Florfenicol powder with high bio-benefit and preparation method of florfenicol powder

Abstract

The invention discloses stable and efficient florfenicol powder. The florfenicol powder is prepared from florfenicol, D-mannitol, cross-linked glucan, calcium carboxymethyl cellulose, deoxycholic acid and a lubricant. According to the florfenicol powder provided by the invention, the high-content florfenicol powder can be prepared without complex processes such as inclusion, so that the production cost is greatly reduced. In addition, the florfenicol powder disclosed by the invention is good in stability, has high intestinal absorption permeability, is remarkably improved in bioavailability, has extremely high moisture absorption resistance and caking resistance, and is more convenient to store and transport for a long distance.

Description

Technical Field

[0001] The present invention relates to the technical field of medicine, and in particular to a florfenicol powder with high bioavailability and a preparation method thereof. Background Art

[0002] Florfenicol, also known as florfenicol, is a new generation of chloramphenicol-based broad-spectrum veterinary antibiotics. It boasts broad antibacterial activity, good absorption, wide distribution throughout the body, and is safe and highly effective. It is highly effective in treating bacterial diseases in poultry caused by sensitive bacteria, and is effective against both Gram-positive and Gram-negative bacteria. It is the drug of choice for various infections caused by Salmonella typhi, Salmonella paratyphi, and Salmonella. Therefore, florfenicol holds broad application prospects in animal disease prevention and control, especially in food-producing animals. However, florfenicol powder is insoluble in water and only soluble in some organic solvents, significantly limiting its route of administration. Developing a water-soluble florfenicol formulation offers significant market advantages. Available florfenicol formulations primarily come in four dosage forms: injection, solution, powder, and premix. Each formulation has distinct application objectives and varying efficacy. Florfenicol injection offers unique advantages in treating severe bacterial infections, primarily due to its rapid onset of action, complete absorption, and high blood concentrations. However, most commercially available injections are high-concentration solutions that require appropriate dilution before use in poultry. This makes practical application inconvenient and requires significant manpower and resources. Florfenicol solutions are prone to precipitation at low temperatures and also precipitate after dilution with water. While florfenicol premixes offer convenient and effective prophylactic administration, in the event of a more severe infection, the animal's feed intake often decreases significantly, leading to even complete loss of appetite, making mixed-feed treatment less effective.

[0003] Florfenicol has a solubility of only 1.2 mg / mL in water and is slowly absorbed in the body, with only 17.9% absorbed within two hours of oral administration. This results in low bioavailability of florfenicol in the body, which limits its application in veterinary clinics. Therefore, domestic researchers have done a lot of research in this area. Patent CN1947699A discloses a method for producing water-soluble florfenicol, which mixes 10% florfenicol with 90% pure glucose powder. Patent CN101406456A discloses a process for preparing florfenicol soluble powder, which mixes approximately 5% florfenicol, 5% polyethylene glycol 6000, and 90% oral sugar or lidocaine powder. These methods can only produce low concentrations of water-soluble florfenicol, resulting in low active ingredient content, and a large amount of product needs to be applied to achieve the desired effect. Patents CN103536536A, CN104706629A, CN106798731A, CN110882220A, CN111588698A, etc. use cyclodextrin inclusion or polyethylene glycol co-dissolution techniques to prepare florfenicol solid dispersions in order to obtain better water solubility. The processes are complex, and the dissolution rate, bioavailability, moisture resistance, and anti-caking properties of the prepared products are all irrational. Some require more than an hour to dissolve, which cannot meet the actual needs of poultry drinking water administration. In addition, the solid dispersions are unstable during storage and may experience aging problems due to size increase, recrystallization, etc.

[0004] Currently, veterinary drugs are primarily administered in large groups, including feed and drinking water. Drinking water administration, due to its advantages of ease of use, minimal labor, and scalability, has become increasingly popular in large-scale farms. Florfenicol powder formulations are simple to prepare and suitable for drinking water administration. Therefore, finding a florfenicol powder formulation with a rapid dissolution rate, high bioavailability, and excellent moisture and caking resistance is an urgent need in the field. Summary of the Invention

[0005] The present invention aims to overcome the problems of the prior art florfenicol powder, such as easy moisture absorption and agglomeration, slow dissolution rate and low bioavailability, and to provide a florfenicol powder preparation that is not easy to agglomerate, convenient to transport and store, has good stability, dissolves rapidly and has significantly improved bioavailability.

[0006] On the one hand, the present invention provides a stable and efficient florfenicol powder, which comprises the following ingredients: florfenicol, D-mannitol, cross-linked dextran, carboxymethylcellulose calcium, deoxycholic acid and a lubricant.

[0007] Preferably, the lubricant is one or more of magnesium stearate, sodium stearyl fumarate and talc.

[0008] In a preferred embodiment, the florfenicol powder comprises the following components in parts by weight: 20-50% florfenicol, 10-60% D-mannitol, 1-20% cross-linked dextran, 1-10% carboxymethylcellulose calcium, 1-5% deoxycholic acid, and 0.5-5% lubricant.

[0009] Preferably, the average particle size of the D-mannitol is 70-120 μm; more preferably, the average particle size of the D-mannitol is 80-100 μm.

[0010] Further preferably, the florfenicol powder comprises the following components in parts by weight: 30-40% florfenicol, 30-50% D-mannitol, 10-15% cross-linked dextran, 5-10% carboxymethylcellulose calcium, 2-4% deoxycholic acid, and 1-3% lubricant.

[0011] Preferably, the florfenicol powder comprises the following components in parts by weight: 35% florfenicol, 40% D-mannitol, 12% cross-linked dextran, 8% carboxymethylcellulose calcium, 3% deoxycholic acid, and 2% lubricant.

[0012] Preferably, the florfenicol powder comprises the following components in parts by weight: 30% florfenicol, 50% D-mannitol, 10% cross-linked dextran, 5% carboxymethylcellulose calcium, 4% deoxycholic acid, and 1% lubricant.

[0013] Preferably, the florfenicol powder comprises the following components in parts by weight: 40% florfenicol, 30% D-mannitol, 15% cross-linked dextran, 10% carboxymethylcellulose calcium, 2% deoxycholic acid, and 3% lubricant.

[0014] On the other hand, the present invention provides a method for preparing florfenicol powder, which specifically comprises the following steps: Florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid are placed in a three-dimensional mixer and mixed at a speed of 20-30 rpm for 15-30 minutes to ensure that the materials are evenly dispersed to prepare a premixed material; the premixed material is uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, the material is squeezed into flakes under the pressure of the flakes, and the flakes are crushed; the crushed material and lubricant are placed in a two-dimensional mixer and mixed at a speed of 10-20 rpm for 10-20 minutes to obtain florfenicol powder.

[0015] Preferably, the material is crushed into a particle size of 80-150 mesh, more preferably 100-120 mesh.

[0016] In a third aspect, the present invention provides a use of the aforementioned florfenicol soluble powder in the preparation of veterinary antibacterial drugs. Veterinary antibacterial drugs can be prepared by combining the florfenicol powder of the present invention with other pharmaceutically acceptable excipients or drugs.

[0017] Beneficial effects of the present invention: The florfenicol powder provided by the present invention can be prepared with a high content of florfenicol without complex processes such as inclusion, greatly reducing production costs. Furthermore, the florfenicol powder of the present invention has good stability, high intestinal permeability, and significantly improved bioavailability. Furthermore, its strong anti-hygroscopicity and anti-caking properties make it more convenient for storage and long-distance transportation. DETAILED DESCRIPTION

[0018] The present invention is further illustrated by the following examples. Unless otherwise specified, the experimental methods used in the following examples are conventional methods; the materials and reagents used are commercially available reagents and materials unless otherwise specified.

[0019] The following are only some embodiments of the present invention and are not intended to limit the present invention in any other form. Any person skilled in the art may use the above technical content as inspiration to make changes or modifications. These are equivalent embodiments of equivalent changes. However, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention that do not deviate from the technical concept of the present invention still fall within the scope of protection of the claims of the present invention. Example 1 Table 1 Composition formula of Example 1 (100g) The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material formed flakes under the extrusion of the flakes, and the flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0020] Example 2 Table 2 Composition prescription of Example 2 (100g) The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 20 rpm for 30 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material formed flakes under the extrusion of the flakes, and the flakes were crushed to an average particle size of 100 mesh; the crushed material and sodium stearyl fumarate were placed in a two-dimensional mixer and mixed at a speed of 10 rpm for 20 minutes to obtain florfenicol powder.

[0021] Example 3 Table 3 Composition prescription of Example 3 (100g) The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material formed flakes under the extrusion of the flakes, and the flakes were crushed to an average particle size of 120 mesh; the crushed material and talc were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0022] Example 4 Table 4 Composition formula of Example 4 (100g) The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material was formed into flakes under the compression of the flakes. The flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0023] Example 5 Table 5 Composition prescription of Example 5 (100g) The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material was formed into flakes under the compression of the flakes. The flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0024] Comparative Example 1 Table 6 Composition prescription of Comparative Example 1 The specific preparation process is as follows: The prescribed amount of florfenicol, lactose, microcrystalline cellulose, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material was formed into flakes under the compression of the flakes. The flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0025] Comparative Example 2 Table 7 Comparative Example 2 Composition Prescription The specific preparation process is as follows: The prescribed amount of florfenicol, hydroxypropyl-β-cyclodextrin, hydroxypropyl chitosan, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material formed flakes under the compression of the flakes, and the flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0026] Comparative Example 3 Table 8 Composition prescription of Comparative Example 3 The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material was formed into flakes under the compression of the flakes. The flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0027] Comparative Example 4 Table 9 Prescription of the composition of Comparative Example 4 The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, and hydroxymethylcellulose calcium were placed into a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material was formed into flakes under the extrusion of the flakes, and the flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed into a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0028] Comparative Example 5 Table 10 Prescription of the composition of Comparative Example 5 The specific preparation process is as follows: The prescribed amount of florfenicol, D-mannitol, cross-linked dextran, sodium carboxymethyl starch, and deoxycholic acid were placed in a three-dimensional mixer and mixed at a speed of 30 rpm for 15 minutes to ensure that the materials were evenly dispersed to prepare a premixed material; the premixed material was uniformly added to the gap between the granulating wheels of the dry granulator through a screw feeder, and the material formed flakes under the compression of the flakes, and the flakes were crushed to an average particle size of 120 mesh; the crushed material and magnesium stearate were placed in a two-dimensional mixer and mixed at a speed of 20 rpm for 10 minutes to obtain florfenicol powder.

[0029] Comparative Example 6 Table 11 Composition formula of Comparative Example 6 The specific preparation process is as follows: The prescribed amount of polyethylene glycol 12000, copovidone, β-cyclodextrin, mannitol, lactose, and poloxamer 188 were added to 140 g of water and dissolved and clarified to prepare a solution; florfenicol was added to the prepared solution and dissolved to prepare a florfenicol solution; the florfenicol solution was spray-dried (at an inlet air temperature of 95° C.) to obtain florfenicol powder.

[0030] Comparative Example 7 Table 12 Prescription of the composition of Comparative Example 7 The specific preparation process is as follows: Add the prescribed amount of polyethylene glycol 6000, palm oil, and florfenicol to 110 g of distilled water and dissolve them; add the prescribed amount of polyvinyl pyrrolidone PVPK30, lactose, sodium lauryl sulfate, and trimethoprim lactate to the mixture, spray dry after dissolution, pass through a 40-mesh sieve, add the prescribed amount of citric acid, mix well, and pass through a 40-mesh sieve to obtain florfenicol powder.

[0031] Verification example: 1. Moisture absorption test Three groups (10 mg) of each sample prepared in Examples 1-5 and Comparative Examples 1-7 were taken for hygroscopic weight gain experiments at 25°C and 90% relative humidity (after equilibrium). The hygroscopicity of each sample was tested for 48 hours using a dynamic moisture sorption (DVS) instrument, and the average value was taken. The experimental results are shown in Table 13.

[0032] Table 13 Moisture absorption test results The results show that the florfenicol powder prepared by the present invention exhibits low hygroscopicity and good stability, especially when encountering a humid environment. There is no need to worry about the problem of drug powder agglomeration due to moisture absorption, and the storage environment requirements are low, making it more suitable for long-term storage.

[0033] 2. Agglomeration performance test Sample pretreatment: The samples prepared according to Examples 1-5 and Comparative Examples 1-7 were placed in a drying oven at 40°C and dried for 24 hours. After cooling to room temperature, they were sieved through a 20-mesh sieve. 20 g of the sieved samples were taken and evenly spread into the sample container, and the surface was leveled.

[0034] Pressure application: Place the pressing block gently on the sample surface, ensuring that the pressing block is in full contact with the sample, and superimpose the 25kg method. Place the sample on top of the briquette and transfer the sample and the container to a constant temperature and humidity chamber for 24h, 48h, and 72h respectively.

[0035] Agglomeration test: Agglomerated and unagglomerated technical drug particles were separated by sieving, and the proportion of agglomerated mass to total mass was calculated. A sample of the technical drug after pressure testing was gently poured onto a sieve and manually sieved for 2 minutes (amplitude ≤ 5 cm to avoid breaking agglomerates with force). After sieving, the remaining agglomerates on the sieve were weighed. The results are shown in Table 14.

[0036] Table 14 Sample agglomeration rate data According to the caking rate test data in Table 14, the florfenicol powder of the present application has significantly improved anti-caking performance.

[0037] 3. Drinking water stability Florfenicol powder samples prepared in Examples 1-5 of the present invention and Comparative Examples 1-7 were taken to verify the stability of florfenicol powder in low-hardness water (calculated as CaCO3, 50 mg / L) and high-hardness water (calculated as CaCO3, 400 mg / L).

[0038] Florfenicol solution: Dissolve in high-hardness drinking water. Prepare water according to the clinically recommended concentration of 100 μg / mL (calculated as florfenicol). Prepare 3 parallel samples per group and store at room temperature away from light.

[0039] Sampling and testing: The initial concentration was tested by taking samples for HPLC testing at the initial time of 2 h, 6 h, 12 h, 24 h, and 48 h (covering the drinking water cycle of poultry and livestock within 2 days), and the degradation rate of florfenicol was calculated: degradation rate (%) = (initial concentration - sampling concentration) / initial concentration × 100%; the results are shown in Tables 15 and 16.

[0040] Table 15 Degradation rate results of florfenicol samples in low hardness water Table 16 Degradation rate results of florfenicol samples in high hardness water As can be seen from Tables 15 and 16, the florfenicol powder of the present invention has excellent stability in water, especially in high-hardness drinking water. Calcium carbonate in high-hardness water significantly increases the degradation of florfenicol. The florfenicol powder of the present invention exhibits excellent stability in high-hardness water and is therefore suitable for use in different regions with different water qualities, without the need for specific treatment of drinking water.

[0041] 4. Permeability test Test conditions: A porcine intestinal membrane permeation cell model was used to simulate the transmembrane permeation process of drugs in the intestine. The porcine small intestinal mucosa (the serosal and muscle layers were removed, and the mucosal and submucosal layers were retained) was treated with 10% sodium bicarbonate solution, 10 mM EDTA solution, and deionized water at 70°C for 20 minutes as a biomembrane barrier. The biomembrane barrier was then fixed between the donor and receiver chambers of a Franz diffusion cell (effective surface area 4.15 cm 2 ), a permeability test was conducted using a Franz diffusion cell method at a water temperature of (37±0.5)°C; the florfenicol powder (5 mg, calculated as florfenicol) prepared in Example 1 and Comparative Examples 1-7 was respectively suspended in 2 ml of distilled water in the donor chamber; the receptor chamber was filled with phosphate buffer (pH=7.4), maintained at room temperature, air bubbles were removed, and magnetic stirring was performed at 45±5 RPM; the cumulative permeation amount was tested after 24 hours.

[0042] Table 17 Cumulative permeation of florfenicol samples From the above permeability test results, it can be seen that the permeability of the florfenicol powder of the present invention is significantly improved, thereby having a significantly improved bioavailability.

[0043] 5. Drug efficacy testing The efficacy proof test described below was used to test the evaluation indicators of each group in terms of the number of ineffective cases, the number of effective cases, the number of cured cases, the cure rate, etc.

[0044] Experimental Animals: 30-day-old broiler chickens of similar weight suffering from respiratory tract infection were selected. The broiler chickens exhibited symptoms such as grunting, wheezing, runny nose, and reluctance to move. The chickens were randomly divided into 13 groups, each containing 30 chickens.

[0045] The experimental groups were as follows: Groups 1 to 5 corresponded to the florfenicol powder prepared in Examples 1-5; Groups 6 to 12 corresponded to the florfenicol powder prepared in Comparative Examples 1-7; and Group 13 served as a blank control group, to which no drug was added. All 13 groups of chickens were fed the same way. Groups 1 to 12 were treated with drinking water, while Group 13 was provided with unadulterated drinking water. The chickens were housed in 13 separate enclosures.

[0046] Administration: Calculated as florfenicol, the dose of Groups 1 to 12 was 100 μg / mL administered in drinking water for 6 hours for 5 days. Group 13 was provided with drinking water without any drug, and the other aspects remained the same as Groups 1 to 12.

[0047] Efficacy evaluation: Ineffective means that there is no significant change in the symptoms of the disease and the symptoms before treatment remain; effective means that some or all symptoms are improved and the effect is better than before treatment; cured means that all symptoms disappear and health is completely restored, and its data is included in the effective data; the results are shown in Table 18.

[0048] Table 18 Efficacy evaluation indexes of each sample By analyzing the experimental data obtained in Table 18, it can be found that the cure rate of the florfenicol powder prepared in Examples 1-5 of the present invention for chicken respiratory tract infections can reach more than 90%, showing a high cure rate. During the medication period, the sick chickens did not show any adverse or abnormal behaviors, and their feeding and drinking were normal, indicating that the florfenicol powder provided by the present invention is stable, efficient, palatable, and has high bioavailability.

Claims

1. A stable and efficient florfenicol powder, characterized in that, The florfenicol powder consists of florfenicol, D-mannitol, cross-linked dextran, carboxymethylcellulose calcium, deoxycholic acid and a lubricant.

2. Florfenicol powder as claimed in claim 1, characterized in that, The lubricant is one or more of magnesium stearate, sodium stearyl fumarate and talc.

3. The florfenicol powder according to claim 1, wherein The florfenicol powder comprises 20-50% florfenicol, 10-60% D-mannitol, 1-20% cross-linked dextran, 1-10% carboxymethylcellulose calcium, 1-5% deoxycholic acid, and 0.5-5% lubricant.

4. The florfenicol powder according to claim 1, wherein The average particle size of the D-mannitol is 70-120 μm.

5. The florfenicol powder according to claim 1, wherein The average particle size of the D-mannitol is 80-100 μm.

6. The florfenicol powder according to claim 1, wherein The florfenicol powder contains 30-40% florfenicol, 30-50% D-mannitol, 10-15% cross-linked dextran, 5-10% carboxymethylcellulose calcium, 2-4% deoxycholic acid, and 1-3% lubricant.

7. The florfenicol powder according to claim 6, wherein The florfenicol powder consists of 35% florfenicol, 40% D-mannitol, 12% cross-linked dextran, 8% carboxymethylcellulose calcium, 3% deoxycholic acid, and 2% lubricant.

8. The florfenicol powder according to claim 6, wherein The florfenicol powder consists of 30% florfenicol, 50% D-mannitol, 10% cross-linked dextran, 5% carboxymethylcellulose calcium, 4% deoxycholic acid, and 1% lubricant.

9. The florfenicol powder according to claim 6, wherein The florfenicol powder consists of 40% florfenicol, 30% D-mannitol, 15% cross-linked dextran, 10% carboxymethylcellulose calcium, 2% deoxycholic acid, and 3% lubricant.

10. A method for preparing florfenicol powder, comprising the following steps: placing florfenicol, D-mannitol, cross-linked dextran, hydroxymethylcellulose calcium, and deoxycholic acid into a three-dimensional mixer and mixing at a speed of 20-30 rpm for 15-30 minutes to ensure uniform dispersion of the materials to prepare a premix; adding the premix at a uniform speed into the gap between the rollers of a dry granulator through a screw feeder, the materials forming a sheet under the pressure of the rollers, and crushing the sheet; placing the crushed material and a lubricant into a two-dimensional mixer and mixing at a speed of 10-20 rpm for 10-20 minutes to obtain florfenicol powder.

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