Suspension for fluticasone propionate aerosol inhalation and preparation method thereof
By replacing polysorbate 20 with isooctanol phosphate and optimizing the high-pressure homogenization and mixing process, the foaming problem of fluticasone propionate nebulized inhalation suspension was solved, achieving drug stability and content uniformity, and ensuring the accuracy and safety of drug administration.
Patent Information
- Application Number
- CN202511709947.4
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-11-20
- Publication Date
- 2026-01-13
AI Technical Summary
The existing fluticasone propionate nebulized suspension is prone to foaming during the production scale-up process, resulting in poor uniformity of drug content and affecting the efficacy and accuracy of dosage.
Isooctanol phosphate was used to replace polysorbate 20 as a surfactant, and the proportions and parameters of each component were optimized through specific high-pressure homogenization, sterilization and mixing processes to ensure the stability and uniformity of the drug solution.
It significantly inhibited foaming in the suspension, improved the uniformity and stability of the drug content, and ensured the accuracy of the dosage and product quality.
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Abstract
Description
Technical Field
[0001] This invention relates to the field of pharmaceutical formulation technology, and in particular to a fluticasone propionate nebulized inhalation suspension and its preparation method. Background Technology
[0002] Inhalation is an important method of drug delivery for treating respiratory diseases such as asthma and chronic obstructive pulmonary disease. Compared with systemic drug delivery methods (such as oral or injection), inhalation delivers drugs directly to the site of action, increasing the concentration of the drug in the respiratory tract or lungs. It has the advantages of rapid onset of action, avoiding the first-pass effect of the liver (as with oral administration), reducing side effects (as with injection), reducing the dosage of the drug, and improving bioavailability.
[0003] Inhaled liquid formulations are administered via nebulizer and nebulizer cup, resulting in good patient compliance, minimal side effects, and suitability for long-term treatment. They are particularly beneficial for children and the elderly. The World Health Organization has recommended them as the first-line treatment for respiratory diseases such as asthma, expectorants, tracheitis, bronchitis, pneumonia, and COPD.
[0004] Fluticasone propionate is an inhaled corticosteroid with significant anti-inflammatory effects in the lungs. In asthma patients previously treated with bronchodilators or other prophylactic therapies, fluticasone propionate can reduce asthma symptoms and acute exacerbations. While relatively short-lived acute exacerbations can generally be relieved with the use of rapid-acting bronchodilators, prolonged acute exacerbations require prompt corticosteroid treatment to control inflammation. The main formulation of fluticasone propionate is a nebulized suspension, which can be used to treat mild to moderate acute asthma exacerbations in children and adolescents aged 4 to 16 years. For suspensions, the uniformity of fluticasone propionate content is a key factor determining its efficacy; variations in content can affect drug release and clinical efficacy. During storage, fluticasone propionate particles in the suspension are also prone to aggregation, leading to decreased particle size uniformity and affecting efficacy. Therefore, it is of great significance to develop a new preparation process for fluticasone propionate nebulized inhalation suspension with uniform content and good stability. Summary of the Invention
[0005] In view of this, the present invention provides a fluticasone propionate nebulized inhalation suspension and its preparation method. By rationally designing the composition and method of the fluticasone propionate nebulized inhalation suspension, the present invention significantly reduces the amount of foaming in the suspension, increases the uniformity of the suspension content, and thus ensures product quality.
[0006] To achieve the above-mentioned objectives, the present invention adopts the following technical solution: This invention provides a fluticasone propionate nebulized suspension, comprising fluticasone propionate, isooctyl phosphate, stabilizer, sodium dihydrogen phosphate, disodium hydrogen phosphate, and osmotic pressure regulator.
[0007] Existing fluticasone propionate nebulized suspensions consist of fluticasone propionate, surfactants, stabilizers, osmotic pressure regulators, and water for injection. Polysorbate 20 is a commonly used surfactant. However, during scale-up production, fluticasone propionate nebulized suspensions prepared using this formulation tend to foam, reducing the uniformity of the drug concentration. Therefore, there is an urgent need for a fluticasone propionate nebulized suspension with high stability and good drug concentration uniformity.
[0008] Through extensive experimental research, the inventors discovered that when isooctanol phosphate is used instead of polysorbate 20, foaming of fluticasone propionate nebulized inhalation suspension can be significantly inhibited. Furthermore, the resulting suspension exhibits good uniformity of drug content and high stability, thereby ensuring the storage stability of fluticasone propionate nebulized inhalation suspension, ensuring the accuracy of dosage, and improving product quality and medication safety.
[0009] Preferably, the particle size of the fluticasone propionate is D50≤3µm and D90≤6µm.
[0010] Preferably, the stabilizer includes sorbitan lauryl tannin.
[0011] Preferably, the osmotic pressure regulator includes sodium chloride.
[0012] Preferably, the concentration of fluticasone propionate is 0.225~0.275 mg / mL.
[0013] Preferably, the concentration of isooctanol phosphate is 0.063–0.077 mg / mL.
[0014] This invention further optimizes the concentration of isooctanol phosphate, which can further inhibit foaming of fluticasone propionate nebulized inhalation suspension, thereby improving the uniformity and stability of the drug solution content.
[0015] Preferably, the concentration of the stabilizer is 0.0081 to 0.0099 mg / mL.
[0016] Preferably, the concentration of sodium dihydrogen phosphate is 8.91–10.89 mg / mL.
[0017] Preferably, the concentration of disodium hydrogen phosphate is 1.575–1.925 mg / mL.
[0018] Preferably, the concentration of the osmotic pressure regulator is 4.32–5.28 mg / mL.
[0019] This invention provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, comprising the following steps: S1. Add the prescribed amounts of isooctanol phosphate, fluticasone propionate and water for injection to the preparation tank, and perform high-pressure homogenization at 1100~1200 bar, sterilize, and obtain homogenized concentrated solution. S2. Add the prescribed amount of stabilizer, sodium dihydrogen phosphate, disodium hydrogen phosphate and osmotic pressure regulator to water for injection to obtain an excipient solution. S3. Mix the excipient solution and the homogenized concentrated solution evenly to obtain a fluticasone propionate nebulization suspension.
[0020] Currently, the preparation method of fluticasone propionate nebulized inhalation suspension includes: ultra-finely pulverizing fluticasone propionate raw material to a preset particle size distribution to obtain fluticasone propionate ultrafine powder; weighing surfactant, stabilizer, and osmotic pressure regulator according to the designed ratio; dissolving the weighed components and surfactant (polysorbate 20) in water; adding the weighed fluticasone propionate ultrafine powder; mixing to obtain a primary emulsion; and homogenizing the primary emulsion using microfluidics to obtain fluticasone propionate nebulized inhalation suspension. However, the suspension prepared by the above method has a serious foaming problem, which significantly reduces the uniformity of the active ingredient content and thus reduces the accuracy of the dosage.
[0021] Compared to existing technologies, the preparation method of fluticasone propionate nebulized inhalation suspension provided by this invention involves first mixing isooctanol phosphate, water for injection, and fluticasone propionate, and then subjecting the mixture to high-pressure homogenization and sterilization under specific pressure to obtain a homogenized concentrated solution. Furthermore, the excipient solution and the homogenized concentrated solution are mixed evenly, resulting in a fluticasone propionate nebulized inhalation suspension with good content uniformity, controllable particle size of the active pharmaceutical ingredient, and suitability for inhalation administration. Moreover, the specific preparation method can also prevent the degradation of fluticasone propionate.
[0022] This invention, by optimizing the order of addition of fluticasone propionate and various excipients, can significantly improve the uniformity and stability of the drug content in fluticasone propionate nebulized inhalation suspension, and ensure that the particle size of the active ingredient reaches a specific range, thereby improving product quality and medication accuracy.
[0023] Preferably, in S1, the mass ratio of fluticasone propionate, water for injection, and isooctanol phosphate is 1:8:0.28.
[0024] The inventors have demonstrated through numerous experiments that by limiting the mass ratio of fluticasone propionate, water for injection, and isooctanol phosphate in the homogenized concentrated solution, the particle size of fluticasone propionate in the prepared fluticasone propionate nebulization suspension can be further guaranteed to reach a specific range. Experiments show that when the above range is exceeded, the particle size of the prepared product increases significantly, and the content uniformity is poor, which reduces the product quality.
[0025] Preferably, in S1, the high-pressure homogenization time is 10~12 minutes.
[0026] Preferably, in S1, the high-pressure homogenization is performed 5 to 10 times.
[0027] This invention optimizes the time and number of high-pressure homogenization cycles through multiple experiments. Specific high-pressure homogenization conditions can ensure that the fluticasone propionate nebulized inhalation suspension reaches a specific particle size range, improve the content uniformity of the suspension, and thus ensure the stability of the fluticasone propionate nebulized inhalation suspension during storage and the accuracy of the dosage.
[0028] Preferably, in S1, the sterilization is moist heat sterilization.
[0029] More preferably, in S1, the sterilization temperature is 121~123℃ and the time is 12~15min.
[0030] Preferably, in S1, the temperature of the homogenized concentrated solution is ≤40℃.
[0031] Preferably, in S3, the conditions for uniform mixing are: simultaneous stirring, circulation, and homogenization.
[0032] More preferably, the stirring frequency is 10~12Hz.
[0033] More preferably, the frequency of the cycle is 25~27Hz.
[0034] More preferably, the homogeneous frequency is 25~27Hz.
[0035] More preferably, in S3, the time for uniform mixing is 60-65 minutes.
[0036] The fluticasone propionate nebulized inhalation suspension provided by this invention significantly reduces the amount of foaming and increases the uniformity of the suspension content by replacing the surfactant with isooctanol phosphate, thereby ensuring product quality.
[0037] During their research, the inventors discovered that factors affecting the quality of fluticasone propionate nebulized inhalation suspension include the type of surfactant, isooctanol phosphate in the homogenized concentrate, the ratio of water for injection to fluticasone propionate, and the parameters of stirring, circulation, and homogenization during mixing. These factors interact and significantly impact the quality of the fluticasone propionate nebulized inhalation suspension. This invention addresses these issues by replacing the surfactant with isooctanol phosphate, controlling the proportions of each component in the homogenized concentrate, and simultaneously controlling the pressure, number of cycles, and time of high-pressure homogenization, as well as the conditions for uniform mixing. Through the combined control of multiple process parameters, the invention avoids the problems of poor content uniformity and uncontrollable particle size in fluticasone propionate nebulized inhalation suspension, thereby improving its quality. Detailed Implementation
[0038] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention.
[0039] Example 1 This embodiment provides a fluticasone propionate nebulized inhalation suspension, wherein each 1 mL of the fluticasone propionate nebulized inhalation suspension comprises: 0.225 mg fluticasone propionate, 0.063 mg isooctyl phosphate, 0.0099 mg lauryl sorbitan, 8.91 mg sodium dihydrogen phosphate, 1.575 mg disodium hydrogen phosphate, and 5.15 mg sodium chloride; This embodiment provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, including the following steps: S1. Add the prescribed amount of isooctanol phosphate, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:8. Homogenize at 1100 bar for 10 min, repeat 10 times, and perform moist heat sterilization at 121℃ for 12 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 60 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0040] Example 2 This embodiment provides a fluticasone propionate nebulized inhalation suspension, wherein each 1 mL of the fluticasone propionate nebulized inhalation suspension comprises: 0.265 mg fluticasone propionate, 0.0742 mg isooctyl phosphate, 0.0081 mg lauryl sorbitan, 10.89 mg sodium dihydrogen phosphate, 1.925 mg disodium hydrogen phosphate, and 4.32 mg sodium chloride; This embodiment provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, including the following steps: S1. Add the prescribed amount of isooctanol phosphate, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:8. Homogenize at 1200 bar for 12 min, repeat 8 times, and perform moist heat sterilization at 121℃ for 15 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 62 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0041] Example 3 This embodiment provides a fluticasone propionate nebulized inhalation suspension, wherein each 1 mL of the fluticasone propionate nebulized inhalation suspension comprises: 0.275 mg fluticasone propionate, 0.077 mg isooctyl phosphate, 0.009 mg lauryl sorbitan, 9.7 mg sodium dihydrogen phosphate, 1.9 mg disodium hydrogen phosphate, and 5.28 mg sodium chloride; This embodiment provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, including the following steps: S1. Add the prescribed amount of isooctanol phosphate, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:8. Homogenize at 1150 bar for 10 min, repeat 5 times, and perform moist heat sterilization at 121℃ for 15 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 65 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0042] Example 4 This embodiment provides a fluticasone propionate nebulized inhalation suspension, which differs from Example 1 in that the mass ratio of fluticasone propionate to water for injection is 1:3. Specifically, each 1 mL of fluticasone propionate nebulized suspension contains: 0.225 mg fluticasone propionate, 0.063 mg isooctyl phosphate, 0.0099 mg lauryl sorbitan, 8.91 mg sodium dihydrogen phosphate, 1.575 mg disodium hydrogen phosphate, and 5.15 mg sodium chloride. This embodiment provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, including the following steps: S1. Add the prescribed amount of isooctanol phosphate, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:3. Homogenize at 1100 bar for 10 min, repeat 10 times, and perform moist heat sterilization at 121℃ for 12 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 60 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0043] Example 5 This embodiment provides a fluticasone propionate nebulized inhalation suspension, which differs from Example 1 in that the mass ratio of fluticasone propionate to water for injection is 1:5. Specifically, each 1 mL of fluticasone propionate nebulized suspension contains: 0.225 mg fluticasone propionate, 0.063 mg isooctyl phosphate, 0.0099 mg lauryl sorbitan, 8.91 mg sodium dihydrogen phosphate, 1.575 mg disodium hydrogen phosphate, and 5.15 mg sodium chloride. This embodiment provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, including the following steps: S1. Add the prescribed amount of isooctanol phosphate, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:5. Homogenize at 1100 bar for 10 min, repeat 10 times, and perform moist heat sterilization at 121℃ for 12 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 60 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0044] Comparative Example 1 This comparative example provides a fluticasone propionate nebulized inhalation suspension, which differs from Example 1 in that isooctanol phosphate is replaced with an equal amount of polysorbate 20. Specifically, each 1 mL of fluticasone propionate nebulized suspension contains: 0.225 mg fluticasone propionate, 0.063 mg polysorbate 20, 0.0099 mg lauryl sorbitan, 8.91 mg sodium dihydrogen phosphate, 1.575 mg disodium hydrogen phosphate, and 5.15 mg sodium chloride. This comparative example provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, comprising the following steps: S1. Add the prescribed amount of polysorbate 20, water for injection and fluticasone propionate to the preparation vessel at a mass ratio of fluticasone propionate to water for injection of 1:8. Homogenize at 1100 bar for 10 min, repeat 10 times, and perform moist heat sterilization at 121℃ for 12 min to obtain a homogenized concentrated solution with a temperature ≤40℃. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the homogenized concentrated solution for 60 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 25 Hz, and the homogenization frequency at 25 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0045] Comparative Example 2 This comparative example provides a fluticasone propionate nebulized inhalation suspension, which differs from Example 1 in that isooctanol phosphate is replaced with an equal amount of polysorbate 20, and the high-pressure homogenization step is omitted. Specifically, each 1 mL of fluticasone propionate nebulized suspension contains: 0.225 mg fluticasone propionate, 0.063 mg polysorbate 20, 0.0099 mg lauryl sorbitan, 8.91 mg sodium dihydrogen phosphate, 1.575 mg disodium hydrogen phosphate, and 5.15 mg sodium chloride. This comparative example provides a method for preparing the above-mentioned fluticasone propionate nebulized inhalation suspension, comprising the following steps: S1. Add the prescribed amount of polysorbate 20, water for injection and fluticasone propionate to the preparation tank at a mass ratio of fluticasone propionate to water for injection of 1:8, and perform moist heat sterilization at a temperature of 121°C for 12 min to obtain a concentrated solution with a temperature ≤40°C. S2. Add the prescribed amounts of sorbitan lauryl phosphate, sodium dihydrogen phosphate, disodium hydrogen phosphate, and sodium chloride to water for injection and prepare to the set volume to obtain the excipient solution. S3. Simultaneously stir, circulate, and homogenize the excipient solution and the concentrated solution for 60 minutes. Control the stirring frequency at 10 Hz, the circulation frequency at 50 Hz, and the homogenization frequency at 50 Hz to obtain a fluticasone propionate nebulized inhalation suspension.
[0046] The fluticasone propionate nebulized inhalation suspensions prepared in Examples 1-5 and Comparative Examples 1-2 were tested. The structural formula of impurity A is as follows: ; The detection method is as follows: Related substances: Experimental instruments: High performance liquid chromatograph, drying oven, electronic balance; Reagents and solutions: fluticasone propionate reference standard, acetonitrile solution of 0.05% phosphoric acid and 3.0% methanol, aqueous solution of 0.05% phosphoric acid and 3.0% methanol, acetonitrile; Determination method: Determine according to the "Standard Operating Procedure for High Performance Liquid Chromatography"; Chromatographic conditions: Octadecylsilane-bonded silica gel was used as the stationary phase (Venusi1 MpC). 18 A 4.6 mm * 250 mm, 5 μm or equivalent chromatographic column was used. Mobile phase A consisted of acetonitrile solution containing 0.05% phosphoric acid and 3.0% methanol, and mobile phase B consisted of an aqueous solution containing 0.05% phosphoric acid and 3.0% methanol. Gradient elution was performed according to the table below. The flow rate was 1.0 mL per minute; the column temperature was 40 °C; the detection wavelength was 239 nm; and the injection volume was 100 μL.
[0047] Preparation of test solution Take one vial of this product, shake well, transfer the contents to a 10mL volumetric flask, add 1mL of acetonitrile to dissolve, then dilute to the mark with mobile phase A-mobile phase B (43:57), sonicate to dissolve, shake well, and the product is ready.
[0048] Preparation of reference solution Accurately measure 1 mL of the test solution into a 100 mL volumetric flask, dilute to the mark with mobile phase A-mobile phase B (43:57), shake, then accurately measure 5 mL into a 10 mL volumetric flask, dilute to the mark with mobile phase A-mobile phase B (43:57), and the solution is ready.
[0049] System suitability solution Take appropriate amounts of fluticasone propionate, impurity A, impurity D and impurity E as references, accurately weigh them, dissolve and dilute them with mobile phase A-mobile phase B (43:57) to prepare a solution containing 5 μg of fluticasone propionate and 0.5 μg each of impurity A, impurity D and impurity E per 1 mL.
[0050] System applicability requirements In the system solution chromatogram, the elution order is impurity A, impurity D, fluticasone propionate, and impurity E. The separation of impurities D and E from fluticasone propionate should be greater than 1.5.
[0051] Measurement Accurately measure the test solution and reference solution, inject them separately into the liquid chromatograph, and record the chromatograms. Calculation formula: Impurities % = [A 样 / (A 对 *V 对 )*100%; A 对 As the control peak area, A 样 V represents the peak area of impurities in the test sample. 对 This is the volume of the reference standard diluted.
[0052] Particle size: The sample to be tested was added to the dispersion medium and the parameters were set for particle size detection. The dispersion medium was an aqueous solution. The circulation speed was 7 revolutions, the ultrasonic time was 15 minutes, and the ultrasonic power was 5 kW.
[0053] Maximum shading rate: 20%; Minimum shading rate: 5%.
[0054] Turn on the laser particle size analyzer and the circulating dispersion system, and add the dispersion medium; start the circulation, enter the measurement interface, calibrate the background to normal, take the sample and add it to the circulating dispersion system, measure the refractive index in the system, and perform detection after the refractive index stabilizes. Click "Start" on the test page to automatically inject and analyze the sample.
[0055] To assess the uniformity of content, samples were taken every 4 minutes after the initial sampling, and this process was repeated 7 times for uniformity evaluation. ①~⑦ represent the results of the 7 tests, respectively.
[0056] The test results are shown in Tables 1 and 2: Table 1
[0057] Table 2
[0058] Note: The closer the uniformity of the suspension content is to 100%, the more uniform the product content is. Poor content uniformity will result in a lower or higher content result. The overall content is 100%.
[0059] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions or improvements made within the spirit and principles of the present invention should be included within the protection scope of the present invention.
Claims
1. A fluticasone propionate nebulized suspension, characterized in that, It includes fluticasone propionate, isooctyl phosphate, stabilizers, sodium dihydrogen phosphate, disodium hydrogen phosphate, and osmotic pressure regulators.
2. The fluticasone propionate nebulized suspension as described in claim 1, characterized in that, The stabilizer includes lauryl sorbitan.
3. The fluticasone propionate nebulized suspension as described in claim 1, characterized in that, The osmotic pressure regulator includes sodium chloride.
4. The fluticasone propionate nebulized suspension as described in claim 1, characterized in that, The concentration of fluticasone propionate is 0.225~0.275 mg / mL.
5. The fluticasone propionate nebulized suspension as described in claim 1, characterized in that, The concentration of isooctanol phosphate is 0.063–0.077 mg / mL.
6. The fluticasone propionate nebulized suspension as described in claim 1, characterized in that, The concentration of the stabilizer is 0.0081–0.0099 mg / mL; The concentration of sodium dihydrogen phosphate is 8.91–10.89 mg / mL; The concentration of the disodium hydrogen phosphate is 1.575–1.925 mg / mL; The concentration of the osmotic pressure regulator is 4.32–5.28 mg / mL.
7. A method for preparing a fluticasone propionate nebulized inhalation suspension according to any one of claims 1 to 6, characterized in that, Includes the following steps: S1. Add the prescribed amounts of isooctanol phosphate, fluticasone propionate and water for injection to the preparation tank, and perform high-pressure homogenization at 1100~1200 bar, sterilize, and obtain homogenized concentrated solution. S2. Add the prescribed amount of stabilizer, sodium dihydrogen phosphate, disodium hydrogen phosphate and osmotic pressure regulator to water for injection to obtain an excipient solution. S3. Mix the excipient solution and the homogenized concentrated solution evenly to obtain a fluticasone propionate nebulization suspension.
8. The method for preparing the fluticasone propionate nebulized inhalation suspension as described in claim 7, characterized in that, In S1, the high-pressure homogenization time is 10~12 min; In S1, the high-pressure homogenization is performed 5 to 10 times.
9. The method for preparing the fluticasone propionate nebulized inhalation suspension as described in claim 7, characterized in that, In S3, the condition for uniform mixing is that stirring, circulation, and homogenization are performed simultaneously.
10. The method for preparing the fluticasone propionate nebulized inhalation suspension as described in claim 9, characterized in that, The stirring frequency is 10~12Hz; The frequency of the cycle is 25~27Hz; The homogeneous frequency is 25~27Hz.