Mometasone furoate cream and preparation method thereof

Abstract

The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to mometasone furoate cream and a preparation method thereof. The mometasone furoate emulsifiable paste is prepared from mometasone furoate and pharmaceutic adjuvants used for preparing water-in-oil type emulsifiable paste, and after phase inversion is completed in a paste body cooling stage, the steps of homogenizing, stirring and dispersing are added, so that the mometasone furoate emulsifiable paste is prepared. The pharmaceutic adjuvant comprises an oil phase component, an emulsifier, a skin feeling regulator, an opacifying agent, a pH regulator, a cosolvent and water. According to the preparation method provided by the invention, the release rate of the product can be obviously increased, the absorption rate of the product is obviously increased, so that the curative effect of the product is improved, the viscosity of paste can be obviously reduced, the comfort degree of a patient during smearing is obviously increased, and the compliance of the product used by the patient is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a mometasone furoate cream and a preparation method thereof. Background Art

[0002] Mometasone furoate, its chemical name is: 9α,21-dichloro-11β,17-dihydroxy-16α-methylpregna-1,4-diene-3,20-dione-17-(2-furoate), the chemical structure is shown in Formula I:

[0003]

[0004] Mometasone furoate is a synthetic steroidal glucocorticoid that has the effect of reducing inflammation and itching. It is suitable for skin diseases that are effective against glucocorticoids. It has the characteristics of strong efficacy and low suppression of adrenal cortex function. The main indication of this drug is to treat inflammation and itching caused by psoriasis (excluding generalized plaque psoriasis) and atopic dermatitis.

[0005] Currently, most mometasone furoate creams on the market are water-in-oil creams. Taking the original product Eloson as an example, the paste viscosity of this product is relatively high, and it is not easy to apply evenly after applying it to the affected skin. The release rate after use is slow, which is not conducive to the drug penetrating into the skin to exert its therapeutic effect.

[0006] The prior art has studied the composition and preparation process of mometasone furoate cream. For example, invention patents with publication numbers CN116421549A, CN114272203A, and CN112754990A have studied mometasone furoate cream and its preparation process. However, in the above patents and the existing cream preparation process, stirring and discharging are stopped after the paste is completely inverted, and the process is no longer continued.

[0007] At present, the way to improve the viscosity and release rate of the paste is usually to adjust the process parameters (such as stirring speed, homogenization speed, emulsification time, emulsification temperature, etc.) during the emulsification stage. In the process of studying the preparation process of mometasone furoate cream, the applicant found that the effect of adjusting the process parameters in the emulsification stage to improve the viscosity and release rate of the paste was not good, and there is no relevant patent or literature report on improving the release rate and viscosity of the product by homogenizing and stirring again after the paste cooling process is completed. Summary of the invention

[0008] In view of this, one of the objects of the present invention is to provide a method for preparing mometasone furoate cream. The present invention has found that by adding simple homogenization and stirring steps after the paste is completely phase-changed in the cooling stage, the mometasone furoate cream prepared in this way has a higher release rate and a lower viscosity, further improving the absorption speed and skin feel of the product.

[0009] To achieve the above object, the present invention adopts the following technical solutions:

[0010] A method for preparing mometasone furoate cream comprises the following steps: preparing the mometasone furoate cream by using mometasone furoate and a pharmaceutical excipient for preparing a water-in-oil cream, and homogenizing, stirring and dispersing the paste after the paste completes phase transition in a cooling stage to obtain the mometasone furoate cream.

[0011] At present, the commercially available mometasone furoate cream, including the original research product, is basically a water-in-oil emulsion. When the patient applies the product to the skin of the affected area, due to the high viscosity of the paste, it will produce a large greasy feeling and discomfort. In addition, the product release rate is low, which affects the penetration rate of the active substance in the skin of the affected area after the product is applied, resulting in reduced efficacy. The focus of the present invention is to wait for the paste to completely change phases when the temperature is lowered, and continue to start homogenization and stirring after the paste temperature is lowered to apply shear stress to it. After adding the above process, the product release rate can be significantly improved, and the viscosity of the paste can be significantly reduced.

[0012] Furthermore, the pharmaceutical excipients for preparing the water-in-oil cream include an oil phase component, an emulsifier, a skin feel regulator, a sunscreen, a pH regulator, a cosolvent and water; the oil phase component is any one or more of white vaseline, white beeswax, and synthetic beeswax; the emulsifier is any one or more of soybean lecithin, egg yolk lecithin, and hydrogenated soybean lecithin; the skin feel regulator is aluminum starch octenylsuccinate; the sunscreen is titanium dioxide; the pH regulator is any one or more of phosphoric acid, hydrochloric acid, sulfuric acid, and nitric acid; and the cosolvent is any one or more of propylene glycol, hexylene glycol, butylene glycol, and sorbitol.

[0013] Furthermore, the mass percentages of the components in the mometasone furoate cream are as follows: 0.1-0.15% of mometasone furoate, 68-75% of oil phase component, 1.0-3.0% of emulsifier, 8-13% of skin feel regulator, 0.5-1.5% of sunscreen, 0.05-0.15% of pH regulator, 10-18% of cosolvent and 2-6% of water.

[0014] Preferably, the mass percentages of the components in the mometasone furoate cream are as follows: 0.1% mometasone furoate, 67.4% white vaseline, 5.0% white beeswax, 1.5% hydrogenated soybean lecithin, 10.0% aluminum starch octenylsuccinate, 1.0% titanium dioxide, 0.05% hydrochloric acid, 11.95% hexylene glycol, and 3.0% water.

[0015] Furthermore, the method specifically comprises the following steps:

[0016] (1) preparing an aqueous phase: dissolving mometasone furoate, a pH adjuster and a cosolvent in water to prepare an aqueous phase;

[0017] (2) Preparation of oil phase: melt the oil phase components, add emulsifier, skin feel regulator and sunscreen, homogenize and stir to evenly disperse the auxiliary materials to prepare the oil phase;

[0018] (3) Emulsification: adding the aqueous phase obtained in step (1) to the oil phase obtained in step (2), stirring, homogenizing and emulsifying to obtain an emulsion;

[0019] (4) Phase inversion: cooling the emulsion obtained in step (3) until the paste phase inversion occurs;

[0020] (5) After the phase inversion in step (4) is completed, homogenization and stirring and dispersion are performed again to obtain the mometasone furoate cream.

[0021] Preferably, the reaction temperature in step (1) is 60-80°C; the reaction temperature in step (2) is 60-80°C; and the reaction temperature in step (3) is 60-80°C.

[0022] Preferably, in step (2), the stirring speed is 30 to 50 rpm, the homogenizing speed is 2000 to 3000 rpm, and the time is 10 to 20 min.

[0023] Preferably, in step (3), the stirring speed is first set to 40-50 rpm, and the stirring is performed for 20-40 min; then the stirring speed is set to 40-50 rpm, the homogenizing speed is set to 2500-3000 rpm, and the stirring and homogenizing are performed for 15-30 min.

[0024] Preferably, in step (4), the stirring speed is set to 10-40 rpm, the cooling temperature is set to 36-40° C., and the cooling time is set to 50-100 min.

[0025] Preferably, in step (5), the stirring speed is 15-30 rpm, and the stirring time is 30-120 min; the homogenizing speed is 1000-1500 rpm, and the homogenizing time is 5 min.

[0026] As a preferred technical solution, the preparation method of the mometasone furoate cream is as follows:

[0027] (1) Mometasone furoate, a pH adjuster, a cosolvent and water are dissolved in purified water at 60 to 80° C., and stirred to form a clear and transparent aqueous solution.

[0028] (2) Melt the oil phase matrix at 60-80° C. and mix well, then add the emulsifier, skin feel regulator and sunscreen, and mix and disperse the above auxiliary materials for 10-20 minutes at a stirring speed of 30-50 rpm and a homogenizing speed of 2000-3000 rpm to form a milky white oily liquid.

[0029] (3) Add (1) to (2), then set the stirring speed to 40-50 rpm, start stirring, and stir for 20-40 minutes. Then set the stirring speed to 40-50 rpm and the homogenizing speed to 2500-3000 rpm, start stirring and homogenizing, and continue for 15-30 minutes. During the entire emulsification process, the material temperature is controlled within the range of 60-80°C.

[0030] (4) Setting the stirring speed to 10-40 rpm and the cooling temperature to 36-40° C., cooling the paste, and controlling the cooling time to 50-100 min until the paste is completely inverted.

[0031] (5) After the paste has completely changed phases, turn off the cooling water, let it stand for 20 to 40 minutes, set the stirring speed to 15 to 30 rpm and the homogenization speed to 1000 to 1500 rpm, start stirring and homogenization, and continue to shear the completely changed phase paste. The homogenization time lasts for 5 minutes and the stirring time lasts for 30 to 120 minutes.

[0032] (6) Fill the paste into an aluminum tube.

[0033] The second object of the present invention is to provide a mometasone furoate cream prepared by the above method, which has a better drug release rate and a lower paste viscosity than the mometasone furoate cream prepared by a conventional process.

[0034] The third object of the present invention is to provide a method for increasing the release rate of mometasone furoate cream and improving the viscosity of the cream.

[0035] To achieve the above object, the present invention adopts the following technical solutions:

[0036] A method for increasing the release rate of mometasone furoate cream and improving the viscosity of the cream. The mometasone furoate cream is prepared by the above method.

[0037] In the preparation process of water-in-oil mometasone furoate cream, after the paste has completely changed phases during the cooling stage, a homogenizing and stirring step is added to further increase the release rate of the mometasone furoate cream and improve the paste viscosity.

[0038] The beneficial effects of the present invention are:

[0039] 1. The present invention improves the preparation process of mometasone furoate cream, and effectively improves the release rate and viscosity of the product by adding simple steps of homogenization and stirring after the paste cooling process. The mometasone furoate cream prepared by the process of the present invention has better paste viscosity and better skin feel than the existing product. In addition, the drug release rate is higher, and the penetration speed of the active substance in the affected skin is faster after the product is applied.

[0040] 2. The mometasone furoate cream prepared by the process of the present invention has no obvious changes in various indicators after long-term storage, and has excellent stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0041] none DETAILED DESCRIPTION

[0042] The technical solution of the present invention will be further described clearly and completely in conjunction with specific embodiments below. Obviously, the described embodiments are only part of the embodiments of the present invention, rather than all the embodiments. Therefore, based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative work belong to the protection scope of the present invention.

[0043] Example 1

[0044] 1. The prescription of mometasone furoate cream is shown in Table 1.

[0045] Table 1. Prescription and ratio of mometasone furoate cream

[0046]

[0047]

[0048] 2. Preparation method

[0049] (1) Weigh the prescribed amount of purified water, hydrochloric acid and hexylene glycol, stir and mix them evenly, then add the prescribed amount of mometasone furoate, and stir at 60 to 70° C. until they are completely dissolved to prepare an aqueous phase.

[0050] (2) Weigh the prescribed amount of white vaseline and white beeswax, stir them at 70-80° C. until they are completely melted, then add the prescribed amount of hydrogenated soy lecithin, aluminum octenyl succinate starch and titanium dioxide, set the stirring speed to 30 rpm and the homogenizing speed to 2000 rpm, stir and homogenize for 10 minutes to prepare the oil phase.

[0051] (3) Add (1) to (2), set the stirring speed to 40 rpm, start stirring, and stir for 20 minutes. Then set the stirring speed to 40 rpm and the homogenization speed to 2500 rpm, start stirring and homogenization, and continue for 15 minutes. During the entire emulsification process, the material temperature is controlled within the range of 70-80°C.

[0052] (4) Set the stirring speed to 10rpm, the cooling temperature of the emulsification tank to 36°C, and turn on the cooling water of the emulsification tank to cool down. The cooling time is controlled at 50-70min until the paste is completely inverted. After the paste is completely inverted and the material temperature is 30-33°C, turn off the cooling water. After standing for 20min, set the stirring speed to 15rpm and the homogenization speed to 1000rpm, start stirring and homogenization, where the homogenization time lasts for 5min and the stirring time lasts for 30min. Discharge the material after stirring is completed.

[0053] (5) Use aluminum tubes to fill the cream.

[0054] Example 2

[0055] In this embodiment, the prescription composition of mometasone furoate cream is the same as that in Example 1. The preparation method is as follows:

[0056] (1) Weigh the prescribed amount of purified water, hydrochloric acid and hexylene glycol, stir and mix them evenly, then add the prescribed amount of mometasone furoate, and stir at 70 to 80° C. until they are completely dissolved to prepare an aqueous phase.

[0057] (2) Weigh the prescribed amount of white vaseline and white beeswax, stir them at 70-80° C. until they are completely melted, then add the prescribed amount of hydrogenated soy lecithin, aluminum octenyl succinate starch and titanium dioxide, set the stirring speed to 50 rpm and the homogenizing speed to 3000 rpm, stir and homogenize for 20 minutes to prepare an oil phase.

[0058] (3) Add (1) to (2), set the stirring speed to 50 rpm, start stirring, and stir for 40 minutes. Then set the stirring speed to 50 rpm and the homogenization speed to 3000 rpm, start stirring and homogenization, and continue for 30 minutes. During the entire emulsification process, the material temperature is controlled within the range of 70-80°C.

[0059] (4) Set the stirring speed to 40rpm, the emulsification tank cooling temperature to 40℃, and turn on the cooling water of the emulsification tank to cool down. The cooling time is controlled at 70-100min until the paste is completely inverted. After the paste is completely inverted and the material temperature is 30-33℃, turn off the cooling water. After standing for 40min, set the stirring speed to 30rpm and the homogenization speed to 1500rpm, start stirring and homogenization, where the homogenization time lasts for 5min and the stirring time lasts for 120min. Discharge the material after stirring is completed.

[0060] (5) Use aluminum tubes to fill the cream.

[0061] Example 3

[0062] In this embodiment, the prescription composition of mometasone furoate cream is the same as that in Example 1. The preparation method is as follows:

[0063] (1) Weigh the prescribed amount of purified water, phosphoric acid and propylene glycol, stir and mix them evenly, then add the prescribed amount of mometasone furoate, and stir at 70 to 80° C. until they are completely dissolved to prepare an aqueous phase.

[0064] (2) Weigh the prescribed amount of white vaseline and synthetic beeswax, stir them at a temperature of 60-80° C. until they are completely melted, then add the prescribed amount of soybean lecithin, aluminum starch octenylsuccinate and titanium dioxide, set the stirring speed to 40 rpm and the homogenization speed to 2500 rpm, stir and homogenize for 15 minutes to prepare an oil phase.

[0065] (3) Add (1) to (2), set the stirring speed to 45 rpm, start stirring, and stir for 30 minutes. Then set the stirring speed to 45 rpm and the homogenization speed to 2700 rpm, start stirring and homogenization, and continue for 20 minutes. During the entire emulsification process, the material temperature is controlled within the range of 60-70°C.

[0066] (4) Set the stirring speed to 25rpm, the emulsification tank cooling temperature to 36℃, and turn on the cooling water of the emulsification tank to cool down. The cooling time is controlled at 50-80min until the paste is completely inverted. After the paste is completely inverted and the material temperature is 30-33℃, turn off the cooling water. After standing for 30min, set the stirring speed to 25rpm and the homogenization speed to 1200rpm, start stirring and homogenization, where the homogenization time lasts for 5min and the stirring time lasts for 70min. Discharge the material after stirring is completed.

[0067] (5) Use aluminum tubes to fill the cream.

[0068] Comparative Example 1

[0069] In this comparative example, the formula composition of mometasone furoate cream is the same as that in Example 1. The preparation method is as follows:

[0070] (1) Weigh the prescribed amount of purified water, hydrochloric acid and hexylene glycol, stir and mix them evenly, then add the prescribed amount of mometasone furoate, and stir at 60 to 70° C. until they are completely dissolved to prepare an aqueous phase.

[0071] (2) Weigh the prescribed amount of white vaseline and white beeswax, stir them at 70-80° C. until they are completely melted, then add the prescribed amount of hydrogenated soy lecithin, aluminum octenyl succinate starch and titanium dioxide, set the stirring speed to 30 rpm and the homogenizing speed to 2000 rpm, stir and homogenize for 10 minutes to prepare the oil phase.

[0072] (3) Add (1) to (2), set the stirring speed to 40 rpm, start stirring, and stir for 20 minutes. Then set the stirring speed to 40 rpm and the homogenization speed to 2500 rpm, start stirring and homogenization, and continue for 15 minutes. During the entire emulsification process, the material temperature is controlled within the range of 70-80°C.

[0073] (4) Set the stirring speed to 10 rpm, the cooling temperature of the emulsification tank to 36°C, and turn on the cooling water of the emulsification tank to cool down. The cooling time is controlled within 50 to 70 minutes, and the paste is discharged after the phase transition is complete.

[0074] (5) Use aluminum tubes to fill the cream.

[0075] Comparative Example 2

[0076] In this comparative example, the formula composition of mometasone furoate cream is the same as that in Example 1. The preparation method is as follows:

[0077] (1) Weigh the prescribed amount of purified water, hydrochloric acid and hexylene glycol, stir and mix them evenly, then add the prescribed amount of mometasone furoate, and stir at 70 to 80° C. until they are completely dissolved to prepare an aqueous phase.

[0078] (2) Weigh the prescribed amount of white vaseline and white beeswax, stir them at 70-80° C. until they are completely melted, then add the prescribed amount of hydrogenated soy lecithin, aluminum octenyl succinate starch and titanium dioxide, set the stirring speed to 50 rpm and the homogenizing speed to 3000 rpm, stir and homogenize for 20 minutes to prepare an oil phase.

[0079] (3) Add (1) to (2), set the stirring speed to 50 rpm, start stirring, and stir for 40 minutes. Then set the stirring speed to 50 rpm and the homogenization speed to 3500 rpm, start stirring and homogenization, and continue for 30 minutes. During the entire emulsification process, the material temperature is controlled within the range of 70-80°C.

[0080] (4) Set the stirring speed to 30 rpm, the cooling temperature of the emulsification tank to 40°C, and turn on the cooling water of the emulsification tank to cool down. The cooling time is controlled at 70 to 100 minutes, and the paste is discharged after the phase transition is complete.

[0081] (5) Use aluminum tubes to fill the cream.

[0082] Example 4

[0083] The in vitro release rate and dynamic viscosity of the mometasone furoate cream prepared in Examples 1 to 3 and Comparative Examples 1 to 2 were tested, and the test results are as follows:

[0084] 1. In vitro release comparison

[0085] This experiment can reflect the speed and degree of drug release from the preparation to the inside of the skin to a certain extent. The present invention uses the Franz diffusion cell method to perform an in vitro release experiment on the furoate mometasone cream prepared in the embodiment and the comparative example. The semipermeable membrane selects a 0.45 μm polyethersulfone artificial membrane, the medium selects 35% isopropanol, and the stirring speed selects 600 rpm. The amount of drug released per unit area is measured at 0.5h, 1h, 2h, 4h, and 6h after administration, and a straight line is generated by plotting the square root of the relative time. The slope of the straight line represents the release rate of the preparation (method reference source: "Technical Evaluation Requirements for Newly Registered Skin External Generic Drugs (Draft for Comments)" issued by the Drug Review Center of the State Food and Drug Administration). The results are shown in Table 2. The in vitro release rate of the furoate mometasone cream prepared by the method of Examples 1-3 is significantly higher than that of the comparative example. The furoate mometasone cream prepared by the present invention has better drug release performance and can reach the concentration of therapeutic drugs more quickly.

[0086] Table 2. In vitro release rate determination results of mometasone furoate cream

[0087] Example In vitro release rate (slope) Example 1 1293～1485 Example 2 1186～1386 Example 3 1164～1351 Comparative Example 1 722～775 Comparative Example 2 702～757

[0088] 2. Viscosity measurement

[0089] The viscosity reflects the viscosity of the paste. The greater the viscosity, the closer the paste is to a non-fluid, the less likely it is to flow, and the worse the skin feel is when applied. The present invention uses a rotational viscometer according to the viscosity determination method (the third method of 0633 of the fourth general rule of the 2020 edition of the Chinese Pharmacopoeia), with a TD (No. 96) rotor, a test temperature of 25 ° C, a speed of 10 revolutions per minute, and runs for 3 minutes to measure the dynamic viscosity of the paste. The dynamic viscosity should be 200-400Pa·s. The viscosity test results are shown in Table 3. When the same prescription is prepared by conventional methods, the viscosity of the furoate mometasone cream is greater than 800Pa·s, which is not easy to flow, and the skin feel is worse when applied. The viscosity of the furoate mometasone cream obtained by the method of Examples 1-3 of the present invention is between 300-400Pa·s, has good fluidity, and has a good skin feel when applied.

[0090] Table 3. Dynamic viscosity measurement results of mometasone furoate cream

[0091] Example Dynamic viscosity (Pa·s) Example 1 358 Example 2 364 Example 3 342 Comparative Example 1 845 Comparative Example 2 819

[0092] 3. Stability test

[0093] The mometasone furoate creams prepared in Examples 1 to 3 were placed at 25°C ± 2°C and RH 60% ± 10% for 6 months, and various index tests were performed. The test results are shown in Table 4 below.

[0094] Table 4. Stability test results of mometasone furoate cream

[0095]

[0096]

[0097] According to the above test data analysis, the mometasone furoate cream prepared by the technical solution of the present invention has a significantly increased product release rate and a significantly reduced paste viscosity compared with the product prepared by the conventional process, and no obvious changes are observed in various indicators after long-term stability, that is, the cream of the present invention has excellent stability.

Claims

1. A method for preparing mometasone furoate cream, characterized in that, The mometasone furoate cream is prepared by using mometasone furoate and pharmaceutical excipients for preparing water-in-oil creams, and homogenization, stirring and dispersion are performed after the phase transition is completed in the paste cooling stage to prepare the mometasone furoate cream.

2. The method according to claim 1, characterized in that The pharmaceutical excipients for preparing the water-in-oil cream include an oil phase component, an emulsifier, a skin feel regulator, a sunscreen, a pH regulator, a cosolvent and water; the oil phase component is any one or more of white vaseline, white beeswax and synthetic beeswax; the emulsifier is any one or more of soybean lecithin, egg yolk lecithin and hydrogenated soybean lecithin; the skin feel regulator is aluminum starch octenylsuccinate; the sunscreen is titanium dioxide; the pH regulator is any one or more of phosphoric acid, hydrochloric acid, sulfuric acid and nitric acid; the cosolvent is any one or more of propylene glycol, hexylene glycol, butylene glycol and sorbitol.

3. The method according to claim 1, characterized in that The mass percentages of the components in the mometasone furoate cream are as follows: 0.1-0.15% of mometasone furoate, 68-75% of oil phase components, 1.0-3.0% of emulsifier, 8-13% of skin feel regulator, 0.5-1.5% of sunscreen, 0.05-0.15% of pH regulator, 10-18% of cosolvent and 2-6% of water.

4. The method according to claim 1, characterized in that The method specifically comprises the following steps: (1) preparing an aqueous phase: dissolving mometasone furoate, a pH adjuster and a cosolvent in water to prepare an aqueous phase; (2) Preparation of oil phase: melt the oil phase components, add emulsifier, skin feel regulator and sunscreen, homogenize and stir to evenly disperse the auxiliary materials to prepare the oil phase; (3) Emulsification: adding the aqueous phase obtained in step (1) to the oil phase obtained in step (2), stirring, homogenizing and emulsifying to obtain an emulsion; (4) Phase inversion: cooling the emulsion obtained in step (3) until the paste phase inversion occurs; (5) After the phase inversion in step (4) is completed, homogenization and stirring and dispersion are performed again to obtain the mometasone furoate cream.

5. The method according to claim 4, characterized in that The reaction temperature in step (1) is 60-80°C; the reaction temperature in step (2) is 60-80°C; the reaction temperature in step (3) is 60-80°C.

6. The method according to claim 4, characterized in that In step (2), the stirring speed is 30 to 50 rpm, the homogenizing speed is 2000 to 3000 rpm, and the time is 10 to 20 min.

7. The method according to claim 4, characterized in that In step (3), first set the stirring speed to 40-50 rpm and stir for 20-40 min; then set the stirring speed to 40-50 rpm and the homogenizing speed to 2500-3000 rpm, and stir and homogenize for 15-30 min.

8. The method according to claim 4, characterized in that In step (5), the stirring speed is 15-30 rpm, and the stirring time is 30-120 min; the homogenizing speed is 1000-1500 rpm, and the homogenizing time is 5 min.

9. The mometasone furoate cream prepared by the method according to claim 1.

10. A method for increasing the release rate of mometasone furoate cream and improving the viscosity of the cream, characterized in that: The mometasone furoate cream is prepared by the method described in claim 1.

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