Preparation method of trazodone hydrochloride sustained release tablet

Abstract

The invention provides a preparation method of a trazodone hydrochloride sustained release tablet, and belongs to the technical field of medicine processing. The preparation method comprises the following steps: (1) mixing a trazodone hydrochloride raw material medicine, cane sugar, povidone and carnauba wax to obtain a mixture; (2) preparing the mixture into molten particles by adopting a hot-melt extrusion technology; and (3) cooling and sieving the molten particles, adding magnesium stearate, uniformly mixing, and tabletting to obtain the trazodone hydrochloride sustained-release tablet. The trazodone hydrochloride sustained release tablet comprises the following components in percentage by mass: 45%-55% of trazodone hydrochloride raw material medicine, 15%-35% of cane sugar, 5%-15% of povidone, 5%-15% of carnauba wax and 1%-5% of magnesium stearate. According to the invention, a hot melt extrusion technology is adopted, so that the raw materials can be highly dispersed within a short heating time, the loss of the raw materials is avoided, the production cost is reduced, and commercialized production is facilitated.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical processing, and in particular relates to a method for preparing a trazodone hydrochloride sustained-release tablet. Background Art

[0002] Depression is a common mental disorder characterized by a significant and persistent low mood, accompanied by a loss of interest and pleasure, which often affects an individual's work, study and social functions. Depression may be caused by a variety of factors, including genetic, biological, psychosocial and environmental factors. The clinical symptom criteria are continuous attacks for more than two weeks. Typical symptoms include low mood, insomnia or excessive sleep, changes in appetite, fatigue, inferiority or worthlessness, excessive self-blame, difficulty concentrating, etc. Severe cases may experience symptoms such as hallucinations and delusions, and even suicidal thoughts or behaviors.

[0003] Trazodone hydrochloride is mainly used to treat depression and anxiety disorders accompanied by depressive symptoms, as well as mood disorders after withdrawal of drug addicts. Dosage: The dosage should start from a low dose, gradually increase the dose and observe the treatment response. Trazodone is a tetracyclic atypical antidepressant that can selectively antagonize the reuptake of 5-hydroxytryptamine (5-HT) and has a weak effect of preventing the reuptake of norepinephrine (NA), but has no effect on dopamine (DA), histamine and acetylcholine, and does not inhibit the activity of monoamine oxidase inhibitors (MAO) in the brain. In addition, this product also has an antagonistic effect on 5-HT2A receptors or 5-HT2C receptors. The 5-HT2 receptor located in the presynaptic membrane is an autoreceptor that plays a negative feedback regulatory role on the release of 5-HT; this product also increases the release of 5-HT by inhibiting negative feedback regulation, thereby achieving an antidepressant effect. This product also has central sedative and slight muscle relaxant effects, but no antispasmodic and central excitatory effects. It can improve sleep, significantly shorten the latency period of falling asleep in patients with depression, prolong overall sleep time, and improve sleep quality.

[0004] Trazodone hydrochloride is a triazole pyridine derivative, and its structure is 2-[3-[4-(3-chlorophenyl)-1-piperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridine-3(2H)-hydrochloric acid, which is a white, odorless, solid powder that is easily soluble in water. CN101252932 provides the formula and preparation process of trazodone hydrochloride sustained-release tablets produced by Angelini, which is listed in the United States. It mainly uses a sustained-release excipient cross-linked high-amylose starch (trade name ) and a small amount of adhesive hydroxypropyl methylcellulose and other materials to control the release of drugs. At present, there is no pharmaceutical grade cross-linked high-amylose starch (trade name ) can be used. It is reported that the listed product has a low release in the intestinal environment above pH 6.8, and the 24h release is not thorough enough, and accumulation in the body may occur. CN102935074A provides a preparation method of a trazodone hydrochloride osmotic pump controlled-release tablet disclosed by Chengdu Kanghong Pharmaceutical Group Co., Ltd., and the controlled-release tablet comprises a tablet core, a semipermeable membrane coating and a drug release hole. Trazodone hydrochloride osmotic pump controlled-release tablets can better control the drug release rate, but its preparation process is relatively complex, and the equipment configuration and performance requirements are high. The industrialization difficulty is relatively large, which easily leads to uneven drug quality and poor reproducibility, which is not conducive to the production and promotion of sustained-release drugs. CN116549406A provides a trazodone hydrochloride sustained-release tablet disclosed by Beijing Fengke Ruitai Pharmaceutical Technology Co., Ltd., which is directly pressed by mixing with a lubricant through fluidized bed melt granulation, and Brazilian palm wax and polyoxyethylene are sustained-release materials. The direct compression process has high requirements on the particle size of the material, and the fluidized bed hot melt granulation has high energy consumption. There is material loss in the granulation process, which easily leads to the risk of over-feeding and high production costs.

[0005] Generally, the preparation of oral solid sustained-release preparations mainly involves adding sustained-release materials to form a gel skeleton, or film coating such as sustained-release pellets, sustained-release pumps, etc. However, the trazodone hydrochloride sustained-release tablets obtained by these methods are too large, basically exceeding 500 mg / tablet, and the sustained-release pellets and sustained-release pumps have high technical requirements, which will affect the compliance of medication; fluidized bed hot melting will cause the loss of raw materials, increase costs, and bring about feeding risks. Therefore, a preparation method of trazodone hydrochloride sustained-release tablets with low production cost and simple process is urgently needed. Summary of the invention

[0006] In view of this, the object of the present invention is to provide a method for preparing a trazodone hydrochloride sustained-release tablet. The present invention adopts hot melt extrusion technology to achieve the purpose of highly dispersing the raw materials in a shorter heating time, and the present invention uses hot melt extrusion granulation, which avoids raw material loss compared to fluidized bed hot melt granulation, reduces production costs, and is conducive to commercial production.

[0007] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0008] The present invention provides a method for preparing a trazodone hydrochloride sustained-release tablet, comprising the following steps:

[0009] (1) mixing trazodone hydrochloride raw material, sucrose, povidone and carnauba wax to obtain a mixture;

[0010] (2) preparing the mixture into molten particles by hot melt extrusion technology;

[0011] (3) cooling the molten granules, sieving, adding magnesium stearate, mixing, and tableting to obtain trazodone hydrochloride sustained-release tablets;

[0012] The trazodone hydrochloride sustained-release tablet comprises the following components in percentage by mass: 45% to 55% of trazodone hydrochloride raw material, 15% to 35% of sucrose, 5% to 15% of povidone, 5% to 15% of carnauba wax and 1% to 5% of magnesium stearate.

[0013] Preferably, the hot melt extrusion is set with five temperature sections, wherein the temperature of the first section is 70-100°C, the temperature of the second section is 100-120°C, the temperature of the third section is 130-150°C, the temperature of the fourth section is 130-150°C, and the temperature of the fifth section is 150-170°C.

[0014] Preferably, the constant time of each temperature section is 20 to 40 minutes.

[0015] Preferably, the rotation speed of the hot melt extrusion is set to a step-by-step increase mode, and the rotation speed increases step-by-step from 20 to 40 rpm to 60 to 80 rpm.

[0016] Preferably, the stepwise increase is to increase the speed by 20 revolutions after each speed is maintained for 5 to 15 minutes.

[0017] Preferably, the cooling temperature is ≤35°C.

[0018] Preferably, the mesh size of the sieving is 40 to 80 meshes.

[0019] Preferably, the tablet weight difference of the trazodone hydrochloride sustained-release tablets is controlled within ±5%.

[0020] Preferably, after obtaining the trazodone hydrochloride sustained-release tablets in step (3), the method further comprises the step of aluminum-plastic packaging the obtained trazodone hydrochloride sustained-release tablets.

[0021] The present invention also provides the preparation method for obtaining the trazodone hydrochloride sustained-release tablets.

[0022] Compared with the prior art, the present invention has the following beneficial effects: the present invention provides a method for preparing a trazodone hydrochloride sustained-release tablet, which adopts hot melt extrusion technology, has a short heating time, can achieve a highly dispersed effect, has a simple process, good reproducibility, high production efficiency, and is easy to operate. The trazodone hydrochloride sustained-release tablet prepared by the method of the present invention has no sudden release phenomenon, can release the drug steadily over a long period of time, thereby improving the solubility and in vivo bioavailability of the drug, and reducing the frequency of administration. Compared with processes such as fluidized bed melt granulation, the method of the present invention reduces the loss of raw materials, reduces production costs, can be produced in a closed manner, reduces production costs, and is conducive to commercial production. DETAILED DESCRIPTION

[0023] The present invention provides a method for preparing a trazodone hydrochloride sustained-release tablet, comprising the following steps:

[0024] (1) mixing trazodone hydrochloride raw material, sucrose, povidone and carnauba wax to obtain a mixture;

[0025] (2) preparing the mixture into molten particles by hot melt extrusion technology;

[0026] (3) cooling the molten granules, sieving, adding magnesium stearate, mixing, and tableting to obtain trazodone hydrochloride sustained-release tablets;

[0027] The trazodone hydrochloride sustained-release tablet comprises the following components in percentage by mass: 45% to 55% of trazodone hydrochloride raw material, 15% to 35% of sucrose, 5% to 15% of povidone, 5% to 15% of carnauba wax and 1% to 5% of magnesium stearate.

[0028] In the present invention, the mass percentage of the trazodone hydrochloride raw material in the trazodone hydrochloride sustained-release tablet is preferably 48% to 53%, more preferably 50%, the mass percentage of sucrose is preferably 25% to 33%, more preferably 30%, the mass percentage of povidone is preferably 8% to 10%, more preferably 9%, the mass percentage of carnauba wax is preferably 8% to 10%, more preferably 9%, and the mass percentage of magnesium stearate is preferably 1.5% to 3%, more preferably 2%.

[0029] In the present invention, trazodone hydrochloride bulk drug, sucrose, povidone and carnauba wax are mixed to obtain a mixture, wherein sucrose is a filler, povidone is a carrier binder, and carnauba wax is a release retardant.

[0030] In the present invention, the mixture is prepared into molten particles by hot melt extrusion technology; the mixture is added into a hot melt extruder to obtain molten particles; the hot melt extrusion is set with five temperature sections, wherein the temperature of the first section is 70-100°C, preferably 75-90°C, and more preferably 80°C, the temperature of the second section is 100-120°C, preferably 105-115°C, and more preferably 110°C, the temperature of the third section is 130-150°C, preferably 135-145°C, and more preferably 140°C, the temperature of the fourth section is 130-150°C, preferably 135-145°C, and more preferably 140°C, the temperature of the fifth section is 150-170°C, preferably 155-165°C, and more preferably 160℃; the constant time of each temperature section is 20-40min, preferably 25-35min, and more preferably 30min; the speed of the hot melt extruder is set to a step-by-step increase mode, the speed increases step by step from 20-40rpm to 60-80rpm, preferably from 25-35rpm to 65-75rpm, and more preferably from 30rpm to 70rpm, the step-by-step increase is to increase 20 revolutions after each speed is maintained for 5-15min, preferably maintained for 7-12min, and more preferably maintained for 10min, the discharge port temperature of the hot melt extruder is 110-130℃, preferably 115-125℃, and more preferably 120℃.

[0031] In the present invention, the molten particles are cooled, sieved, magnesium stearate is added, mixed, and tableted to obtain trazodone hydrochloride sustained-release tablets; the cooling temperature is ≤35°C; the mesh size of the sieve is 40 to 80 meshes, preferably 50 to 70 meshes, and more preferably 60 meshes; the magnesium stearate is a lubricant; the pre-compression pressure of the tableting is 2 to 8 mm, preferably 4 to 6 mm, the main compression pressure of the tableting is 2 to 7 mm, preferably 3 to 5 mm, and the feed speed during tableting is 5 to The filling speed is 20rpm, preferably 10-15rpm, and more preferably 12rpm. The filling depth is 3-6mm. The weight of the obtained trazodone hydrochloride sustained-release tablets is 285-315mg. The weight difference of the trazodone hydrochloride sustained-release tablets is controlled within ±5%. The hardness of the trazodone hydrochloride sustained-release tablets is 30-90N, preferably 50-70N, and more preferably 60N. The friability of the trazodone hydrochloride sustained-release tablets is ≤1%, and the moisture content of the trazodone hydrochloride sustained-release tablets is ≤5.0%.

[0032] In the present invention, after the trazodone hydrochloride sustained-release tablets are obtained in step (3), the step further includes an aluminum-plastic packaging step for the obtained trazodone hydrochloride sustained-release tablets, wherein the aluminum-plastic packaging adopts tablet blister sealing, the blister sealing has a molding temperature of 60 to 120° C., a heat sealing temperature of 140 to 200° C., and a blister sealing speed of 20 to 40 rpm.

[0033] The present invention also provides the preparation method for obtaining the trazodone hydrochloride sustained-release tablets.

[0034] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0035] Example 1

[0036] Preparation method of trazodone hydrochloride sustained-release tablets:

[0037] (1) Weigh 150.0 g of trazodone hydrochloride API, 90.0 g of sucrose, 27.0 g of povidone and 27.0 g of carnauba wax, and mix them uniformly to obtain a mixture;

[0038] (2) The temperatures in the hot melt extruder are set as follows: feed port - first section temperature is 80°C - second section temperature is 110°C - third section temperature is 140°C - fourth section temperature is 140°C - fifth section temperature is 160°C - discharge port (orifice plate) temperature is 120°C, each temperature is kept constant for preheating for 30 min, the mixture is added, and the speed is set to increase step by step from 30 rpm to 70 rpm, i.e. 30 rpm-50 rpm-70 rpm, and each speed is maintained for 10 min. To ensure that the feeding speed is compatible with the speed, the feeding speed is set to increase step by step from 5 kg / h to 15 kg / h, i.e. 5 kg / h-10 kg / h-15 kg / h, to obtain molten particles.

[0039] (3) The molten granules were cooled to below 35° C., passed through a 60-mesh sieve, and mixed evenly with 6.0 g of magnesium stearate. The granules were compressed on a tablet press with a pre-compression pressure of 4.5 mm, a main compression pressure of 4.0 mm, a feed starting speed of 12 rpm, and a filling depth of 3.9 mm to obtain trazodone hydrochloride sustained-release tablets.

[0040] The average tablet weight of the obtained trazodone hydrochloride sustained-release tablets was 300 mg, the tablet weight difference was ±1.5%, the hardness range of the trazodone hydrochloride sustained-release tablets was 60±10N, the friability was 0.26%, and the moisture content was 1.2%.

[0041] Example 2

[0042] Preparation method of trazodone hydrochloride sustained-release tablets:

[0043] (1) Weigh 150.0 g of trazodone hydrochloride API, 72.0 g of sucrose, 27.0 g of povidone and 45.0 g of carnauba wax, and mix them uniformly to obtain a mixture;

[0044] (2) The temperatures in the hot melt extruder are set as follows: feed port - first section temperature is 80°C - second section temperature is 110°C - third section temperature is 140°C - fourth section temperature is 140°C - fifth section temperature is 160°C - discharge port (orifice plate) temperature is 120°C, each temperature is kept constant for preheating for 30 min, the mixture is added, and the speed is set to increase step by step from 30 rpm to 70 rpm, i.e. 30 rpm-50 rpm-70 rpm, and each speed is maintained for 10 min. To ensure that the feeding speed is compatible with the speed, the feeding speed is set to increase step by step from 5 kg / h to 15 kg / h, i.e. 5 kg / h-10 kg / h-15 kg / h, to obtain molten particles.

[0045] (3) The molten granules were cooled to below 35° C., passed through a 60-mesh sieve, and mixed evenly with 6.0 g of magnesium stearate. The granules were compressed on a tablet press with a pre-compression pressure of 4.5 mm, a main compression pressure of 4.0 mm, a feed starting speed of 12 rpm, and a filling depth of 3.9 mm to obtain trazodone hydrochloride sustained-release tablets.

[0046] The average tablet weight of the obtained trazodone hydrochloride sustained-release tablets was 300 mg, the tablet weight difference was ±1.5%, the hardness range of the trazodone hydrochloride sustained-release tablets was 60±10N, the friability was 0.31%, and the moisture content was 1.0%.

[0047] Example 3

[0048] Preparation method of trazodone hydrochloride sustained-release tablets:

[0049] (1) Weigh 150.0 g of trazodone hydrochloride API, 102.0 g of sucrose, 27.0 g of povidone and 15.0 g of carnauba wax, and mix them uniformly to obtain a mixture;

[0050] (2) The temperatures in the hot melt extruder are set as follows: feed port - first section temperature is 80°C - second section temperature is 110°C - third section temperature is 140°C - fourth section temperature is 140°C - fifth section temperature is 160°C - discharge port (orifice plate) temperature is 120°C, each temperature is kept constant for preheating for 30 min, the mixture is added, and the speed is set to increase step by step from 30 rpm to 70 rpm, i.e. 30 rpm-50 rpm-70 rpm, and each speed is maintained for 10 min. To ensure that the feeding speed is compatible with the speed, the feeding speed is set to increase step by step from 5 kg / h to 15 kg / h, i.e. 5 kg / h-10 kg / h-15 kg / h, to obtain molten particles.

[0051] (3) The molten granules were cooled to below 35° C., passed through a 60-mesh sieve, and mixed evenly with 6.0 g of magnesium stearate. The granules were compressed on a tablet press with a pre-compression pressure of 4.5 mm, a main compression pressure of 4.0 mm, a feed starting speed of 12 rpm, and a filling depth of 3.9 mm to obtain trazodone hydrochloride sustained-release tablets.

[0052] The average tablet weight of the obtained trazodone hydrochloride sustained-release tablets was 300 mg, the tablet weight difference was ±1.5%, the hardness range of the trazodone hydrochloride sustained-release tablets was 60±10N, the friability was 0.22%, and the moisture content was 0.9%.

[0053] Comparative Example 1

[0054] Preparation method of trazodone hydrochloride sustained-release tablets:

[0055] (1) Weigh 150.0 g of trazodone hydrochloride API and 27.0 g of carnauba wax, mix them evenly to obtain a mixture;

[0056] (2) The temperatures in the hot melt extruder are set as follows: feed port - first section temperature is 80°C - second section temperature is 110°C - third section temperature is 140°C - fourth section temperature is 140°C - fifth section temperature is 160°C - discharge port (orifice plate) temperature is 120°C, each temperature is kept constant for preheating for 30 min, the mixture is added, and the speed is set to increase step by step from 30 rpm to 70 rpm, i.e. 30 rpm-50 rpm-70 rpm, and each speed is maintained for 10 min. To ensure that the feeding speed is compatible with the speed, the feeding speed is set to increase step by step from 5 kg / h to 15 kg / h, i.e. 5 kg / h-10 kg / h-15 kg / h, to obtain molten particles.

[0057] (3) The molten granules were cooled to below 35° C. and passed through a 60-mesh sieve. The granules were mixed evenly with 27.0 g of povidone, 90.0 g of sucrose, and 6.0 g of magnesium stearate. The granules were compressed on a tablet press with a pre-compression pressure of 4.5 mm, a main compression pressure of 4.0 mm, a feed speed of 12 rpm, and a filling depth of 3.9 mm to obtain trazodone hydrochloride sustained-release tablets.

[0058] Comparative Example 2

[0059] The trazodone hydrochloride sustained-release tablets were obtained by the preparation method of Example 1, except that the temperatures of the hot melt extruder were: the feed port - the first section temperature was 35°C - the second section temperature was 50°C - the third section temperature was 60°C - the fourth section temperature was 80°C - the fifth section temperature was 80°C - the discharge port (orifice plate) temperature was 80°C.

[0060] Comparative Example 3

[0061] The trazodone hydrochloride sustained-release tablets were obtained by the preparation method of Example 1, except that the temperatures of the hot melt extruder were: feed port - first section temperature was 100°C - second section temperature was 130°C - third section temperature was 160°C - fourth section temperature was 160°C - fifth section temperature was 180°C - discharge port (orifice plate) temperature was 160°C.

[0062] Comparative Example 4

[0063] Trazodone hydrochloride sustained-release tablets were obtained by the preparation method of Example 1, except that the rotation speed was set to 20 rpm and the feeding rate was set to 3 kg / h.

[0064] Comparative Example 5

[0065] Trazodone hydrochloride sustained-release tablets were obtained by the preparation method of Example 1, except that the rotation speed was set to 90 rpm and the feeding rate was set to 20 kg / h.

[0066] Comparative Example 6

[0067] Preparation method of trazodone hydrochloride sustained-release tablets:

[0068] (1) Weigh 150.0 g of trazodone hydrochloride API, 90.0 g of sucrose, 27.0 g of povidone and 27.0 g of carnauba wax, and mix them evenly to obtain a mixture;

[0069] (2) putting the mixture into a fluidized bed and granulating with purified water, setting the temperature of the fluidized bed to 80-120° C., setting the inlet air temperature to 50-60° C. during granulation, setting the material temperature to 30-60° C., setting the air volume to 1000 rpm-2000 rpm, setting the inlet air temperature to 60-80° C. during drying, and obtaining granules with a moisture content of 1.0%-3.0%;

[0070] (3) The granules were sized (1.2 mm mesh size, 100-300 rpm granulation speed), mixed evenly with 6.0 g of magnesium stearate, and compressed on a tablet press with a pre-compression pressure of 4.5 mm, a main compression pressure of 4.0 mm, a feed starting speed of 12 rpm, and a filling depth of 3.9 mm to obtain trazodone hydrochloride sustained-release tablets.

[0071] Experimental example

[0072] The trazodone hydrochloride sustained-release tablets obtained by the methods described in Examples 1 to 3 and Comparative Examples 1 to 6 were used as samples, and the trazodone hydrochloride sustained-release tablets purchased from Guangzhou Tonghui Pharmaceutical Co., Ltd. were used as samples. For the reference preparation, an in vitro release test was carried out according to the second method of dissolution and release determination method in Part 4 of the Pharmacopoeia 2020 edition, general chapter 0931, paddle method, 100 rpm, 900 mL of dissolution cup medium (pH 6.8 phosphate buffer), and sampling and testing at 0.5 h, 1 h, 2 h, 3 h, 4 h, 6 h, 8 h, 10 h, and 12 h. The similarity, yield and content of the sample were compared with the reference preparation. The results are shown in Tables 1 to 3.

[0073] Yield (%) = mass of molten particles (g) / mass of mixture (g) * 100.

[0074] Table 1 Comparison of in vitro release of trazodone hydrochloride API in different samples with reference

[0075]

[0076]

[0077] Note: F2 is the similarity factor. FDA and EMEA stipulate that if the F2 value of the dissolution curve of the sample and the reference preparation is not less than 50, the two are considered similar.

[0078] Table 2 Comparison of the yield of trazodone hydrochloride mixed granules before total mixing in different samples

[0079]

[0080] Table 3 Comparison of content of different trazodone hydrochloride sustained-release tablets samples

[0081]

[0082] As can be seen from Table 1, the dissolution of the trazodone hydrochloride sustained-release tablets obtained by the method of Example 1 of the present invention is highly consistent with the reference preparation, and the preparation process is smooth and the preparation time is reasonable. After stability inspection and comparison of the samples prepared by the method provided by the present invention, it is found that the stability change trend of the samples obtained by the method of the present invention is comparable to that of the reference preparation, and the quality is consistent. When the amount of carnauba wax is adjusted to 5% to 15%, the in vitro release requirements can be met. As can be seen from Comparative Examples 1 to 5, changing the order of material addition, the temperature of each section of hot melt extrusion, the rotation speed and the feeding speed will affect the dissolution of the obtained preparation. The temperature of the hot melt extrusion process is controlled at 70-100°C in the first stage, 100-120°C in the second stage, 130-150°C in the third stage, 130-150°C in the fourth stage, 150-170°C in the fifth stage, and 110-130°C in the discharge port. The rotation speed is set to increase step by step from 30rpm to 70rpm, and the feeding speed is set to increase step by step from 5kg / h to 15kg / h. The prepared trazodone hydrochloride mixed granules are sieved or granulated and then pressed to obtain a trazodone hydrochloride sustained-release tablet similar to the reference preparation, without a sudden release phenomenon, and can release the drug stably over a long period of time. Compared with the fluidized bed melt granulation process (Comparative Example 6), the operation is simpler, the loss is small, and the cost is low.

[0083] It can be seen from the results of the content of trazodone hydrochloride sustained-release tablets in Table 3 that the content of trazodone hydrochloride in Comparative Example 6 is lower than that in the reference preparation and the examples, and it is speculated that there is a loss of raw materials in the preparation process; combined with Table 2, it can be obtained that the yield of Comparative Example 6 is low. If this process requires excessive feeding, there is a risk and the production cost is high.

[0084] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a trazodone hydrochloride sustained-release tablet, characterized in that: The following steps are involved: (1) mixing trazodone hydrochloride raw material, sucrose, povidone and carnauba wax to obtain a mixture; (2) preparing the mixture into molten particles by hot melt extrusion technology; (3) cooling the molten granules, sieving, adding magnesium stearate, mixing, and tableting to obtain trazodone hydrochloride sustained-release tablets; The trazodone hydrochloride sustained-release tablet comprises the following components in percentage by mass: 45% to 55% of trazodone hydrochloride raw material, 15% to 35% of sucrose, 5% to 15% of povidone, 5% to 15% of carnauba wax and 1% to 5% of magnesium stearate.

2. The preparation method according to claim 1, characterized in that: The hot melt extrusion is set with five temperature sections, wherein the temperature of the first section is 70-100°C, the temperature of the second section is 100-120°C, the temperature of the third section is 130-150°C, the temperature of the fourth section is 130-150°C, and the temperature of the fifth section is 150-170°C.

3. The preparation method according to claim 2, characterized in that: The constant time of each temperature section is 20 to 40 minutes.

4. The preparation method according to claim 3, characterized in that: The rotation speed of the hot melt extrusion is set in a step-by-step increase mode, and the rotation speed increases step-by-step from 20 to 40 rpm to 60 to 80 rpm.

5. The preparation method according to claim 4, characterized in that: The stepwise increase is that each speed is maintained for 5 to 15 minutes and then increased by 20 revolutions.

6. The preparation method according to claim 1, characterized in that: The cooling temperature is ≤35°C.

7. The preparation method according to claim 1, characterized in that: The mesh number of the sieving is 40 to 80 meshes.

8. The preparation method according to claim 1, characterized in that: The tablet weight difference of the trazodone hydrochloride sustained-release tablet is controlled within ±5%.

9. The preparation method according to claim 1, characterized in that: After the trazodone hydrochloride sustained-release tablets are obtained in step (3), the method further comprises the step of aluminum-plastic packaging the obtained trazodone hydrochloride sustained-release tablets.

10. Trazodone hydrochloride sustained-release tablets obtained by the preparation method according to any one of claims 1 to 9.

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