Stable external pharmaceutical composition containing fluticasone propionate

Abstract

The invention relates to the technical field of external medicine, and discloses a stable external medicine composition containing fluticasone propionate, which comprises the following components: 0.05% of fluticasone propionate; 10.00% of propylene glycol; 0.05% of triethanolamine; 0.20% of imidazolidinyl urea; 0.8% to 1.2% of carbomer; 5%-20% of paraffin; 0.75% of poly (simtrol); 5.00% of isopropyl myristate; and the balance of purified water. Carbomer is added into the stable external pharmaceutical composition containing fluticasone propionate to replace octadecanol in an original formula, so that the high-temperature stability of fluticasone propionate cream is improved in the preparation and optimization process of the fluticasone propionate cream, and the molecular structure of the Carbomer can be matched with other components in the cream, so that the stability of the fluticasone propionate cream is improved. For example, grease phase molecules and water phase molecules form more stable interaction, at high temperature, grease molecules can be effectively prevented from being excessively gathered due to thermal motion, meanwhile, the stability of the water phase can be enhanced, and water is prevented from being separated out of a cream system.

Description

Technical Field

[0001] The invention relates to the technical field of external medicines, in particular to a stable external medicine composition containing fluticasone propionate. Background Art

[0002] Fluticasone propionate cream is a glucocorticoid drug for external use in dermatology. Its main ingredient is fluticasone propionate, which is a synthetic fluorinated glucocorticoid with strong anti-inflammatory and anti-allergic effects. Its chemical structure enables it to exert its medicinal effects on local skin and produce therapeutic effects on a variety of skin inflammatory reactions.

[0003] The prior art publication number is CN102885762B, which provides a method for preparing a fluticasone propionate cream, the method comprising: 1. Preparation of an oil phase: mixing 1860 alcohol, liquid paraffin, and pergola-20, heating and melting, and keeping warm at 75°C for later use; 2. Preparation of an aqueous phase: mixing citric acid, sodium citrate, imidazolidinyl urea, and purified water, heating, and keeping warm at 75°C for later use; 3. Weighing a propylene glycol solution, heating it to 65°C and keeping warm for later use, and weighing fluticasone propionate, adding it to the prepared propylene glycol solution, and stirring to dissolve; quickly pouring the aqueous phase into the oil phase, stirring while adding until emulsification is complete, and cooling the emulsified solution to 65°C while stirring; adding the fluticasone propionate solution to the emulsified liquid, stirring evenly, and placing it at room temperature to condense into a cream.

[0004] The above-mentioned prior art uses 1860 alcohol as a raw material to prepare fluticasone propionate cream. The samples produced by this method have good properties and meet the quality requirements when placed at room temperature in a short period of time. However, the samples have oil-water separation during accelerated stability (40°C / 75%RH); the samples have uneven properties under low-temperature freeze-thaw conditions, resulting in uneven content, which affects the safety and effectiveness of the drug.

[0005] In order to solve the stability of fluticasone propionate cream under high or low temperature conditions, reduce the risk of product stratification caused by short-term temperature fluctuations, and ensure the safety and effectiveness of medication. It can be seen that a stable topical pharmaceutical composition containing fluticasone propionate is needed to improve the poor stability of fluticasone propionate cream under ambient temperature fluctuations and solve the problems mentioned in the above background technology. Summary of the invention

[0006] The object of the present invention is to provide a stable external pharmaceutical composition containing fluticasone propionate, so as to solve the stability problem of fluticasone propionate cream placed under high temperature conditions proposed in the above background technology.

[0007] In order to solve the above technical problems, the present invention provides the following technical solution: a stable external pharmaceutical composition containing fluticasone propionate, comprising 0.05% fluticasone propionate; 10.00% propylene glycol; 0.05% triethanolamine; 0.20% imidazolidinyl urea; 0.8%-1.2% carbomer; 5%-20% paraffin; 0.75% cetomacrogol; 5.00% isopropyl myristate; and the remainder is purified water.

[0008] Preferably, the ingredients are: fluticasone propionate 0.05%, propylene glycol 10.00%, triethanolamine 0.05%, imidazolidinyl urea 0.20%, carbomer 1.0%, paraffin 10.00%, cetomacrogol 0.75%, isopropyl myristate 5.00%, and the remainder is purified water.

[0009] Preferably, the triethanolamine is used to adjust the pH value to 4.5-6.5.

[0010] Preferably, the paraffin is liquid paraffin.

[0011] Compared with the prior art, the beneficial effects achieved by the present invention are:

[0012] The present invention improves the high-temperature and low-temperature stability of the fluticasone propionate cream during the preparation and optimization process by adding carbomer to replace the 1860 alcohol in the original formula. The carbomer molecular structure can form a more stable interaction with other components in the cream, such as the oil phase and the water phase molecules. At high temperature, it can effectively prevent the excessive aggregation of the oil molecules due to thermal motion, and can also enhance the stability of the water phase to prevent the precipitation of water from the cream system. At low temperature, the carbomer swollen in the water phase has good structural flexibility, and it is not easy to cause the matrix to agglomerate and cause the two phases of the cream to separate. Compared with the existing fluticasone propionate cream that only relies on the traditional raw material combination, the present formula reconstructs the microstructure and interaction network inside the cream by adding the raw material carbomer, thereby greatly improving the stability of the drug under high and low temperature conditions, reducing or even avoiding the occurrence of oil-water separation, providing a more reliable guarantee for the storage, transportation and clinical application of the fluticasone propionate cream in a temperature fluctuation environment, and ensuring that the drug can always exert its due pharmacological effect in a stable and uniform state. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] Figure 1 It is a schematic diagram of the preparation steps of the present invention. DETAILED DESCRIPTION

[0014] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0015] See also Figure 1 A stable external pharmaceutical composition containing fluticasone propionate, comprising 0.05% fluticasone propionate; 10.00% propylene glycol; 0.05% triethanolamine; 0.20% imidazolidinyl urea; 1.0% carbomer; 10.00% paraffin; 0.75% cetomacrogol; 5.00% isopropyl myristate; and the rest is purified water.

[0016] Compared with the existing formula, please refer to the following table

[0017]

[0018] In this embodiment, the traditional fluticasone propionate cream often faces severe oil-water separation problems under high temperature environment due to its original formula system. Under low temperature environment, the matrix is ​​prone to hard lumps and unevenness, which not only affects the appearance quality of the cream, but also has a great negative impact on the stability and uniformity of its efficacy. Carbomer has unique chemical properties that can remain stable under high and low temperature conditions. Adding it to the raw material composition of fluticasone propionate cream can significantly improve this situation and reduce or even avoid the occurrence of oil-water separation.

[0019] The preparation steps of the raw and auxiliary materials using the above optimized formula can be:

[0020] Step 1: Accurately weigh a certain proportion of fluticasone propionate as the main drug;

[0021] Step 2: Put liquid paraffin, cetomacrogol and isopropyl myristic acid into a suitable container (such as a stainless steel heating container), heat and melt at a certain temperature (usually 70-80°C), and stir continuously during the heating process to form a uniform oil phase;

[0022] Step 3: Add an appropriate amount of purified water to another container, add carbomer while stirring, and after the carbomer is completely swollen, add imidazolidinyl urea and propylene glycol, mix well, add triethanolamine to adjust the pH value of the carbomer phase, and obtain the aqueous phase for use. There is no need to heat the aqueous phase.

[0023] Step 4: slowly add the heated and melted oil phase into the water phase, and use a suitable stirring device (such as a mechanical stirrer) to stir at high speed while adding. The stirring speed is generally about 1000-2000 revolutions per minute, so that the oil phase and the water phase can be fully mixed to form a preliminary cream. Continue stirring for a period of time, usually 10-20 minutes, to make the emulsion more delicate and uniform;

[0024] Step 5: When the cream reaches the ideal emulsified state, add the fluticasone propionate accurately weighed in advance into the cream and continue stirring. The speed can be appropriately reduced, generally about 500-1000 revolutions per minute, and the stirring time is 5-10 minutes to ensure that the main drug is evenly dispersed in the cream;

[0025] Step 6: After stirring, transfer it to a suitable packaging container (such as an aluminum tube or plastic ointment box). The packaging process must be carried out in a clean and sterile environment to prevent microbial contamination and ensure the quality of the cream and its stability during its shelf life.

[0026] In the above steps, the heating temperature of the oil phase is usually 70-80°C.

[0027] The disodium hydrogen phosphate dodecahydrate added to the original formula system contains crystalline water. If the crystalline water is lost, its chemical composition may change, thereby affecting its function as a pH regulator and buffer in the cream. For example, after losing the crystalline water, the ability of disodium hydrogen phosphate to adjust pH may change, causing the pH value of the cream to fluctuate, affecting the stability of fluticasone propionate, because fluticasone propionate may degrade in an inappropriate pH environment, reducing the effectiveness of the drug, so in the improved formula, triethanolamine with adjusted pH value is used instead, further enhancing the stability of the formula system.

[0028] In this formula and the original technology, carbomer and cetostearyl alcohol play the role of thickeners in the formula and exist as the matrix of the cream. Similar substances include hydroxypropyl cellulose, polyethylene glycol stearate, cetyl alcohol, octyl alcohol, etc. Hydroxypropyl cellulose is used as the matrix for preparing the cream. The finished product has uniform properties and meets the quality requirements. It is subjected to high temperature and low temperature sample, taken out after 30 days, and observed under a microscope. Demulsification occurs. After viscosity testing, it is found that the test results have poor parallelism. It can be seen that the cream has an uneven matrix.

[0029] Polyethylene glycol-7 stearate is used as a matrix to prepare the cream. It also acts as an emulsifier, so the droplet size in the finished product is very small, resulting in a high viscosity of the cream, poor fluidity, and difficulty in applying it in daily use. The skin feel is poor, so no stability study was conducted;

[0030] When single hexadecanol or stearyl alcohol is used as the matrix for preparing the cream, similar to stearyl alcohol, phase separation occurs under high and low temperature conditions. Therefore, carbomer is the best choice as the matrix of this product.

[0031] At the same time, different amounts of carbomer were also explored, and 0.5%, 0.8%, 1.0%, 1.2%, and 1.5% carbomer were selected for cream preparation. Among them, the cream prepared with 0.5% carbomer has low viscosity, low yield stress, and high fluidity. During use, it is not easy to stay on the skin, affecting effective use. The cream prepared with 1.5% carbomer has high viscosity and high yield stress. During use, it is not easy to apply. Therefore, the cream with 0.8% to 1.2% carbomer was selected for high temperature and low temperature inspection. After 30 days, the cream was taken out and the properties were good, and the quality met the requirements.

[0032] The existing technology is adopted, the amount of liquid paraffin is kept unchanged, carbomer is used as a matrix, the amount of purified water is 39%, and carbomer is swelled in the water phase. It is found that it is difficult to swell completely, so the amount of liquid paraffin is reduced, and the amount of liquid paraffin is set to 5%, 10%, 20%, and 25%, respectively. The remaining variables are supplemented with purified water. In the preparation process, the prescription of 5% to 20% liquid paraffin, when preparing the water phase, the carbomer swelling phenomenon is good, the prepared finished product has uniform properties, fine texture, and the quality meets the requirements.

[0033] Although the embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to these embodiments without departing from the principles and spirit of the present application. The scope of the present application is defined by the appended claims and their equivalents.

Claims

1. A stable external pharmaceutical composition containing fluticasone propionate, characterized in that: The composition includes the following ingredients: Fluticasone propionate 0.05%; Propylene glycol 10.00%; Triethanolamine 0.05%; Imidazolidinyl urea 0.20%; Carbomer 0.8%-1.2%; paraffin 5%-20%; cetomacrogol 0.75%; isopropyl myristate 5.00%; the rest is purified water.

2. A stable external pharmaceutical composition containing fluticasone propionate, characterized in that: The composition includes the following ingredients: Fluticasone propionate 0.05%; Propylene glycol 10.00%; Triethanolamine 0.05%; Imidazolidinyl urea 0.20%; Carbomer 1.0%; paraffin 10.00%; cetomacrogol 0.75%; isopropyl myristate 5.00%; the rest is purified water.

3. A stable external pharmaceutical composition containing fluticasone propionate according to claim 1, characterized in that: The triethanolamine adjusts the pH value to 4.5-6.

5.

4. A stable external pharmaceutical composition containing fluticasone propionate according to claim 1, characterized in that: The paraffin wax is liquid paraffin wax.

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