A fusidic acid cream composition and preparation method thereof

Abstract

The present application provides a fusidic acid cream composition and a preparation method thereof. The fusidic acid cream composition comprises or consists of the following components: fusidic acid, liquid paraffin, cyclomethicone, an emulsifier, a co-emulsifier, a thickener, a preservative, an antioxidant, and water; wherein the emulsifier is polysorbate 80, the co-emulsifier is ethylene glycol palmitostearate, the thickener is isopropyl palmitate, the preservative is potassium sorbate, and the antioxidant is butylated hydroxyanisole. The fusidic acid cream composition exhibits good emulsification and excellent stability during preparation and long-term storage, making it suitable for industrial production.

Description

Technical Field

[0001] The present application relates to the field of pharmaceutical preparations, and in particular to a fusidic acid cream composition and a preparation method thereof. Background Art

[0002] Any discussion of the prior art throughout the specification should not be considered as an admission that such prior art is widely known or forms part of the common general knowledge in the field.

[0003] Fusidic acid, a fusidic acid antibacterial drug, was first extracted from the fungus Lipocystis in 1962 by LEO Pharma of Denmark. It exerts its antibacterial effects by inhibiting ribosome translocation, interfering with elongation factor G and thereby hindering bacterial protein synthesis. Fusidic acid is a highly effective, narrow-spectrum antibacterial drug with strong activity against Gram-positive bacteria and a variety of anaerobic bacteria, while being insensitive to most Gram-negative bacteria. It is particularly sensitive to Staphylococcus aureus, Staphylococcus epidermidis, Clostridium spp., and Corynebacterium spp. It is primarily used to treat skin infections caused by Staphylococci, Streptococci, Propionibacterium acnes, Corynebacterium parvum, and other fusidic acid-sensitive bacteria. It is widely used in the treatment of acne, impetigo in children, eczema, and bacterial skin infections.

[0004] Fusidic acid contains unconjugated olefin side chains in its molecular structure, which can easily generate impurities during sample preparation and storage, leading to an increase in related substances and affecting product stability.

[0005] The purpose of this application is to overcome or improve at least one disadvantage of the prior art, or to provide a useful alternative. Unless the context clearly requires otherwise, throughout the specification and claims, words such as "include", "comprise", and "includes" should be interpreted from an inclusive perspective, rather than from an exclusive or exhaustive perspective; that is, from the perspective of "including, but not limited to". Summary of the Invention

[0006] The present application provides a fusidic acid cream composition and a preparation method thereof. The fusidic acid cream prepared in the present application has a good emulsification state, is very stable during preparation and long-term storage, and is suitable for industrial production.

[0007] Specifically, the technical solution of this application is as follows:

[0008] In a first aspect of the present application, the present application provides a fusidic acid cream composition, which comprises or consists of the following components: fusidic acid, liquid paraffin, cyclomethicone, an emulsifier, a co-emulsifier, a thickener, a preservative, an antioxidant and water;

[0009] Wherein, the emulsifier is polysorbate 80, the co-emulsifier is ethylene glycol stearate palmitate, the thickener is isopropyl palmitate, the preservative is potassium sorbate, and the antioxidant is butylated hydroxyanisole.

[0010] The weight ratio of ethylene glycol stearate palmitate to polysorbate 80 is 1-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1.

[0011] In an embodiment of the present application, ethylene glycol stearate palmitate is added to fusidic acid cream as a co-emulsifier and isopropyl palmitate is added as a thickener, which not only increases the emulsifying ability of the emulsifier, but also has a very positive effect on the stability of fusidic acid. During the preparation and stability study, there is no significant change in the related substances, and the stability of the fusidic acid cream during storage can be ensured.

[0012] For example, in the embodiments of the present application, in the formulation of the present application, when the weight ratio of ethylene glycol palmitate stearate to polysorbate 80 is 1-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, the fusidic acid cream has good stability, does not undergo emulsion breaking, and there is no significant change in the related substances.

[0013] Furthermore, in some embodiments of the present application, in the formulation of the present application, when the weight ratio of ethylene glycol palmitate stearate to polysorbate 80 is 1.2-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1.2-4:1, the stability and emulsification properties of fusidic acid cream are better.

[0014] In some embodiments, the inventors attempted to use substances commonly used in the art for preparing fusidic acid, such as glyceryl monostearate and cetostearyl alcohol, as co-emulsifiers. However, under the same accelerated conditions, the related substances significantly increased, resulting in poor stability. Furthermore, in some embodiments, the inventors attempted to use substances commonly used in the art for preparing fusidic acid, such as xanthan gum, stearic acid, and cocoyl monoisopropanolamide, as thickeners. However, at the same viscosity, demulsification occurred during stability studies.

[0015] In some embodiments of the present application, the present application provides a fusidic acid cream composition, which is composed of: 2% fusidic acid, 5%-20% liquid paraffin, 4%-20% cyclomethicone, 2%-10% polysorbate 80, 0.1%-1% potassium sorbate, 0.01%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

[0016] Furthermore, in these embodiments, when the weight ratio of ethylene glycol palmitate stearate to polysorbate 80 is 1.2-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1.2-4:1, the fusidic acid cream composition described in the present application has better stability and emulsification properties.

[0017] In other embodiments of the present application, the present application provides a fusidic acid cream composition, which is composed of: 2% fusidic acid, 5%-15% liquid paraffin, 4%-16% cyclomethicone, 2%-8% polysorbate 80, 0.1%-0.8% potassium sorbate, 0.01%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

[0018] Furthermore, in these embodiments, when the weight ratio of ethylene glycol palmitate stearate to polysorbate 80 is 1.2-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1.2-4:1, the fusidic acid cream composition described in the present application has better stability and emulsification properties.

[0019] In some other embodiments of the present application, the present application provides a fusidic acid cream composition, which is composed of: 2% fusidic acid, 10%-15% liquid paraffin, 5%-16% cyclomethicone, 2%-6% polysorbate 80, 0.2%-0.8% potassium sorbate, 0.05%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

[0020] Furthermore, in these embodiments, when the weight ratio of ethylene glycol palmitate stearate to polysorbate 80 is 1.2-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1.2-4:1, the fusidic acid cream composition described in the present application has better stability and emulsification properties.

[0021] In a second aspect of the present application, the present application provides a method for preparing the fusidic acid cream composition described in the first aspect, comprising:

[0022] Prepare the oil phase: Place liquid paraffin, cyclomethicone, part of polysorbate 80, glycol stearate palmitate, isopropyl palmitate and butylated hydroxyanisole in an oil phase container and heat until melted;

[0023] Prepare the aqueous phase: place purified water, potassium sorbate and the remaining amount of polysorbate 80 in an aqueous phase container, heat, add fusidic acid, and stir to obtain an aqueous phase;

[0024] Emulsification: Add water phase to oil phase under vacuum, heat, stir homogeneously, and condense to obtain the product.

[0025] In some preferred embodiments of the present application, the amount of polysorbate 80 used in preparing the oil phase and the water phase is the same.

[0026] In some embodiments of the present application, the method comprises:

[0027] Add liquid paraffin, cyclomethicone, 1 / 2 of the prescribed amount of polysorbate 80, glycol stearate palmitate, isopropyl palmitate and butylated hydroxyanisole to the oil phase container and heat to 70-75°C to melt;

[0028] Add purified water, potassium sorbate, and 1 / 2 of the prescribed amount of polysorbate 80 to the aqueous phase container, heat to 60°C, add fusidic acid, and stir to disperse evenly to obtain an aqueous phase;

[0029] Adding the water phase to the oil phase container under vacuum, thoroughly mixing the resulting mixture with a stirrer at 10 to 60 rpm, maintaining the mixture at 65-75° C., and homogenizing the mixture at 3000 rpm to 5000 rpm;

[0030] The homogenized mixture was cooled to 30-40°C by condensation.

[0031] Furthermore, the cooled cream can be filled into an aluminum tube to prepare a cream preparation, and the filling amount of the preparation can be, for example, 15 g per tube.

[0032] Compared with the existing technology, the advantages of this application are:

[0033] The present application provides a fusidic acid cream composition and a preparation method thereof. The present application uses ethylene glycol palmitate stearate as a co-emulsifier and isopropyl palmitate as a thickener, and specifies the amounts of ethylene glycol palmitate stearate and isopropyl palmitate. The use of ethylene glycol palmitate stearate as a co-emulsifier not only increases the emulsifying ability of the emulsifier but also has a very positive effect on the stability of fusidic acid, with no significant changes in related substances during the preparation and stability studies. Furthermore, the use of isopropyl palmitate as a thickener also positively impacts the stability of the cream, ensuring its stability during storage. DETAILED DESCRIPTION

[0034] The present application will be further described below in conjunction with specific examples. It should be understood that these examples are intended to illustrate the present application only and are not intended to limit the scope of the present application. The experimental methods in the following examples where specific conditions are not specified are generally performed under conventional conditions or as recommended by the manufacturer.

[0035] Unless otherwise defined, all professional and scientific terms used herein have the same meaning as those familiar to those skilled in the art. The reagents or raw materials used in this application can be purchased through conventional channels. Unless otherwise specified, the reagents or raw materials used in this application are used in a conventional manner in this area or in accordance with the product instructions. In addition, any methods and materials similar to or equivalent to those described herein can be applied to the present method. The preferred embodiments and materials described herein are for demonstration purposes only.

[0036] Example 1

[0037] Prescription: By weight, fusidic acid 2%, liquid paraffin 10%, cyclomethicone 9%, polysorbate 806%, potassium sorbate 0.3%, butylated hydroxyanisole 0.06%, glycol stearate palmitate 12%, isopropyl palmitate 14.64%, purified water 46%.

[0038] The amount of ethylene glycol stearate palmitate was 2 times that of polysorbate 80, and the amount of isopropyl palmitate was 2.4 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the following method, and the emulsion state and related substances of the product were investigated.

[0039] Preparation method of fusidic acid cream:

[0040] Step 1: Add liquid paraffin, cyclomethicone, 1 / 2 of the prescription amount of polysorbate 80, glycol stearate palmitate, isopropyl palmitate and butylated hydroxyanisole to the oil phase container and heat to a molten state at 70-75°C;

[0041] Step 2: Add purified water, potassium sorbate, and 1 / 2 of the prescribed amount of polysorbate 80 to the aqueous phase container, heat to 60°C, add fusidic acid, stir and disperse evenly, and set aside;

[0042] Step 3: adding the water phase to the oil phase container under vacuum, using a stirrer to thoroughly mix the resulting mixture at 10 to 60 rpm, maintaining the mixture at 65-75° C., and homogenizing the mixture at 3000 rpm to 5000 rpm;

[0043] Step 4: The above cream was cooled to 30-40°C by circulating in a cold water bath using a container jacket, and then filled into aluminum tubes at a filling amount of 15 g per tube.

[0044] Example 2

[0045] Prescription: By weight, fusidic acid 2%, liquid paraffin 15%, cyclomethicone 16%, polysorbate 802%, potassium sorbate 0.8%, butylated hydroxyanisole 0.1%, glycol stearate palmitate 6%, isopropyl palmitate 8%, purified water 50.10%.

[0046] The amount of ethylene glycol stearate palmitate was 3 times that of polysorbate 80, and the amount of isopropyl palmitate was 4 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0047] Example 3

[0048] Prescription: By weight, fusidic acid 2%, liquid paraffin 5%, cyclomethicone 4%, polysorbate 80 8%, potassium sorbate 0.1%, butylated hydroxyanisole 0.01%, glycol stearate palmitate 8%, isopropyl palmitate 8%, purified water 64.89%.

[0049] The amount of ethylene glycol stearate palmitate was 1 times that of polysorbate 80, and the amount of isopropyl palmitate was 1 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0050] Comparative Example 1

[0051] Prescription: By weight, fusidic acid 2%, liquid paraffin 13%, cyclomethicone 16%, polysorbate 806%, potassium sorbate 0.5%, butylated hydroxyanisole 0.04%, glycol stearate palmitate 4.5%, isopropyl palmitate 4.5%, purified water 53.46%.

[0052] The amount of ethylene glycol palmitate stearate was 0.75 times that of polysorbate 80, and the amount of isopropyl palmitate was 0.75 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0053] Comparative Example 2

[0054] Prescription: By weight, fusidic acid 2%, liquid paraffin 5%, cyclomethicone 4%, polysorbate 80 4%, potassium sorbate 0.2%, butylated hydroxyanisole 0.08%, glycol stearate palmitate 16%, isopropyl palmitate 20%, purified water 48.72%.

[0055] The amount of ethylene glycol stearate palmitate is 4 times that of polysorbate 80, and the amount of isopropyl palmitate is 5 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0056] Comparative Example 3

[0057] Prescription: By weight, fusidic acid 2%, liquid paraffin 10%, cyclomethicone 9%, polysorbate 806%, potassium sorbate 0.3%, butylated hydroxyanisole 0.06%, glyceryl monostearate 12%, isopropyl palmitate 14.64%, purified water 46%.

[0058] The amount of ethylene glycol stearate palmitate was changed to glyceryl monostearate, and the amount of isopropyl palmitate was 2.4 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0059] Comparative Example 4

[0060] Prescription: By weight, fusidic acid 2%, liquid paraffin 15%, cyclomethicone 16%, polysorbate 802%, potassium sorbate 0.8%, butylated hydroxyanisole 0.1%, cetostearyl alcohol 6%, isopropyl palmitate 8%, purified water 50.1%.

[0061] The amount of ethylene glycol stearate palmitate was changed to cetostearyl alcohol, and the amount of isopropyl palmitate was 3 times that of polysorbate 80, and the amount of isopropyl palmitate was 1.3 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0062] Comparative Example 5

[0063] Prescription: By weight, fusidic acid 2%, liquid paraffin 5%, cyclomethicone 4%, polysorbate 80 8%, potassium sorbate 0.1%, butylated hydroxyanisole 0.01%, glycol stearate palmitate 8%, xanthan gum 8%, purified water 64.89%.

[0064] The amount of ethylene glycol palmitate stearate was 1 times that of polysorbate 80, and isopropyl palmitate was replaced with xanthan gum in an amount 1 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0065] Comparative Example 6

[0066] Prescription: By weight, fusidic acid 2%, liquid paraffin 11%, cyclomethicone 8.5%, polysorbate 80 5.5%, potassium sorbate 0.31%, butylated hydroxyanisole 0.05%, glycol stearate palmitate 12%, stearic acid 14.64%, purified water 46.00%.

[0067] The amount of ethylene glycol stearate palmitate was 2.2 times that of polysorbate 80, and isopropyl palmitate was replaced with stearic acid in an amount 2.7 times that of polysorbate 80. 100 tubes of fusidic acid cream were prepared according to the method described in Example 1, and the emulsion state and related substances of the product were investigated.

[0068] Experimental example

[0069] Twenty tubes of each of the fusidic acid creams of Examples 1-3 and Comparative Examples 1-6 were placed in an accelerated test chamber (conditions: temperature 30°C, relative humidity RH 65%). Samples were taken on day 0 and day 30, respectively, to examine the emulsification state and related substances of the creams. The results are shown in Table 1.

[0070] Emulsion status detection: Take this product, add it to a 10mL centrifuge tube, turn on the centrifuge, set the speed to 5000rpm, centrifuge for 30min, and observe whether there is oil-water separation. If there is, it is demulsification, if not, it is in good condition.

[0071] Detection method for related substances: Take an appropriate amount of this product, accurately weigh it, add diluent (methanol-5g / L phosphoric acid solution-acetonitrile = 10:40:50) to dissolve and dilute it to make a solution containing approximately 2.5 mg per 1 mL, which is used as the test solution; accurately measure 1 mL and quantitatively dilute it with diluent to make a solution containing approximately 25 μg per 1 mL, which is used as control solution b; accurately measure an appropriate amount of control solution b and quantitatively dilute it with diluent to make a solution containing approximately 2.5 μg per 1 mL, which is used as control solution c. The test was performed according to the high performance liquid chromatography method (Appendix ⅤD, Part II of the Chinese Pharmacopoeia 2010 edition), using octadecylsilane bonded silica gel as the filler (Agilent Eclipse Plus C18 150×4.6 mm, suitable for 3.5 μm); methanol-5 g / L phosphoric acid solution-acetonitrile (20:40:40) as the mobile phase A, and methanol-5 g / L phosphoric acid solution-acetonitrile (20:10:70) as the mobile phase B, and linear elution was performed according to the table below; the detection wavelength was 235 nm; the column temperature was 30°C; and the flow rate was 1.0 mL per minute (the flow rate was adjusted if necessary). Take an appropriate amount of fusidic acid peak identification standard (containing impurities A, B, C, D, F, G, H, and N), dissolve it in diluent, and quantitatively dilute it to a solution containing approximately 2 mg per 1 mL. This is referred to as control solution a. Inject 20 μL into the liquid chromatograph to achieve a retention time of approximately 16-20 minutes for the fusidic acid peak. Record the chromatogram, ensuring a resolution of at least 1.5 between impurities G and H. Separately, dissolve one bottle of fusidic acid peak mixed impurity standard (containing impurities I, K, L, and M) in 1.0 mL of diluent to create control solution d. Take 20 μL each of control solution b, control solution c, control solution d, and test solution and inject them into the liquid chromatograph to record the chromatogram. If there are impurity peaks in the chromatogram of the test solution (see the table below for the relative retention time and correction factor of each impurity), calculate according to the corrected peak area, then impurity M shall not be greater than the main peak area of ​​control solution b (1.0%), impurity G shall not be greater than 0.7 times the main peak area of ​​control solution b (0.7%), impurity L shall not be greater than 0.5 times the main peak area of ​​control solution b (0.5%), impurity B shall not be greater than 4 times the main peak area of ​​control solution c (0.4%), impurity A shall not be greater than 3 times the main peak area of ​​control solution c (0.3%), impurities C, D, F, I, K, and N shall not be greater than 2 times the main peak area of ​​reference solution c (0.2%), and other individual impurities shall not be greater than the main peak area of ​​reference solution c (0.10%), and the sum of the peak areas of each impurity shall not be greater than 2 times the main peak area of ​​control solution b (2.0%). Peaks in the test solution with an area less than 0.5 times the area of ​​the main peak in the control solution c can be ignored (0.05%).

[0072] Quality control standards for fusidic acid cream finished products: the maximum single impurity should not exceed 0.7%, and the total impurities should not exceed 2.0%.

[0073] Table 1. Stability of fusidic acid cream

[0074]

[0075] According to the experimental results, we can know that:

[0076] The fusidic acid cream products prepared in Examples 1-3 had good emulsion state, the maximum single impurities and the total impurities were relatively small, and the various indicators did not change significantly after being placed under accelerated conditions for 30 days, indicating good stability.

[0077] In the fusidic acid cream products prepared in Comparative Examples 1 and 2, the dosages of ethylene glycol stearate palmitate and isopropyl palmitate were too high, and the prepared creams had a rough appearance and oil-water separation and demulsification on the 0th day of the test.

[0078] In the fusidic acid cream products prepared in Comparative Examples 3 and 4, ethylene glycol stearate palmitate was replaced with commonly used glyceryl monostearate and cetostearyl alcohol as co-emulsifiers. The emulsification state of the cream was good, but the related substances showed a significant increase during the preparation process and stability investigation, affecting product safety.

[0079] In the fusidic acid cream products prepared in Comparative Examples 5 and 6, isopropyl palmitate was replaced with commonly used xanthan gum and stearic acid as thickeners. The cream had a good emulsion state at 0 days, but when the stability test was extended to 30 days, oil-water separation and demulsification occurred, indicating that isopropyl palmitate not only increased the viscosity of the cream, but also played a very positive role in the emulsion state and stability of the cream.

[0080] In summary, the use of ethylene glycol stearate palmitate as a co-emulsifier not only improves the emulsifying ability of the emulsifier and produces a well-performing cream, but also significantly protects the related substances of fusidic acid. Furthermore, the simultaneous use of isopropyl palmitate as a thickener not only increases the viscosity of the cream but also plays a very positive role in the emulsification state and stability of the cream. The fusidic acid cream prepared in this application has a good emulsification state, is very stable during preparation and long-term storage, and is suitable for industrial production.

[0081] The above description is merely a preferred embodiment of the present application and is not intended to limit the present application. Although the present application has been described in detail with reference to the aforementioned embodiments, those skilled in the art may still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein with equivalents. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principles of the present application shall be included within the scope of protection of the present application.

Claims

1. A fusidic acid cream composition, characterized in that, The composition is as follows by weight: 2% fusidic acid, 5%-20% liquid paraffin, 4%-20% cyclomethicone, 2%-10% polysorbate 80, 0.1%-1% potassium sorbate, 0.01%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

2. The fusidic acid cream composition according to claim 1, wherein The composition is as follows by weight: 2% fusidic acid, 5%-15% liquid paraffin, 4%-16% cyclomethicone, 2%-8% polysorbate 80, 0.1%-0.8% potassium sorbate, 0.01%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

3. The fusidic acid cream composition according to claim 1, wherein The composition is as follows by weight: 2% fusidic acid, 10%-15% liquid paraffin, 5%-16% cyclomethicone, 2%-6% polysorbate 80, 0.2%-0.8% potassium sorbate, 0.05%-0.1% butylated hydroxyanisole, the weight ratio of ethylene glycol palmitostearate to polysorbate 80 is 1-3:1, the weight ratio of isopropyl palmitate to polysorbate 80 is 1-4:1, and the balance is water.

4. The fusidic acid cream composition according to any one of claims 1 to 3, characterized in that The weight ratio of ethylene glycol stearate palmitate to polysorbate 80 is 1.2-3:1, and the weight ratio of isopropyl palmitate to polysorbate 80 is 1.2-4:

1.

5. A method for preparing the fusidic acid cream composition according to any one of claims 1 to 4, comprising: Prepare the oil phase: Place liquid paraffin, cyclomethicone, part of polysorbate 80, glycol stearate palmitate, isopropyl palmitate and butylated hydroxyanisole in an oil phase container and heat until melted; Prepare the aqueous phase: place purified water, potassium sorbate and the remaining amount of polysorbate 80 in an aqueous phase container, heat, add fusidic acid, and stir to obtain an aqueous phase; Emulsification: Add water phase to oil phase under vacuum, heat, stir homogeneously, and condense to obtain the product.

6. The method according to claim 5, characterized in that The same amount of polysorbate 80 was used in the preparation of the oil phase and the water phase.

7. The method according to claim 6, characterized in that The method comprises: Add liquid paraffin, cyclomethicone, 1 / 2 of the prescribed amount of polysorbate 80, glycol stearate palmitate, isopropyl palmitate and butylated hydroxyanisole to the oil phase container and heat to 70-75°C to melt; Add purified water, potassium sorbate, and 1 / 2 of the prescribed amount of polysorbate 80 to the aqueous phase container, heat to 60°C, add fusidic acid, and stir to disperse evenly to obtain an aqueous phase; Adding the water phase to the oil phase container under vacuum, thoroughly mixing the resulting mixture with a stirrer at 10 to 60 rpm, maintaining the mixture at 65-75° C., and homogenizing the mixture at 3000 rpm to 5000 rpm; The homogenized mixture was cooled to 30-40°C by condensation.

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