Preparation method of three-dimensional B tablet

Abstract

The invention discloses a preparation method of a three-dimensional tablet B. According to the preparation method, firstly, vitamin B12 is wetted and subjected to wet pre-granulation, and then the vitamin B12 is mixed with vitamin B1 and vitamin B6, so that on one hand, the flowability of granules during total mixing can be remarkably improved, and the uniformity is improved; on the other hand, through the set raw material proportion, pores formed by filling large particles with small particles during tabletting can further improve the uniformity, it is guaranteed that the content and content uniformity of all vitamins meet the requirements, then the preparation efficiency and quality of the three-dimensional B tablets are effectively improved, and the three-dimensional B tablets are suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the technical field of drug preparation, and in particular to a method for preparing a three-dimensional B-sheet. Background Art

[0002] With the improvement of people's living standards and the enhancement of health awareness, the structure of pharmaceutical products has changed significantly, from the traditional "treating existing diseases" to the more comprehensive and forward-looking "preventing diseases before they occur". This change reflects consumers' higher pursuit of health management and their emphasis on preventing diseases and improving the quality of life. Optimizing life products has become another key category in pharmacies. Among them, vitamin products, as the main representative of this trend, are of self-evident importance. Three-dimensional B tablets are a kind of vitamins (B 1 100mg, B 6 100mg, B 12 0.2mg) of multivitamin tablets, vitamin B1 and vitamin B6 are often used together in clinical practice to supplement B 1 , B 6 Due to the deficiency of B vitamins, neurological diseases require large doses of multiple B vitamins for treatment. The three-dimensional B compound oral preparation can not only enhance the therapeutic effect, but also is easy to use and has no toxic side effects. It is most suitable for patients who use large doses of vitamins for a long time, especially those who are not convenient for injection. It is also suitable for the treatment of mononeuropathy or multiple peripheral neuritis and neuralgia caused by different causes.

[0003] Vitamin B 1 (Vitamin B 1 ,VB 1 ) participates in sugar metabolism in the form of coenzymes, which can maintain the normal functions of the heart, nerves and digestive system, and can also inhibit the activity of cholinesterase. When it is deficient, the activity of cholinesterase increases, affecting gastrointestinal and myocardial functions and causing various neuroinflammations. 6 (Vitamin B 6 ,VB 6 ) is converted into pyridoxal phosphate in red blood cells and acts as a coenzyme for various metabolic functions of proteins, carbohydrates, and lipids. It can also promote the synthesis of γ-aminobutyric acid and 5-hydroxytryptamine in tissues and participate in lipid metabolism. When it is deficient, a variety of neurological symptoms will occur, mainly central nervous system excitement, convulsions, ataxia, limb weakness, etc. Vitamin B 12 (Vitamin B 12 ,VB 12 ) participates in methyl conversion and folic acid metabolism in the body, promotes the conversion of methylmalonic acid into succinic acid, and then participates in the tricarboxylic acid cycle. The clinical symptoms caused by deficiency are mainly anemia, fatigue, constipation, loss of appetite, dementia, forgetfulness, etc. It can also cause the occurrence of cardiovascular and cerebrovascular diseases, so early diagnosis and prevention are very necessary.

[0004] However, 3D B tablets are a compound preparation of three vitamins. In the preparation process of traditional 3D B tablets, vitamin B 12 With vitamin B 1 , Vitamin B 6 The preparation process is complicated and causes a high probability of sample contamination and loss. 12 The amount added is small. During large-scale production in the workshop, trace amounts of materials are often transferred into plastic bags and mixed manually, which is time-consuming and labor-intensive, and the mixing effect is poor. The product often has uneven content and is frequently reworked. 12 It is easily oxidized and deteriorated by light, high temperature, etc., and is easily decomposed under strong acid and strong alkali conditions. Its stability is one of the key factors affecting the quality stability of three-dimensional B-sheets.

[0005] Therefore, it is urgent to develop a three-dimensional B-sheet production process that is simple in preparation and can ensure product quality and stability. Summary of the invention

[0006] The present invention aims to provide a method for preparing a three-dimensional B-sheet, which is used to solve the defects of the prior art three-dimensional B-sheet preparation process, such as complex process, low efficiency, large loss and uneven content.

[0007] In view of this, the scheme of the present invention is:

[0008] A method for preparing a three-dimensional B-sheet, comprising the following steps:

[0009] S1. Add corn starch, sucrose, tartaric acid and dextrin into a wet granulator and mix well. Add vitamin B 12 Wetting agent, mixed granulation, drying and granulation to obtain vitamin B 12 Particles;

[0010] S2. Weigh the dose of vitamin B 1 , Vitamin B 6 , magnesium stearate and silicon dioxide, and add the vitamin B 12 The particles are mixed to obtain three-dimensional B particles;

[0011] S3. The three-dimensional B particles are compressed and coated to obtain three-dimensional B tablets;

[0012] By weight, the above components are: Vitamin B 1 100-200 servings, Vitamin B 6 100-200 servings, Vitamin B 120.1-0.5 parts, corn starch 80-200 parts, sucrose 10-50 parts, dextrin 80-100 parts, tartaric acid 10-20 parts, magnesium stearate 0.5-2 parts, silicon dioxide 0.5-5 parts, wetting agent 60-100 parts.

[0013] Furthermore, the three-dimensional B tablets are composed of the following components by weight: vitamin B 1 100-110 servings, Vitamin B 6 100-110 servings, Vitamin B 12 0.227 parts, corn starch 100 parts, sucrose 30 parts, dextrin 80 parts, tartaric acid 10 parts, magnesium stearate 1 part, silicon dioxide 3 parts, wetting agent 60 parts.

[0014] More preferably, the three-dimensional B tablets contain, by weight, vitamin B 1 100 servings, Vitamin B 6 100 servings, Vitamin B 12 0.227 parts, corn starch 100 parts, sucrose 30 parts, dextrin 80 parts, tartaric acid 10 parts, magnesium stearate 1 part, silicon dioxide 3 parts, wetting agent 60 parts.

[0015] Preferably, the wetting agent is an ethanol aqueous solution with a volume ratio of 1:1, and the ethanol is 95% ethanol.

[0016] Furthermore, the sucrose particle size is 80 mesh.

[0017] Furthermore, in step S1, the drying process controls the moisture content of the particles to be ≤5%;

[0018] And / or, the drying process is set with an inlet air temperature of 70-80°C, an outlet air temperature of 35-40°C, and a duration of 15-20 minutes.

[0019] Furthermore, in step S1, the granulation process controls the vitamin B 12 The particle size is less than 1.5 mm.

[0020] Furthermore, in step S1, the mixing time in the wet granulator is 5 to 10 minutes, and the mixture containing vitamin B 12 After adding the wetting agent, adjust the speed and mix for 5 to 10 minutes to granulate.

[0021] Furthermore, in step S2, the mixing process uses a V-shaped high-efficiency mixer.

[0022] Another object of the present invention is to provide a three-dimensional B tablet obtained by the preparation method described above, wherein the vitamin B 12 The content uniformity is less than 10.

[0023] Furthermore, the vitamin B in the three-dimensional B tablet 1 , Vitamin B 6 The content uniformity is less than 10.

[0024] Compared with the prior art, the present invention has the following beneficial effects:

[0025] The preparation method of the present invention firstly 12 Wetting and wet pre-granulation, then with vitamin B 1 , Vitamin B 6 Mixing can significantly improve the fluidity and uniformity of particles during total mixing on the one hand, and on the other hand, the set raw material ratio can make it possible to fill the pores formed by large particles with small particles during tableting to further improve the uniformity, thereby ensuring that the content and uniformity of each vitamin meet the requirements, thereby effectively improving the preparation efficiency and quality of three-dimensional B tablets, and making them suitable for industrial production.

[0026] The present invention introduces tartaric acid as an antioxidant and pH regulator to maintain the pH of the granules at 4.5-5.5, i.e., vitamin B 12 The most stable state, accelerated test and long-term test results show that vitamin B 12 The properties are stable and no unqualified cases occur, which proves the effectiveness of the method. The addition method is simple, which is conducive to industrial implementation.

[0027] The production process provided by the present invention only undergoes one granulation process, which reduces the production process, improves production efficiency, and effectively reduces labor costs. DETAILED DESCRIPTION

[0028] The technical solution of the present invention will be clearly and completely described and verified in conjunction with the preferred embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0029] If the manufacturer of reagents or instruments is not specified in the examples, conventional products can be purchased from the market. If specific conditions are not specified, conventional conditions or conditions recommended by the manufacturer can be used.

[0030] Example 1

[0031] A method for preparing a three-dimensional B-sheet, the method comprising:

[0032] prescription:

[0033]

[0034] Preparation process:

[0035] S1. Weigh vitamin B according to production instructions 12 Raw materials, tartaric acid, corn starch, sucrose (powder 80 mesh) and dextrin, vitamin B 12、 Tartaric acid was dispersed and dissolved in a 50% ethanol aqueous solution as a wetting agent. Corn starch, sucrose and dextrin were added to a wet granulator and mixed for 5 minutes. 12 of wetting agent, adjust the speed and mix for 10 minutes to granulate;

[0036] S2. Add the wet granules obtained above to a boiling dryer and dry for 20 minutes. Set the air inlet temperature to 75°C and the air outlet temperature to 38°C. Detect the moisture content of the granules to ≤5%. Put the dried granules into a mobile granulator and use a φ1.5mm round stainless steel screen to granulate to obtain vitamin B. 12 Particles;

[0037] S3. Vitamin B obtained in step S2 12 The particles are transferred to a V-type high-efficiency mixer, and tartaric acid and vitamin B are weighed according to the production instructions. 1 Raw materials, vitamin B 6 The raw materials, magnesium stearate and silicon dioxide were placed in a V-type high-efficiency mixer, the speed was set to 10 rpm, and the total mixing time was 15 min;

[0038] S4. Pressing the mixed granules into tablets;

[0039] S5. Prepare coating solution with coating powder, ethanol and purified water, place the plain tablet in a coating pan and preheat for 30 minutes, set the tablet core temperature to 30℃~40℃, set the air inlet temperature to 80℃~85℃, set the coating pan speed to 2~6rpm, and carry out coating. The coating weight gain is 4%. After coating, ventilate and cool to obtain the three-dimensional B tablet to be packaged.

[0040] Embodiment 2-6

[0041] A method for preparing a three-dimensional B-sheet, the prescription is as follows:

[0042]

[0043] The preparation process of the three-dimensional B-sheet in the above-mentioned embodiments 2-6 is the same as that in embodiment 1.

[0044] Comparative Example 1

[0045] A method for preparing a three-dimensional B-sheet, the method comprising:

[0046] prescription:

[0047]

[0048] Preparation process:

[0049] S1. Weigh vitamin B according to production instructions 12 Raw materials, vitamin B 1 Raw materials, vitamin B 6 Raw materials, corn starch, sucrose (powder 80 mesh), dextrin, tartaric acid, vitamin B 12 With Vitamin B 1 , Vitamin B 6 The raw materials were mixed evenly in equal increments, put into the wet granulation pot together with the other materials and dry mixed for 5 minutes, then the wetting agent was added to adjust the speed and mix for 10 minutes to granulate;

[0050] S2. Add the wet granules obtained above to a boiling dryer and dry for 20 minutes, set the air inlet temperature to 70°C, the air outlet temperature to 40°C, control the moisture content of the granules to ≤5%, release the dried granules and place them in a mobile granulator. Round stainless steel sieve to get the vitamin B 1 , Vitamin B 6 , Vitamin B 12 of particles;

[0051] S3. The dry granules obtained in step S2 are transferred to a V-type high-efficiency mixer, and the external materials magnesium stearate and silicon dioxide are added to the dry granules, the speed is set to 10 rpm, and mixed for 15 min;

[0052] S4. Pressing the mixed granules into tablets;

[0053] S5. The coating method is the same as in Example 1.

[0054] Comparative Example 2

[0055] Compared with Example 1, in this example, vitamin B12, vitamin B1 and vitamin B6 are granulated separately, and the prescription is as follows:

[0056]

[0057] Preparation process:

[0058] S1. Weigh vitamin B according to production instructions 1 Raw materials, vitamin B 6 The raw materials, corn starch, dextrin, sucrose and tartaric acid were put into a wet granulator and dry mixed for 5 minutes, 5% corn starch slurry was added for wet granulation, and wet granulation was performed through a 8mm×8mm square hole sieve. The wet granules were transferred to a boiling dryer and dried for 20 minutes. The inlet air temperature was set at 70°C and the outlet air temperature was set at 40°C. The moisture content of the granules was controlled to be ≤5%. The dried granules were released and placed in a mobile granulator, and granulated with a φ1.5mm round stainless steel sieve to obtain granules 1;

[0059] S2. Weigh vitamin B according to production instructions 12 The raw materials, corn starch, sucrose and microcrystalline cellulose were put into a wet granulator and dry mixed for 5 minutes. An ethanol aqueous solution wetting agent was added for wet granulation. The wet granules were passed through a 8mm×8mm square hole sieve for wet granulation. The wet granules were transferred to a boiling dryer and dried for 20 minutes. The inlet air temperature was set at 70°C and the outlet air temperature was set at 40°C. The moisture content of the granules was controlled to be ≤5%. The dried granules were released and placed in a mobile granulator. The granules were granulated with a φ1.5mm round stainless steel sieve to obtain granules 2.

[0060] S3. Transfer granules 1 and 2 to a V-type high-efficiency mixer, add magnesium stearate and silicon dioxide to the dry granules, set the speed to 10 rpm, and mix for 15 min;

[0061] S4. Pressing the mixed granules into tablets;

[0062] S5. The coating method is the same as in Example 1.

[0063] Comparative Example 3

[0064] The method for preparing a three-dimensional B-sheet is different from that of Example 1 in that tartaric acid is not added to the prescription, and the other components and preparation process are the same.

[0065] Comparative Example 4

[0066] The preparation method of a three-dimensional B-sheet is different from that of Example 1 in that the amount of tartaric acid added is 20 parts, and the other components and preparation process are the same.

[0067] Detection and evaluation of related indicators of three-dimensional B-film

[0068] 1. Liquidity test

[0069] The method for determining the fluidity of the 3D B tablet mixed granules is as follows:

[0070] (1) Angle of repose

[0071] Using the fixed cone method, the three-dimensional B total mixed particles are gently and evenly dropped into the center of the disk to form a cone of powder. When the material falls freely from the inclined edge of the powder along the edge of the disk, the feeding is stopped and the repose angle is measured with a protractor.

[0072] Although there are some differences in the qualitative evaluation of powder flow behavior using the angle of repose, a large number of studies still recommend the use of the Carr classification method to evaluate and grade fluidity, as shown in Table 1. Studies have shown that prescriptions with an angle of repose in the range of 40° to 50° can meet the requirements of powder fluidity in the production process. When the angle of repose exceeds 50°, the powder fluidity is difficult to meet production needs.

[0073] Table 1: Powder flowability and corresponding angle of repose

[0074]

[0075]

[0076] (2) Hausner

[0077] Weigh about 100 g of the 3D B total mixed granules accurately, add them gently into a 250 mL measuring cylinder, measure the volume, and calculate the bulk density (ρ B ) ; Install the measuring cylinder on the tapping tester and tap it several times to measure the final volume until the volume remains unchanged, calculate and record the tap density ρ T .

[0078] The calculation formula is as follows:

[0079] Hausner ratio = ρ T / ρ B

[0080] Table 2 Liquidity evaluation based on Hausner ratio

[0081]

[0082] (3) Flow rate

[0083] Take 50 g of the material in the example and gently put it into the triangular funnel, open the lower outlet slide door, and measure the time required for all the material to flow out.

[0084] The fluidity of the mixed particles of Example 1 and Comparative Examples 1-2 was compared, and the results are shown in Table 3.

[0085] Table 3:

[0086]

[0087] It can be seen from the data in Table 3 that compared with its comparative examples 1 and 2, the angle of repose and Hausner ratio of Example 1 are smaller, and the flow velocity is faster. Therefore, in Example 1, only VB 12 Wet granulation was performed, and VB 1 and VB 6 The granules prepared by the method of directly mixing as an external material without granulation have better fluidity and are conducive to large-scale tableting.

[0088] 2. Assay and content uniformity testing

[0089] 2.1 The contents and content uniformity of the three main components in the total mixed granules and plain tablets of Example 1 and Comparative Examples 1-2 were tested. The results are shown in Tables 4 and 5.

[0090] Table 4: Content and uniformity of the three main components in the total mixed granules (n=15)

[0091]

[0092] Table 5: Content and uniformity of the three main components in plain tablets (n=15)

[0093]

[0094] From the results in Table 4 and Table 5, it can be seen that Example 1 and direct mixing granulation (Comparative Example 1), VB 1 ,VB 6 and VB 12 The content and uniformity of the samples obtained by granulation (Comparative Example 2) meet the requirements. 12 The content is low, close to the lower limit of the qualified content range (85% to 115%). The quantitative index of content uniformity is calculated according to the formula: A+1.8S≤20 is qualified, where:

[0095] A=|"100-mean"|, S is the standard deviation.

[0096] Example 1 Preparation of VB in the total mixed granules and plain tablets 12 The content uniformity of the two samples VB was 7.11 and 9.71, which was much less than 20. 12 The content uniformity was 19.04 and 18.29, respectively, and the VB 1 ,VB 6 and VB 12 Separately granulated samples VB 12 The content uniformity was 17.96 and 16.79 respectively, close to the upper limit of 20.0. The slightest carelessness during the mixing process would lead to VB 12 Unqualified content uniformity. In comparison, the sample prepared in Example 1 has a greater advantage in the control of "content uniformity", so it is meaningful to improve this process.

[0097] 2.2 Vitamin B 12 Granules, Vitamin B 1 Raw materials and vitamin B 6 The influence of the weight ratio of raw materials on the content and content uniformity was analyzed by comparing the content and content uniformity of the three main components in the total mixed particles and plain tablets of the above Example 1 and Examples 2-6. The results are shown in Table 6.

[0098] Table 6: Content and uniformity test results after adjusting the weight ratio of the three raw materials

[0099]

[0100] From the results in Table 7, we can see that when VB 12 Particles: VB 1 Raw material: VB 6 When the raw materials = 22.0227:10:10, the total mixing and tableting were carried out, and the content and content uniformity of the obtained three-dimensional B tablet samples met the requirements. The reason is that VB 12 Particles and VB 1 ,VB 6 The raw materials are maintained in dynamic balance and the VB 1 ,VB 6 Small particles of raw materials to fill VB 12 The pores formed by large particles allow large and small particles to be evenly distributed, improving the uniformity of the content of each main component.

[0101] Because a small amount of VB is added to the three-dimensional B film 12 In actual production, these trace amounts of VB 12 It is difficult to mix evenly with other raw materials and auxiliary materials, resulting in the problem of unqualified product content uniformity. The present invention firstly 12 Separate wet granulation, then VB 1 ,VB 6 Add together with external materials in a certain proportion. Make VB 12 The particle size is increased, and then mixed with a certain proportion of VB 1 ,VB 6 Raw material mixing, through the design of VB 12 Particles and VB 1 ,VB 6 The proportion of raw materials is such that VB 12 Particles and VB 1 ,VB 6 The raw materials are always maintained in a dynamic balance of equal mixing, thereby effectively improving the uniformity of the content of each main component.

[0102] 3. pH determination

[0103] In Comparative Example 3 and Comparative Example 4, 0 weight part and 20 weight parts of tartaric acid were added to the prescription respectively, and the tablets were pressed into tablets. The tablets obtained in Example 1, Comparative Example 3 and Comparative Example 4 were dissolved in purified water to measure the pH of the aqueous solution. The results are shown in Table 7.

[0104] Table 7: pH value measurement results

[0105]

[0106] From the results in Table 6, it can be seen that when the pH of the aqueous solution of Example 1 is 4.9, and VB 12 It is most stable under weak acid conditions of pH 4.5-5.0. When no tartaric acid is added and 20 parts by weight of tartaric acid is added, the pH of the aqueous solution of the plain tablets is 6.8 and 2.9 respectively, which are not VB 12 In addition, the above conclusions were verified by storage stability tests, indicating that the introduction of an appropriate amount of tartaric acid can effectively improve VB 12 The stability is conducive to long-term storage of the product.

[0107] 4. Inspection of the appearance and properties of three-dimensional B-film

[0108] The products to be packaged obtained by the preparation processes of Examples 1-6 were examined for their appearance and shape, and all met the requirements for appearance and properties. Taking Example 1 as an example, the results obtained are as follows: the product is a white film-coated tablet, and after removing the film coating, it is a light pink tablet, the disintegration time of the plain tablet is 6 minutes, the hardness is 7.6 kg, and the friability is ≤0.9%.

[0109] 5. Three-dimensional B-film stability test

[0110] Accelerated experiments and long-term experiments were designed to investigate the stability of the self-made three-dimensional B-film.

[0111] 5.1 Acceleration Experiment

[0112] Three batches of homemade tablets from Example 1 were packaged according to the market packaging specifications and placed at a temperature of 40°C ± 2°C and a relative humidity of 75% ± 5%. Samples were taken and tested once in 1, 2, and 3 months, and compared with those on day 0. The main comparisons were appearance, disintegration time, VB 1 Content, VB 6 Content, VB 12 The results of content and content uniformity are shown in Table 8.

[0113] Table 8: Three-dimensional B-sheet accelerated test stability results

[0114]

[0115]

[0116] The results in Table 8 show that the appearance, disintegration time, main component content and VB of the self-made three-dimensional B tablets under the accelerated experimental conditions of three months 12 The content uniformity meets the requirements, indicating that it is stable under this process.

[0117] 5.2 Long-term stability study

[0118] Three batches of homemade tablets were packaged according to commercial specifications and placed at a temperature of 30°C ± 2°C and a relative humidity of 65% ± 5% for 12 months. Samples were taken and tested once in the 3rd, 6th, and 12th months, and compared on day 0. The main comparisons were appearance, disintegration time, VB 1 Content, VB 6 Content, VB 12 The results of content and content uniformity are shown in Table 9.

[0119] Table 9: Results of long-term stability study of three-dimensional B-sheet

[0120]

[0121] It can be seen from the data in Table 9 that in the long-term stability experiment, all parameters of the homemade three-dimensional B-sheet meet the requirements, indicating that the process and method provided by the present invention can effectively improve the quality stability of the three-dimensional B-sheet.

[0122] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a three-dimensional B-sheet, characterized in that the steps include: S1. Add corn starch, sucrose, tartaric acid and dextrin into a wet granulator and mix well. Add vitamin B 12 Wetting agent, mixed granulation, drying and granulation to obtain vitamin B 12 Particles; S2. Weigh the dose of vitamin B1, vitamin B6, magnesium stearate and silicon dioxide, and add the vitamin B 12 The particles are mixed to obtain three-dimensional B particles; S3. The three-dimensional B particles are compressed and coated to obtain three-dimensional B tablets; By weight, the components of the three-dimensional B tablet are: 100-200 parts of vitamin B1, 100-200 parts of vitamin B6, 12 0.1-0.5 parts, corn starch 80-200 parts, sucrose 10-50 parts, dextrin 80-100 parts, tartaric acid 10-20 parts, magnesium stearate 0.5-2 parts, silicon dioxide 0.5-5 parts, wetting agent 60-100 parts.

2. The preparation method according to claim 1, characterized in that: By weight, the components of the three-dimensional B tablet are: 100 parts of vitamin B1, 100 parts of vitamin B6, and 100 parts of vitamin B 12 0.227 parts, corn starch 100 parts, sucrose 30 parts, dextrin 80 parts, tartaric acid 10 parts, magnesium stearate 1 part, silicon dioxide 3 parts, wetting agent 60 parts.

3. The preparation method according to claim 2, characterized in that: The wetting agent is an ethanol aqueous solution with a volume ratio of 1:1, and the ethanol is 95% ethanol.

4. The preparation method according to claim 1, characterized in that: In step S1, the drying process controls the moisture content of the particles to ≤ 5%; And / or, the drying process is set with an inlet air temperature of 70-80°C, an outlet air temperature of 35-40°C, and a duration of 15-20 minutes.

5. The preparation method according to claim 1, characterized in that: In step S1, the granulation process controls the vitamin B 12 The particle size is less than 1.5 mm.

6. The preparation method according to claim 1, characterized in that: In step S1, the mixing time in the wet granulator is 5 to 10 minutes, and the mixture containing vitamin B 12 After adding the wetting agent, adjust the speed and mix for 5 to 10 minutes to granulate.

7. The preparation method according to claim 1, characterized in that: In step S2, the mixing process uses a V-shaped high-efficiency mixer.

8. The three-dimensional B-sheet obtained by the preparation method according to any one of claims 1 to 7, characterized in that: Vitamin B in the three-dimensional B tablet 12 The content uniformity is less than 10.

9. The three-dimensional B-film according to claim 8, characterized in that: The content uniformity of vitamin B1 and vitamin B6 in the three-dimensional B tablet is less than 10.

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