A kind of fusidic acid cream and its preparation method and application

Abstract

The invention discloses a method for preparing fusidic acid cream, and the specific process of the method is: according to the prescription composition of fusidic acid cream, after mixing the water phase and the oil phase, a first homogenization is performed to obtain a mixture, and then the fusidic acid raw material is added to the mixture for a second homogenization and cooling to obtain the fusidic acid cream. The present invention first prepares the water phase and the oil phase separately, then mixes the water phase and the oil phase for a first homogenization, and then adds the fusidic acid raw material for a second homogenization, and through two homogenization treatments and strictly controlling the final temperature after cooling of the second homogenization, the water phase, the oil phase, and the fusidic acid raw material are fully fused, the particle size of the droplets is reduced, the mixing uniformity and stability of the fusidic acid ointment are improved, the organizational structure of the fusidic acid cream is improved and its stability is improved, the droplet aggregation phenomenon is effectively avoided, and the preparation process is simple and suitable for large-scale production.

Description

Technical Field

[0001] The invention belongs to the technical field of medicines, and in particular relates to a fusidic acid cream and a preparation method and application thereof. Background Art

[0002] Fusidic acid (FA) belongs to the fusidic acid antibiotics. It was discovered and extracted by Leo Pharma in Denmark in 1962 from the fermentation broth of Fusidium coccineum. Fusidic acid has steroidal structural characteristics and a unique mechanism of action. It inhibits the translocation of ribosomes by interfering with elongation factor G, thereby hindering the synthesis of bacterial proteins. Strains resistant to penicillin, methicillin and other antibiotics are highly sensitive to fusidic acid.

[0003] Fusidic acid is a colorless crystal containing half of the crystal water. It is insoluble in water but soluble in organic solvents such as benzene, methanol, and ethyl acetate. Fusidic acid is a weak acid with a pKa of 5.7. It has the highest degree of ionization in tissues and body fluids at a pH of 7.4.

[0004] Usually, the raw materials in fusidic acid cream are in a suspended state. The invention patent with the grant number CN102325524B discloses that fusidic acid as API (active pharmaceutical ingredient) is not heat-resistant, so the stability of API in fusidic acid cream is unreliable due to the heat-resistant nature of fusidic acid. The invention patent with the publication number CN101378728A discloses a composition containing fusidic acid derivatives, monoglycerides of one or more fatty acids, stabilizers, and emulsifiers, which are prepared into fusidic acid derivative cream preparations. Specifically, a preparation method of a fusidic acid derivative cream preparation is provided in paragraphs

[0149] to

[0160] of the specification. However, in the process of small-scale trial development, the sample droplets of fusidic acid cream prepared according to the process have the phenomenon of aggregation, so the process is only suitable for preparation in the laboratory stage and cannot be industrialized. Summary of the invention

[0005] The technical problem to be solved by the present invention is to provide a method for preparing fusidic acid cream in view of the deficiencies of the above-mentioned prior art. The method first prepares an aqueous phase and an oil phase separately, then mixes the aqueous phase and the oil phase for a first homogenization, and then adds a fusidic acid raw material for a second homogenization, and the two homogenization treatments promote the full fusion of the aqueous phase, the oil phase, and the fusidic acid raw material, reduce the particle size of the droplets, improve the mixing uniformity and stability of the fusidic acid ointment, and solve the droplet aggregation phenomenon in the finished fusidic acid cream.

[0006] In order to solve the above technical problems, the technical solution adopted by the present invention is: a preparation method of fusidic acid cream, characterized in that the specific process of the method is: according to the prescription composition of fusidic acid cream, an aqueous phase and an oil phase are mixed and then a first homogenization is performed to obtain a mixture, and then a fusidic acid raw material is added to the mixture for a second homogenization and cooling to obtain fusidic acid cream; the aqueous phase comprises glycerol, potassium sorbate and purified water with a volume fraction of 85%, and the oil phase comprises hexadecanol, white vaseline, polysorbate 60, liquid paraffin and butylated hydroxyanisole.

[0007] It should be noted that the mixing method is not strictly limited in the present invention, as long as the various substances can be dissolved and evenly dispersed. Generally, the various substances are fully mixed under stirring conditions.

[0008] The above-mentioned method for preparing fusidic acid cream is characterized in that the temperature of the first homogenization is 50° C. to 100° C. Preferably, the temperature of the first homogenization is 50° C. to 90° C.; more preferably, the temperature of the first homogenization is 60° C. to 90° C.

[0009] The above-mentioned method for preparing fusidic acid cream is characterized in that the first homogenization time is 10 min to 50 min. Preferably, the first homogenization time is 20 min to 40 min.

[0010] The above-mentioned method for preparing fusidic acid cream is characterized in that the temperature after cooling is 38°C to 52°C, and the cooling rate is 1°C / min.

[0011] The above-mentioned method for preparing fusidic acid cream is characterized in that after cooling to 38°C to 52°C, the temperature is maintained and the second homogenization is continued.

[0012] During the research process of the present invention, it was found that the second homogenized processing conditions are crucial to the formation of the organizational structure and stability of fusidic acid cream. Specifically, when the final temperature after cooling of the second homogenized is below 40°C, there are droplets in the obtained fusidic acid cream finished product. When the final temperature after cooling of the second homogenized is above 50°C, the droplet particle size in the obtained fusidic acid cream finished product is mostly above 30μm. Therefore, the present invention comprehensively considers the industrial production conditions, and controls the final temperature after cooling of the second homogenized to be 38°C to 52°C, thereby controlling the droplet particle size in the fusidic acid cream finished product, and avoiding the droplet aggregation in the fusidic acid cream finished product. Further, by controlling the final temperature after cooling of the second homogenized to be 40°C to 50°C, the droplet particle size in the fusidic acid cream finished product is less than 20μm, even less than 10μm, and the droplets with good stability are difficult to aggregate, which solves the droplet aggregation phenomenon in the fusidic acid cream finished product.

[0013] At the same time, the change in the particle size of the droplets during the second homogenization process is reversible, that is, the ideal state of the finished fusidic acid cream can be obtained by adjusting the final temperature of the second homogenization. When the second homogenization final temperature undergoes temperature changes during homogenization greater than 50°C, homogenization at 40°C to 50°C, homogenization below 40°C, and homogenization at 40°C to 50°C, the droplets successively undergo changes from unqualified to qualified, unqualified, and qualified. Further, the ideal droplet size can be obtained by adjusting the final temperature after cooling of the second homogenization, and after the finished fusidic acid cream undergoes the process verification process of the method of the present invention, its droplet particle size and content uniformity are qualified, which can ensure the stability of the product.

[0014] The above-mentioned method for preparing fusidic acid cream is characterized in that the temperature is maintained after cooling to 40°C to 50°C and the second homogenization is continued for 10min to 50min. Preferably, the second homogenization time is 10min to 40min, and more preferably, the second homogenization time is 10min to 30min.

[0015] In addition, the present invention also provides a fusidic acid cream prepared by the above method, characterized in that the droplet size of the fusidic acid cream does not exceed 20 μm. Preferably, the droplet size of the fusidic acid cream does not exceed 10 μm.

[0016] The present invention also provides a use of the fusidic acid cream as described above, characterized in that the fusidic acid cream is used to treat bacterial skin infections, wherein the bacterial skin infections are selected from pustule sores, furuncle, paronychia, traumatic infection, scurvy, hidradenitis, erythrasma, folliculitis, acne vulgaris, eczema infection, and ulcer infection.

[0017] Compared with the prior art, the present invention has the following advantages:

[0018] 1. According to the prescription amount of fusidic acid cream, the present invention first prepares an aqueous phase and an oil phase separately, then mixes the aqueous phase and the oil phase for a first homogenization, and then adds a fusidic acid raw material for a second homogenization. The two homogenization treatments promote full fusion of the aqueous phase, the oil phase, and the fusidic acid raw material, reduce the particle size of the droplets, improve the mixing uniformity and stability of the fusidic acid ointment, effectively avoid the droplet aggregation phenomenon, and the preparation process is simple, which is suitable for large-scale production.

[0019] 2. The present invention controls the final temperature after cooling of the second homogenization, thereby controlling the particle size of the droplets in the finished fusidic acid cream, thereby improving the organizational structure of the fusidic acid cream and enhancing its stability, and solving the droplet aggregation phenomenon in the finished fusidic acid cream.

[0020] 3. The present invention realizes reversible change of droplet particle size by controlling the change of the final temperature after cooling of the second homogenization, and further adjusts the droplet particle size in the finished fusidic acid cream to obtain an ideal fusidic acid cream finished product state. The method is flexible, convenient, and easy to implement, thereby improving the operability of the preparation method of the present invention and being suitable for industrial production.

[0021] The technical solution of the present invention is further described in detail below through the accompanying drawings and embodiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 The present invention is a flow chart of the preparation process of fusidic acid cream.

[0023] Figure 2 This is a micrograph of the finished fusidic acid cream prepared in Example 2 of the present invention.

[0024] Figure 3 This is a micrograph of the finished fusidic acid cream prepared in Comparative Example 1 of the present invention.

[0025] Figure 4 This is a micrograph of the finished fusidic acid cream prepared in Comparative Example 2 of the present invention.

[0026] Figure 5 This is a micrograph of the finished fusidic acid cream prepared in Comparative Example 3 of the present invention. DETAILED DESCRIPTION

[0027] The particle size distribution determination method in the specific embodiment of the present invention (including D 90 and D 50 ) Refer to the first method (microscope method) in the "General Rules 0982 of the 2020 Edition of the Chinese Pharmacopoeia", which is as follows: Take the test sample and shake it vigorously. If the viscosity is high, add an appropriate amount of glycerol solution (1→2) to dilute it according to the regulations under each variety. According to the regulations under the dosage form or each variety, measure the test sample, place it on a slide, cover it with a cover glass, and press lightly to make the particles evenly distributed. Be careful to prevent bubbles from mixing in. Semi-solids can be directly applied to the slide. Immediately examine the entire field of view of the cover glass under a 50-100x microscope. There should be no agglomeration phenomenon, and no particles of 5μm and above specified in the dosage form or each variety should be detected; then examine the total number of particles and the number of particles of the specified size in the field of view specified in the dosage form or each variety under a 200-500x microscope, and calculate their proportion (%).

[0028] The method for determining the mixing uniformity in the specific embodiment of the present invention refers to the high performance liquid chromatography method in the "General Rules 0512 of the Four Parts of the Chinese Pharmacopoeia 2020 Edition", which is as follows:

[0029] Chromatographic conditions: using blocked octadecylsilane bonded silica gel as filler (150 mm × 4.6 mm, 3.5 μm), mobile phase A is methanol-0.05 M phosphoric acid-acetonitrile (volume ratio 20:40:40), mobile phase B is methanol-0.05 M phosphoric acid-acetonitrile (volume ratio 20:10:70), elution is performed according to the gradient in Table 1 below; column temperature is 30 ° C, detection wavelength is 235 nm, flow rate is 1.0 mL / min, injection volume is 20 μL;

[0030] Table 1 Elution conditions of HPLC

[0031] Time (min) Mobile phase A volume content (%) Volume content of mobile phase B (%) 0～2 100 0 3～28 100～0 0～100 28～33 0 100 33～34 0～100 100～0 34～40 100 0

[0032] Test solution: Disperse the cream containing about 25 mg of anhydrous fusidic acid in 8 mL of solvent A, which is methanol-0.05 M phosphoric acid-acetonitrile (10:40:50). Heat until the cream is dispersed and shake vigorously for 15 min. Allow the mixture to cool to room temperature and dilute to 100 mL. Further cool the mixture to below 10 ° C and filter (0.7 μm GMF syringe filter), discard the initial filtrate, and place at room temperature to obtain;

[0033] Reference substance solution: Take an appropriate amount of potassium sorbate reference substance, weigh it accurately, dissolve it in solvent A, and dilute it to make a solution containing 0.8 mg per 1 mL as the potassium sorbate reference substance stock solution. Accurately weigh 25 mg of fusidic acid reference substance and put it into a 100 ml volumetric flask, accurately add 5 mL of potassium sorbate reference substance stock solution, dissolve it in solvent A, dilute to the scale and shake well to use as the reference substance solution;

[0034] System suitability requirements: The number of theoretical plates calculated based on the fusidic acid peak should be no less than 5000, and the tailing factor should be no greater than 1.5;

[0035] Determination method: Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph respectively, record the chromatogram, and calculate the content of fusidic acid in the test sample by the peak area according to the external standard method (C 31 H 48 O6).

[0036] Example 1

[0037] The prescription composition of the fusidic acid cream of the present embodiment is shown in Table 2 below:

[0038] Table 2 Prescription composition of fusidic acid cream

[0039] Prescription ingredients Prescription dosage (g / 10g) Mass ratio (%) Fusidic acid 0.2 2 Butylated Hydroxyanisole 0.04 0.004 Cetyl Alcohol 1.11 11.1 85% glycerol 1.11 11.1 Liquid paraffin 1.11 11.1 Potassium Sorbate 0.027 0.27 Polysorbate 60 0.056 5.6 White Vaseline 0.056 5.6 hydrochloric acid Moderate Moderate Purified water Add to total weight 10.000g Replenish to 100%

[0040] like Figure 1 As shown, the preparation method of the fusidic acid cream of this embodiment comprises the following steps:

[0041] Step 1, at room temperature, adding the aqueous phase of the prescription composition of fusidic acid cream, including 85% by volume of glycerol, potassium sorbate and purified water, into a stirring tank and stirring evenly, then adjusting the pH to about 5 with a hydrochloric acid solution, and then heating to 75° C. and stirring evenly to obtain an aqueous phase mixture;

[0042] Step 2: at room temperature, adding the oil phase of the fusidic acid cream, including cetyl alcohol, white vaseline, polysorbate 60, liquid paraffin and butylated hydroxyanisole, into an emulsifying homogenizer, stirring and heating to 75° C. to melt, to obtain an oil phase mixture;

[0043] Step 3, mixing the aqueous phase mixture obtained in step 1 with the oil phase mixture obtained in step 2, and performing a first homogenization at 75° C. for 20 minutes to obtain a mixture;

[0044] Step 4: adding the fusidic acid raw material to the mixture obtained in step 3 for a second homogenization, and slowly cooling to obtain a crude fusidic acid cream; the starting temperature of the cooling process is 75.8°C, the final temperature is 42.3°C, the cooling time is 33min, and the cooling rate is 1°C / min;

[0045] Step 5: Maintain the crude fusidic acid cream obtained in step 4 at 42° C. and continue to perform a second homogenization for 10 minutes, and obtain a finished fusidic acid cream after cooling and filling.

[0046] After testing, the appearance of the finished fusidic acid cream obtained in this example is a delicate white cream, and the droplet size D90 is 4.09 μm, which is less than 10 μm.

[0047] Example 2

[0048] The difference between this embodiment and embodiment 1 is that the final temperature of the cooling process in step 4 is 45°C, the cooling time is 30 minutes, and the cooling rate is 1°C / min.

[0049] Comparative Example 1

[0050] The difference between this comparative example and Example 2 is that the final temperature of the cooling process in step 4 is 35°C, the cooling time is 40 minutes, and the cooling rate is 1°C / min.

[0051] Comparative Example 2

[0052] The difference between this comparative example and Example 2 is that the final temperature of the cooling process in step 4 is 55°C, the cooling time is 20 minutes, and the cooling rate is 1°C / min.

[0053] The finished fusidic acid creams prepared in Example 2 and Comparative Examples 1-2 were tested, and the results are shown in Table 3 below.

[0054] Table 3 Test results of the finished fusidic acid cream prepared in Example 2 and Comparative Examples 1 to 2

[0055]

[0056]

[0057] As can be seen from Table 3, when the final temperature after cooling in the second homogenization step in Example 2 is 38°C to 52°C, the obtained fusidic acid cream product has a certain viscosity and fluidity, and the droplet size is less than 10 μm. Figure 2 As shown; when the final temperature after cooling of the second homogenization in Comparative Example 1 is below 38°C, the obtained fusidic acid cream product is viscous, has poor fluidity and has droplet aggregation, such as Figure 3 As shown; when the final temperature after cooling of the second homogenization in Comparative Example 2 is below 52°C, the obtained fusidic acid cream has low viscosity and good fluidity, but the droplet size is mostly above 30μm, such as Figure 4 Therefore, the present invention controls the final temperature after the second homogenization cooling, thereby controlling the droplet size in the fusidic acid cream finished product, thereby improving the organizational structure of the fusidic acid cream and improving its stability, and solving the droplet aggregation phenomenon in the fusidic acid cream finished product.

[0058] Comparative Example 3

[0059] The difference between this comparative example and Example 2 is that the process of continuing the second homogenization for 10 minutes is omitted in step 5.

[0060] After testing, the droplets of the fusidic acid cream product prepared in this comparative example have obvious aggregation phenomenon, such as Figure 5 shown.

[0061] (1) Process reversibility analysis

[0062] The second homogenization process in step 5 of the preparation method of the present invention is subjected to a change of cooling and then heating, and the specific process is as follows:

[0063] Step 1, at room temperature, adding the aqueous phase of the prescription composition of fusidic acid cream, including 85% by volume of glycerol, potassium sorbate and purified water, into a stirring tank and stirring evenly, then adjusting the pH to about 5 with a hydrochloric acid solution, and then heating to 75° C. and stirring evenly to obtain an aqueous phase mixture;

[0064] Step 2: at room temperature, adding the oil phase of the fusidic acid cream, including cetyl alcohol, white vaseline, polysorbate 60, liquid paraffin and butylated hydroxyanisole, into an emulsifying homogenizer, stirring and heating to 75° C. to melt, to obtain an oil phase mixture;

[0065] Step 3, mixing the aqueous phase mixture obtained in step 1 with the oil phase mixture obtained in step 2, and performing a first homogenization at 75° C. for 20 minutes to obtain a mixture;

[0066] Step 4: adding the fusidic acid raw material to the mixture obtained in step 3 for a second homogenization, and slowly cooling to obtain a crude fusidic acid cream; the starting temperature of the cooling process is 75.8°C, the final temperature is 52°C to 55°C, and the cooling rate is 1°C / min;

[0067] Step 5. Maintain the crude fusidic acid cream obtained in step 4 at 52°C to 55°C for a second homogenization for 10 minutes to obtain intermediate A, cool intermediate A to a final temperature of 42°C to 45°C for a second homogenization for 10 minutes to obtain intermediate B, continue to cool intermediate B to a final temperature of 35°C to 38°C for a second homogenization for 10 minutes to obtain intermediate C, heat intermediate C to a final temperature of 42°C to 45°C for a second homogenization for 10 minutes to obtain intermediate D, and then cool and fill to obtain a finished fusidic acid cream.

[0068] The appearance properties and droplet size of intermediates A, B, C and D were observed and tested respectively, and the effect of temperature change on the appearance properties and droplet size of the finished fusidic acid cream was analyzed. The results showed that when the final temperature of the second homogenization was between 52°C and 55°C, the droplets of intermediate A were prone to aggregation and merging, and sampling and extending the second homogenization time still could not improve the linearity; when the final temperature of the second homogenization dropped to 42°C to 45°C, the product was obtained after homogenization for 10 minutes. The intermediate product B can obtain small and uniform droplets, and its particle size distribution is consistent with the commercially available fusidic acid cream (Leo Pharmaceuticals, Denmark) by microscopic observation, which meets the requirements; when the second homogenization final temperature continues to drop to 35℃~38℃, the droplets of the intermediate product C obtained become larger, indicating that the droplets have merged and aggregated again, resulting in a larger particle size and uneven distribution; when the second homogenization final temperature is raised to 42℃~45℃ again, the droplets of the intermediate product D obtained after homogenization for 10 minutes become smaller and uniform again. Further, the droplet size and distribution of each intermediate product are shown in Table 4 below.

[0069] Table 4 Droplet size and distribution of intermediate products

[0070]

[0071]

[0072] Combining the above observation and detection results with the contents of Table 4, it can be seen that when the second homogenization final temperature undergoes temperature changes of greater than 50°C homogenization, 40°C to 50°C homogenization, lower than 40°C homogenization, and 40°C to 50°C homogenization, the droplets successively undergo changes of unqualified, qualified, unqualified, and qualified, indicating that the preparation method of fusidic acid cream of the present invention obtains an ideal droplet size by adjusting the final temperature after cooling of the second homogenization, and after the finished fusidic acid cream undergoes the process verification process of the method of the present invention, its droplet particle size and content uniformity are qualified, which can ensure the stability of the product.

[0073] (2) Particle size distribution and mixing uniformity test

[0074] A 200 kg batch of finished products was prepared according to the method of Example 2 of the present invention, and in step 5, the crude fusidic acid cream was maintained at 40°C to 50°C for a second homogenization for 30 min to obtain the fusidic acid cream, and samples were taken after the second homogenization for 15 min, 20 min and 30 min, respectively, and the particle size distribution of each sample was detected. At the same time, 10 samples were taken from the upper, middle and lower layers of the homogenization tank after the second homogenization for 15 min, 20 min and 30 min, i.e., samples ① to ⑩, and the mixing uniformity of each sample was detected. The results are shown in Tables 5 and 6.

[0075] Table 5 Particle size distribution results of samples

[0076]

[0077]

[0078] As can be seen from Table 5, the droplet particle size of the finished product of the fusidic acid cream obtained by the preparation method of the present invention does not exceed 10 μm, indicating that the preparation method of the present invention reduces the droplet particle size of the fusidic acid cream, effectively avoids the droplet aggregation phenomenon, and is suitable for large-scale production.

[0079] Table 6 Mixing uniformity test results of samples

[0080]

[0081]

[0082] As can be seen from Table 6, the mixing uniformity of the fusidic acid cream prepared by the method of the present invention is between 95.0% and 105.0%, and the RSD is less than 5%, which meets the quality standards in the pharmacopoeia.

[0083] (3) Stability test

[0084] The finished fusidic acid cream (homogenized for 30 min) prepared in Example 5 was sampled for accelerated stability and freeze-thaw stability tests, and the particle size distribution was measured. The specific process was as follows: 1) the fusidic acid cream sample was placed at a temperature of 40°C ± 2°C and a RH humidity of 65% ± 5% and the droplet particle size was detected at the 0th month, the 1st month, and the 2nd month of standing. The results are shown in Table 7; 2) the fusidic acid cream sample was placed at a temperature of -20°C and allowed to stand for 2 days, and then transferred to 40°C and allowed to stand for 2 days. The above placement and transfer process were repeated 3 times to complete the freeze-thaw test, and the droplet particle size was detected by sampling. The results are shown in Table 8.

[0085] Table 7 Accelerated stability test results

[0086] Accelerated 40℃±2℃ Month 0 Month 1 Month 2 <![CDATA[Droplet size distribution (D 90 , μm)]]> 4.94 3.22 3.78 <![CDATA[Droplet size distribution (D 50 , μm)]]> 2.22 1.70 2.13

[0087] As can be seen from Table 7, with the increase of the standing time in the accelerated stability test, the droplets of the fusidic acid cream sample are small and dense, the droplet size is gradually stabilized, and no aggregation occurs, indicating that the fusidic acid cream prepared by the present invention has good kinetic stability.

[0088] Table 8 Freeze-thaw stability test results

[0089] sample Before freeze-thaw test After freeze-thaw test <![CDATA[Droplet size distribution (D 90 , μm)]]> 2.34 2.35 <![CDATA[Droplet size distribution (D 50 , μm)]]> 1.28 1.28

[0090] As can be seen from Table 8, the properties and spreadability of the fusidic acid cream sample did not change before and after the freeze-thaw test, and the droplet size distribution was also basically stable, indicating that the fusidic acid cream prepared by the present invention has good kinetic stability.

[0091] It can be seen from Tables 7 and 8 that the accelerated stability and freeze-thaw stability of the fusidic acid cream prepared by the method of the present invention meet the quality standards in the pharmacopoeia.

[0092] Example 3

[0093] The fusidic acid cream of the present embodiment is used to treat bacterial skin infections, and the bacterial skin infections are selected from pustule, furuncle, paronychia, trauma complicated with infection, scurvy, hidradenitis, erythrasma, folliculitis, acne vulgaris, eczema complicated with infection, and ulcer complicated with infection.

[0094] The above is only a preferred embodiment of the present invention and does not limit the present invention in any way. Any simple modification, change and equivalent change made to the above embodiment according to the technical essence of the invention still falls within the protection scope of the technical solution of the present invention.

Claims

1. A method for preparing fusidic acid cream, characterized in that: The specific process of the method is: according to the prescription composition of fusidic acid cream, the water phase and the oil phase are mixed and then subjected to the first homogenization, the temperature of the first homogenization is 50°C-100°C, to obtain a mixture, and then the fusidic acid raw material is added to the mixture for the second homogenization and the mixture is cooled to 40°C-50°C and then maintained at the temperature to continue the second homogenization to obtain fusidic acid cream; the water phase comprises glycerin with a volume fraction of 85%, potassium sorbate and purified water, and the oil phase comprises hexadecanol, white vaseline, polysorbate 60, liquid paraffin and butylated hydroxyanisole; the droplet particle size D90 of the fusidic acid cream does not exceed 10 μm.

2. A method for preparing fusidic acid cream according to claim 1, characterized in that, The first homogenization time is 10 min to 50 min.

3. A method for preparing fusidic acid cream according to claim 1, characterized in that, The cooling rate is 1°C / min.

4. A method for preparing fusidic acid cream according to claim 1, characterized in that, The time for continuing the second homogenization is 10min to 50min.

5. Use of fusidic acid cream prepared by the method according to any one of claims 1 to 4 in preparing a medicament for treating bacterial skin infections, characterized in that: The bacterial skin infection is selected from pustule, furuncle, paronychia, traumatic infection, scurvy, hidradenitis, erythrasma, folliculitis, acne vulgaris, eczema infection or ulcer infection.

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