Ibuprofen suspension and preparation method thereof

Abstract

The invention belongs to the technical field of ibuprofen suspensions, and particularly relates to an ibuprofen suspension and a preparation method thereof. The ibuprofen suspension is prepared from ibuprofen, microcrystalline cellulose, stearate and citrate, the particle size D90 of the ibuprofen is 68 to 130 [mu] m; the bulk density of the microcrystalline cellulose is 0.10-0.25 g / cm < 3 >. According to the ibuprofen suspension, the microcrystalline cellulose with specific bulk density and the ibuprofen raw material with specific particle size are adopted, and the microcrystalline cellulose and the ibuprofen raw material have a synergistic effect with the flocculating agent and the anionic surfactant, so that the problem that the anionic surfactant is inactivated under an acidic condition is solved; meanwhile, the problems of suspension particle aggregation and precipitation during product production and storage are solved; the invention further provides a preparation method of the ibuprofen suspension, and the preparation process is simple.

Description

Technical Field

[0001] The invention belongs to the technical field of ibuprofen suspension, and particularly relates to an ibuprofen suspension and a preparation method thereof. Background Art

[0002] Ibuprofen suspension is mainly used to treat various inflammatory and pain symptoms, such as arthritis, muscle pain, toothache and menstrual pain. Due to its good anti-inflammatory and analgesic effects, ibuprofen suspension is widely used in both children and adult patients. In addition, ibuprofen suspension can accurately control the dosage, is easy to take and has a more acceptable taste. Therefore, ibuprofen suspension is especially suitable for children.

[0003] Ibuprofen suspension belongs to the suspension dosage form. Suspension is a kinetically and thermodynamically unstable system with the following main problems: first, the particle size of the dispersed phase microparticles of the suspension-type liquid medicine is larger than that of the colloid particles, the Brownian motion of the microparticles is not significant, and they are easily settled under the action of gravity, affecting the uniformity and efficacy of the drug; second, the suspension system has a small particle size, a large specific surface area, a high surface free energy, and is easy to aggregate, which leads to inconsistent drug release and affects the efficacy; finally, during the stability period of the suspension, there are mainly problems such as floating, sedimentation, flocculation, and particle growth of drug particles, which affect the uniformity of the drug content during storage and further affect the accuracy of the dosage, especially for pediatric patients, affecting their safety and effectiveness of medication.

[0004] Patent CN101912360A discloses an ibuprofen suspension and a preparation method thereof, which adopts a method of fully homogenizing 18-20 μm ibuprofen with a wetting agent and a surfactant through a homogenizer, and then fully mixing with a solution containing other ingredients to reduce the floating phenomenon of the ibuprofen suspension, and solves the common problems of poor stability, poor uniformity, and easy aggregation and floating after long-term storage. However, this process is only applicable to ibuprofen with smaller particle sizes, and it is necessary to select and purchase a suitable homogenizer to achieve the homogenization of ibuprofen, wetting agents, and surfactants, which is complicated to operate and has a high production cost; Patent CN118766843A uses whey protein isolate / nicotinamide mononucleotide complex to replace xanthan gum, which effectively solves the problem of uneven ibuprofen suspension content and poor stability caused by uneven swelling of xanthan gum, but the operation is relatively cumbersome and the complex needs to be prepared in advance, which brings inconvenience to industrial production; Patent CN101991 531A adopts the method of adding dispersant to disperse cellulose. The ibuprofen oral suspension is a thixotropic colloid with uniformly distributed ibuprofen particles, ensuring that the ibuprofen micropowder particles in the suspension are dispersed in the colloid and will not settle. However, the amount of dispersant, sedimentation volume ratio, viscosity and other parameters need to be carefully screened. The process requires the use of high shear and violent stirring of the suspension. Under this condition, the particle size of the raw materials and some auxiliary materials may be affected, requiring very high control ability, and nitrogen needs to be introduced during production. The process operation is complicated and industrial production has certain difficulties. Patent CN106727303A discloses an oral suspension and a preparation method thereof. By adding crushed ibuprofen under vacuum conditions, the bubbles generated during the preparation process can be effectively reduced. However, the published prescription only adjusts the auxiliary materials such as the suspending agent in the prescription, and the preparation process requires the vacuum degree to reach a certain value, and it takes 6-8h of defoaming time to prepare a 100ml sample, which does not utilize industrial production.

[0005] The growth of particles in the suspension is also an important factor affecting the stability of the suspension. The size of the drug particles in the suspension cannot be completely consistent. During the placement of the suspension, the size and number of the particles are constantly changing, that is, the number of small particles is constantly decreasing, and the number of large particles is constantly increasing, which accelerates the sedimentation rate of the particles, thereby affecting the stability of the suspension. Therefore, it is very important to control the particle size of the suspension.

[0006] Microcrystalline cellulose is a kind of extremely fine short rod-shaped or powdery porous particles that can flow freely. Due to its structural characteristics, it can be used as a dispersing medium in suspensions, which can help maintain the uniform dispersion of drug particles, prevent particle aggregation and precipitation, and ensure the stability and consistency of the drug during use. It can also be used as a thickener to increase the viscosity of the preparation, thereby improving the taste and swallowability of the drug and enhancing the patient's medication experience. However, the difficulty of using it as a dispersing medium and stabilizer in suspensions is that its binding force with drug particles (mainly van der Waals force) is relatively weak, and the loose and porous form is conducive to the retention of air and even bubbles. During the stability period, the binding force gradually weakens under the influence of the external environment and internal air, which can easily lead to wetting of the surface of the suspended particles, and then the binding effect becomes worse, resulting in adverse phenomena such as particle aggregation and precipitation.

[0007] Adding surfactants, such as anionic surfactants, can help the surface of suspended particles to be better wetted by the liquid dispersion medium, and the solid particles have good wettability, and are easy to make into uniformly dispersed and stable suspensions; however, compared with ibuprofen suspensions, the use of surfactants has the following problems: anionic surfactants with carboxyl as hydrophilic groups, including potassium, sodium, ammonium salts and triethanolammonium salts of higher fatty acids, are quickly inactivated in acidic media with a pH below 7, and according to the requirements of the "Chinese Pharmacopoeia", the pH of ibuprofen suspension drops is 2.0-6.5. Therefore, under normal circumstances, anionic surfactants, such as stearate, cannot be selected as surfactants to wet the particle surface; if nonionic surfactants are used, the wetting effect of solid particles is poor; and cationic surfactants can generate hydrophobic cations in aqueous solutions, which interact with the free positive ions of the carboxyl group in the ibuprofen structure, affecting the adsorption strength of ibuprofen.

[0008] Therefore, how to design an ibuprofen suspension and a preparation method thereof, which can better maintain the quality stability of the ibuprofen suspension, ensure the stability of the sedimented suspended particles and prevent agglomeration, is a problem that urgently needs to be solved. Summary of the invention

[0009] The technical problem to be solved by the present invention is to overcome the above-mentioned defects of the prior art, provide an ibuprofen suspension, adopt microcrystalline cellulose with a specific bulk density and an ibuprofen raw material with a controlled specific particle size, the two of which work synergistically with a flocculant sodium citrate and an anionic surfactant stearate, solve the problem of inactivation of anionic surfactants under acidic conditions, and solve the difficult problem of aggregation and precipitation of suspended particles during the production and storage of the ibuprofen suspension; at the same time, the present invention also provides a preparation method for the ibuprofen suspension, and the preparation process is simple.

[0010] The ibuprofen suspension of the present invention comprises ibuprofen, microcrystalline cellulose, stearate and citrate; wherein the mass ratio of ibuprofen, microcrystalline cellulose, stearate and citrate is 1:(0.3-0.6):(0.01-0.03):(0.1-0.25).

[0011] The D90 particle size of the ibuprofen is 68-130 μm, wherein the D50 is 35-56 μm, and the D10 is 11-27 μm.

[0012] The bulk density of the microcrystalline cellulose is 0.10-0.25 g / cm 3 .

[0013] The ibuprofen suspension further comprises the following components in concentration:

[0014] Xanthan gum: 1.8-2.2 g / L;

[0015] Glycerol: 80-100g / L.

[0016] The ibuprofen suspension further comprises a sweetener, a flavoring agent, a preservative, a pigment, a pH regulator and purified water, wherein the sweetener is preferably sucrose, the flavoring agent is preferably strawberry essence, the preservative is preferably sorbic acid, the pigment is preferably carmine, and the pH regulator is preferably citric acid.

[0017] The stearate is one or more of sodium stearate, lead stearate, aluminum stearate, cadmium stearate, iron stearate, and potassium stearate, preferably sodium stearate.

[0018] The citrate is one or more of sodium citrate, potassium citrate and aluminum citrate, preferably sodium citrate.

[0019] The preparation method of the ibuprofen suspension comprises the following steps:

[0020] (1) preparing a gum solution: adding xanthan gum to glycerin and stirring evenly to obtain a gum solution; adding a sweetener to purified water and stirring to dissolve to obtain a sugar solution; transferring the gum solution to the sugar solution and stirring to obtain a gum solution;

[0021] (2) Grinding of gum solution: transfer the gum solution to a colloid mill, grind it, then transfer it to the original container and stir to mix evenly;

[0022] (3) preparing ibuprofen dispersion: mixing microcrystalline cellulose, stearate, citrate and ibuprofen uniformly to obtain a solid mixture for later use; stirring and mixing purified water and glycerin uniformly, then adding a preservative, stirring to dissolve it, and finally adding the solid mixture, stirring and dispersing it uniformly;

[0023] (4) preparing a formulation liquid: adding the mixed solution obtained in step (3) to the ground gum solution, adding a flavoring agent and a pigment, and maintaining stirring, then adding a pH adjuster to adjust the pH to 5.5-6.5, stirring thoroughly to mix evenly, and then adding purified water to make up the volume to obtain an ibuprofen suspension.

[0024] The present invention adopts microcrystalline cellulose of specific bulk density and ibuprofen raw material of controlling specific particle size, and the two cooperate with flocculant sodium citrate and anionic surfactant stearate, and can better maintain the quality stability of ibuprofen suspension, ensure the stability of sedimentation suspension particles and prevent agglomeration. The synergistic principle of the present invention is: microcrystalline cellulose of certain bulk density has a loose and porous structure with relatively controllable distribution, ibuprofen raw material particles of specific particle size distribution can be adsorbed or embedded in the inside of microcrystalline cellulose holes by relying on principles such as van der Waals force, adopt a certain proportion of the above-mentioned mixture and flocculant sodium citrate and anionic surfactant stearate, adopt certain process steps, in a suspension of a certain pH range, particles and charged substances (ibuprofen) form large loose aggregates through the effect of adsorption bridging, in addition to van der Waals force, hydrogen bond, coordination bond, the intermolecular potential increases, thereby solving the production and stability problems of ibuprofen suspension described in the present invention.

[0025] Compared with the prior art, the present invention has the following beneficial effects:

[0026] The ibuprofen suspension of the present invention studies the unstable suspension system, utilizes anionic surfactants and flocculants under special conditions, cooperates with microcrystalline cellulose with a certain bulk density, and utilizes the synergistic effect between the substances to solve the problem of poor stability of the ibuprofen suspension during storage, prolongs the stability of the ibuprofen suspension, is beneficial to the efficacy of the product, and is simple to operate, does not require special equipment and instruments, is conducive to product industrialization, reduces production costs, and has high pharmacoeconomic value. DETAILED DESCRIPTION

[0027] The present invention is further explained below in conjunction with the embodiments and comparative examples. Unless otherwise specified, the raw materials used in the embodiments and comparative examples are all commercially available products, the processes adopted are all conventional processes in the art, the concentration of ibuprofen in the suspension is 20 g / L, which is the concentration of conventional ibuprofen suspension on the market. In the preparation process of the suspension, the amounts of sweeteners, flavoring agents, preservatives, and pigments are all conventional amounts, which can be increased or decreased according to actual conditions; the amount of pH adjuster is the amount used to adjust the suspension to a pH of 5.5-6.5.

[0028] The preparation method of the ibuprofen suspension comprises the following steps:

[0029] (1) preparing a gum solution: adding xanthan gum to glycerin and stirring evenly to obtain a gum solution; adding sucrose to purified water and stirring to dissolve to obtain a sugar solution; transferring the gum solution to the sugar solution and stirring to obtain a gum solution;

[0030] (2) Grinding of gum solution: transfer the gum solution to a colloid mill, grind it, then transfer it to the original container and stir to mix evenly;

[0031] (3) preparing an ibuprofen dispersion: mixing microcrystalline cellulose, sodium stearate, sodium citrate and ibuprofen uniformly to obtain a solid mixture for later use; stirring and mixing purified water and glycerin uniformly, then adding sorbic acid, stirring to dissolve, and finally adding the solid mixture, stirring and dispersing uniformly;

[0032] (4) preparing a preparation liquid: adding the mixed solution obtained in step (3) to the ground gum solution, adding strawberry essence and carmine, and keeping stirring, then adding citric acid to adjust the pH to 5.5-6.5, stirring thoroughly to mix evenly, and then adding purified water to make up to volume to obtain an ibuprofen suspension.

[0033] Taking the preparation of 100L of ibuprofen suspension as an example, except for the different raw material formulas, the preparation methods adopted in the following examples and comparative examples for preparing ibuprofen suspension are all the above-mentioned preparation methods.

[0034] Example 1

[0035] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0036] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.6kg; sodium stearate: 0.02kg; sodium citrate: 0.2kg; sorbic acid: 0.3kg; xanthan gum: 0.2kg; sucrose: 25kg; glycerol: 8kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 6.0, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0037] The ibuprofen particle sizes are: D90: 80 μm, D50: 45 μm, D10: 15 μm; the bulk density of microcrystalline cellulose is 0.21 g / cm 3 .

[0038] Example 2

[0039] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0040] Ibuprofen: 2.0kg; microcrystalline cellulose: 1.2kg; sodium stearate: 0.06kg; sodium citrate: 0.5kg; sorbic acid: 0.3kg; xanthan gum: 0.18kg; sucrose: 25kg; glycerol: 8kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 6.2, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0041] The ibuprofen particle size is: D90: 80 μm, D50: 45 μm, D10: 15 μm; the bulk density of microcrystalline cellulose is 0.21 g / cm 3 .

[0042] Example 3

[0043] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0044] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.9kg; sodium stearate: 0.04kg; sodium citrate: 0.35kg; sorbic acid: 0.3kg; xanthan gum: 0.22kg; sucrose: 25kg; glycerol: 8kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 5.9, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0045] The ibuprofen particle size is: D90: 130 μm, D50: 45 μm, D10: 15 μm; the bulk density of microcrystalline cellulose is 0.21 g / cm 3 .

[0046] Example 4

[0047] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0048] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.6kg; sodium stearate: 0.02kg; sodium citrate: 0.2kg; sorbic acid: 0.3kg; xanthan gum: 0.2kg; sucrose: 25kg; glycerol: 10kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 6.0, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0049] The ibuprofen particle size is: D90: 68 μm, D50: 35 μm, D10: 11 μm; the bulk density of microcrystalline cellulose is 0.21 g / cm 3 .

[0050] Example 5

[0051] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0052] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.6kg; sodium stearate: 0.02kg; sodium citrate: 0.2kg; sorbic acid: 0.3kg; xanthan gum: 0.2kg; sucrose: 25kg; glycerol: 9kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 6.1, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0053] The ibuprofen particle size is: D90: 110 μm, D50: 56 μm, D10: 27 μm; the bulk density of microcrystalline cellulose is 0.21 g / cm 3 .

[0054] Example 6

[0055] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0056] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.6kg; sodium stearate: 0.02kg; sodium citrate: 0.2kg; sorbic acid: 0.3kg; xanthan gum: 0.2kg; sucrose: 25kg; glycerol: 8kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 5.8, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0057] The ibuprofen particle size is: D90: 80 μm, D50: 45 μm, D10: 15 μm; the bulk density of microcrystalline cellulose is 0.10 g / cm 3 .

[0058] Example 7

[0059] The ibuprofen suspension described in this embodiment takes the preparation of 100L of ibuprofen suspension as an example, and the raw material prescription is as follows:

[0060] Ibuprofen: 2.0kg; microcrystalline cellulose: 0.6kg; sodium stearate: 0.02kg; sodium citrate: 0.2kg; sorbic acid: 0.3kg; xanthan gum: 0.18kg; sucrose: 25kg; glycerol: 8kg; strawberry flavor: 0.5kg; carmine: 0.005kg; the amount of citric acid used is the amount used when the pH of the suspension is adjusted to 6.0, and the amount of purified water used is the amount used when the suspension is fixed to 100L.

[0061] The ibuprofen particle size is: D90: 80 μm, D50: 45 μm, D10: 15 μm; the bulk density of microcrystalline cellulose is 0.25 g / cm 3 .

[0062] Example 8

[0063] The raw material prescription of this example is the same as that of Example 1, except that citric acid is added to adjust the pH to 5.5, and the remaining steps are the same as those of Example 1.

[0064] Example 9

[0065] The raw material prescription of this example is the same as that of Example 1, except that citric acid is added to adjust the pH to 6.5, and the remaining steps are the same as those of Example 1.

[0066] Comparative Examples 1-5

[0067] The preparation processes of the ibuprofen suspensions described in Comparative Examples 1-5 are the same as those in the examples. The raw material prescriptions involved in Comparative Examples 1-5 are shown in Table 1. The preparation methods of the ibuprofen suspensions are the same as those in the examples.

[0068] Table 1 Comparative Examples 1-5 Raw Materials Prescription Table

[0069]

[0070] Comparative Examples 6-11

[0071] The preparation process of the ibuprofen suspension described in Comparative Examples 6-11 is the same as that in the examples. The raw material prescriptions involved in Comparative Examples 6-11 are shown in Table 2. The preparation methods of the ibuprofen suspensions are the same as those in the examples.

[0072] Table 2 Comparative Examples 6-11 Raw Materials Prescription

[0073]

[0074] The products obtained in the examples and comparative examples were tested for appearance, sedimentation volume ratio, redispersibility, solubility, stability and other indicators according to the following methods. The test results are shown in Tables 3 to 9.

[0075] Appearance: After the suspension sample is prepared, place it in a white 25ml colorimetric tube and visually observe the appearance under natural light at 0h, 12h, 24h, and 48h to see if the ibuprofen drug particles are dissolved, agglomerated, or sticking to the wall; Sedimentation volume ratio: Refer to the sedimentation volume ratio (2020 edition of the Chinese Pharmacopoeia, Part IV) method, use a stoppered measuring cylinder to measure 50mL of the test sample, stopper it, shake it vigorously for 1min, and record the starting height of the suspension (H 0), let it stand for 3 hours, record the final height of the suspension (H), and calculate according to the following formula: sedimentation volume ratio = (H / H 0 ), the sedimentation volume ratio should not be less than 0.90; Redispersibility: take 50mL, stopper the test tube, let it stand for 24h, then rotate 360°10 times and record the redispersibility.

[0076] The changes in the solubility of the products of the embodiment and the comparative example at 0 o'clock, 1 month, 3 months and 6 months after being placed under accelerated conditions (40°C ± 2°C, 75% ± 5% RH) were investigated. The inspection method is as follows: the paddle method was used to investigate the dissolution behavior of the suspension samples in a pH 7.2 medium. The test solution and the reference solution were injected into a liquid chromatograph respectively, and the chromatograms were recorded. The dissolution amount was calculated by the peak area using the external standard method (acceptable standard: the dissolution amount in 60 minutes is not less than 85% of the labeled amount).

[0077] The suspension samples were placed in a refrigerator at 2-10°C, and samples were taken at 0, 1, 3, and 6 months, respectively, and parameters such as shading were measured using a laser scattering instrument to examine changes in particle size and its distribution.

[0078] Table 3 Comparison of appearance between the examples and the comparative examples

[0079]

[0080] Note: “√” indicates that the suspension meets the appearance standard, with no agglomeration, sedimentation or wall adhesion; “×” indicates that the suspension does not meet the appearance standard, with varying degrees of agglomeration, sedimentation or (and) wall adhesion. “ / ” indicates that no further examination is required.

[0081] Table 4 Comparison of sedimentation volume ratio and redispersibility between the examples and the comparative examples

[0082]

[0083] Table 5 Comparison of dissolution rates between examples and comparative examples during stability period

[0084]

[0085] Note: “ / ” means no further examination.

[0086] Table 6 Particle size and distribution of the examples during stability period 0 day

[0087]

[0088] Table 7 Particle size and distribution comparison of examples during stability period 1 month

[0089]

[0090] Table 8 Particle size and distribution comparison of examples during stability period 3 months

[0091]

[0092] Table 9 Particle size and distribution comparison of examples during stability period 6 months

[0093]

[0094] During the particle size detection process during the stability period, the comparative example showed stratification and agglomeration in the initial stage of stability and the detection process, and due to the occurrence of unqualified reactions, the comparative example could not obtain the test results during the detection process, so the particle size distribution during the stability period of the comparative example could not be detected. As shown in Tables 3 and 4, in the initial stage of suspension configuration, the embodiments and the comparative example can achieve good results at the end of preparation, but after being placed for a period of time, such as 24 hours, the auxiliary materials used in the comparative example 1 and 2 exceed the proportion range of the present invention, and the appearance has an undesirable phenomenon, and the redispersibility is not good; when the comparative examples 9 and 10 use the pH exceeding the technical solution of the present invention, due to the influence of pH, the components such as the surfactant in the suspension are inactivated, which leads to unqualified appearance and redispersibility, and the comparative example 11 removes sodium citrate, although it performs well in the preparation stage, but with the extension of time, the loose aggregates formed by microcrystalline cellulose, ibuprofen and surfactant are unstable, without the presence of sodium citrate, the adsorption effect of surfactant and ibuprofen is poor, and the uniform suspension state cannot be quickly restored after vibration, which leads to unqualified products.

[0095] As can be seen from Table 5, both the 0-day embodiment and the comparative example meet the dissolution requirement of ≥85%. Comparative Example 3 does not add microcrystalline cellulose, and ibuprofen cannot be further combined with the surfactant through van der Waals force, etc., resulting in unqualified dissolution during stability; Comparative Examples 5, 6, 7, and 8 use raw material particle sizes and microcrystalline cellulose bulk densities that are beyond the scope of the present invention, and the dissolution during stability is unqualified. The reason is that due to particle size and bulk density problems between microcrystalline cellulose and ibuprofen, even if ibuprofen can be adsorbed or embedded in the microcrystalline cellulose pores by partial van der Waals force, it is extremely unstable due to its mismatch. This result further shows that a suitable combination of raw material particle size and microcrystalline cellulose bulk density can avoid unqualified product quality during stability; Comparative Example 5 uses a nonionic surfactant polysorbate 80, which can better maintain product stability, but at the end of the accelerated test, unqualified phenomena occur, and the use of nonionic surfactants on the surface cannot obtain products with a long stability period.

Claims

1. An ibuprofen suspension, characterized in that, Includes ibuprofen, microcrystalline cellulose, stearate, and citrate; The mass ratio of ibuprofen, microcrystalline cellulose, stearate and citrate is 1:(0.3-0.6):(0.01-0.03):(0.1-0.25); The D90 particle size of the ibuprofen is 68-130 μm; The bulk density of the microcrystalline cellulose is 0.10-0.25 g / cm 3 .

2. The ibuprofen suspension according to claim 1, wherein Also included are ingredients in the following concentrations: Xanthan gum: 1.8-2.2 g / L; Glycerol: 80-100g / L.

3. The ibuprofen suspension according to claim 1, wherein Also included are sweeteners, flavoring agents, preservatives, coloring agents, pH adjusters and purified water.

4. The ibuprofen suspension according to claim 1, wherein The stearate is one or more of sodium stearate, lead stearate, aluminum stearate, cadmium stearate, iron stearate, and potassium stearate.

5. The ibuprofen suspension according to claim 1, characterized in that The citrate is one or more of sodium citrate, potassium citrate and aluminum citrate.

6. A method for preparing the ibuprofen suspension according to any one of claims 1 to 5, characterized in that: The following steps are involved: (1) preparing a gum solution: adding xanthan gum to glycerin and stirring evenly to obtain a gum solution; adding a sweetener to purified water and stirring to dissolve to obtain a sugar solution; transferring the gum solution to the sugar solution and stirring to obtain a gum solution; (2) Grinding of gum solution: transfer the gum solution to a colloid mill, grind it, then transfer it to the original container and stir to mix evenly; (3) preparing ibuprofen dispersion: mixing microcrystalline cellulose, stearate, citrate and ibuprofen uniformly to obtain a solid mixture for later use; stirring and mixing purified water and glycerin uniformly, then adding a preservative, stirring to dissolve it, and finally adding the solid mixture, stirring and dispersing it uniformly; (4) preparing a formulation liquid: adding the mixed solution obtained in step (3) to the ground gum solution, adding a flavoring agent and a pigment, and maintaining stirring, then adding a pH adjuster to adjust the pH, stirring thoroughly to mix uniformly, and then adding purified water to make up the volume to obtain an ibuprofen suspension.

7. The method for preparing ibuprofen suspension according to claim 6, wherein The pH is adjusted to 5.5-6.5 by adding the pH regulator.

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