Non-steroidal anti-inflammatory drug suspension drop and preparation method thereof

Abstract

The invention discloses a non-steroidal anti-inflammatory drug suspension drop and a preparation method thereof. The suspension drop comprises ibuprofen, xanthan gum, pregelatinized starch, glycerin, sucrose, anhydrous citric acid, sodium benzoate, polysorbate 80, strawberry essence and water. The preparation method comprises the following steps: 1) sieving ibuprofen with a 20-mesh sieve for later use; the preparation method comprises the following steps: adding polysorbate 80 into purified water, stirring and dissolving, adding ibuprofen according to the prescription amount, and stirring and dispersing uniformly; 2) adding 100 DEG C purified water and glycerol into the liquid preparation tank, and stirring and mixing; (3) starting a rotor pump and a homogenizing pump to form internal circulation in the liquid preparation tank, opening a ball valve of a charging hopper, adding xanthan gum and pregelatinized starch, closing the valve of the hopper, and homogenizing and stirring until the step (6) is finished; (4) weighing cane sugar, adding the cane sugar into boiling water at 100 DEG C, and stirring for dissolving; 5) continuously stirring in the liquid preparation tank, adding a sucrose solution, washing the container with water, and adding into the liquid preparation tank; 6) adding anhydrous citric acid and sodium benzoate into the liquid preparation tank, and stirring for more than 1 hour after the steps 3-6 are finished; 7) closing the homogenizing pump, adding an ibuprofen dispersion liquid into the liquid preparation tank, washing the dispersion container with water for several times, and stirring; (8) adding essence into the liquid preparation tank, and stirring; 9) adding the total amount of purified water, and stirring; and 10) filling. The drops with good dispersibility and good stability are obtained by screening the prescription and optimizing the preparation process.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical formulation technology, and specifically relates to an ibuprofen suspension drop and its preparation method. Background Technology

[0002] Ibuprofen (chemical name 2-(4-isobutylphenyl)propionic acid) is a widely used nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic, and antipyretic effects. Since its discovery in 1961, ibuprofen has become one of the world's best-selling over-the-counter medications due to its good efficacy and safety. It exerts its analgesic and anti-inflammatory effects by inhibiting cyclooxygenase, thereby reducing prostaglandin synthesis.

[0003] For children and elderly people with swallowing difficulties, liquid formulations, especially suspension drops, are the preferred choice due to their ease of administration and rapid onset of action. However, ibuprofen has poor water solubility; this water-insoluble active drug is prone to sedimentation, stratification, or even flocculation in liquid formulations, making it difficult to prepare stable and readily available ibuprofen liquid formulations.

[0004] Commercially available ibuprofen suspension drops may show no significant changes in appearance in the short term, but after prolonged storage (e.g., more than 6 months), problems such as unstable viscosity and accelerated ibuprofen dissolution may occur. This phenomenon can easily cause differences in the rate of drug absorption in the body, thus affecting the safety and efficacy of the medication. Therefore, improving the stability of ibuprofen suspension drops has become an urgent technical problem to be solved.

[0005] Currently, in response to the above problems, the ibuprofen suspension drops in the patent application have improved the dispersibility and long-term stability of the suspension drops by improving the process steps. Summary of the Invention

[0006] The purpose of this application is to provide a nonsteroidal anti-inflammatory drug suspension drop and its preparation method, which reduces sedimentation and improves the stability of ibuprofen suspension drop by optimizing the component content and improving the preparation process.

[0007] On one hand, this application provides a nonsteroidal anti-inflammatory drug suspension drop comprising ibuprofen, xanthan gum, pregelatinized starch, glycerin, sucrose, anhydrous citric acid, sodium benzoate, polysorbate 80, and fragrance, wherein the mass percentage content of each component is as follows:

[0008] Ibuprofen 4%, xanthan gum 0.18%-0.26%, pregelatinized starch 1%-1.4%, polysorbate 80%-0.075%, anhydrous citric acid 0.18%, sodium benzoate 0.2%, sucrose 30%, glycerin 10%, flavoring 0.04%, water 53.85-54.4%.

[0009] The preparation method of the ibuprofen suspension drops includes the following steps:

[0010] 1) Ibuprofen is passed through a 20-mesh sieve and set aside.

[0011] Weigh out purified water, add polysorbate 80, stir to dissolve, add the prescribed amount of ibuprofen, and stir to disperse evenly; 2) Add 100℃ purified water and glycerin to the mixing tank, and stir to mix for 5-10 minutes;

[0012] 3) Start the rotor pump and homogenizer pump to form an internal circulation in the liquid preparation tank. Open the ball valve of the feeding funnel, add xanthan gum and pregelatinized starch, close the funnel valve, and homogenize until step 6 is completed.

[0013] 4) Weigh out the sucrose, add it to boiling water at 100℃, and stir to dissolve;

[0014] 5) Continue stirring in the mixing tank, add sucrose solution, rinse the container with water, and add it to the mixing tank;

[0015] 6) Add anhydrous citric acid and sodium benzoate to the mixing tank and stir for about 5-10 minutes. Ensure that the mixture is kept warm for more than 1 hour from the end of step 3 to step 6.

[0016] 7) Turn off the homogenizer pump, add ibuprofen dispersion to the mixing tank, rinse the dispersion container with water several times, and add stirring;

[0017] 8) Add flavoring to the mixing tank and stir;

[0018] 9) Add the full amount of purified water and stir for 60 minutes (take samples from the top, middle and bottom of the mixture to determine viscosity and content uniformity).

[0019] 10) Filling.

[0020] In some embodiments of ibuprofen suspension drops, the xanthan gum content is 0.18%-0.26%, preferably 0.24%.

[0021] In some embodiments of ibuprofen suspension drops, the pregelatinized starch is selected from PGS or UITRA.

[0022] In some embodiments, the amount of pregelatinized starch used is 1%-1.4%; preferably 1.2%-1.4%, and more preferably 1.2%.

[0023] In some embodiments of ibuprofen suspension drops, the amount of polysorbate 80 is 0%-0.075%, preferably 0.05%.

[0024] In some embodiments of ibuprofen suspension drops, the flavoring includes at least one selected from apple, orange, grape, strawberry, banana, cherry, lemon, and pear flavorings. Preferably, strawberry flavoring is used at an amount of 0.04%.

[0025] In some embodiments of the method for preparing ibuprofen suspension drops, step 1) involves maintaining stirring for at least 2 hours.

[0026] In some embodiments of the preparation method of ibuprofen suspension drops, before adding the ibuprofen dispersion in step 7), the temperature inside the mixing tank is reduced to below 40°C.

[0027] In some embodiments of the preparation method of ibuprofen suspension drops, the homogenization internal circulation time at the end of steps 3-6 is at least 3 hours.

[0028] Compared with existing technologies, this invention has the following advantages by controlling key steps in the ibuprofen raw material pretreatment process, such as sieving and stirring time:

[0029] 1. Optimize sedimentation performance: By adjusting the types and amounts of suspending agents, stabilizers, wetting agents and other excipients, and by adopting appropriate homogenization and dispersion techniques, ibuprofen particles can be uniformly and stably dispersed in the liquid medium, reducing particle aggregation and sedimentation tendency, thereby improving the sedimentation performance of the suspension drops.

[0030] 2. Improved physical stability: The optimized formula and preparation process help to form a more stable physical system that can resist the influence of environmental factors such as temperature, humidity, and light, reduce physical changes in the drug during storage (such as stratification, discoloration, crystallization, etc.), and ensure the consistency of drug quality within its shelf life.

[0031] 3. Ensuring the quality of medication for patients: The excellent sedimentation properties and physical stability ensure the uniformity and stability of ibuprofen suspension drops during storage and use, thereby ensuring that patients receive accurate and effective drug dosages each time they take the medication, improving treatment efficacy and patient satisfaction. Attached Figure Description

[0032] Figure 1 This is a process flow diagram for ibuprofen suspension drops.

[0033] Figure 2 This is the dissolution curve of ibuprofen suspension drops in pH 5.5 medium. Detailed Implementation

[0034] The technical solutions of the embodiments of this application will be clearly described below with reference to the accompanying drawings. Obviously, the described embodiments are only some, not all, of the embodiments of this application. All other embodiments obtained by those skilled in the art based on the embodiments of this application are within the scope of protection of this application.

[0035] Unless otherwise defined, all technical terms and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the embodiments of this invention pertain. If any definition stated in this section is contrary to or otherwise inconsistent with a definition stated in a patent, patent application, published patent application, or other publication incorporated herein by reference, the definitions listed here shall prevail over those incorporated herein by reference.

[0036] Furthermore, the mass of the relevant components mentioned in the specification of the embodiments of this invention can refer not only to the specific content of each component, but also to the proportional relationship between the masses of the components. Therefore, any scaling up or down of the content of the relevant components according to the specification of the embodiments of this invention is within the scope disclosed in the specification of the embodiments of this invention. Specifically, the mass described in the specification of the embodiments of this invention can be a mass unit known in the chemical industry, such as μg, mg, g, or kg.

[0037] Unless otherwise specified, the experimental methods used in the following embodiments are conventional methods. Unless otherwise specified, the materials and reagents used in the following embodiments are commercially available. This application will now be described in detail with reference to specific embodiments.

[0038] An ibuprofen suspension drop, comprising ibuprofen, xanthan gum, pregelatinized starch, glycerin, sucrose, anhydrous citric acid, sodium benzoate, polysorbate 80, and fragrance, wherein the mass percentage content of each component is as follows:

[0039] Ibuprofen 4%, xanthan gum 0.18%-0.26%, pregelatinized starch 1%-1.4%, polysorbate 80%-0.075%, anhydrous citric acid 0.18%, sodium benzoate 0.2%, sucrose 30%, glycerin 10%, fragrance 0.04%, water 53.85-54.4%.

[0040] The preparation method of the ibuprofen suspension drops includes the following steps:

[0041] 1) Ibuprofen is passed through a 20-mesh sieve and set aside.

[0042] Weigh out purified water, add polysorbate 80, stir to dissolve, add the prescribed amount of ibuprofen, and stir to disperse evenly; 2) Add 100℃ purified water and glycerin to the mixing tank, and stir to mix for 5-10 minutes;

[0043] 3) Start the rotor pump and homogenizer pump to form an internal circulation in the liquid preparation tank. Open the ball valve of the feeding funnel, add xanthan gum and pregelatinized starch, close the funnel valve, and homogenize until step 6 is completed.

[0044] 4) Weigh out the sucrose, add it to boiling water at 100℃, and stir to dissolve;

[0045] 5) Continue stirring in the mixing tank, add sucrose solution, rinse the container with water, and add it to the mixing tank;

[0046] 6) Add anhydrous citric acid and sodium benzoate to the mixing tank and stir for about 5-10 minutes. Ensure that the mixture is kept warm for more than 1 hour from the end of step 3 to step 6.

[0047] 7) Turn off the homogenizer pump, add ibuprofen dispersion to the mixing tank, rinse the dispersion container with water several times, and add stirring;

[0048] 8) Add flavoring to the mixing tank and stir;

[0049] 9) Add the full amount of purified water and stir for 60 minutes (take samples from the top, middle and bottom of the mixture to determine viscosity and content uniformity).

[0050] 10) Filling.

[0051] In one embodiment of the ibuprofen suspension drops, the xanthan gum content is 0.18%-0.26%, preferably 0.24%.

[0052] In one embodiment of ibuprofen suspension drops, the pregelatinized starch is selected from PGS or UITRA.

[0053] In some embodiments, the amount of pregelatinized starch used is 1%-1.4%; preferably 1.2%-1.4%, and more preferably 1.2%.

[0054] In one embodiment of ibuprofen suspension drops, the amount of polysorbate 80 is 0%-0.075%, preferably 0.05%.

[0055] In one embodiment of the ibuprofen suspension drops, the flavoring includes at least one selected from apple, orange, grape, strawberry, banana, cherry, lemon, and pear flavorings. Preferably, strawberry flavoring is used, and the amount of strawberry flavoring is 0.04%.

[0056] In one embodiment of the method for preparing ibuprofen suspension drops, step 1) involves maintaining stirring for at least 2 hours.

[0057] In one embodiment of the method for preparing ibuprofen suspension drops, before adding the ibuprofen dispersion in step 7), the temperature inside the mixing tank is lowered to below 40°C.

[0058] In one embodiment of the method for preparing ibuprofen suspension drops, the homogenization internal circulation time at the end of steps 3-6 is at least 3 hours.

[0059] In one embodiment of the preparation method of ibuprofen suspension drops, the gelation time is 30 min to 3 hours, preferably 3 hours.

[0060] The features and performance of this application will be further described in detail below with reference to the embodiments.

[0061] Measurement method:

[0062] 1. Chromatographic method for dissolution determination: HPLC method

[0063] Column: Welch Ultimate XB-C18 (4.6×150mm, 5μm);

[0064] Mobile phase: acetonitrile-0.01M phosphoric acid solution (65:35);

[0065] Flow rate: 1.0 ml / min;

[0066] Detection wavelength: 220nm;

[0067] Injection volume: 10 μL;

[0068] Column temperature: 30℃

[0069] 2. Determination of sodium benzoate and ibuprofen content: HPLC method

[0070] Column: Welch Ultimate XB-C18 (4.6×150mm, 5μm) — 78#

[0071] Mobile phase A: 0.01M phosphoric acid solution

[0072] Mobile phase B: Acetonitrile

[0073] Perform gradient elution according to the table below:

[0074]

[0075] Flow rate: 1.0 ml / min

[0076] Detection wavelength: 220nm

[0077] Injection volume: 10 μl

[0078] Column temperature: 30℃

[0079] Solvent: Water (with 1 ml of 1 mol / L sodium hydroxide solution)

[0080] Preparation concentration: Ibuprofen 0.8 mg / ml

[0081] Liquid Chromatograph: LC14

[0082] Example 1: Ibuprofen suspension drops (20ml: 0.8g)

[0083] 1. Formulation of Ibuprofen Suspension Drops

[0084]

[0085]

[0086] 2. The preparation process of ibuprofen suspension drops (20L) includes the following steps:

[0087] 1) Ibuprofen is passed through a 20-mesh sieve and set aside.

[0088] In a beaker, add 1.3 kg of purified water, add polysorbate 80, stir for 10-30 minutes to dissolve, add the prescribed amount of ibuprofen, and stir to disperse.

[0089] 2) Add 6.2 kg of purified water and glycerol to the mixing tank and stir for 5-10 minutes;

[0090] 3) Start the rotor pump and homogenizer pump to form an internal circulation in the liquid preparation tank. Open the ball valve of the feeding funnel, add xanthan gum and pregelatinized starch, close the funnel valve, and homogenize until step 6 is completed.

[0091] 4) In another container, weigh out 4 kg of purified water, add 6 kg of sucrose, and stir to dissolve;

[0092] 5) Add sucrose solution to the mixing tank, rinse the container with 400g of water, and add the solution to the mixing tank;

[0093] 6) Add anhydrous citric acid and sodium benzoate to the mixing tank and stir for 5-10 minutes. Continue stirring for at least 1 hour from step 3 to the end of step 6.

[0094] 7) Turn off the homogenizer pump, add ibuprofen dispersion to the mixing tank, rinse the dispersion container several times with 400g of water, and add stirring;

[0095] 8) Add flavoring to the mixing tank and stir;

[0096] 9) Add purified water to a total volume of 22.8 kg and stir for 60 min (take samples at 40 min, 50 min, and 60 min to determine the uniformity of content);

[0097] 10) Filling: Fill into oral liquid pharmaceutical polypropylene bottles.

[0098] Example 2. Reference formulation

[0099]

[0100]

[0101] Example 3: Study on the quality characteristics of the formulation

[0102] In Example 1, the small-scale batch of ibuprofen suspension drops (20 ml: 0.8 g) was compared with the reference formulation in terms of pH, relative density, sedimentation volume ratio, content, sodium benzoate, related substances, dissolution (pH 7.2), dissolution curve (pH 5.5), dispersibility, and particle size.

[0103]

[0104] (1) Particle size

[0105]

[0106]

[0107] The small-scale test batches (such as 201015, 201109, and 201110) showed relatively uniform particle size distribution, with D50 values ​​ranging from 16.77 to 18.70 μm, indicating good particle size control.

[0108] The reference formulations (such as Motrin and Children's Motrin) have relatively large D50 values, at 42.53 μm and 37.58 μm, respectively, indicating that their particle size is relatively large.

[0109] (2) Key quality attributes

[0110] Comparison of key quality attributes between pilot batch and reference formulation

[0111]

[0112] Comparison of key quality attributes between pilot batch and reference formulation (60℃ for 10 days)

[0113]

[0114] Comparison of key quality attributes between pilot batch and reference formulation (40℃ for 10 days)

[0115]

[0116] After being stored at 60℃ and 40℃ for 10 days, the sedimentation volume ratio, content, sodium benzoate content, redispersibility and related substances of the small-scale test batch (e.g., 201015) and the reference preparation (e.g., Motrin) remained stable, showing good long-term storage stability.

[0117] (3) Dissolution curve

[0118] Dissolution curve of ibuprofen suspension drops in small batch at pH 5.5 medium ( Figure 2 )

[0119]

[0120] Comparing the self-made product with the reference product, the results showed that all the above-mentioned indicators met the requirements, and the formulation of this application even performed better in terms of dispersibility and particle size.

[0121] Example 4: Investigation of excipients and dosage in the prescription

[0122] (1) Investigation on the dosage of xanthan gum

[0123] Based on the example formulation disclosed in the original US patent US 5374659, the xanthan gum content is 0.18%. This study investigates the impact of different xanthan gum dosages on key quality attributes, such as pH, sodium benzoate content, dissolution, viscosity, ibuprofen content, and particle size. Specific formulation parameters are shown in the table below.

[0124]

[0125]

[0126] The quality attribute results of xanthan gum dosage are shown in the table below:

[0127]

[0128] The results of the xanthan gum dosage study - dissolution curves (pH 5.5 medium) are shown in the table below:

[0129]

[0130]

[0131] The above results show that:

[0132] Dissolution analysis: Within the range of xanthan gum dosage of 0.18%-0.26%, the dissolution rate at both the minimum and maximum dosages was greater than 85% at 15 min, and the curves were consistent with the reference formulation. After 3 months of accelerated dissolution of the product, there was no significant change in the dissolution curve. Therefore, within the range of xanthan gum dosage of 0.18%-0.26%, xanthan gum has no effect on the dissolution of ibuprofen.

[0133] Viscosity analysis: When the amount of xanthan gum was in the range of 0.18%-0.26%, the viscosity was 810-1665 mPa·s, which increased with the increase of the amount. After 3 months of accelerated testing, it decreased to 567-1172 mPa·s. The initial measured values ​​of the reference preparation were 717 and 660 mPa·s. It was assessed that maintaining a relatively high viscosity is beneficial to the stability of the suspension.

[0134] pH, sodium benzoate content, ibuprofen content, particle size and related substances analysis: The sodium benzoate content, ibuprofen content, particle size distribution, pH and related substances were tested at the lowest and highest xanthan gum dosages after 3 months of accelerated treatment. The initial values ​​were consistent with the reference preparation. After 3 months of accelerated treatment, the results of the self-prepared product showed no significant changes.

[0135] (2) Investigation on the amount of pregelatinized starch used

[0136] Pregelatinized starch (PGS) and pregelatinized starch (UITRA) were used at concentrations of 1%, 1.2%, and 1.4%. Specific formulation parameters are shown in the table below.

[0137] Components Prescription 4 (g) Prescription 6g Prescription 7g Prescription 8g Prescription 9g Prescription 10g Prescription 1 (g) batch number 20011701 20011901 20011902 20011903 20011904 20011905 20011601 Ibuprofen 4 4 4 4 4 4 4 Xanthan Gum 0.24 0.24 0.24 0.24 0.24 0.18 0.18 Pregelatinized starch (PGS) 1.2 1 1.4 / / / 1.2 Pregelatinized starch (UITRA) / / / 1 1.2 1.2 / glycerin 10 10 10 10 10 10 10 sucrose 30 30 30 30 30 30 30 Polysorbate 80 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Anhydrous citric acid 0.18 0.18 0.18 0.18 0.18 0.18 0.18 Sodium benzoate 0.2 0.2 0.2 0.2 0.2 0.2 0.2 strawberry flavoring 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Add purified water to 100ml 100ml 100ml 100ml 100ml 100ml 100ml

[0138] The results of screening quality attributes for pregelatinized starch types and dosages are shown in the table below:

[0139]

[0140]

[0141] The results of the dissolution profile (pH 5.5 medium) for different types and amounts of pregelatinized starch are shown below:

[0142]

[0143] Dissolution analysis: There was no significant difference in dissolution rate between different types and dosages of pregelatinized starch PGS (1% and 1.4%) and UITRA (1% and 1.2%). All samples showed dissolution rates greater than 85% at 15 min, and the curves were consistent with the reference formulation. Therefore, pregelatinized starch in the range of 1%-1.4% has no effect on the dissolution of ibuprofen.

[0144] pH analysis: The pH of both types of pregelatinized starch showed no significant change, consistent with the reference preparation, indicating that pregelatinized starch had no effect on pH.

[0145] Viscosity analysis: Among the two types of pregelatinized starch, with other dosages kept constant, UITRA's viscosity was too high. The combination of PGS and xanthan gum could meet the expected requirements. With a dosage of 1%-1.4%, the viscosity was within 800-1500 mPa·s, which could satisfy the suspension effect.

[0146] Particle size analysis: The particle size of the suspensions of both types of pregelatinized starch did not exceed that of the reference formulation, and the pregelatinized starch will not affect the particle size of ibuprofen in the formulation.

[0147] Content analysis: The ibuprofen content remained unchanged between the two types of pregelatinized starch, indicating that pregelatinized starch does not affect the ibuprofen content in the formulation.

[0148] (4) Investigation on the dosage of polysorbate 80

[0149] The effects of polysorbate 80 dosage ranging from 0% to 0.075% on dissolution and particle size were investigated. Specific formulation parameters are shown in the table below:

[0150]

[0151]

[0152] The effect of polysorbate 80 on dissolution (pH 5.5 medium) is shown in the table below:

[0153]

[0154] The effect of polysorbate 80 on the content is shown in the table below:

[0155] batch number content% RSD% 20021304 101.0 0.6 20021301 99.2 1.5

[0156] Dissolution analysis: There was no significant difference in dissolution rate between 0% and 0.075% polysorbate 80 dosages, both exceeding 85% at 15 min. The dissolution curves were consistent with the reference formulation. Therefore, polysorbate 80 dosages within the range of 0%-0.075% have no effect on the dissolution of ibuprofen, and polysorbate 80 can play a wetting role.

[0157] Content analysis: There was no significant difference in ibuprofen content between polysorbate 80 dosages of 0% and 0.075%, and the content was consistent with the theoretical value, with no significant effect on the content.

[0158] Example 5: Investigation of the preparation process

[0159] (1) Effect of gelling time on viscosity, particle size and dissolution

[0160]

[0161]

[0162] The effects of curing time on viscosity and content are shown in the table below:

[0163] Melting time 30min 1h 2h 3h batch number 200311 200312 200313 200316 intermediate viscosity 1585 1387 1552 1355 Sample viscosity 997 932 1082 1010 content 101.5 / / 99.3

[0164] The effect of gelling time on particle size is shown in the table below:

[0165] granularity D10 value (μm) D50 value (μm) D90 value (μm) 200311 4.371 20.28 51.05 200312 4.53 21.02 55.71 200313 4.394 20.04 48.45 200316 4.804 20.86 47.91 Batch 190515266 22.05 45.7 70.39

[0166] The effect of gelling time on dissolution (pH 5.5 medium) is shown in the table below:

[0167]

[0168] Therefore, it can be seen that there is no significant difference in viscosity, particle size, and content when the gel is prepared for 30 minutes, 1 hour, 2 hours, and 3 hours. The dissolution curve is consistent with the reference preparation. Therefore, the gel preparation time can be from 30 minutes to 3 hours.

[0169] (2) Effect of stirring time on content uniformity after adding ibuprofen

[0170] The uniformity of ibuprofen content was investigated after stirring for 15 min, 30 min, and 60 min. The results of stirring time on the uniformity of content are shown in the table below:

[0171]

[0172]

[0173] Therefore, it can be seen that after adding ibuprofen and stirring for more than 30 minutes, the RSD ≤ 1.0%, indicating that the uniformity of the controlled dose unit of the sample is very good.

[0174] (3) Effect of melting temperature on viscosity and content uniformity

[0175] Boil the sucrose to achieve a gelling temperature of 100℃. Before adding the ibuprofen dispersion, lower the temperature inside the mixing tank to below 40℃. The specific process is as follows:

[0176] 1. Ibuprofen is passed through a 20-mesh sieve and set aside.

[0177] Weigh 325g of purified water, add polysorbate 80, stir to dissolve, add the prescribed amount of ibuprofen, and stir to disperse evenly.

[0178] 2. Weigh 1.5 kg of sucrose and add it to 1 kg of boiling water at 100℃, stirring until dissolved;

[0179] 3. Add 1.55 kg of purified water at 100℃ and glycerol to the mixing tank, and stir for 5-10 minutes;

[0180] 4. Start the rotor pump and homogenizer pump to create an internal circulation in the mixing tank. Open the ball valve of the feeding funnel, add xanthan gum and pregelatinized starch, close the funnel valve, start timing, and observe the dissolution of xanthan gum and pregelatinized starch until completely dissolved. 5. Continue stirring in the main tank, add sucrose solution (using a 50g water-sucrose container) to the mixing tank.

[0181] 6. Add anhydrous citric acid and sodium benzoate and mix for about 5-10 minutes, then cool to below 40°C;

[0182] 7. Turn off the homogenizer pump, add ibuprofen dispersion to the mixing tank, rinse the dispersion container several times with 100g of water, and stir; 8. Add flavoring and stir;

[0183] 9. Add 5.7 kg of purified water, stir for 60 min, and take samples from the top, middle, bottom, left, and right sides to determine the viscosity and content uniformity (5 samples). Let stand, and take samples from the top, middle, and bottom at 2 h, 4 h, and 12 h to determine the content.

[0184] 10. Filling.

[0185] The effect of melting temperature on content uniformity is shown in the table below:

[0186]

[0187]

[0188] Results of the effect of melting temperature on viscosity:

[0189] batch number 200806X Sample viscosity 785 Viscosity of samples after 10 days at 60℃ 832

[0190] The gel was melted at 100℃, which had no significant impact on the uniformity of the content. After the sample was placed at 60℃ for 10 days, the viscosity did not change significantly.

[0191] Example 6 Stability Study

[0192] The product from Example 1 and the reference sample were placed in an incubator with a relative humidity (RH) of 65% ± 5% and a temperature of 30℃ ± 2℃ for 24 consecutive months. Solution stability was observed at 0 months, 6 months, and 24 months. During observation, the samples were shaken and then allowed to stand for 2.5 hours to observe sedimentation. Details are as follows:

[0193]

[0194] Based on the long-term storage stability study of the samples in the table above, the ibuprofen suspension drops provided in this application, through optimization of the content of each component and the combination of refined preparation process steps, can produce suspension drops with good sedimentation performance and good physical stability during long-term storage, thus ensuring the quality of medication for patients.

[0195] The embodiments of this application have been described above with reference to the accompanying drawings. However, this application is not limited to the specific embodiments described above. The specific embodiments described above are merely illustrative and not restrictive. Those skilled in the art can make many other forms under the guidance of this application without departing from the spirit and scope of the claims, and all of these forms are within the protection scope of this application.

Claims

1. An ibuprofen suspension drop, said drop comprising: The ingredients are ibuprofen, xanthan gum, pregelatinized starch, glycerin, sucrose, anhydrous citric acid, sodium benzoate, polysorbate 80, flavoring, and water, with the following mass percentage content: ibuprofen 4%, xanthan gum 0.18%-0.26%, pregelatinized starch 1%-1.4%, polysorbate 80 0%-0.075%, anhydrous citric acid 0.18%, sodium benzoate 0.2%, sucrose 30%, glycerin 10%, flavoring 0.04%, and water 53.85-54.4%. The preparation method of the ibuprofen suspension drops includes the following steps: 1) Ibuprofen is passed through a 20-mesh sieve and set aside. Weigh out purified water, add polysorbate 80, stir to dissolve, add the prescribed amount of ibuprofen, and stir to disperse evenly; 2) Add purified water and glycerin at 100℃ to the mixing tank and stir for 5-10 minutes; 3) Start the rotor pump and homogenizer pump to form an internal circulation in the liquid preparation tank. Open the ball valve of the feeding funnel, add xanthan gum and pregelatinized starch, close the funnel valve, and homogenize until step 6 is completed. 4) Weigh out the sucrose, add it to boiling water at 100℃, and stir to dissolve; 5) Continue stirring in the mixing tank, add sucrose solution, rinse the container with water, and add it to the mixing tank; 6) Add anhydrous citric acid and sodium benzoate to the mixing tank and stir for about 5-10 minutes. Ensure that the mixture is kept warm for more than 1 hour from the end of step 3 to step 6. 7) Turn off the homogenizer pump, add ibuprofen dispersion to the mixing tank, rinse the dispersion container with water several times, and add stirring; 8) Add flavoring to the mixing tank and stir; 9) Add the full amount of purified water and stir for 60 minutes (take samples from the top, middle and bottom of the mixture to determine viscosity and content uniformity). 10) Filling.

2. The ibuprofen suspension drops according to claim 1, characterized in that, The amount of xanthan gum used is 0.24%.

3. The ibuprofen suspension drops according to claim 1, characterized in that, The amount of pregelatinized starch used is 1.2%.

4. The ibuprofen suspension drops according to claim 1, characterized in that, The amount of polysorbate 80 used is 0.05%.

5. The ibuprofen suspension drops according to claim 1, characterized in that, The flavoring is strawberry flavoring.

6. The method for preparing ibuprofen suspension drops according to claim 1, characterized in that, Step 1) Maintain stirring for at least 2 hours.

7. The method for preparing ibuprofen suspension drops according to claim 1, characterized in that, Before adding the ibuprofen dispersion in step 7), the temperature inside the mixing tank should be lowered to below 40°C.

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