temperature; 5) The granules prepared in step 4) are continued to be boiled in the fluidized bed, with the air inlet temperature set at 30-50°C and the fan frequency at 20-50 Hz, and purified water is sprayed into the fluidized bed for secondary granulation until the moisture content of the granules is 1-3%, at which time granulation is stopped; 6) granulating the granules prepared in 5), adding a lubricant and mixing, and finally tableting; The waxy skeleton material is carnauba wax; The porogen is sucrose; The adhesive is povidone; The lubricant is magnesium stearate.

2. The sustained-release tablet according to claim 1, characterized in that The sustained-release tablet is composed of the following components by weight: 49.50% to 51.19% of trazodone hydrochloride, 6.83% to 13.65% of a waxy sustained-release skeleton material, 27.30% to 34.13% of a porogen, 3.53% to 9.90% of a binder, and 0.99% to 1.06% of a lubricant.

3. The sustained-release tablet according to claim 1, characterized in that The weight ratio of the trazodone sustained-release tablets is as follows:

4. The sustained-release tablet according to claim 1, characterized in that Trazodone extended-release tablets are composed of:

5. The sustained-release tablet according to claim 1, characterized in that Trazodone extended-release tablets are composed of:

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