Milnacipran hydrochloride film coated tablet and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to milnacipran hydrochloride film-coated tablets and a preparation method thereof. The invention provides a milnacipran hydrochloride film-coated tablet which is prepared by wet granulation and comprises the following components in percentage by weight: 20-30% of milnacipran hydrochloride, 39-76% of filler, 0.5-15% of disintegrating agent, 0-5% of adhesive, 1-5% of lubricant and 1-6% of film coating premix, wherein the disintegrating agent is internally added and contains colloidal silicon dioxide. The milnacipran hydrochloride film-coated tablet has good uniformity, dissolution rate and storage stability, and the preparation method is short in time consumption, simple to operate and easy to realize large-scale production.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pharmaceutical preparations, and particularly relates to a minaprine hydrochloride film-coated tablet and a preparation method thereof. BACKGROUND

[0002] The minaprine hydrochloride tablet is mainly used for treating depression, and its mechanism is to control the specific inhibition of 5-hydroxytryptamine and norepinephrine reuptake. The mechanism of its effect on the depressive state of depression is considered to be the specific inhibition of serotonin and norepinephrine reuptake. At present, there are minaprine hydrochloride capsules and minaprine hydrochloride ordinary tablets on the domestic market. Since the main drug minaprine hydrochloride accounts for a small proportion in the minaprine hydrochloride tablet, about 25% of the prescription proportion, and the raw material itself is prone to agglomeration, the difficulty of uniform mixing in the sample preparation process is increased, which causes the unqualified mixing uniformity in the preparation process, and finally leads to a great increase in the risk of unqualified content uniformity of the sample.

[0003] Due to the special structure of minaprine hydrochloride, it is very sensitive to moisture. In a humid environment, minaprine hydrochloride is prone to produce impurity B (structure as shown in formula I), which eventually greatly increases the risk of unqualified related substances of the sample. In a relatively dry condition, it is also easy to be adsorbed on the surface of the stainless steel equipment used for preparation, causing material loss and reducing the yield of finished products. Moreover, the adsorption amount on the equipment will be different with the progress of the tabletting process, and the adsorption amount in the early stage of tabletting is obviously higher than that in the later stage, which causes the drug content of the tablet in the early stage to be low and the loss to increase. Moreover, due to its special structure, minaprine hydrochloride is usually used with anhydrous calcium hydrogen phosphate as a filler to improve the stability of minaprine hydrochloride. However, anhydrous calcium hydrogen phosphate has a large density, and in the dissolution process, the main drug is prone to deposit under the anhydrous calcium hydrogen phosphate, causing the accumulation of the main drug, which is easy to cause unqualified dissolution.

[0004]

[0005] Formula I One study used a direct powder compression process to prepare immediate-release formulations of mirtazapine hydrochloride. This involved using a vibrating sieve to disperse the raw materials and excipients before mixing them with magnesium stearate and compressing them into tablets. However, this method resulted in poor material flowability because the vibrating sieve couldn't effectively mix the materials, leading to inconsistent mixing uniformity and ultimately a higher rate of non-compliance in product content uniformity. Furthermore, this process, which compresses mirtazapine hydrochloride with excipients to obtain unmixed tablets, utilized a significant amount of stainless steel equipment in the pretreatment, mixing, and compression processes. The lack of wet or dry granulation of the raw materials and excipients prevented tight bonding, resulting in substantial adsorption of the raw materials on the stainless steel equipment and a significantly reduced tablet yield. Another study employed a direct powder compression process: first, the raw materials and a portion of the excipients were added in equal increments and mixed multiple times in a three-dimensional mixer; then, the mixture was dispersed twice in a granulator and passed through a 30-mesh sieve; the remaining excipients were then passed through 30-mesh sieves and repeatedly added in equal increments in a three-dimensional mixer; finally, a lubricant was added and mixed in a three-dimensional mixer. This process ensures the uniformity of mirtazapine hydrochloride tablet content, but the operation is relatively cumbersome. Errors are prone to occur in the weighing and incremental addition processes, making it unsuitable for large-scale production. Furthermore, this process also involves the use of a significant amount of stainless steel equipment in the pretreatment, mixing, and tableting processes, and the lack of granulation for raw materials and excipients prevents them from binding tightly together. This results in substantial adsorption of raw materials on the stainless steel equipment, significantly reducing the tableting yield. In addition, most mirtazapine hydrochloride formulations currently use a wet granulation process, which easily introduces large amounts of aqueous solution, potentially increasing the content of impurity B during the preparation and storage of mirtazapine hydrochloride tablets, thus affecting product quality. Summary of the Invention

[0006] In view of this, the present invention provides a mirtazapine hydrochloride film-coated tablet and its preparation method. The mirtazapine hydrochloride film-coated tablet has good uniformity, dissolution and storage stability. Moreover, the preparation method requires a short mixing time, is simple to operate, and is easy to scale up for production.

[0007] To solve the above technical problems, the present invention provides a mirtazapine hydrochloride film-coated tablet, comprising, by weight percentage: 20%-30% mirtazapine hydrochloride, 39%-76% filler, 0.5%-15% disintegrant, 0%-5% binder, 1%-5% lubricant, and 1%-6% film-coating premix; The disintegrant is a mixture of at least one of calcium carboxymethyl cellulose, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl cellulose, or croscarmellose sodium carboxymethyl cellulose with colloidal silica.

[0008] The colloidal silica in the mirtazapine hydrochloride film-coated tablets provided by this invention is an internally added disintegrant, ensuring that the sample maintains a good state during the granulation process.

[0009] Preferably, the mass percentage of colloidal silica in the disintegrant is 0.5%-10%.

[0010] More preferably, the colloidal silica accounts for 1%-5% of the total mass.

[0011] Colloidal silica, used as a disintegrant, enables mirtazapine hydrochloride granules to disintegrate uniformly during dissolution, thus facilitating absorption. Furthermore, since the active pharmaceutical ingredient tends to become sticky after absorbing moisture, colloidal silica provides excellent dispersion and wetting, ensuring uniform particle size in the prepared soft material.

[0012] Preferably, the filler is selected from at least one of anhydrous dicalcium phosphate, mannitol, microcrystalline cellulose, anhydrous lactose, and pregelatinized starch.

[0013] More preferably, the filler is at least one of anhydrous dicalcium phosphate, microcrystalline cellulose, and anhydrous lactose.

[0014] When anhydrous dicalcium phosphate is used as a filler, its high density can cause the active pharmaceutical ingredient (API) to deposit beneath it during dissolution, leading to API accumulation and resulting in substandard dissolution rates. Using colloidal silica as an internal disintegrant avoids this issue of API accumulation causing dissolution rate failures in dissolution testing.

[0015] Preferably, the adhesive is selected from at least one of pregelatinized starch, dextrin, polyvinylpyrrolidone, hydroxypropyl cellulose and hydroxypropyl methylcellulose.

[0016] More preferably, the adhesive is hydroxypropyl methylcellulose.

[0017] Preferably, the lubricant is selected from at least one of magnesium stearate, calcium stearate, glyceryl monostearate, sodium stearate fumarate, and talc.

[0018] More preferably, the lubricant is magnesium stearate.

[0019] The present invention also provides a method for preparing the above-mentioned mirtazapine hydrochloride film-coated tablets, the steps of which include: The active pharmaceutical ingredient mirtazapine hydrochloride was premixed with filler, disintegrant and binder in a wet granulator according to the prescription amount, and a wetting agent was added in the prescription amount to prepare a soft mass, which was then dried to obtain mirtazapine hydrochloride granules. The mirtazapine hydrochloride granules were granulated and mixed with a lubricant in a mixer, and then compressed and coated to obtain mirtazapine hydrochloride film-coated tablets.

[0020] The method for preparing mirtazapine hydrochloride film-coated tablets provided by this invention uses a wet granulation mixer for premixing during the premixing process. This method has a short mixing time, is simple to operate, has good mixing uniformity, and greatly reduces production time and costs, making it suitable for large-scale production.

[0021] Preferably, the wetting agent is ethanol or an ethanol solution.

[0022] Preferably, the ethanol solution has a mass concentration of 60% to 95%.

[0023] Preferably, the moisture content of the mirtazapine hydrochloride granules is ≤0.5%.

[0024] Milnacipran hydrochloride is unstable in moisture and constitutes a small proportion in milnacipran hydrochloride film-coated tablets, making it prone to issues with non-uniformity of related substances and their content. This invention employs wet granulation, enabling rapid and uniform dispersion of the raw material in the excipients, achieving excellent mixing. Milnacipran hydrochloride and excipients are premixed in a wet granulator, and then a soft material is prepared using ethanol of varying concentrations as a wetting agent. This allows the soft material to rapidly lose moisture during drying, resulting in milnacipran hydrochloride granules with a moisture content not exceeding 0.5%, ensuring sample stability during storage and reducing impurity generation.

[0025] This invention utilizes colloidal silica as an internal disintegrant in the wet granulation process. This not only yields a well-formed soft mass but also effectively solves the problem of unsatisfactory dissolution rates caused by the accumulation of anhydrous dicalcium phosphate when the filler is anhydrous dicalcium phosphate. Furthermore, the wet granulation process of this invention results in a tighter bond between the raw materials and excipients in the mirtazapine hydrochloride granules, avoiding the low tablet content caused by raw material adsorption in the stainless steel hopper and large tray during the initial stage of tableting. The resulting formulation exhibits good uniformity in content. Using a certain concentration of ethanol as a wetting agent instead of purified water ensures stable storage of the resulting formulation, reduces the generation of impurity B during storage, and provides a favorable guarantee for formulation quality. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to specific embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

[0027] It will be understood by those skilled in the art that, unless otherwise defined, all terms used herein (including technical and scientific terms) have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. It should also be understood that terms such as those defined in general dictionaries should be understood to have the meaning consistent with their meaning in the context of the prior art, and should not be interpreted in an idealized or overly formal sense unless specifically defined.

[0028] Milnacipran hydrochloride is sensitive to water. Wet granulation can easily lead to the formation of impurity B, affecting drug quality. However, direct compression of the powder causes a large amount of milnacipran hydrochloride to be adsorbed onto the surface of stainless steel equipment during preparation, reducing tablet uniformity, lowering the yield of qualified products, and causing material loss. Furthermore, the commonly used filler, anhydrous calcium phosphate, can easily reduce the dissolution rate of the resulting milnacipran hydrochloride tablets due to density differences.

[0029] In view of this, the present invention provides a mirtazapine hydrochloride film-coated tablet and its preparation method. The mirtazapine hydrochloride film-coated tablet uses colloidal silica as an internal disintegrant, which effectively solves the problem of unqualified dissolution rate caused by the accumulation of anhydrous calcium hydrogen phosphate during the dissolution test. Moreover, the preparation method adopts wet granulation and uses a certain concentration of ethanol solution as a wetting agent instead of water, which ensures the uniformity of the tablets and their stability during storage.

[0030] Unless otherwise specified, the raw materials, reagents and equipment used in this invention are all conventional commercially available reagents and equipment.

[0031] Example 1 This embodiment provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following prescription:

[0032] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Anhydrous calcium hydrogen phosphate, mirtazapine hydrochloride, calcium carboxymethyl cellulose, hydroxypropyl methyl cellulose and colloidal silica were placed in a GHL-100 wet granulator in sequence. The stirring (150 rpm) and chopping (2400 rpm) were started and premixed for 3 minutes. The liquid inlet on the top cover of the wet granulator was opened, and the stirring (150 rpm) and chopping (1200 rpm) were started. The prescribed amount of ethanol was added. After the ethanol was added, the soft material was prepared. The total preparation time of the soft material was 120 seconds.

[0033] The prepared soft material was placed in a DFL-30 multi-functional granulation and coating machine, the air inlet temperature was controlled at 70±5℃, the induced draft fan frequency was set at 45±5Hz, and it was dried for 10 minutes. The moisture content was determined by the drying method to be ≤0.5%, and mirtazapine hydrochloride granules were obtained.

[0034] Install a 24-mesh sieve on a YK-160 oscillating pellet mill, add the obtained mirtazapine hydrochloride granules to the hopper of the oscillating pellet mill for granulation, and then mix them together with magnesium stearate in a mixer for 10 minutes to obtain a total mixture. After compression, the mixture is coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0035] Example 2 This embodiment provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following prescription:

[0036] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Microcrystalline cellulose, mirtazapine hydrochloride, calcium carboxymethyl cellulose, hydroxypropyl methyl cellulose and colloidal silica were placed in a GHL-100 wet granulator in sequence. The stirring (150 rpm) and chopping (2400 rpm) were started and premixed for 3 minutes. The liquid inlet on the top cover of the wet granulator was opened, and the stirring (150 rpm) and chopping (1200 rpm) were started. The prescribed amount of 90% ethanol was added, and the soft material was prepared. The total preparation time for the soft material was 120 seconds.

[0037] The prepared soft material was placed in a DFL-30 multi-functional granulation and coating machine, the air inlet temperature was controlled at 75±5℃, the induced draft fan frequency was set at 45±5Hz, and it was dried for 10 minutes. The moisture content was determined by the drying method to be ≤0.5%, and mirtazapine hydrochloride granules were obtained.

[0038] Install a 24-mesh sieve on a YK-160 oscillating pellet mill, add the obtained mirtazapine hydrochloride granules to the hopper of the oscillating pellet mill for granulation, and then mix them together with magnesium stearate in a mixer for 10 minutes to obtain a total mixture. After compression, the mixture is coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0039] Example 3 This embodiment provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following prescription:

[0040] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Anhydrous lactose, mirtazapine hydrochloride, calcium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and colloidal silica were placed in a GHL-100 wet granulator in sequence. The stirring (150 rpm) and chopping (2400 rpm) were started, and the mixture was premixed for 3 minutes. The liquid inlet on the top cover of the wet granulator was opened, and the stirring (150 rpm) and chopping (1200 rpm) were started. Then, the prescribed amount of 80% ethanol was added, and the mixture was continued to be made into a soft mass. The total time for making the soft mass was 120 seconds.

[0041] The prepared soft material was placed in a DFL-30 multi-functional granulation and coating machine, the air inlet temperature was controlled at 75±5℃, the induced draft fan frequency was set at 48±2Hz, and the drying time was 12min. The moisture content was determined by the drying method to be ≤0.5%, and mirtazapine hydrochloride granules were obtained.

[0042] Install a 24-mesh sieve on a YK-160 oscillating pellet mill, add the obtained mirtazapine hydrochloride granules to the hopper of the oscillating pellet mill for granulation, and then mix them together with magnesium stearate in a mixer for 10 minutes to obtain a total mixture. After compression, the mixture is coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0043] Comparative Example 1 This comparative example provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following formulation:

[0044] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Anhydrous calcium hydrogen phosphate, mirtazapine hydrochloride, calcium carboxymethyl cellulose, hydroxypropyl methyl cellulose, and colloidal silica were placed in a GHL-100 wet granulator in sequence. The stirring (150 rpm) and chopping (2400 rpm) were started, and the mixture was premixed for 3 minutes. The liquid inlet on the top cover of the wet granulator was opened, and the stirring (150 rpm) and chopping (1200 rpm) were started. The prescribed amount of purified water was added, and the mixture was then prepared into a soft mass. The total preparation time for the soft mass was 120 seconds.

[0045] The prepared soft material was placed in a DFL-30 multi-functional granulation and coating machine, the air inlet temperature was controlled at 70±5℃, the induced draft fan frequency was set at 45±5Hz, and it was dried for 10 minutes. The moisture content was determined by the drying method to be ≤0.5%, and mirtazapine hydrochloride granules were obtained.

[0046] Install a 24-mesh sieve on a YK-160 oscillating pellet mill, add the obtained mirtazapine hydrochloride granules to the hopper of the oscillating pellet mill for granulation, and then mix them together with magnesium stearate in a mixer for 10 minutes to obtain a total mixture. After compression, the mixture is coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0047] Comparative Example 2 This comparative example provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following formulation:

[0048] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Anhydrous calcium hydrogen phosphate, mirtazapine hydrochloride, calcium carboxymethyl cellulose and hydroxypropyl methylcellulose were placed in a GHL-100 wet granulator in sequence. The stirring (150 rpm) and chopping (2400 rpm) were turned on and premixed for 3 minutes. The liquid inlet on the top cover of the wet granulator was opened, and the stirring (150 rpm) and chopping (1200 rpm) were turned on. The prescribed amount of ethanol was added. After the ethanol was added, the soft material was prepared. The total preparation time of the soft material was 120 seconds.

[0049] The prepared soft material was placed in a DFL-30 multi-functional granulation and coating machine, the air inlet temperature was controlled at 70±5℃, the induced draft fan frequency was set at 45±5Hz, and it was dried for 10 minutes. The moisture content was determined by the drying method to be ≤0.5%, and mirtazapine hydrochloride granules were obtained.

[0050] Install a 24-mesh sieve on a YK-160 oscillating granulator, add the obtained mirtazapine hydrochloride granules and the prescribed amount of colloidal silica to the hopper of the oscillating granulator for granulation, and then mix them together with magnesium stearate in a mixer for 10 minutes to obtain a total mixture. After compression, the mixture is coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0051] Comparative Example 3 This comparative example provides a mirtazapine hydrochloride film-coated tablet (200,000 tablets), with the following formulation:

[0052] The preparation steps for this mirtazapine hydrochloride film-coated tablet are as follows: Anhydrous calcium hydrogen phosphate, mirtazapine hydrochloride, calcium carboxymethyl cellulose and hydroxypropyl methyl cellulose were placed in a mixer and mixed for 30 minutes to obtain a mixture.

[0053] Install a 40-mesh sieve on the YK-160 gyratory pellet mill, add the resulting mixture into the hopper of the gyratory pellet mill and disperse it 3 times, then continue to mix it in the mixer for 30 minutes.

[0054] Magnesium stearate was added to the mixer and mixed with the material for 10 minutes to obtain a total mixture. The mixture was then compressed into tablets and coated in a high-efficiency coating machine to obtain mirtazapine hydrochloride film-coated tablets.

[0055] Test Example 1 The content of total mixed materials in the preparation process of mirtazapine hydrochloride film-coated tablets obtained in Examples 1-3 and Comparative Examples 1-3 was determined, and the results are shown in Table 1.

[0056] Table 1 Results of determination of total mixture content and uniformity

[0057] As shown in Table 1, the total content of the mixed materials in Examples 1-3 and Comparative Examples 1-2 did not change significantly, and the premixing uniformity (RSD) was good, indicating that the raw materials and excipients were effectively mixed. However, in Comparative Example 3, due to the use of a direct powder mixing process (without wet granulation), the active pharmaceutical ingredient was adsorbed more on the stainless steel equipment, resulting in a lower content and poorer mixing effect, leading to a poorer premixing uniformity (RSD). Therefore, it can be concluded that using wet granulation for premixing can achieve better mixing results with virtually no raw material loss.

[0058] Test Example 2 The content and content uniformity of the uncoated mirtazapine hydrochloride film-coated tablets (before coating) prepared in Examples 1-3 and Comparative Examples 1-3 were measured, and the results are shown in Table 2.

[0059] Table 2. Content and content uniformity results of samples in the early stage of tableting.

[0060] As shown in Table 2, in the initial stage of tableting, the content of the unprocessed tablets obtained in Examples 1-3 and Comparative Examples 1-2 did not change significantly, and the content uniformity of the unprocessed tablets was good. However, in Comparative Example 3, due to the use of direct powder compression, even after content conversion in the total mixing process, the adsorption of the active pharmaceutical ingredient by the stainless steel hopper and large pan of the tablet press resulted in a lower content of unprocessed tablets in the initial stage of tableting, and the content uniformity was unqualified, leading to raw material waste (the content and content uniformity of the first 10,000 unprocessed tablets in Comparative Example 3 were unqualified), increasing the risk caused by the low content. Therefore, using ethanol of different concentrations in a wet granulation machine to prepare soft materials can effectively reduce the adsorption of the active pharmaceutical ingredient by the stainless steel equipment, improve the content uniformity of the unprocessed tablets obtained in the early stage of tableting, and save raw materials.

[0061] Test Example 3 Twenty tablets were randomly selected from the mirtazapine hydrochloride film-coated tablets prepared in Examples 1-3 and Comparative Examples 1-3, respectively, for dissolution testing. The results are shown in Table 3.

[0062] Table 3 Dissolution test data for multiple tablets (unit: %)

[0063] As can be seen from Table 3, the dissolution rates of Examples 1-3 and Comparative Example 1 are all within the limit range, while the dissolution rate of most tablets in Comparative Example 2 is unqualified. This indicates that when using the wet granulation process, adding colloidal silica as an internal disintegrant rather than as an external glidant can make the tablets have a better dissolution effect.

[0064] Test Example 4 The mirtazapine hydrochloride film-coated tablets prepared in Examples 1-3 and Comparative Examples 1-3 were packaged and placed in an accelerated stability test chamber (temperature: 40℃, relative humidity: 75%). Samples were taken and tested for relevant substances at 1 month, 2 months, 3 months and 6 months of accelerated testing, and compared with 0 days. The comparison results are shown in Table 4.

[0065] Table 4. Detection data of related substances under accelerated conditions (main degradation impurities: impurity B) (%)

[0066] As can be seen from Table 4, the growth trend of related substance impurity B in the mirtazapine hydrochloride film-coated tablets obtained in Examples 1-3 and Comparative Examples 2-3 was basically the same during the 6-month accelerated reaction. However, the content of related substance impurity B in the mirtazapine hydrochloride film-coated tablets obtained in Comparative Example 1, which used water as a wetting agent, was unqualified after 6 months of accelerated reaction. This indicates that using ethanol or a certain concentration of ethanol solution as a wetting agent during wet granulation can effectively improve the storage stability of tablets and reduce the growth of impurity B.

[0067] In summary, the formulation and preparation method provided by this invention can effectively avoid the problems of unqualified mixing and reduced content in the preparation of mirtazapine hydrochloride film-coated tablets. At the same time, it solves the problems of unqualified dissolution caused by the accumulation of anhydrous dicalcium phosphate when using anhydrous dicalcium phosphate as a filler, as well as the increase or even exceeding of limits of related substance impurity B during storage.

[0068] The above description is merely a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A mirtazapine hydrochloride film-coated tablet, characterized in that, According to the weight percentage, it includes: 20%-30% mirtazapine hydrochloride, 39%-76% filler, 0.5%-15% disintegrant, 0%-5% binder, 1%-5% lubricant, and 1%-6% film coating premix; The disintegrant is a mixture of at least one of calcium carboxymethyl cellulose, sodium carboxymethyl starch, low-substituted hydroxypropyl methyl cellulose, or croscarmellose sodium carboxymethyl cellulose with colloidal silica.

2. The mirtazapine hydrochloride film-coated tablet as described in claim 1, characterized in that, The disintegrant contains colloidal silica at a mass ratio of 0.5%-10%.

3. The mirtazapine hydrochloride film-coated tablet as described in claim 1, characterized in that, The filler is selected from at least one of anhydrous dicalcium phosphate, mannitol, microcrystalline cellulose, anhydrous lactose, and pregelatinized starch.

4. The mirtazapine hydrochloride film-coated tablet as described in claim 1, characterized in that, The adhesive is selected from at least one of pregelatinized starch, dextrin, polyvinylpyrrolidone, hydroxypropyl cellulose, and hydroxypropyl methylcellulose.

5. The mirtazapine hydrochloride film-coated tablet as described in any one of claims 1 to 4, characterized in that, The lubricant is selected from at least one of magnesium stearate, calcium stearate, glyceryl monostearate, sodium stearate fumarate, and talc.

6. The method for preparing mirtazapine hydrochloride film-coated tablets according to any one of claims 1 to 5, characterized in that, step include: The active pharmaceutical ingredient mirtazapine hydrochloride was premixed with filler, disintegrant and binder in a wet granulator according to the prescription amount, and a wetting agent was added in the prescription amount to prepare a soft mass, which was then dried to obtain mirtazapine hydrochloride granules. The mirtazapine hydrochloride granules were granulated and mixed with a lubricant in a mixer, and then compressed and coated to obtain mirtazapine hydrochloride film-coated tablets.

7. The method for preparing mirtazapine hydrochloride film-coated tablets as described in claim 6, characterized in that, The wetting agent is ethanol or an ethanol solution.

8. The method for preparing mirtazapine hydrochloride film-coated tablets as described in claim 7, characterized in that, The ethanol solution has a mass concentration of 60% to 95%.

9. The method for preparing mirtazapine hydrochloride film-coated tablets as described in claim 7, characterized in that, The moisture content of the mirtazapine hydrochloride granules is ≤0.5%.

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