A process for the preparation of a suspension of acetaminophen and ibuprofen

Abstract

The present application relates to the technical field of pharmaceutical preparation, in particular to a preparation method of acetaminophen ibuprofen suspension. The method constructs a stable three-dimensional gel network through specific liquid preparation sequence, temperature control strategy, acetaminophen adding mode and dispersion means, inhibits crystal growth and aggregation, so that the particle size of the preparation almost does not increase within the effective period, the drug release behavior remains stable, and the problem of particle size increase, even flocculation and caking of acetaminophen ibuprofen suspension during storage is effectively solved.

Description

Technical Field

[0001] This invention relates to the field of pharmaceutical formulation technology, specifically to a method for preparing an acetaminophen-ibuprofen suspension. Background Technology

[0002] Acetaminophen and ibuprofen oral suspension is a commonly used antipyretic and analgesic drug in clinical practice, especially suitable for children and patients with dysphagia. In this liquid formulation, the particle size distribution of the active ingredients directly affects the drug's dissolution, bioavailability, and taste. Acetaminophen-ibuprofen suspension with substandard particle size may have a gritty feel when taken.

[0003] In existing technologies, suspensions commonly suffer from particle size increase and even flocculation and clumping during long-term storage. Particle size increase can cause dissolution profiles to drift within the drug's shelf life, and can also lead to uneven drug distribution in the suspension system, affecting batch-to-batch consistency of efficacy, drug effectiveness, and even posing safety risks. Therefore, developing a production process that can maintain long-term particle size stability has significant clinical and commercial value.

[0004] Patent CN116370441A discloses a method for preparing an inhaled budesonide suspension, which is obtained by sterilizing and diluting a budesonide concentrate with a concentration of less than 15 mg / ml. The suspension comprises, by weight-volume ratio: 0.025–0.20% micronized budesonide, 0.0025–0.02% stabilizer, 0.00125–0.01% chelating agent, isotonic agent, and buffer salt; wherein the particle size range of the budesonide is D. 50 <4μm and D 90 <7μm. The method for preparing budesonide inhalation suspension provided by this invention utilizes the synergistic effect of buffer salts, chelating agents, and stabilizers in the concentrate to prevent significant particle size increase before and after sterilization of budesonide concentrate with concentrations below 15mg / ml; and further reduces the risk of the concentrate dilution process by preferably using polyethylene glycol or poloxamer as the stabilizer, ensuring that the sedimentation volume ratio and related substances of the final product meet quality requirements. This invention discloses the synergistic effect of buffer salts, chelating agents, and stabilizers in the concentrate to prevent significant particle size increase before and after sterilization of budesonide concentrate with concentrations below 15mg / ml, but this method is not suitable for acetaminophen-ibuprofen suspension.

[0005] Patent CN118766843A discloses an ibuprofen suspension and its preparation method, belonging to the field of pharmaceutical preparation technology. The ibuprofen suspension of this invention is composed of ibuprofen, sucrose, whey protein isolate / xanthan gum complex, pregelatinized starch, glycerol, Tween 80, citric acid, sodium benzoate, flavoring, coloring, and water. Compared with existing technologies, this invention uses a whey protein isolate / nicotinamide mononucleotide complex to replace xanthan gum, effectively solving the problem of uneven ibuprofen suspension content and poor stability caused by uneven swelling of xanthan gum. While this method can solve the problem of uneven ibuprofen suspension content caused by uneven xanthan gum swelling, it cannot solve the problem of particle size increase and even flocculation and clumping that commonly occurs during long-term storage of acetaminophen-ibuprofen suspension. Summary of the Invention

[0006] The purpose of this invention is to provide a method for preparing acetaminophen-ibuprofen suspension. This method constructs a stable three-dimensional gel network by using a specific solution preparation sequence, temperature control strategy, acetaminophen addition method and dispersion means, which inhibits crystal growth and aggregation, so that the particle size of the formulation hardly increases during its shelf life and the drug release behavior remains stable.

[0007] To solve the technical problem of this invention, the present invention provides the following technical solution: A method for preparing an acetaminophen-ibuprofen suspension includes the following steps: S1 API Pretreatment: Acetaminophen and ibuprofen are pulverized, and the D of acetaminophen is controlled. 90 Particle size ≤70μm and D 10 Particle size ≥3μm, ibuprofen D 90 Particle size ≤250μm; S2 microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product dispersion: Add 25-45% of the total amount of purified water to the mixing tank, heat to 40-50℃, add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product and 20-40% of the pretreated acetaminophen under stirring, homogenize and disperse using a batch homogenizer head, the gap of the homogenizer head teeth should be less than 0.4mm, the shear line speed is 15m / s-30m / s, homogenize for 10-30 minutes, and then lower the material temperature to 15-30℃; S3 Xanthan Gum Predispersion and Auxiliary Material Mixing: In a separate container, glycerol and xanthan gum are stirred and mixed evenly to form a uniform slurry premix; the resulting premix and liquid maltitol are added to the system cooled in step S2 and stirred and mixed. S4 API predispersion: Add 6% to 10% of the total formulation amount of purified water to an independent container, first add polysorbate 80 to dissolve, then add the remaining pulverized acetaminophen and stir to disperse evenly, then add ibuprofen and stir to disperse evenly to obtain a suspension. S5 Final Mixing: Add the suspension obtained in step S4 to the container in step S3, add sodium benzoate solution pre-dissolved in 2% purified water of the total prescription volume; check pH 3.5-5.0; add the remaining purified water to the total volume, and stir to mix well; S6 filling.

[0008] Preferably, in the above-mentioned method for preparing acetaminophen-ibuprofen suspension, the D of the acetaminophen... 90 Particle size ≤65μm and D 10 Particle size ≥ 6μm.

[0009] Preferably, in the above-mentioned method for preparing acetaminophen-ibuprofen suspension, step S2 is: Add 30-40% of the total amount of purified water to the mixing tank, heat to 40-45℃, and add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated material and 25-35% of the pretreated acetaminophen while stirring. Use a batch homogenizer head to homogenize and disperse the material. The gap between the teeth of the homogenizer head should be 0.25-0.35mm, the shear speed should be 20m / s-25m / s, and the homogenization should last for 10-30 minutes. Then, reduce the material temperature to 15-30℃.

[0010] More preferably, in the above method for preparing acetaminophen-ibuprofen suspension, step S2 is: Add 35% of the total amount of purified water to the mixing tank, heat to 40-45℃, and add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated material and 28-32% of the pretreated acetaminophen while stirring. Use a batch homogenizer head to homogenize and disperse the material. The gap between the teeth of the homogenizer head should be 0.25-0.35mm, the shear speed should be 20m / s-25m / s, and the homogenization should be carried out for 10-30 minutes. Then, reduce the material temperature to 15-30℃.

[0011] The preparation method of the above-mentioned acetaminophen ibuprofen suspension may further include step S3 as follows: dissolving sucralose, citric acid, sodium citrate and coloring agent in 3% of the prescribed amount of purified water, and adding the dissolved solution to the system cooled in step S2.

[0012] Preferably, in the above-mentioned method for preparing acetaminophen-ibuprofen suspension, the pH is measured to be 4.0-4.5 in step S4.

[0013] If pH needs to be adjusted in step S4, it must be adjusted with citric acid or sodium citrate.

[0014] Step S6 is: filling into 100ml or other suitable packaging and sealing.

[0015] In the above-mentioned method for preparing acetaminophen-ibuprofen suspension, the acetaminophen-ibuprofen suspension contains, per 1000 mL volume, 32 g of acetaminophen, 9.6 g of ibuprofen, 0.3–0.8 g of polysorbate 80, 5–10 g of microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product, 2–5 g of xanthan gum, 150 g of glycerol, 250 g of liquid maltitol, and the remainder is purified water.

[0016] Preferably, the acetaminophen-ibuprofen suspension contains, per 1000 mL volume, 32 g of acetaminophen, 9.6 g of ibuprofen, 0.7 g of polysorbate 80, 8 g of microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product, 3 g of xanthan gum, 150 g of glycerol, 250 g of liquid maltitol, and the remainder is purified water.

[0017] In the above-mentioned method for preparing acetaminophen-ibuprofen suspension, the acetaminophen-ibuprofen suspension, based on a volume of 1000 mL, also contains 1-3 g of sucralose, 3-5 g of citric acid, 3-5 g of sodium citrate, and 0.8-1.2 g of sodium benzoate.

[0018] The preferred acetaminophen-ibuprofen suspension, per 1000 mL volume, also contains 1.2 g sucralose, 4 g citric acid, 4.2 g sodium citrate, and 1 g sodium benzoate.

[0019] In the above-mentioned method for preparing acetaminophen-ibuprofen suspension, the colorant is one or more selected from carmine, tartrazine, sunset yellow, allura red, amaranth, brilliant blue, and erythrosine. The amount of colorant used is 0.1-0.5g per 1000mL volume of acetaminophen-ibuprofen suspension.

[0020] In the above-mentioned method for preparing acetaminophen-ibuprofen suspension, a flavoring agent may be added. The flavoring agent is one of the following: strawberry flavoring, grape flavoring, orange flavoring, banana flavoring, cherry flavoring, watermelon flavoring, or raspberry flavoring. The amount of flavoring agent used is 0.2-0.8 g per 1000 mL volume of acetaminophen-ibuprofen suspension. The flavoring agent is added together with the colorant in step S3.

[0021] In this invention, the term "active pharmaceutical ingredient" refers to the active pharmaceutical ingredient, namely acetaminophen and ibuprofen.

[0022] Beneficial effects: The main reasons for the particle size increase and even flocculation of acetaminophen-ibuprofen suspension during long-term storage are: 1) the dissolution-re-precipitation process of the slightly soluble drug acetaminophen crystals in the aqueous medium; 2) the hydration state of the excipients microcrystalline cellulose, sodium carboxymethyl cellulose, and xanthan gum in the suspension system is greatly affected by temperature. If the hydration network is not fully constructed, it cannot effectively inhibit particle sedimentation and collision; 3) due to the influence of the surface charge of insoluble particles, the active ingredient ibuprofen is prone to heterogeneous flocculation during conventional mixing.

[0023] This invention inhibits Ostwald ripening and flocculation by controlling the particle size of the active pharmaceutical ingredient and employing a unique preparation process, achieving unexpected technical results. The main advantages of this invention are: (1) Optimization of particle size control: The pretreatment of the active pharmaceutical ingredient established the optimal particle size and particle size distribution control range for acetaminophen, which weakened the dissolution tendency of small particles and the sedimentation risk of large particles.

[0024] (2) Excellent particle size stability: The “heating and hydration followed by cooling and shaping” operation of the microcrystalline cellulose-sodium carboxymethyl cellulose co-treatment dispersion makes the microcrystalline cellulose segments shrink after cooling to form a dense protective gel fence, which significantly reduces the free movement space of drug particles; the addition and dissolution of some acetaminophen in advance accelerates the establishment of dissolution-precipitation equilibrium and stabilizes the insoluble acetaminophen particles.

[0025] (3) Inhibition of heterogeneous coagulation: The pre-dispersion of the active pharmaceutical ingredient clearly defines the order of adding acetaminophen first and then ibuprofen. Polysorbate 80 preferentially adsorbs on the hydrophobic surface of acetaminophen to form a protective layer, avoiding direct charge neutralization flocculation of the two drugs due to the difference in surface charge - the difference in Zeta potential.

[0026] (4) Rheological advantages: The xanthan gum pre-dispersion step uses glycerol as the dispersion medium for xanthan gum, which eliminates the phenomenon of xanthan gum hydrating and swelling instantly upon contact with water to form "fish eye" clumps, ensuring that the xanthan gum molecular chains are uniformly extended in the system and synergistically form a thixotropic fluid with microcrystalline cellulose.

[0027] The method for preparing acetaminophen-ibuprofen suspension of the present invention effectively solves the problems of particle size growth and even flocculation and agglomeration during the storage of acetaminophen-ibuprofen suspension by using microcrystalline cellulose treatment technology of "heating and hydration followed by cooling and shaping", acetaminophen particle size control and secondary addition method, xanthan gum and glycerol non-aqueous pre-dispersion technology, and active ingredient sequence technology of "adding acetaminophen first and then ibuprofen". Attached Figure Description

[0028] Figure 1 The initial particle size diagram of acetaminophen in Example 1; Figure 2 The particle size distribution of acetaminophen after 6 months of accelerated stability testing (40°C / 75%RH) in Example 1 is shown. Figure 3 The initial particle size diagram of acetaminophen in Comparative Example 1; Figure 4 The particle size distribution of acetaminophen after 6 months of accelerated stability testing (40℃ / 75%RH) for Comparative Example 1 is shown.

[0029] The scale and magnification of all figures in this specification are consistent. Detailed Implementation

[0030] The present invention will be further described below with reference to specific embodiments, so that those skilled in the art can better understand the present invention, but it is not intended to limit the present invention.

[0031] Unless otherwise specified, the experimental materials and reagents used in the embodiments of this invention are all consumables and reagents that are conventionally available from commercial sources.

[0032] Unless otherwise specified, experimental methods in the following examples are generally performed under standard conditions or as recommended by the manufacturer. Percentages and parts are by weight.

[0033] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as are familiar to those skilled in the art. Furthermore, any methods and materials similar to or equivalent to those described herein may be applied to the methods of this invention. The preferred embodiments and materials described herein are for illustrative purposes only.

[0034] In this embodiment of the invention, the liquid maltitol used was purchased from Tianjin Xincheng Kangda Pharmaceutical Co., Ltd., specification: 75 / 55A; quality characteristics: total solids content 75%, of which maltitol accounts for 55% of the total solids, all by weight. The microcrystalline cellulose sodium carboxymethyl cellulose co-processed product was purchased from International N&H USA, Inc.

[0035] In this embodiment of the invention, the dispersion step of the microcrystalline cellulose-sodium carboxymethyl cellulose co-processed material is carried out using a homogenizer, which is a commonly used pharmaceutical instrument.

[0036] Example 1: Preparation of acetaminophen-ibuprofen suspension Prescription: 100L suspension volume 3.2 kg of acetaminophen; Ibuprofen 0.96kg; Polysorbate 80 0.07kg; 0.8 kg of microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product; Xanthan gum 0.3kg; 15 kg of glycerin; 25 kg of liquid maltitol; 0.12 kg of sucralose; Citric acid 0.4 kg; Sodium citrate 0.42 kg; Sodium benzoate 0.1 kg; Strawberry flavoring 0.5kg; Carmine 0.03kg Add purified water to the total volume; Total weight: 112.4 kg (100 L, ρ = 1.124 g / ml).

[0037] Preparation process S1 API pretreatment: Acetaminophen pulverization, laser particle size analyzer detection. 10 =7,D 90 =63μm; Ibuprofen particle size: D 90 ≤250μm.

[0038] S2 microcrystalline cellulose-sodium carboxymethyl cellulose co-processed material dispersion: Add 35 kg of purified water to a 100 L mixing tank, heat to 43 °C, start shearing and stirring, slowly add 0.7 kg of microcrystalline cellulose-sodium carboxymethyl cellulose co-processed material and 1.0 kg (accounting for 31.25% of the total amount) of acetaminophen that has been pulverized in the above-mentioned raw material pretreatment steps, and use a batch homogenizing head shearing with a toothed gap of 0.3 mm and a shearing linear speed of 23 m / s (approximately 2500 rpm as displayed on the equipment). After homogenizing and dispersing for 15 minutes, stop and maintain slow stirring at 50-80 rpm. Turn on the circulating cold water to cool down the material to 22 °C.

[0039] S3 Xanthan Gum Predispersion and Excipient Mixing: Take 15 kg of glycerol and, in a separate container, sprinkle in 0.25 kg of xanthan gum while stirring to form a uniform slurry premix. Add the glycerol-xanthan gum slurry and 25 kg of liquid maltitol to the mixing tank; separately, dissolve 0.12 kg of sucralose, 0.4 kg of citric acid, 0.42 kg of sodium citrate, and 0.03 kg of carmine in 10 kg of purified water, stir until clear, and then transfer to the mixing tank.

[0040] S4 API pre-dispersion: Take 8 kg of purified water in a separate container, add 0.05 kg of polysorbate 80 and stir well. First add 2.2 kg of acetaminophen and stir for 10 minutes, then add 0.96 kg of ibuprofen and stir for 10 minutes to form a drug suspension.

[0041] S5 Final Mixing: Transfer the above drug suspension to the mixing tank and add 0.5 kg of fragrance; separately take 2 kg of purified water to dissolve 0.1 kg of sodium benzoate and add it to the mixing tank, with a pH value of 4.0. Add the remaining purified water to a total weight of 112.4 kg (equivalent to 100 L, ρ = 1.124 g / ml), and stir to mix well.

[0042] S6 Filling: Fill into 100ml or other suitable packaging and seal.

[0043] Example 2 Preparation of acetaminophen-ibuprofen suspension The prescription is the same as in Example 1; the difference in preparation process compared to Example 1 lies in the different key process parameters, and the control of key process parameters is shown in Table 1.

[0044] Comparative Example 1: Preparation of Acetaminophen-Ibuprofen Suspension The prescription is the same as in Example 1; except that acetaminophen is not added in the dispersion of the microcrystalline cellulose-sodium carboxymethyl cellulose co-treatment product in step S2, the other basic preparation processes are the same as in Example 1, except that the key process parameters are different. The control of the key process parameters is shown in Table 1.

[0045] Comparative Example 2: Preparation of Acetaminophen-Ibuprofen Suspension The prescription is the same as in Example 1; except that acetaminophen is not added in the dispersion of the microcrystalline cellulose-sodium carboxymethyl cellulose co-treatment product in step S2, the other basic preparation processes are the same as in Example 1, except that the key process parameters are different. The control of the key process parameters is shown in Table 1.

[0046] The key process differences between Example 1, Example 2, Comparative Example 1, and Comparative Example 2 are listed below for comparison: Table 1. List of key processes in Examples 1, 2, Comparative Example 1, and Comparative Example 2 .

[0047] Experimental Example: Particle size stability and dissolution curve analysis of acetaminophen-ibuprofen suspension In the suspension of this invention, ibuprofen is almost insoluble in the system and is not prone to particle size increase (Ostwald ripening); acetaminophen has relatively higher solubility in this system, existing in a partially dissolved and partially suspended state, and its solubility is significantly affected by temperature, making Ostwald ripening more pronounced. Therefore, the particle size analysis mainly focuses on the particle size of acetaminophen, and the dissolution curve only needs to be examined for acetaminophen.

[0048] Experimental Example 1: Investigation of Particle Size Stability Methods: Accelerated testing was conducted on samples from Examples 1 and 2 and Comparative Examples 1 and 2 at 40℃±2℃ and RH 75%±5%. Samples were taken at 0 days, 1 month, 3 months, and 6 months, and the particle size distribution (D) of acetaminophen was determined according to Section 0982, Particle Size and Particle Size Distribution Determination (Method I: Microscopic Method), Part IV, Chinese Pharmacopoeia 2025. 90 The physical stability was evaluated by the settling volume ratio. The results are shown in Table 2.

[0049] Table 2 Results of the particle size stability test As can be seen from the above data, in Comparative Examples 1 and 2, due to incomplete gel network construction and Ostwald ripening, the particle size increased significantly within 6 months, forming larger crystalline particles that settled to the bottom of the suspension. This resulted in poor drug uniformity, inaccurate dosage, and consequently, affected efficacy and safety. In contrast, Examples 1 and 2, employing the technology of this patent, successfully inhibited crystal growth and aggregation through temperature-controlled construction of a dense gel network and stepwise adsorption protection technology, maintaining almost no change in particle size over 6 months.

[0050] Experimental Example 2: Investigation of Dissolution Curves Dissolution and release determination method II (paddle method) of Chinese Pharmacopoeia 2025 Edition, Part IV, 0931 was adopted. 0.1 mol / L hydrochloric acid was used as the dissolution medium, the rotation speed was 50 rpm, and the temperature was 37℃±0.5℃. Samples were taken at 5, 10, 15, and 30 minutes to detect the dissolution amount of acetaminophen. The results are shown in Table 3.

[0051] Table 3 Results of Dissolution Curve Examination The results in Table 3 show that after 6 months of accelerated testing, the cumulative dissolution amount and dissolution rate of Comparative Examples 1 and 2 decreased significantly in 5 minutes, which is consistent with the results of increased particle size.

[0052] These results demonstrate that stable particle size directly ensures stable drug release behavior. In the comparative example, due to a significantly increased particle size, the specific surface area decreased, resulting in a significantly slower dissolution rate, delayed drug release, and prolonged onset of action. The process of this invention ensures the consistency of drug quality throughout its entire shelf life.

Claims

1. A method for preparing an acetaminophen-ibuprofen suspension, characterized in that, Includes the following steps: S1 API Pretreatment: Acetaminophen and ibuprofen are pulverized, and the D of acetaminophen is controlled. 90 Particle size ≤70μm and D 10 Particle size ≥3μm, ibuprofen D 90 Particle size ≤250μm; S2 microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product dispersion: Add 25-45% of the total amount of purified water to the mixing tank, heat to 40-50℃, add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product and 20-40% of the pretreated acetaminophen under stirring, homogenize and disperse using a batch homogenizer head, the gap of the homogenizer head teeth should be less than 0.4mm, the shear line speed is 15m / s-30m / s, homogenize for 10-30 minutes, and then lower the material temperature to 15-30℃; S3 Xanthan Gum Predispersion and Auxiliary Material Mixing: In a separate container, glycerol and xanthan gum are stirred and mixed evenly to form a uniform slurry premix; the resulting premix and liquid maltitol are added to the system cooled in step S2 and stirred and mixed. S4 API predispersion: Add 6% to 10% of the total formulation amount of purified water to an independent container, first add polysorbate 80 to dissolve, then add the remaining pulverized acetaminophen and stir to disperse evenly, then add ibuprofen and stir to disperse evenly to obtain a suspension. S5 Final Mixing: Add the suspension obtained in step S4 to the container in step S3, add sodium benzoate solution pre-dissolved in 2% purified water of the total prescription volume; check pH 3.5-5.0; add the remaining purified water to the total volume, and stir to mix well; S6 filling.

2. The method for preparing the acetaminophen-ibuprofen suspension according to claim 1, characterized in that, The D of acetaminophen 90 Particle size ≤65μm and D 10 Particle size ≥ 6μm.

3. The method for preparing the acetaminophen-ibuprofen suspension according to claim 1, characterized in that, Step S2 is as follows: Add 30-40% of the total amount of purified water to the mixing tank, heat to 40-45℃, and add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated material and 25-35% of the pretreated acetaminophen while stirring. Use a batch homogenizer head to homogenize and disperse the material. The gap between the teeth of the homogenizer head should be 0.25-0.35mm, the shear speed should be 20m / s-25m / s, and the homogenization should last for 10-30 minutes. Then, reduce the material temperature to 15-30℃.

4. The method for preparing the acetaminophen-ibuprofen suspension according to claim 3, characterized in that, Step S2 is as follows: Add 35% of the total amount of purified water to the mixing tank, heat to 40-45℃, and add the microcrystalline cellulose-sodium carboxymethyl cellulose co-treated material and 28-32% of the pretreated acetaminophen while stirring. Use a batch homogenizer head to homogenize and disperse the material. The gap between the teeth of the homogenizer head should be 0.25-0.35mm, the shear line speed should be 20m / s-25m / s, and the homogenization should be carried out for 10-30 minutes. Then, reduce the material temperature to 15-30℃.

5. The method for preparing the acetaminophen-ibuprofen suspension according to claim 1, characterized in that, Step S3 may further include: dissolving sucralose, citric acid, sodium citrate and colorant in 3% of the prescribed amount of purified water, and then adding the dissolved sucralose to the system cooled in step S2.

6. The method for preparing the acetaminophen-ibuprofen suspension according to any one of claims 1-4, characterized in that, The acetaminophen-ibuprofen suspension, per 1000 mL volume, contains 32 g of acetaminophen, 9.6 g of ibuprofen, 0.3–0.8 g of polysorbate 80, 5–10 g of microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product, 2–5 g of xanthan gum, 150 g of glycerol, 250 g of liquid maltitol, with the remainder being purified water.

7. The method for preparing the acetaminophen-ibuprofen suspension according to claim 6, characterized in that, The acetaminophen-ibuprofen suspension, per 1000 mL volume, contains 32 g of acetaminophen, 9.6 g of ibuprofen, 800.7 g of polysorbate, 8 g of microcrystalline cellulose-sodium carboxymethyl cellulose co-treated product, 3 g of xanthan gum, 150 g of glycerol, 250 g of liquid maltitol, and the remainder is purified water.

8. The method for preparing the acetaminophen-ibuprofen suspension according to claim 6, characterized in that, The acetaminophen-ibuprofen suspension, per 1000 mL volume, also contains 1–3 g of sucralose, 3–5 g of citric acid, 3–5 g of sodium citrate, and 0.8–1.2 g of sodium benzoate.

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