Broad-spectrum antibacterial agent and preparation method thereof

Abstract

The invention discloses a broad-spectrum antibacterial drug which comprises a tablet core and a coating film, the tablet core comprises 500-1000 parts of levofloxacin, 50-100 parts of a diluent, 30-100 parts of a disintegrating agent, 5-30 parts of an adhesive and 10-54 parts of a lubricant, and the coating film is a gastric-soluble film coating; wherein the disintegrating agent is a compound of carboxymethyl cellulose, polyvinylpolypyrrolidone and croscarmellose sodium; the broad-spectrum antibacterial drug tablet obtained in the invention has good dissolution rate and stability, and can be rapidly disintegrated.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical preparation technology, and specifically relates to a broad-spectrum antibacterial drug and its preparation method. Background Technology

[0002] Levofloxacin is a broad-spectrum fluoroquinolone antibiotic that has attracted considerable attention due to its potent antibacterial activity, favorable pharmacokinetic properties, and wide range of clinical applications. Levofloxacin primarily works by inhibiting the activity of bacterial DNA gyrase (topoisomerase II) and topoisomerase IV, thereby preventing bacterial DNA replication, repair, and recombination, ultimately leading to bacterial death. Due to its unique pharmacological action, levofloxacin is widely used to treat various infectious diseases caused by susceptible bacteria, including respiratory tract infections, genitourinary tract infections, and skin and soft tissue infections.

[0003] Currently, various formulations of levofloxacin are available on the market, including tablets, capsules, and injections. However, developing levofloxacin tablets with good bioavailability and rapid disintegration remains an important research direction in order to improve patient compliance and treatment efficacy.

[0004] Patent CN113750067B describes a preparation process for levofloxacin tablets. This process involves adding starch nanocrystals during tablet core preparation to improve the stability between the active pharmaceutical ingredient (API) and excipients. Additionally, warm air shaping is used to enhance the viscosity and expansion of the API and excipients. This results in high in vitro dissolution of levofloxacin tablets, a controllable and gradual release rate, and improved bioavailability.

[0005] Patent CN112190558A describes a levofloxacin composition that addresses the significant increase in impurity E by controlling the mass ratio of citric acid to sodium acetate.

[0006] CN116637079A A method for preparing levofloxacin tablets and levofloxacin tablets: By optimizing the formulation of levofloxacin tablets, the resulting levofloxacin tablets have moderate hardness, fast disintegration rate, high dissolution rate, and the best effect.

[0007] The above patents are all aimed at addressing some shortcomings of levofloxacin tablets, such as low bioavailability, slow disintegration rate, and inconvenience in taking them. Summary of the Invention

[0008] To address the aforementioned problems in the existing technology, the present invention provides the following technical solution:

[0009] A broad-spectrum antibacterial drug includes a tablet core and a coating film. The tablet core comprises 500-1000 parts of levofloxacin, 50-100 parts of diluent, 30-100 parts of disintegrant, 5-30 parts of binder, and 10-54 parts of lubricant. The coating film is a gastrointestinal film coating. The disintegrant is a compound of carboxymethyl cellulose, crospovidone, and crospovidone sodium carboxymethyl cellulose.

[0010] Furthermore, the mass ratio of the carboxymethyl cellulose, the crospovidone, and the crospovidone sodium carboxymethyl cellulose is (1-3):(1-2):1.

[0011] Further, the mass ratio of the disintegrant to the adhesive is (45-55):(10-20).

[0012] Furthermore, the diluent is microcrystalline cellulose, the lubricant is sodium stearate fumarate, and the binder is hydroxypropyl cellulose.

[0013] Furthermore, the adhesive is a 10% aqueous solution of hydroxypropyl cellulose prepared with water as a solvent.

[0014] On the other hand, the present invention provides a method for preparing the above-mentioned broad-spectrum antibacterial drug, wherein the preparation process adopts wet granulation.

[0015] Furthermore, it includes the following steps:

[0016] 1) Adhesive preparation: Prepare a 10% hydroxypropyl cellulose aqueous solution;

[0017] 2) Premixing: Add the prescribed amount of material to a wet granulation mixer and mix.

[0018] 3) Preparation of soft material: Add the adhesive obtained in step 1) to the mixture obtained in step 2) and mix to obtain soft material;

[0019] 4) Granulation: Add the soft material obtained in step 3) to a wet granulator and granulate it using a sieve to obtain wet granules.

[0020] 5) Drying: Add the wet particles obtained in step 4) to a fluidized bed for drying, and control the moisture content of the particles to be greater than 2%;

[0021] 6) Granulation: Add the granules obtained in step 5) to a wet and dry granulator and granulate them again using a sieve to obtain dry granules.

[0022] 7) Total mixing: Mix the dry granules obtained in step 6) with the prescribed amount of sodium stearate fumarate;

[0023] 8) Tableting: Using a mold to compress tablets to obtain tablet cores;

[0024] 9) Coating: Use a stomach-soluble coating solution to coat the tablet core with a thin film.

[0025] Furthermore, the moisture content of the particles in step 5) is 2-4%.

[0026] Furthermore, all raw materials and auxiliary materials are sieved through an 80-mesh sieve.

[0027] Furthermore, the mixing time for steps 2) and 3) shall not be less than 3 minutes.

[0028] Compared with the prior art, the broad-spectrum antibacterial drug (i.e., levofloxacin tablets) of the present invention has the following advantages:

[0029] (1) Compared with the prior art, the levofloxacin tablets of the present invention exhibit superior dissolution performance. By optimizing the drug formulation and preparation process, the present invention can significantly improve the dissolution rate of levofloxacin in vivo, thereby accelerating drug absorption and improving bioavailability. This means that patients can obtain effective therapeutic concentrations in a shorter time, improving the timeliness and effectiveness of treatment.

[0030] (2) Regarding related substances, this invention effectively reduces the impurity content in levofloxacin tablets through precise control of the preparation process. Low related substance content not only ensures the purity and safety of the drug but also reduces potential adverse reactions, improving patient tolerance and therapeutic efficacy.

[0031] (3) Disintegration time is an important indicator for evaluating the rate at which tablets dissolve in the body. The levofloxacin tablets of the present invention have excellent disintegration properties and can rapidly disintegrate within a specified time, thereby ensuring the rapid release and absorption of the drug in the gastrointestinal tract. This characteristic is of great significance for improving the efficacy of the drug and patient compliance. Detailed Implementation

[0032] The technical solutions in the embodiments of this application will be clearly described below. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.

[0033] The terms "first," "second," etc., used in the specification and claims of this application are used to distinguish similar objects and not to describe a specific order or sequence. It should be understood that such use of data can be interchanged where appropriate so that embodiments of this application can be implemented in orders other than those described herein, and the objects distinguished by "first," "second," etc., are generally of the same class and the number of objects is not limited; for example, a first object can be one or more. Furthermore, in the specification and claims, "and / or" indicates at least one of the connected objects, and the character " / " generally indicates that the preceding and following objects are in an "or" relationship.

[0034] The inventors of this application have discovered that by optimizing the type and amount of disintegrant in levofloxacin tablets, and the relationship between the amount of disintegrant and the binder, not only is the similarity of the release curve of the active ingredient in levofloxacin tablets to that of the reference formulation improved, but related substances in levofloxacin tablets can also be effectively controlled. The levofloxacin tablets specifically include: a tablet core and a coating film. The tablet core includes 500-1000 parts of levofloxacin, 50-100 parts of diluent, 30-100 parts of disintegrant, 5-30 parts of binder, and 10-54 parts of lubricant. The coating film is a gastrointestinal film coating. The disintegrant is a compound of carboxymethyl cellulose, crospovidone, and crospovidone sodium carboxymethyl cellulose.

[0035] In one embodiment of the present invention, the mass ratio of the carboxymethyl cellulose, the crospovidone, and the crospovidone sodium carboxymethyl cellulose is (1-3):(1-2):1, for example 1:1:1, 1:2:1, 2:1:1, 2:2:1, 3:1:1, or 3:2:1, but not limited to the listed values; other unlisted values ​​within this range are also applicable. The mass ratio of the disintegrant to the adhesive is (45-55):(10-20).

[0036] In one embodiment of the present invention, the mass ratio of the disintegrant to the adhesive is (45-55):(10-20), for example 45:10, 45:11, 45:12, 45:13, 45:14, 45:15, 45:16, 45:17, 45:18, 45:19, 45:20, 50:10, 50:11, 50:12, 50:13, 50:14, 50:15, 45:16, 45:17, 45:18, 45:19, 45:20, 50:10, 50:11, 50:12, 50:13, 50:15, 50:16, 50:17, 45:18, 45:19, 0:14, 50:15, 50:16, 50:17, 50:18, 50:19, 50:20, 55:10, 55:11, 55:12, 55:13, 55:14, 55:15, 55:16, 55:17, 55:18, 55:19, or 55:20, but not limited to the listed values; other unlisted values ​​within this range also apply.

[0037] In one embodiment of the present invention, the diluent is microcrystalline cellulose, the lubricant is sodium stearate fumarate, and the binder is hydroxypropyl cellulose. The binder is a 10% aqueous solution of hydroxypropyl cellulose prepared with water as a solvent.

[0038] In one embodiment of the present invention, the preparation method of the levofloxacin tablets adopts wet granulation.

[0039] Includes the following steps:

[0040] 1) Adhesive preparation: Prepare a 10% hydroxypropyl cellulose aqueous solution;

[0041] 2) Premixing: Add the prescribed amount of material to a wet granulation mixer and mix.

[0042] 3) Preparation of soft material: Add the adhesive obtained in step 1) to the mixture obtained in step 2) and mix to obtain soft material.

[0043] 4) Granulation: Add the soft material obtained in step 3) to a wet granulator and granulate it using a sieve to obtain wet granules.

[0044] 5) Drying: Add the wet particles obtained in step 4) to a fluidized bed for drying, and control the moisture content of the particles to be greater than 2%;

[0045] 6) Granulation: Add the granules obtained in step 5) to a wet and dry granulator and granulate them again using a sieve to obtain dry granules.

[0046] 7) Total mixing: Mix the dry granules obtained in step 6) with the prescribed amount of sodium stearate fumarate;

[0047] 8) Tableting: Using a mold to compress tablets to obtain tablet cores;

[0048] 9) Coating: Use a stomach-soluble coating solution to coat the tablet core with a thin film.

[0049] In one embodiment of the present invention, the moisture content of the particles in step 5) is 2 to 4%, for example 2%, 3% or 4%, but is not limited to the listed values. Other unlisted values ​​within this range are also applicable.

[0050] The moisture content of dried granules is related to granule flowability and the quality of subsequent levofloxacin tablets. The inventors investigated different moisture ranges, such as less than 2%, 2-3%, 3-4%, and slightly more than 4%. Although the specific reasons are not yet clear, the experimental results show that when the moisture content of the granules is controlled between 2 and 4%, the prepared levofloxacin tablets exhibit superior performance in terms of dissolution and stability.

[0051] In one embodiment of the present invention, the raw materials and all auxiliary materials are passed through an 80-mesh sieve.

[0052] In one embodiment of the present invention, the mixing time of steps 2) and 3) is not less than 3 minutes.

[0053] The specific embodiments and comparative examples of the present invention are listed below, but the present invention is not limited to the following examples.

[0054] The equipment information used in the embodiments and comparative examples of this invention is as follows:

[0055] Table 1. Equipment information used in the embodiments and comparative examples of the present invention.

[0056] Equipment Name model factory Wet mixing granulator HLSG50A Beijing Aeronautical Manufacturing Engineering Research Institute, AVIC Multi-functional granulator DPL-3 / 5 Chongqing Jinggong Pharmaceutical Machinery Co., Ltd. Mobile dry and wet pellet mill GZL-100 Chongqing Jinggong Pharmaceutical Machinery Co., Ltd. Rotary tablet press ZP10A Beijing Xinlongli Technology Co., Ltd. High-efficiency coating machine CHC-48 Chuangzhi Electromechanical Technology Development (Shanghai) Co., Ltd.

[0057] Table 2. Information on the Role and Source of Raw and Auxiliary Materials

[0058] Components effect factory Levofloxacin Active ingredients Zhejiang Sitaili Pharmaceutical Co., Ltd. Microcrystalline cellulose PH101 diluent Jiangsu Xidian Pharmaceutical Excipients Co., Ltd. Carboxymethyl cellulose Disintegrant Zhuhai Dongchen Pharmaceutical Co., Ltd. Cross-linked polyvinylpyrrolidone Disintegrant Ashland (China) Investment Co., Ltd. Cross-linked carboxymethyl cellulose sodium Disintegrant Fullman (Shanghai) Trading Co., Ltd. Hydroxypropyl cellulose-SL adhesives Anhui Shanhe Pharmaceutical Excipients Co., Ltd. Sodium stearate lubricant Tianjin Xinherui Biotechnology Co., Ltd. Pharmaceutical film-coated premixed powder (gastric-soluble type) Coating agent Zhejiang Oulun Coating Technology Co., Ltd.

[0059] Levofloxacin tablets were prepared in Examples 1-6 and Comparative Examples 1-7, and the raw materials and proportions (by weight) are shown in Table 3:

[0060] Table 3. Raw material and excipient dosage information for levofloxacin tablets in the examples and comparative examples (unit: mg / tablet)

[0061]

[0062]

[0063] The preparation methods of levofloxacin tablets provided in Examples 1-6 and Comparative Examples 1-7 are as follows (taking the preparation of 10,000 tablets as an example):

[0064] 1) Adhesive preparation: Prepare a 10% hydroxypropyl cellulose aqueous solution;

[0065] 2) Premixing: After passing the prescribed amounts of levofloxacin, microcrystalline cellulose, carboxymethyl cellulose, crospovidone, and crospovidone sodium carboxymethyl cellulose through an 80-mesh sieve, add them to a wet granulation mixer. Set the shear speed to 1000 rpm and the stirring speed to 200 rpm, mix for 3 minutes, and then remove the mixture for later use.

[0066] 3) Preparation of soft material: Add the adhesive obtained in step 1) to the mixture obtained in step 2), set the shear speed to 1000 rpm and the stirring speed to 200 rpm for mixing, and after mixing for 3 minutes, the soft material is obtained;

[0067] 4) Granulation: Add the soft material obtained in step 3) to a wet and dry granulator, set the rotation speed to 25Hz, and granulate using a Ф2.0mm sieve to obtain wet granules;

[0068] 5) Drying: Add the wet particles obtained in step 4) to a fluidized bed for drying. Set the material temperature to 60℃, the air inlet temperature to 60~70℃, the air velocity to 20Hz, and the moisture content to 2~4%.

[0069] 6) Granulation: Add the granules obtained in step 5) to a wet and dry granulator. Set the rotation speed to 18Hz and use a Ф2.0mm sieve for re-granulation to obtain dry granules;

[0070] 7) Total mixing: Mix the dry granules obtained in step 6) with sodium stearate fumarate; use a cone mixer to mix, set the speed to 15 rpm and the mixing time to 15 minutes;

[0071] 8) Tableting: Add the granules obtained in step 7) to a rotary tablet press for tableting to obtain tablet cores;

[0072] 9) Coating: Prepare a 15% coating powder aqueous solution, add the tablets to the coating pan for coating, set the heating temperature to 45℃, the pan rotation speed to 4 rpm, adjust the atomization pressure to 0.08 MPa, and the spraying speed to 5.0~8.5 rpm, and the coating weight gain is 3~5%.

[0073] Comparative Example 8

[0074] The moisture content of the particles obtained by adjusting step 5) is 1.8%, and the formulation composition and other preparation processes are as in Example 1.

[0075] Comparative Example 9

[0076] The moisture content of the granules obtained by adjusting step 5) is 4.2%, and the formulation composition and other preparation processes are as in Example 1.

[0077] The dissolution rate, related substances, and disintegration time of levofloxacin in Examples 1-6, Comparative Examples 1-9, and the reference formulation were tested using the following methods. The results are shown in Tables 4, 6, and 7. Levofloxacin tablets (license holder: Daiichi Sankyo Pharmaceutical (Beijing) Co., Ltd., trade name: Clenbuterol) were used as the reference formulation, batch number: BA011G1.

[0078] Dissolution test

[0079] Dissolution and release determination method (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0931, Method 1). Use 900 ml of hydrochloric acid solution (9→1000) as the dissolution medium. Rotate the turbine at 100 rpm. After 30 minutes, take an appropriate amount of solution, filter, and accurately measure an appropriate amount of the filtrate. Dilute quantitatively with the dissolution medium. Measure the absorbance at a wavelength of 294 nm using ultraviolet-visible spectrophotometry (Chinese Pharmacopoeia 2020 Edition, Part IV, General Chapter 0401), and calculate the amount dissolved per tablet.

[0080] Table 4. Dissolution results of levofloxacin tablets in the examples and comparative examples.

[0081]

[0082] Table 4 shows that the cumulative dissolution rates of Examples 1-4 were all greater than 85% at 15 minutes, and were close to the dissolution rate of the reference formulation. Under the same conditions, Comparative Examples 1-3, using only two disintegrants, also achieved a cumulative dissolution rate of over 85% for levofloxacin tablets at 15 minutes, but this was slightly lower than the reference formulation. Under the same conditions, Comparative Example 4 adjusted the proportion of carboxymethyl cellulose as the disintegrant, and the resulting levofloxacin tablets also achieved a cumulative dissolution rate of over 85% at 15 minutes, but this was slightly lower than the reference formulation. Under the same conditions, Comparative Example 5 adjusted the proportion of crospovidone as the disintegrant, and the resulting levofloxacin tablets also achieved a cumulative dissolution rate of over 85% at 15 minutes, but this was slightly lower than the reference formulation. Under the same conditions, Comparative Example 6 adjusted the proportion of the disintegrant croscarmellose sodium, and the cumulative dissolution rate of the levofloxacin tablets obtained therein also reached greater than 85% at 15 minutes, but the dissolution rate was slightly lower than that of the reference formulation. Under the same conditions, Comparative Example 7 adjusted the proportion of the three disintegrants, and the cumulative dissolution rate of the levofloxacin tablets obtained therein also reached greater than 85% at 15 minutes, but compared with the reference formulation, it just reached 85%, and the dissolution rate was slightly lower. Under the same conditions, Comparative Example 8 had a moisture content of less than 2% after particle drying during the preparation process, and the cumulative dissolution rate of the levofloxacin tablets obtained therein failed to reach 85% at 15 minutes. Under the same conditions, Comparative Example 9 had a moisture content of more than 4% after particle drying during the preparation process, and the cumulative dissolution rate of the levofloxacin tablets obtained there just reached 85% at 15 minutes, which was significantly lower than that of the reference formulation.

[0083] Related substance detection methods

[0084] Chromatographic column: Yuexu Ultimate XB-C18 (100mm×4.6mm, 5μm);

[0085] Mobile phase A: Copper sulfate ammonium acetate L-valine solution (dissolve 1.25g copper sulfate pentahydrate, 1.76g L-valine, and 3.855g ammonium acetate in 1000ml of water, and adjust the pH to 5.7 with triethylamine) - methanol (86:14);

[0086] Mobile phase B: methanol; perform gradient elution according to the table below;

[0087] Table 5

[0088] Time (min) Mobile phase A (%) Mobile phase B (%) 0 100 0 75 100 0 105 60 40 105.1 100 0 120 100 0

[0089] Detection wavelength: 340 nm; column temperature: 45 ℃; injection volume: 10 μl; flow rate: 1.0 ml / min.

[0090] Solution preparation

[0091] Solvent: 0.1 mol / L hydrochloric acid solution.

[0092] Test solution: Accurately weigh an appropriate amount of the fine powder of this product, dissolve it in 0.1 mol / L hydrochloric acid solution, and quantitatively dilute it to prepare a solution containing approximately levofloxacin per 1 ml (according to C). 18 H 20 A solution containing 3 mg of FN3O4 was filtered, and the filtrate was collected.

[0093] Reference solution: Weigh an appropriate amount of levofloxacin reference standard accurately, dissolve it in 0.1 mol / L hydrochloric acid solution and dilute quantitatively to prepare a solution containing approximately 6 μg per ml.

[0094] System suitability solution: Take appropriate amounts of each of impurity A (dextrofloxacin), impurity B (N-demethyllevofloxacin), impurity C (levofloxacin N-oxide), impurity E (decarboxyl-levofloxacin), impurity G (diamine derivative), and levofloxacin reference standard, dissolve and dilute with 0.1 mol / L hydrochloric acid solution to prepare a mixed solution containing approximately 3 mg of levofloxacin and 15 μg each of impurities A, B, C, E, and G per ml.

[0095] System suitability requirements: In the system suitability solution chromatogram, the elution order of each peak is as follows: impurity E, impurity B, impurity G, impurity C, levofloxacin, and impurity A. The resolution between each peak should meet the requirements.

[0096] Assay: Accurately measure the test solution and the reference solution, inject them separately into the liquid chromatograph, and record the chromatograms.

[0097] Table 6. Results of related substance detection in the examples and comparative examples.

[0098]

[0099] As shown in Table 6, the impurity contents in Examples 1-4 were all below the limits and similar to those in the reference formulation. However, the comparative examples did not all meet the impurity content limit requirements, especially impurity A, dextrofloxacin, whose content was poorly controlled and easily exceeded the limit requirements.

[0100] Disintegration time limit determination Take 6 tablets of the medicine and place them in a disintegration apparatus. Add 900ml of purified water at 37℃, start the disintegration apparatus and check the disintegration time. See Table 7 for the actual disintegration time.

[0101] Table 7. Disintegration time detection results for the examples and comparative examples.

[0102] batch Disintegration time limit Reference formulation 8min20s Example 1 2min59s Example 2 3min34s Example 3 4min22s Example 4 4min02s Example 5 3min52s Example 6 4min23s Comparative Example 1 10min22s Comparative Example 2 10min26s Comparative Example 3 11min09s Comparative Example 4 12min51s Comparative Example 5 11min12s Comparative Example 6 10min06s Comparative Example 7 greater than 20 minutes Comparative Example 8 13min42s Comparative Example 9 12min25s

[0103] As shown in Table 7, in the disintegration time assessment, Examples 1-6 had shorter disintegration times, achieving rapid dissolution. In contrast, the comparative formulations had longer disintegration times compared to the reference formulation, resulting in poorer rapid dissolution. Ensuring a sufficient disintegration time ensures rapid release and absorption of the drug in the gastrointestinal tract.

[0104] This invention achieves superior performance in terms of dissolution rate, impurity content, and disintegration time by precisely controlling the type and ratio of disintegrants and strictly controlling the moisture content of the particles.

[0105] The embodiments of this application have been described above, but this application is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of this application.

Claims

1. A broad-spectrum antibacterial agent, characterized in that, The tablet comprises a tablet core and a coating film, the tablet core comprises levofloxacin 500-1000 parts, diluent 50-100 parts, disintegrant 30-100 parts, binder 5-30 parts and lubricant 10-54 parts, and the coating film is a gastric soluble film coating; wherein the disintegrant is a compound of carboxymethyl cellulose, cross-linked povidone and cross-linked sodium carboxymethyl cellulose.

2. The broad-spectrum antimicrobial drug according to claim 1, characterized in that, The mass ratio of the carboxymethyl cellulose, the cross-linked povidone and the cross-linked sodium carboxymethyl cellulose is (1-3):(1-2):

1.

3. The broad-spectrum antimicrobial drug according to claim 2, characterized in that, The mass ratio of the disintegrant and the binder is (45-55):(10-20).

4. The broad-spectrum antimicrobial drug according to claim 3, characterized in that, The diluent is microcrystalline cellulose, the lubricant is sodium stearyl fumarate, and the binder is hydroxypropyl cellulose.

5. The broad-spectrum antimicrobial drug according to claim 4, characterized in that, The binder is 10% hydroxypropyl cellulose aqueous solution prepared by using water as solvent.

6. A process for the preparation of a broad-spectrum antimicrobial agent as claimed in any one of claims 1 to 5, characterized in that, The preparation process adopts wet granulation.

7. The method for preparing the broad-spectrum antibacterial drug according to claim 6, characterized in that, The method comprises the following steps: 1) binder preparation: prepare 10% hydroxypropyl cellulose aqueous solution; 2) premixing: add the prescription amount of materials into a wet granulation mixer and mix; 3) soft material preparation: add the binder obtained in step 1) into the mixture obtained in step 2) and mix to obtain a soft material; 4) granulation: add the soft material obtained in step 3) into a dry-wet granulator, use a screen to granulate, and obtain wet granules after granulation; 5) drying: add the wet granules obtained in step 4) into a fluidized bed for drying, and control the water content of the granules to be greater than 2%; 6) granulation: add the granules obtained in step 5) into a dry-wet granulator, use a screen to granulate again, and obtain dry granules after granulation; 7) total mixing: mix the dry granules obtained in step 6) with the prescription amount of sodium stearyl fumarate; 8) tabletting: tablet using a mold to obtain a tablet core; 9) coating: use a gastric soluble coating solution to coat the tablet core with a film coating.

8. The method for preparing the broad-spectrum antibacterial drug according to claim 7, characterized in that, The water content of the granules in step 5) is 2-4%.

9. The method for preparing the broad-spectrum antibacterial drug according to claim 8, characterized in that, The materials in step 2) are all sieved through an 80-mesh screen.

10. The method for preparing the broad-spectrum antibacterial drug according to claim 9, characterized in that, The mixing time of step 2) and step 3) is not less than 3 min.

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