Ibuprofen pharmaceutical composition as well as preparation method and application thereof

Abstract

The invention discloses an ibuprofen pharmaceutical composition as well as a preparation method and application thereof. The ibuprofen pharmaceutical composition comprises the following components: a sustained-release pellet and a quick-release pellet, wherein the sustained-release pellet comprises ibuprofen, a filling agent and an adhesive; the quick-release pellet comprises ibuprofen, a filling agent, a suspending aid, a disintegrating agent, a flavoring agent and a pH regulator. The ibuprofen pharmaceutical composition takes effect quickly, can maintain the treatment effect for a long time, can effectively improve the administration compliance of children, old people and people with dysphagia, and reduces the administration frequency; the dry suspension particles are large in loading range and exist in the form of the dry suspension particles in the storage and transportation processes, so that the stability of the medicine in the storage and transportation processes can be ensured; the medicine is simple in preparation process, stable in property, convenient to take and suitable for industrial production.

Description

[0001] This application claims priority to the prior application with patent application number 202311314293.6 filed with the State Intellectual Property Office of China on October 10, 2023, and invention name “Ibuprofen pharmaceutical composition, preparation method and application thereof”. Technical Field

[0002] The invention relates to an ibuprofen pharmaceutical composition, a preparation method and application thereof. Background Art

[0003] Ibuprofen, also known as ibuprofen, has a chemical name of 2-(4-isobutylphenyl) propionic acid, which is a propionic acid derivative and a non-steroidal anti-inflammatory analgesic. Its main action pathway is to non-selectively inhibit cyclooxygenase (COX), thereby inhibiting the synthesis and release of prostaglandins, and also inhibiting the release of active substances in leukocytes and lysosomes stimulated by inflammation in the body, reducing the pain impulse of local tissues of the human body and the sensitivity of pain receptors. It has strong anti-inflammatory, anti-rheumatic, antipyretic and analgesic effects.

[0004] In the treatment of patent ductus arteriosus in newborns or premature infants, ibuprofen is also widely used clinically. Studies have reported that it has similar or even stronger efficacy than indomethacin, better safety, and less kidney damage, making it the first-line drug for antipyretic in children.

[0005] Ibuprofen is widely used in the pharmaceutical field. Common ibuprofen preparations include: ibuprofen tablets, ibuprofen sustained-release capsules, ibuprofen sustained-release tablets and ibuprofen suspension, etc. Common indications of ibuprofen include: 1. Relieve acute attacks or persistent joint swelling and pain symptoms of various chronic arthritis such as rheumatoid arthritis, osteoarthritis, rheumatoid arthritis, gouty arthritis, etc., without the role of etiological treatment and control of the course of the disease; 2. Treat various non-articular soft tissue rheumatic pain, such as shoulder pain, tenosynovitis, bursitis, muscle pain, etc.; 3. Acute mild and moderate pain, such as postoperative, post-traumatic, toothache, headache, etc.; 4. It has an antipyretic effect on fever in adults and children.

[0006] For children, the elderly and those with dysphagia, it is difficult to swallow tablets and capsules, and suspensions may have problems such as poor stability and inconvenience in transportation and carrying. Therefore, finding an ibuprofen dosage form with high stability, easy administration and good patient compliance is a technical problem that needs to be solved urgently. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide an ibuprofen pharmaceutical composition, a preparation method and application thereof in order to overcome the defects of the prior art, such as poor stability of ibuprofen suspension, high difficulty in storage and transportation, ibuprofen tablets and capsules not being suitable for patients with dysphagia such as children and the elderly, and poor medication compliance. The ibuprofen pharmaceutical composition of the present invention has rapid onset and can maintain a long-term therapeutic effect, good absorption and high bioavailability; can effectively improve the medication compliance of children, the elderly and those with dysphagia; has a large filling range, which is conducive to ensuring the stability of the drug during storage and transportation; and has a simple preparation process, stable properties, convenient administration, and is suitable for industrial production.

[0008] The present invention provides an ibuprofen pharmaceutical composition, wherein the time for the peak blood concentration (Tmax) is less than 5 hours, and the duration is 8 hours to 12 hours; preferably, the time for the peak blood concentration is less than 3 hours, further preferably less than 2.5 hours, and the duration is 8 hours to 11 hours; further preferably, the time for the peak blood concentration is less than 2 hours, and the duration is 8 hours to 10 hours.

[0009] The present invention provides an ibuprofen pharmaceutical composition, comprising the following components: sustained-release pellets and quick-release pellets, wherein the sustained-release pellets contain ibuprofen, a filler and a binder; and the quick-release pellets contain ibuprofen, a filler, a suspending agent, a disintegrant, a flavoring agent and a pH regulator;

[0010] Preferably, the ibuprofen pharmaceutical composition has the peak time and sustained maintenance time of blood drug concentration as shown above.

[0011] In the present invention, the ibuprofen can be a conventional commercially available ibuprofen bulk drug, or an ibuprofen bulk drug prepared with reference to corresponding literature.

[0012] According to an embodiment of the present invention, the content of ibuprofen can be 1.0% to 80.0%, for example 2.0% to 40.0%, and for example 5.0% to 30.0%, exemplified by 10.0%, 11.0%, 12.0%, 13.0%, 14.0%, 15.00%, 16.0%, 17.0%, 18.0%, 19.0%, 20.0% or 25.0%, wherein the content refers to the percentage of the mass of ibuprofen to the total mass of the ibuprofen pharmaceutical composition.

[0013] According to an embodiment of the present invention, the content of ibuprofen in the sustained-release pellets and the immediate-release pellets is the same or different. In some embodiments, the content of ibuprofen in the sustained-release pellets is greater than the content of ibuprofen in the immediate-release pellets, for example, the mass ratio is greater than 1.1:1, such as a mass ratio of (1.2 to 20):1, exemplified by 1.5:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1 or 19:1.

[0014] According to an embodiment of the present invention, the filler refers to a solid substance added to the material to improve the material properties, or to increase the volume, increase the weight, and reduce the cost of the material, selected from one or more of microcrystalline cellulose, pregelatinized starch, mannitol, sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltitol, galactitol, erythritol, dextrin and trehalose, for example, selected from one or two of microcrystalline cellulose and mannitol. The sustained-release pellets and the immediate-release pellets may contain the same or different fillers.

[0015] According to an embodiment of the present invention, the content of the filler can be 1.0% to 85.0%, for example 10.0% to 70.0%, exemplified by 20.0%, 30.0%, 40.0%, 41.0%, 42.0%, 43.0%, 44.0%, 45.0%, 45.32%, 45.52%, 46.0%, 47.0%, 48.0%, 49.0%, 50.0%, 55.0%, 60.0%, 61.0%, 62.0%, 62.02%, 63.0%, 64.0%, 65.0%, 66.0%, 67.0%, 68.0%, 69.0%, 70.0% or 75.0%; the content refers to the percentage of the mass of the filler to the total mass of the ibuprofen pharmaceutical composition.

[0016] In some embodiments, the content of filler in the sustained-release pellets is less than that in the immediate-release pellets, for example, the mass ratio is 1:(1.5-4), for example, 1:2, 1:2.5, 1:2.6, 1:2.7, 1:3 or 1:3.5.

[0017] According to an embodiment of the present invention, the adhesive refers to various stress materials that connect or fit the same or different materials, selected from one or more of hydroxypropyl methylcellulose, carbomer, hydroxyethyl cellulose, polyoxyethylene, pregelatinized starch, copovidone, hydroxypropyl cellulose, ethyl cellulose, povidone (PVP) and sodium carboxymethyl cellulose.

[0018] According to an embodiment of the present invention, the suspending agent refers to a viscous hydrophilic colloid substance, which can increase the viscosity of the dispersion medium to slow down the sedimentation rate of the particles, and adsorb on the surface of the particles to become a barrier to prevent the particles from agglomerating and clumping, and is selected from one or more of glycerol, gum arabic, agar, xanthan gum, colloidal microcrystalline cellulose, sodium alginate, microcrystalline cellulose-sodium carboxymethyl cellulose, sodium carboxymethyl cellulose and methyl cellulose.

[0019] According to an embodiment of the present invention, the disintegrant refers to an auxiliary material that promotes the rapid disintegration of the drug into small particles in the gastrointestinal tract, and is selected from one or more of low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch and starch.

[0020] According to an embodiment of the present invention, the flavoring agent refers to a substance that has a flavoring effect, selected from one or more of aspartame, sucralose, fructose, sucrose, steviol glycosides, glycyrrhizin, citric acid, flavor, menthol, sodium chloride, neotame, acesulfame potassium, saccharin and saccharin sodium.

[0021] According to an embodiment of the present invention, the pH regulator refers to a substance that has a pH regulating effect, and is selected from one or more of citric acid, L-malic acid, sodium citrate, disodium hydrogen phosphate and sodium hydroxide.

[0022] According to an embodiment of the present invention, the content of ibuprofen in the sustained-release microcapsules can be 1.0% to 30.0%, for example 5.0% to 20.0%, exemplified by 15.00%, 14.00%, 13.00%, 12.00%, 11.00%, 10.00%, 9.00%, 8.00%, 7.00% or 6.00%, wherein the content refers to the percentage of the mass of ibuprofen in the sustained-release microcapsules to the total mass of the ibuprofen pharmaceutical composition.

[0023] According to some embodiments of the present invention, in the sustained-release pellets, the filler may be microcrystalline cellulose.

[0024] According to an embodiment of the present invention, in the sustained-release microcapsules, the content of the filler can be 1.0% to 30.0%, for example 5.0% to 20.0%, exemplified by 10.00%, 11.00%, 12.00%, 12.44%, 13.00%, 14.00%, 15.00%, 16.00%, 17.00%, 18.00% or 19.00%, wherein the content refers to the percentage of the mass of the filler in the sustained-release microcapsules to the total mass of the ibuprofen pharmaceutical composition.

[0025] According to some embodiments of the present invention, in the sustained-release pellets, the binder may be povidone.

[0026] According to an embodiment of the present invention, in the sustained-release microcapsules, the content of the binder can be 0.1% to 10.0%, for example 0.1% to 5.0%, exemplified by 0.2%, 0.3%, 0.4%, 0.5%, 0.56%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 2.0%, 3.0%, 4.0%, wherein the content refers to the percentage of the mass of the binder in the sustained-release microcapsules to the total mass of the ibuprofen pharmaceutical composition.

[0027] According to an embodiment of the present invention, the ibuprofen content in the rapid-release microcapsules may be 1.00% to 10.00%, for example 9.00%, 8.00%, 7.00%, 6.00%, 5.00%, 4.00%, 3.00%, 2.00% or 1.00%, wherein the content refers to the percentage of the mass of ibuprofen in the rapid-release microcapsules to the total mass of the ibuprofen pharmaceutical composition.

[0028] According to some embodiments of the present invention, in the rapid-release pellets, the filler may be microcrystalline cellulose and / or mannitol.

[0029] According to an embodiment of the present invention, in the rapid-release microcapsules, the content of the filler can be 1.0% to 80.0%, for example, 10.0% to 55.0%, and exemplified by 20.0%, 25.0%, 26.0%, 27.0%, 28.0%, 29.0%, 30.0%, 31.0%, 32.0%, 33.0%, 33.08%, 33.5%, 34.0%, 35.0%, 36.0%, 37.0%, 38.0%, 39.0%, 40.0%, 45.0%, 49.13%, 49.58% or 50.0%, wherein the content refers to the percentage of the mass of the filler in the rapid-release microcapsules to the total mass of the ibuprofen pharmaceutical composition.

[0030] According to some embodiments of the present invention, in the rapid-release pellets, the suspending agent may be xanthan gum and / or microcrystalline cellulose-sodium carboxymethyl cellulose.

[0031] According to an embodiment of the present invention, the content of the suspending agent can be 1.0% to 30.0%, for example 5.0% to 20.0%, exemplified by 6.0%, 7.0%, 8.0%, 9.0%, 10.0%, 10.75%, 11.0%, 12.0%, 13.0%, 14.0%, 15.0%, 16.0%, 17.0%, 18.0% or 19.0%, wherein the content refers to the percentage of the mass of the suspending agent to the total mass of the ibuprofen pharmaceutical composition.

[0032] According to some embodiments of the present invention, in the rapid-release pellets, the disintegrant may be sodium starch glycolate.

[0033] According to an embodiment of the present invention, the content of the disintegrant can be 1.0% to 20.0%, for example 5.0% to 15.0%, exemplified by 6.0%, 7.0%, 8.0%, 8.50%, 9.0%, 10.0%, 10.75%, 11.0%, 12.0%, 13.0% or 14.0%, wherein the content refers to the percentage of the mass of the disintegrant to the total mass of the ibuprofen pharmaceutical composition.

[0034] According to some embodiments of the present invention, in the rapid-release pellets, the flavoring agent may be flavor (eg, strawberry flavor) and / or aspartame.

[0035] According to an embodiment of the present invention, the content of the flavoring agent can be 1.0% to 10.0%, for example 1.50%, 2.0%, 2.50%, 3.0%, 4.0%, 5.0%, 6.0%, 7.0%, 8.0% or 9.0%, and the content refers to the percentage of the mass of the flavoring agent to the total mass of the ibuprofen pharmaceutical composition.

[0036] According to some embodiments of the present invention, in the rapid-release pellets, the pH regulator may be citric acid.

[0037] According to an embodiment of the present invention, the content of the pH regulator can be 0.10% to 5.00%, for example 0.10% to 2.00%, exemplified by 0.20%, 0.30%, 0.40%, 0.50%, 0.60%, 0.67%, 0.70%, 0.80%, 0.90%, 1.00% or 1.50%, wherein the content refers to the percentage of the mass of the pH regulator to the total mass of the ibuprofen pharmaceutical composition.

[0038] According to a preferred embodiment of the present invention, the sustained-release pellets contain the following components or are mainly composed of the following components: each component adopts a mass fraction, 1.00% to 30.00% ibuprofen, 1.00% to 30.00% microcrystalline cellulose, 0.1% to 10.00% povidone, and the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0039] Furthermore, the sustained-release pellets contain the following components or are mainly composed of the following components: each component is expressed in mass fraction, 5.00% to 20.00% ibuprofen, 5.00% to 20.00% microcrystalline cellulose, and 0.1% to 5.00% povidone, and the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition.

[0040] According to an embodiment of the present invention, the sustained-release pellets may be any of the following formulations:

[0041] Prescription 1: 10.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages refer to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0042] Prescription 2: 9.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages being the mass of each component relative to the total mass of the ibuprofen pharmaceutical composition;

[0043] Prescription 3: 12.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages being the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0044] Prescription 4: 14.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages refer to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition.

[0045] According to an embodiment of the present invention, the mass ratio of the sustained-release pellets to the immediate-release pellets can be 1:100 to 100:1, or 1:5 to 5:1, such as 23:77, 11:39, 1:3, 27:73 or 7:18.

[0046] According to a preferred embodiment of the present invention, the rapid-release pellets contain the following components or are mainly composed of the following components: each component adopts a mass fraction, 1.00% to 10.00% ibuprofen, 1.00% to 80.00% microcrystalline cellulose and / or mannitol, 1.00% to 30.00% xanthan gum and / or microcrystalline cellulose-sodium carboxymethyl cellulose, 1.00% to 20.00% sodium carboxymethyl starch, 1.00% to 10.00% flavor and / or aspartame, 0.10% to 5.00% citric acid; the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen composition;

[0047] Furthermore, the rapid-release pellets contain the following components or are mainly composed of the following components: each component is expressed in mass fraction, 1.00% to 10.00% ibuprofen, 20.00% to 40.00% microcrystalline cellulose, 10.00% to 25.00% mannitol, 1.00% to 10.00% xanthan gum, 1.00% to 15.00% microcrystalline cellulose-sodium carboxymethyl cellulose, 1.00% to 15.00% sodium carboxymethyl starch, 1.00% to 10.00% flavor and / or aspartame, 0.10% to 5.00% citric acid; the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen composition.

[0048] According to an embodiment of the present invention, the rapid-release pellets may be in any of the following formulations:

[0049] Formula 1: 5.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0050] Formula 2: 6.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0051] Formula 3: 3.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition;

[0052] Formulation 4: 1.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition.

[0053] The present invention also provides a method for preparing the ibuprofen pharmaceutical composition, comprising the following steps:

[0054] The components of the sustained-release pellets are mixed, wet granulated, and a soft material is prepared and then extruded and spheronized to obtain sustained-release pellets;

[0055] The components of the above-mentioned quick-release pellets are mixed, wet granulated, and a soft material is prepared and then extruded and spheronized to obtain quick-release pellets;

[0056] Then the sustained-release pellets and the quick-release pellets are mixed according to a certain ratio to obtain the ibuprofen pharmaceutical composition.

[0057] The present invention also provides an ibuprofen pharmaceutical composition prepared by the preparation method of the ibuprofen pharmaceutical composition.

[0058] The present invention also provides the use of the ibuprofen pharmaceutical composition in preparing a drug for treating and / or alleviating mild to moderate pain diseases.

[0059] According to an embodiment of the present invention, the drug is a suspension preparation, such as a dry suspension preparation.

[0060] The present invention also provides a method for treating and / or alleviating mild to moderate pain diseases, comprising administering a therapeutically effective amount of the ibuprofen pharmaceutical composition to a patient in need thereof.

[0061] According to an embodiment of the present invention, each administration interval is 8 to 12 hours; further, the administration dosage is 140 to 160 mg / time, for example, the administration dosage is 150 mg / time.

[0062] Without violating the common sense in the art, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

[0063] The reagents and raw materials used in the present invention are commercially available.

[0064] Beneficial effects of the present invention:

[0065] The ibuprofen pharmaceutical composition prepared by the invention has rapid onset of action and can maintain a therapeutic effect for a long time, has good absorption and high bioavailability, can effectively improve the medication compliance of children, the elderly and people with dysphagia, has a large filling range of dry mixed suspension particles, exists in the form of dry mixed particles during drug storage and transportation, and is conducive to ensuring the stability of the drug during storage and transportation, and has a simple preparation process, stable properties, and is easy to take, and is suitable for industrial production.

[0066] Definition and explanation of terms

[0067] The term "pellets" refers to small pellets or granules made from raw materials and excipients through a formulation process.

[0068] The term "plurality" refers to a physical mixture of two or more species, for example, a physical mixture of two, three or more species.

[0069] The term "mainly composed of..." means that the sum of the masses of these components accounts for no less than 85% of the total mass of the ibuprofen pharmaceutical composition, for example no less than 90%, exemplified by 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or 100%.

[0070] The term "microcrystalline cellulose-sodium carboxymethyl cellulose" is a compound of microcrystalline cellulose-sodium carboxymethyl cellulose, not a physical mixture.

[0071] The term "patient" refers to any animal including mammals, preferably mice, rats, other rodents, rabbits, dogs, cats, pigs, cows, sheep, horses or primates, and most preferably humans.

[0072] The term "therapeutically effective amount" refers to that amount of an active compound or drug that will elicit the biological or medical response that is being sought by a researcher, veterinarian, medical doctor or other clinician in a tissue, system, animal, individual or human. BRIEF DESCRIPTION OF THE DRAWINGS

[0073] Figure 1 The dissolution curve of the reference preparation commercially available Merlin at pH 5.5 is shown;

[0074] Figure 2 The dissolution curve of the ibuprofen pharmaceutical composition prepared in Example 2 at pH 5.5 is shown;

[0075] Figure 3 The dissolution curve of the ibuprofen pharmaceutical composition prepared in Example 3 at pH 5.5 is shown;

[0076] Figure 4 The dissolution curve of the ibuprofen pharmaceutical composition prepared in Example 4 at pH 5.5 is shown;

[0077] Figure 5 The dissolution curve of the ibuprofen pharmaceutical composition prepared in Example 5 at pH 5.5 is shown;

[0078] Figure 6 The dissolution curve of the ibuprofen pharmaceutical composition prepared in Example 6 at pH 5.5 is shown;

[0079] Figure 7 The drug-time curves of the ibuprofen pharmaceutical composition prepared in Example 3 and the commercially available product Motrin are shown, wherein ○---○ represents the drug-time curve of the ibuprofen pharmaceutical composition prepared in Example 3, and Δ---Δ represents the drug-time curve of the commercially available product Motrin.

[0080] Figure 8 The drug-time curves of the ibuprofen pharmaceutical composition prepared in Example 6 and the commercially available product Motrin are shown, wherein ○---○ represents the drug-time curve of the ibuprofen pharmaceutical composition prepared in Example 6, and Δ---Δ represents the drug-time curve of the commercially available product Motrin.

[0081] Fig. 9 It is a drug-time curve diagram of the ibuprofen pharmaceutical composition prepared in the comparative example. DETAILED DESCRIPTION

[0082] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0083] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available, or can be prepared by known methods, or selected according to commercial instructions.

[0084] Example 1: Dissolution test of reference preparation

[0085] The reference preparation used the commercially available preparation Merlin (ibuprofen immediate release suspension, Shanghai Johnson Pharmaceutical Co., Ltd.), the dissolution conditions were paddle method 65rpm, medium pH 5.5 phosphate buffer, the sample dissolution data results are shown in Table 1, and the dissolution curve is shown in Figure 1 .

[0086] Table 1 Dissolution data of commercially available ibuprofen suspension

[0087]

[0088] Example 2: Ibuprofen pharmaceutical composition

[0089] Table 2-1 Prescription of Example 2

[0090]

[0091] Preparation method:

[0092] Sustained-release pellets:

[0093] 1) Prescription weighing: accurately weigh ibuprofen, microcrystalline cellulose and povidone according to the mass ratio;

[0094] 2) Preparation of soft material: Add the material of step 1) into a wet granulator and mix at a stirring speed of 180 rpm and a cutting speed of 540 rpm for 3 min; then set the parameters: stirring speed of 180 rpm, chopping speed of 1200 rpm, turn on the instrument, and add a certain amount of water (about 80% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±0.5 min to obtain the soft material;

[0095] 3) Preparation of sustained-release pellets: The soft material prepared in step 2) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 120 seconds to obtain sustained-release pellets;

[0096] Immediate-release pellets:

[0097] 4) Prescription weighing: Accurately weigh the materials of the immediate-release pellets according to the mass ratio;

[0098] 5) Preparation of soft material: Add the material of step 4) to the wet granulator and mix at a stirring speed of 180 rpm and a cutting speed of 540 rpm for 3 min; then set the parameters: stirring speed 180 rpm, chopping speed 1500 rpm, turn on the instrument, and add a certain amount of water (about 55% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±1 min to obtain the soft material;

[0099] 6) Preparation of immediate-release pellets: The soft material prepared in step 5) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 60 seconds to obtain immediate-release pellets;

[0100] 7) Mixing the prepared sustained-release pellets and quick-release pellets to obtain an ibuprofen pharmaceutical composition.

[0101] The dissolution conditions were paddle method 65 rpm, pH 5.5 citrate buffer, and the dissolution data of the prepared ibuprofen pharmaceutical composition sample were shown in Table 2-2, and the dissolution curve was shown in Figure 2 .

[0102] Table 2-2 Dissolution data of ibuprofen pharmaceutical composition

[0103]

[0104] Example 3: Ibuprofen pharmaceutical composition

[0105] Table 3-1 Prescription of Example 3

[0106]

[0107] Preparation method:

[0108] Sustained-release pellets:

[0109] 1) Prescription weighing: accurately weigh ibuprofen, microcrystalline cellulose and povidone according to the mass ratio;

[0110] 2) Preparation of soft material: Add the material of step 1) into a wet granulator and mix at a stirring speed of 180 rpm and a cutting speed of 540 rpm for 3 min; then set the parameters: stirring speed 180 rpm, chopping speed 1200 rpm, turn on the instrument, and add a certain amount of water (about 80% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±0.5 min to obtain the soft material.

[0111] 3) Preparation of sustained-release pellets: The soft material prepared in step 2) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 120 seconds to obtain sustained-release pellets;

[0112] Immediate-release pellets:

[0113] 4) Prescription weighing: Accurately weigh the materials of the immediate-release pellets according to the mass ratio;

[0114] 5) Preparation of soft material: Add the material of step 4) into a wet granulator and mix for 3 min at a stirring speed of 180 rpm and a cutting speed of 540 rpm; then set the parameters: stirring speed of 180 rpm, chopping speed of 1500 rpm, turn on the instrument, and add a certain amount of water (about 55% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±1 min to obtain the soft material;

[0115] 6) Preparation of micropellets: The soft material prepared in step 5) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 60 seconds to obtain immediate-release micropellets;

[0116] 7) Mixing the prepared sustained-release pellets and quick-release pellets to obtain an ibuprofen pharmaceutical composition.

[0117] The dissolution conditions were paddle method 65 rpm, pH 5.5 citrate buffer, and the dissolution data of the prepared ibuprofen pharmaceutical composition sample were shown in Table 3-2, and the dissolution curve was shown in Figure 3 .

[0118] Table 3-2 Dissolution data of ibuprofen pharmaceutical composition

[0119]

[0120] Example 4: Ibuprofen pharmaceutical composition

[0121] Table 4-1 Prescription of Example 4

[0122]

[0123]

[0124] Preparation method:

[0125] Sustained-release pellets:

[0126] 1) Prescription weighing: accurately weigh ibuprofen, microcrystalline cellulose and povidone according to the mass ratio;

[0127] 2) Preparation of soft material: Add the material of step 1) into a wet granulator and mix at a stirring speed of 180 rpm and a cutting speed of 540 rpm for 3 min; then set the parameters: stirring speed of 180 rpm, chopping speed of 1200 rpm, turn on the instrument, and add a certain amount of water (about 80% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±0.5 min to obtain the soft material;

[0128] 3) Preparation of sustained-release pellets: The soft material prepared in step 2) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 120 seconds to obtain sustained-release pellets;

[0129] Immediate-release pellets:

[0130] 4) Prescription weighing: Accurately weigh the materials of the immediate-release pellets according to the mass ratio;

[0131] 5) Preparation of soft material: Add the material of step 4) into a wet granulator and mix for 3 min at a stirring speed of 180 rpm and a cutting speed of 540 rpm; then set the parameters: stirring speed of 180 rpm, chopping speed of 1500 rpm, turn on the instrument, and add a certain amount of water (about 55% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±1 min to obtain the soft material;

[0132] 6) Preparation of immediate-release pellets: The soft material prepared in step 5) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 60 seconds to obtain immediate-release pellets;

[0133] 7) Mixing the prepared sustained-release pellets and quick-release pellets to obtain an ibuprofen pharmaceutical composition.

[0134] The dissolution conditions were paddle method 65 rpm, pH 5.5 citrate buffer, and the dissolution data of the prepared ibuprofen pharmaceutical composition sample were shown in Table 4-2, and the dissolution curve was shown in Figure 4 .

[0135] Table 4-2 Dissolution data of ibuprofen pharmaceutical composition

[0136]

[0137] Example 5: Ibuprofen pharmaceutical composition

[0138] Table 5-1 Prescription of Example 5

[0139]

[0140]

[0141] Preparation method:

[0142] Sustained-release pellets:

[0143] 1) Prescription weighing: accurately weigh ibuprofen, microcrystalline cellulose and povidone according to the mass ratio;

[0144] 2) Preparation of soft material: Add the material of step 1) into a wet granulator and mix at a stirring speed of 180 rpm and a cutting speed of 540 rpm for 3 min; then set the parameters: stirring speed of 180 rpm, chopping speed of 1200 rpm, turn on the instrument, and add a certain amount of water (about 80% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±0.5 min to obtain the soft material;

[0145] 3) Preparation of sustained-release pellets: The soft material prepared in step 2) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 120 seconds to obtain sustained-release pellets;

[0146] Immediate-release pellets:

[0147] 4) Prescription weighing: Accurately weigh the materials of the immediate-release pellets according to the mass ratio;

[0148] 5) Preparation of soft material: add the auxiliary materials of step 1) into the wet granulator and mix for 3 min at a stirring speed of 180 rpm and a cutting speed of 540 rpm; then set the parameters: stirring speed of 180 rpm, chopping speed of 1500 rpm, turn on the instrument, and add a certain amount of water (about 55% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 4±1 min to obtain the soft material;

[0149] 6) Preparation of immediate-release pellets: The soft material prepared in step 5) is placed in an extruder and extruded at an extrusion speed of 40 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 60 seconds to obtain immediate-release pellets;

[0150] 7) Mixing the prepared sustained-release pellets and quick-release pellets to obtain an ibuprofen pharmaceutical composition.

[0151] The dissolution conditions were paddle method 65 rpm, pH 5.5 citrate buffer, and the dissolution data of the prepared ibuprofen pharmaceutical composition were shown in Table 5-2, and the dissolution curve was shown in Figure 5 .

[0152] Table 5-2 Dissolution data of ibuprofen pharmaceutical composition

[0153]

[0154]

[0155] Example 6: Ibuprofen pharmaceutical composition

[0156] Table 6-1 Prescription of Example 6

[0157]

[0158] Preparation method:

[0159] Sustained-release pellets:

[0160] 1) Prescription weighing: accurately weigh ibuprofen, microcrystalline cellulose and povidone according to the mass ratio;

[0161] 2) Preparation of soft material: Add the material of step 1) into a wet granulator and mix for 5 min at a stirring speed of 100 rpm and a cutting speed of 500 rpm; then set the parameters: stirring speed of 100 rpm, chopping speed of 800 rpm, turn on the instrument, and add a certain amount of water (about 60% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 3±1 min to obtain the soft material;

[0162] 3) Preparation of sustained-release pellets: The soft material prepared in step 2) is placed in an extruder and extruded at an extrusion speed of 50 rpm, and the extrudate is poured into a spheronizer at 800 rpm and spheronized for 120 seconds to obtain sustained-release pellets;

[0163] Immediate-release pellets:

[0164] 4) Prescription weighing: Accurately weigh the materials of the immediate-release pellets according to the mass ratio;

[0165] 5) Preparation of soft material: Add the material of step 4) to the wet granulator and mix for 5 min at a stirring speed of 100 rpm and a cutting speed of 500 rpm; then set the parameters: stirring speed of 100 rpm, chopping speed of 1000 rpm, turn on the instrument, and add a certain amount of water (about 50% of the prescription amount) at a pump speed of 95 rpm to prepare the soft material. The water adding time is 3±1 min to obtain the soft material.

[0166] 6) Preparation of immediate-release pellets: The soft material prepared in step 5) was placed in an extruder and extruded at an extrusion speed of 70 rpm. The extrudate was poured into a spheronizer at 800 rpm and spheronized for 60 seconds to obtain immediate-release pellets.

[0167] 7) Mixing the prepared sustained-release pellets and quick-release pellets to obtain an ibuprofen pharmaceutical composition.

[0168] The dissolution conditions were paddle method 65 rpm, pH 5.5 citrate buffer, and the dissolution data of the prepared ibuprofen pharmaceutical composition sample were shown in Table 6-2, and the dissolution curve was shown in Figure 6 .

[0169] Table 6-2 Dissolution data of ibuprofen pharmaceutical composition

[0170]

[0171] Inspection of related substances: High performance liquid chromatograph equipped with UV detector, using Waters XTERRAMS C18, 150mm×4.6mm, 5μm chromatographic column, 0.02mol / L sodium dihydrogen phosphate buffer as mobile phase and diluent, injection volume 30μl.

[0172] Table 7 Data table of related substances of ibuprofen pharmaceutical composition

[0173] Related substances Impurity B Impurity C Impurity J Impurity E Impurity A Impurity N Other single unknown impurities Total Miscellaneous content(%) Not detected Not detected Not detected Not detected 0.07 <Reporting Limit <Reporting Limit 0.07

[0174] Other inspections: According to the quality requirements of dry suspensions, the samples prepared in Example 6 were inspected for content, content uniformity and sedimentation volume ratio. The results are shown in Table 8.

[0175] Table 8 Data table of ibuprofen pharmaceutical composition content, content uniformity and sedimentation volume ratio

[0176] project content Content uniformity Sedimentation volume ratio result 100.1％ Comply with regulations 0.99

[0177] Experimental Example 7

[0178] The sample prepared in Example 3 was compared with the commercial product of Example 1 (trade name: Meilin, immediate release suspension) in a clinical trial under fasting conditions in 12 healthy adult Chinese subjects. The sample prepared in Example 3 was administered once every 12 hours, and the commercial preparation of Example 1 was administered once every 6 hours, twice every 12 hours. The results are shown in Table 9, and the drug-time curve is shown in Figure 7 .

[0179] Example 3 Administration of the ibuprofen pharmaceutical composition: The ibuprofen pharmaceutical composition (containing 150 mg of ibuprofen) was brewed with 15 ml of water and then taken orally.

[0180] Table 9 Comparison of clinical results between commercially available preparations and the product of Example 3

[0181] PK parameters Motrin, immediate-release suspension Example 3 Product <![CDATA[T max (h)]]> 0.875 1.917 <![CDATA[C max (ng / mL)]]> 20.039 24.653 <![CDATA[AUC last (hr*ng / mL)]]> 145.240 162.738 <![CDATA[AUC INF (hr*ng / mL)]]> 147.649 166.102

[0182] Experimental Example 8

[0183] The sample prepared in Example 6 was compared with the commercial product of Example 1 (trade name: Meilin, immediate release suspension) in a clinical trial under fasting conditions in 12 healthy adult Chinese subjects. The sample prepared in Example 6 was administered once every 12 hours, and the commercial preparation was administered once every 6 hours, twice every 12 hours. The results are shown in Table 10, and the drug-time curve is shown in Figure 8 .

[0184] Example 6 Administration of the ibuprofen pharmaceutical composition: The ibuprofen pharmaceutical composition (containing 150 mg of ibuprofen) was brewed with 15 ml of water and then taken orally.

[0185] Table 10 Comparison of clinical results between commercially available preparations and the product of Example 6

[0186] PK parameters Motrin, immediate-release suspension Example 6 Product <![CDATA[T max (h)]]> 1.000 3.417 <![CDATA[C max (ng / mL)]]> 24.567 25.02 <![CDATA[AUC last (hr*ng / mL)]]> 195.333 195.931 <![CDATA[AUC INF (hr*ng / mL)]]> 199.637 211.694

[0187] Comparative Example

[0188] The product of Example 8 in CN115702883A was clinically tested on 12 healthy adult Chinese subjects under fasting conditions, where the comparative sample was administered once every 12 hours. The results are shown in Table 11, and the drug-time curve is shown in Table 12. Fig. 9 .

[0189] Table 11 Comparison of clinical results between commercially available preparations and comparative example products

[0190] PK parameters Comparative product <![CDATA[T max (h)]]> 5.477

[0191] As can be seen from Examples 1 to 6, the ibuprofen composition prepared by the present invention can achieve 12h sustained release, and the dry suspension is a suspension granule after adding water, which is more convenient to swallow. The drug can maintain an effective concentration for a long time in the body, thereby reducing the drug dosage, improving the efficacy, prolonging the drug action time and reducing the adverse drug reactions.

[0192] It can be seen from Experimental Examples 7 to 8 that the ibuprofen composition provided by the present invention is compared with the commercially available ibuprofen suspension preparation (trade name: Merlin, manufacturer: Shanghai Johnson Pharmaceutical Co., Ltd.), and it is found that the single administration of the sample is compared with the double administration of the commercial preparation. max It is similar to the conventional drugs and can take effect quickly, reduce the number of medications, improve patient compliance, and is suitable for pediatric patients, with good market prospects.

[0193] According to the human pharmacokinetic data of the comparative example, the present invention can significantly improve the time for the peak blood drug concentration compared with the comparative example, so that it can take effect quickly, while the comparative example takes effect slowly, which is not conducive to the rapid reduction of fever in patients.

[0194] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An ibuprofen pharmaceutical composition, characterized in that: The blood concentration of the ibuprofen pharmaceutical composition reaches a peak time of less than 5 hours and is maintained for 8 hours to 12 hours; Preferably, the peak time of the blood drug concentration is less than 3 hours (preferably less than 2.5 hours) and the duration is 8-11 hours; It is further preferred that the peak time of the blood drug concentration is less than 2 hours and the duration is 8 hours to 10 hours; And / or, the ibuprofen pharmaceutical composition comprises the following components: sustained-release pellets and rapid-release pellets, wherein the sustained-release pellets comprise ibuprofen, a filler and a binder; and the rapid-release pellets comprise ibuprofen, a filler, a suspending agent, a disintegrant, a flavoring agent and a pH regulator.

2. The ibuprofen pharmaceutical composition according to claim 1, wherein: The content of ibuprofen is 1.0% to 80.0%, and the content refers to the percentage of the mass of the ibuprofen to the total mass of the ibuprofen pharmaceutical composition; and / or, The mass ratio of the sustained-release pellets to the immediate-release pellets is 1:100 to 100:

1.

3. The ibuprofen pharmaceutical composition according to claim 1, wherein: The filler is selected from one or more of microcrystalline cellulose, pregelatinized starch, mannitol, sucrose, glucose, maltose, lactose, sorbitol, xylitol, maltitol, galactitol, erythritol, dextrin and trehalose; and / or, The binder is selected from one or more of hydroxypropyl methylcellulose, carbomer, hydroxyethyl cellulose, polyoxyethylene, pregelatinized starch, copovidone, hydroxypropyl cellulose, ethyl cellulose, povidone and sodium carboxymethyl cellulose; and / or, The suspending agent is selected from one or more of glycerol, gum arabic, agar, xanthan gum, colloidal microcrystalline cellulose, sodium alginate, sodium carboxymethyl cellulose, microcrystalline cellulose-sodium carboxymethyl cellulose and methyl cellulose; and / or, The disintegrant is selected from one or more of low-substituted hydroxypropyl cellulose, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch and starch; and / or, The flavoring agent is selected from one or more of aspartame, sucralose, fructose, sucrose, steviol glycosides, glycyrrhizin, citric acid, flavor, menthol, sodium chloride, neotame, acesulfame potassium, saccharin and saccharin sodium; and / or, The pH regulator is selected from one or more of citric acid, L-malic acid, sodium citrate, disodium hydrogen phosphate and sodium hydroxide.

4. The ibuprofen pharmaceutical composition according to claim 1, wherein: In the sustained-release pellets, the filler is microcrystalline cellulose; and / or, In the sustained-release pellets, the binder is povidone; Preferably, in the sustained-release pellets, the content of ibuprofen is 1.0% to 30.0%, and the content refers to the percentage of the mass of the ibuprofen to the total mass of the ibuprofen pharmaceutical composition; and / or, In the sustained-release pellets, the content of the filler is 1.0% to 30.0%, and the content refers to the percentage of the mass of the filler to the total mass of the ibuprofen pharmaceutical composition; and / or, In the sustained-release pellets, the content of the binder is 0.1% to 10.0%, and the content refers to the percentage of the mass of the binder to the total mass of the ibuprofen pharmaceutical composition.

5. The ibuprofen pharmaceutical composition according to claim 1, wherein: In the rapid-release pellets, the filler is microcrystalline cellulose and / or mannitol; and / or, In the rapid-release pellets, the suspending agent is xanthan gum and / or microcrystalline cellulose-sodium carboxymethyl cellulose; and / or, In the instant-release pellets, the disintegrant is sodium carboxymethyl starch; and / or, In the rapid-release pellets, the flavoring agent is flavor and / or aspartame; and / or, In the rapid-release pellets, the pH regulator is citric acid; In the rapid-release pellets, the content of ibuprofen is 1.00% to 10.00%, and the content refers to the percentage of the mass of the ibuprofen to the total mass of the ibuprofen pharmaceutical composition.

6. The ibuprofen pharmaceutical composition according to claim 1, wherein: The content of the filler is 1.0% to 80.0%, and the content refers to the percentage of the mass of the filler to the total mass of the ibuprofen pharmaceutical composition; and / or, The content of the suspending agent is 1.0% to 30.0%, and the content refers to the percentage of the mass of the suspending agent to the total mass of the ibuprofen pharmaceutical composition; and / or, The content of the disintegrant is 1.0% to 20.0%, and the content refers to the percentage of the mass of the disintegrant to the total mass of the ibuprofen pharmaceutical composition; and / or, The content of the flavoring agent is 1.0% to 10.0%, and the content refers to the percentage of the mass of the flavoring agent to the total mass of the ibuprofen pharmaceutical composition; and / or, The content of the pH regulator is 0.10% to 5.00%, and the content refers to the percentage of the mass of the pH regulator to the total mass of the ibuprofen pharmaceutical composition.

7. The ibuprofen pharmaceutical composition according to claim 1, wherein: The sustained-release pellets contain the following components: each component adopts a mass fraction of 1.00% to 30.00% ibuprofen, 1.00% to 30.00% microcrystalline cellulose, and 0.10% to 10.00% povidone, and the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; and / or, The rapid-release pellets contain the following components: each component is measured in mass fraction, 1.00% to 10.00% ibuprofen, 1.00% to 80.00% microcrystalline cellulose and / or mannitol, 1.00% to 30.00% xanthan gum and / or microcrystalline cellulose-sodium carboxymethyl cellulose, 1.00% to 20.00% sodium carboxymethyl starch, 1.00% to 10.00% flavor and / or aspartame, 0.10% to 5.00% citric acid; the mass fraction refers to the percentage of the mass of each component to the total mass of the ibuprofen composition.

8. The ibuprofen pharmaceutical composition according to claim 1, wherein: The sustained-release pellets are any of the following prescriptions: Prescription 1: 10.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages being the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Prescription 2: 9.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages being the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Prescription 3: 12.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages refer to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Prescription 4: 14.00% ibuprofen, 12.44% microcrystalline cellulose and 0.56% povidone, the percentages being the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; and / or, The rapid-release pellets are any of the following formulations: Formula 1: 5.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Formula 2: 6.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Formula 3: 3.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition; Formulation 4: 1.00% ibuprofen, 2.00% xanthan gum, 8.75% microcrystalline cellulose-sodium carboxymethyl cellulose, 33.08% microcrystalline cellulose, 16.50% mannitol, 8.50% sodium carboxymethyl starch, 0.67% citric acid, 2.00% strawberry flavor and 0.50% aspartame, wherein the percentage refers to the percentage of the mass of each component to the total mass of the ibuprofen pharmaceutical composition.

9. Use of the ibuprofen pharmaceutical composition according to any one of claims 1 to 8 in the preparation of a medicament for treating and / or alleviating mild to moderate pain diseases.

10. The method for preparing the ibuprofen pharmaceutical composition according to any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: mixing the components of the sustained-release pellets, wet granulating, preparing a soft material and then extruding and spheronizing to obtain the sustained-release pellets; mixing the components of the quick-release pellets, wet granulating, preparing a soft material and then extruding and spheronizing to obtain the quick-release pellets; and then mixing the sustained-release pellets and the quick-release pellets according to a proportion to obtain the ibuprofen pharmaceutical composition.

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