Ibuprofen pellet with double-layer membrane structure and preparation method of ibuprofen pellet

Abstract

The invention discloses an ibuprofen pellet with a double-layer membrane structure. The ibuprofen pellet comprises a blank pellet core, a drug-loaded sustained-release layer and a drug-loaded quick-release layer, wherein the drug-loaded sustained-release layer and the drug-loaded quick-release layer sequentially coat the outer surface of the blank pellet core; the drug-loaded sustained-release layer is prepared from the following components in parts by mass: 20 to 40 parts of ibuprofen, 5 to 7 parts of microcrystalline cellulose and 5 to 7 parts of starch-based resin. According to the ibuprofen pellet with the double-layer membrane structure provided by the invention, the outer drug-loading quick-release layer adopts a net-shaped structure polymer with strong water absorption and expansion performance, and is quickly disintegrated to be combined with the controlled-release supporting effect of the cross-linked sodium carboxymethyl cellulose, so that the quick and stable drug release of the outer membrane is realized, and the effective concentration is achieved; the inner drug-loaded sustained-release layer forms a three-dimensional network structure by balancing and regulating the proportion of hydrophilic starch-based resin and hydrophobic microcrystalline cellulose, so that the system strength is increased, the diffusion path of active ingredients is limited, the quick release concentration is stably linked, and a more stable sustained-release effect is realized.

Description

Technical Field

[0001] This application relates to the field of pharmaceutical technologies, and particularly to ibuprofen pellets with a bilayer membrane structure and a preparation method thereof. Background Art

[0002] Clinically, ibuprofen is mainly used to relieve mild to moderate pain such as headache, joint pain, migraine, toothache, muscle pain, neuralgia, and dysmenorrhea. It is also used for the fever caused by common cold or influenza. The low solubility of ibuprofen in water results in low bioavailability and a short half-life (1.8 - 2h), and it needs to be administered frequently (3 - 4 times a day). Therefore, it is mostly applied as a sustained-release preparation. Usually, a high-molecular material is used as the drug skeleton carrier or a film-forming high-molecular polymer thin film is used for coating to achieve the purpose of sustained release.

[0003] For conventional ibuprofen sustained-release drug carriers, the drug concentration gradient between the carrier and the release medium is relatively high, and the drug release driving force is high, which may induce drug burst release and result in the "peak-valley" phenomenon, leading to fluctuations in blood drug concentration and affecting the efficacy and safety. Sometimes, a single type of polymer dispersion is not sufficient to produce good drug release behavior.

[0004] Therefore, developing an ibuprofen pellet that can be rapidly released, ensure long-lasting efficacy, and reduce the dosing frequency is an urgent problem to be solved by those skilled in the art. Summary of the Invention

[0005] In view of this, in response to the technical defects of the existing ibuprofen sustained-release preparations, such as the risk of drug burst release, large fluctuations in blood drug concentration, and poor controllability of release behavior, this application proposes an ibuprofen pellet with a bilayer membrane structure: the outer drug-loaded rapid-release membrane layer adopts a reticular structure polymer with strong water absorption and swelling properties for rapid disintegration combined with the controlled-release support of cross-linked sodium carboxymethylcellulose to achieve rapid and stable drug release from the outer layer membrane and reach the effective concentration; the inner drug-loaded sustained-release membrane layer forms a three-dimensional network structure by balancing and regulating the ratio of hydrophilic starch-based resin and hydrophobic microcrystalline cellulose, which not only increases the system strength but also restricts the diffusion path of the active ingredient, smoothly connecting the rapid-release concentration and achieving a more stable sustained-release effect.

[0006] This application provides an ibuprofen pellet with a bilayer membrane structure, which includes a blank pellet core and a drug-loaded sustained-release layer and a drug-loaded rapid-release layer sequentially coated on the blank pellet core; the drug-loaded sustained-release layer includes, by mass: 20 - 40 parts of ibuprofen, 5 - 7 parts of microcrystalline cellulose, and 5 - 7 parts of starch-based resin.

[0007] In some specific implementation manners, the starch-based resin includes, by mass: 3 - 5 parts of carboxymethyl starch physically mixed with 2 - 3 parts of glycerol.

[0008] In some specific implementation manners, the drug-loaded rapid-release layer includes, by mass parts: 20-40 parts of ibuprofen, 5-6 parts of mannitol, 3-6 parts of cross-linked carboxymethylcellulose sodium, and 1-2 parts of povidone k30.

[0009] In some specific implementation manners, the thickness of the drug-loaded sustained-release layer is 2-3 mm; the thickness of the drug-loaded rapid-release layer is 1-2 mm;

[0010] The mass ratio of the blank pill core to the drug-loaded sustained-release layer is (1-2):(5-6);

[0011] The mass ratio of the blank pill core to the drug-loaded rapid-release layer is (1-2):(3-5).

[0012] In some specific implementation manners, the drug-loaded sustained-release layer further includes 1-2 parts of lubricant by mass parts; the lubricant includes one or more of talcum powder and microcrystalline cellulose.

[0013] In some specific implementation manners, a coating layer is further included outside the drug-loaded rapid-release layer; the mass ratio of the blank pill core to the coating layer is 1:(0.5-2).

[0014] The present application also provides a preparation method of ibuprofen pellets with a double-layer film structure, including:

[0015] Forming a drug-loaded sustained-release layer on the surface of the blank pill core, and forming a drug-loaded rapid-release layer on the surface of the drug-loaded sustained-release layer to obtain ibuprofen pellets with a double-layer film structure.

[0016] In some specific implementation manners, the step of forming the drug-loaded sustained-release layer on the surface of the blank pill core includes: mixing an ibuprofen solution, a starch-based resin, and microcrystalline cellulose, coating the mixture on the surface of the blank pill core, and curing to form the drug-loaded sustained-release layer; the preparation method of the ibuprofen solution includes: micronizing ibuprofen and then mixing it with water to obtain the ibuprofen solution.

[0017] In some specific implementation manners, the step of forming the drug-loaded rapid-release layer includes: mixing an ibuprofen solution, mannitol, cross-linked carboxymethylcellulose sodium, and povidone k30, adding the mixture by fluidized bed spraying on the surface of the drug-loaded sustained-release layer, drying in gradient, and curing to form the drug-loaded rapid-release layer.

[0018] The ibuprofen pellets with a bilayer membrane structure provided by this application innovatively constructs a functionalized bilayer membrane controlled-release system for the problem of the fluctuation of the drug-time curve caused by the burst release risk existing in traditional ibuprofen sustained-release preparations. This system realizes precise drug release regulation through the design of a composite membrane structure: the outer drug-loaded rapid-release layer adopts a network structure polymer with strong water absorption and swelling properties for rapid disintegration combined with the controlled-release support of cross-linked sodium carboxymethylcellulose to achieve rapid and stable drug release from the outer layer membrane and reach the effective concentration; the inner drug-loaded sustained-release layer forms a three-dimensional network structure by balancing and regulating the ratio of hydrophilic starch-based resin and hydrophobic microcrystalline cellulose, which not only increases the system strength but also restricts the diffusion path of the active ingredient, smoothly connecting the rapid-release concentration and achieving a more stable sustained-release effect. This structural design realizes: quickly establishing the effective blood drug concentration in the rapid-release phase, maintaining stable drug release in the sustained-release phase, precisely controlling the release, stably connecting the concentrations, and significantly improving the problem of the fluctuation of the drug-time curve of traditional ibuprofen sustained-release preparations.

[0019] The onset-maintenance biphasic regulation shortens the peak time and prolongs the maintenance time of the effective blood drug concentration; the drug release is stable, thereby reducing the fluctuation of the blood drug concentration and significantly reducing the risk of toxic and side reactions caused by the peak-valley phenomenon; the dosing frequency is reduced, improving patient compliance. The system realizes the programmable gradual change of the drug diffusion coefficient through the precise regulation of the particle size of the active ingredient, the interaction between polymers, and the film thickness, successfully solving the kinetic mismatch problem of traditional single-layer sustained-release systems. Description of the Drawings

[0020] Figure 1 It is a schematic structural diagram of the ibuprofen pellets with a bilayer membrane structure provided by the embodiment of this application;

[0021] Figure 2 It is a preparation flow chart of the ibuprofen pellets with a bilayer membrane structure provided by the embodiment of this application;

[0022] Figure 3 It is an in vitro dissolution curve graph of the ibuprofen pellets with a bilayer membrane structure provided by Examples 1-3 and Comparative Examples 1 and 2 of this application at pH 5.5;

[0023] Figure 4 It is an in vitro dissolution curve graph of the ibuprofen pellets with a bilayer membrane structure provided by Examples 1-3 and Comparative Examples 1 and 2 of this application at pH 6;

[0024] Figure 5 It is an in vitro dissolution curve graph of the ibuprofen pellets with a bilayer membrane structure provided by Examples 1-3 and Comparative Examples 1 and 2 of this application at pH 6.8. Detailed Description of the Invention

[0025] It should be understood that the expression "one or more of..." individually includes each of the objects recited after said expression and various different combinations of two or more of the recited objects, unless otherwise understood from the context and usage. The expression "and / or" in combination with three or more recited objects should be understood to have the same meaning, unless otherwise understood from the context.

[0026] The terms "comprising", "having" or "containing", including the use of their grammatical synonyms, should generally be understood as open-ended and non-limiting, for example, not excluding other unrecited elements or steps, unless specifically stated otherwise or otherwise understood from the context.

[0027] It should be understood that as long as the present application remains operable, the order of steps or the order of performing certain actions is not important. In addition, two or more steps or actions can be carried out simultaneously.

[0028] The use of any and all examples or exemplary language such as "for example" or "including" in this document is merely intended to better illustrate the present application and does not limit the scope of the present application unless a claim is made. No language in this specification should be construed as indicating that any unclaimed element is essential for the practice of the present application.

[0029] In addition, the numerical ranges and parameters used to define the present application are approximate values. The relevant values in the specific embodiments have been presented as precisely as possible herein. However, any numerical value inherently and inevitably contains standard deviations due to individual testing methods. Therefore, unless otherwise clearly stated, it should be understood that all ranges, amounts, numerical values and percentages used in this disclosure are modified by "about". Herein, "about" generally means that the actual value is within plus or minus 10%, 5%, 1% or 0.5% of a specific value or range.

[0030] The present application provides ibuprofen pellets with a double-layer film structure, comprising a blank pellet core and a drug-loaded sustained-release layer and a drug-loaded immediate-release layer sequentially coated on the blank pellet core; the drug-loaded sustained-release layer comprises, by mass parts: 20-40 parts of ibuprofen, 5-7 parts of microcrystalline cellulose and 5-7 parts of starch-based resin. The mass parts of the ibuprofen can be 20 parts, 21 parts, 22 parts, 23 parts, 25 parts, 26 parts, 28 parts, 30 parts, 32 parts, 34 parts, 35 parts, 36 parts, 38 parts, 40 parts, the mass parts of the starch-based resin can be 5 parts, 6 parts, 7 parts, and the mass parts of the microcrystalline cellulose can be 5 parts, 6 parts, 7 parts. The structural schematic diagram of the ibuprofen pellets with the double-layer film structure is as Figure 1As shown in the figure, where 1 is a blank pill core. In some specific implementation manners, the particle size of the blank pill core is 1.5 - 2 mm, preferably 2 mm; the component of the blank pill core is a filler, and the filler includes but is not limited to microcrystalline cellulose. There are no special requirements for the selection of the filler in this application; 2 is a drug-loaded sustained-release layer. In some specific implementation manners, the starch-based resin includes 3 to 5 parts by mass of carboxymethyl starch and 2 to 3 parts by mass of glycerol physically mixed. The thickness of the drug-loaded sustained-release layer is 2 - 3 mm, and the mass ratio of the blank pill core to the drug-loaded sustained-release layer is (1 - 2):(5 - 6), which can be 1:6, 1:5.5, 1:5, 1.5:6. In some specific implementation manners, the drug-loaded sustained-release layer further includes 1 to 2 parts by mass of a lubricant. The lubricant includes but is not limited to one or more of talcum powder and microcrystalline cellulose. There are no special requirements for the selection of the lubricant in this application; In some specific implementation manners, the drug-loaded sustained-release layer further includes 1 to 2 parts by mass of a solubilizer; the solubilizer is Tween-80. There are no special requirements for the selection of the lubricant in this application; 3 is a drug-loaded immediate-release layer. In some specific implementation manners, the drug-loaded immediate-release layer includes, by mass: 20 - 40 parts of ibuprofen, 5 - 6 parts of mannitol, 3 - 6 parts of cross-linked carboxymethyl cellulose sodium, and 1 - 2 parts of povidone k30. The mass of ibuprofen can be 20 parts, 21 parts, 22 parts, 23 parts, 25 parts, 26 parts, 28 parts, 30 parts, 32 parts, 34 parts, 35 parts, 36 parts, 38 parts, 40 parts. The mass of cross-linked carboxymethyl cellulose sodium can be 1 part or 2 parts, and the mass of povidone k30 can be 1 part or 2 parts. The thickness of the drug-loaded immediate-release layer is 1 - 2 mm, and the mass ratio of the blank pill core to the drug-loaded immediate-release layer is (1 - 2):(3 - 5), which can be 1:5, 1:4, 1:3, 2:5, 1:2, 2:3; 4 is a coating layer, and the component of the coating layer includes a flavoring agent; the mass ratio of the blank pill core to the coating layer is 1:(0.5 - 2), which can be 1:0.5, 1:1, 1:1.5, 1:2. This system realizes precise drug release regulation through the composite membrane structure design: the outer drug-loaded immediate-release layer adopts a network structure polymer with strong water absorption and swelling properties for rapid disintegration combined with the controlled-release support of cross-linked carboxymethyl cellulose sodium to achieve rapid and stable drug release from the outer layer membrane and reach the effective concentration; the inner drug-loaded sustained-release layer forms a three-dimensional network structure by balancing and regulating the ratio of hydrophilic starch-based resin and hydrophobic microcrystalline cellulose, which not only increases the system strength but also restricts the diffusion path of the active ingredient, smoothly connecting the immediate-release concentration and achieving a more stable sustained-release effect; the onset-maintenance dual-phase regulation shortens the peak time and prolongs the maintenance time of the effective blood drug concentration; the drug release is stable, thereby reducing the fluctuation of blood drug concentration and significantly reducing the risk of toxic and side reactions caused by the peak-valley phenomenon; the frequency of drug use is reduced, improving patient compliance.The system realizes the programmable variation of the drug diffusion coefficient through the precise regulation of the particle size of the active ingredient, the interaction between polymers, and the film thickness, and successfully solves the kinetic mismatch problem of traditional single-layer sustained-release systems.

[0031] This application uses sodium carboxymethylcellulose crosslinked with polyvinylpyrrolidone K30 as a film-forming agent, and realizes rapid and stable drug release under a single dose (dissolution rate ≥ 35% at 30 minutes, pH 6.8) through the synergistic mechanism of disintegration and pore formation. The rapid disintegration of the network structure polymer with strong water absorption and swelling properties is combined with the controlled release support of CMC-Na to achieve rapid and stable drug release from the outer layer membrane, with complementary functions, breaking through the technical bottleneck of the high risk of burst release of traditional single-component rapid-release membranes. The drug-loaded sustained-release layer adopts a synergistic film-forming system composed of microcrystalline cellulose and starch-based resin, and forms a dense three-dimensional network structure through hydrogen bond crosslinking, which not only increases the system strength but also limits the diffusion path of the active ingredient, smoothly connecting the rapid-release concentration and achieving a more stable sustained-release effect. Based on the design of a multi-unit drug release system, a single dose contains multiple pellet units, with a larger specific surface area than tablets and an improved bioavailability. The local drug concentration is reduced through the dose dispersion effect, significantly reducing gastrointestinal irritation. The system adopts a double-layer membrane structure controlled release design, and each micro - This technology realizes gradient weight gain (CV < 2%) and precise film control (thickness deviation ± 5μm) through the fluidized bed bottom spray coating process, with a production qualification rate > 98%, successfully solving the technical bottlenecks of the slow onset and short action time of traditional sustained-release preparations. The batch - to - batch difference in in vitro release is small, and the coefficient of variation of in vivo absorption is low.

[0032] This application also provides a preparation method for ibuprofen pellets with a double-layer membrane structure, including:

[0033] Forming a drug-loaded sustained-release layer on the surface of a blank pellet core, and forming a drug-loaded rapid-release layer on the surface of the drug-loaded sustained-release layer to obtain ibuprofen pellets with a double-layer membrane structure. The preparation flow chart is as Figure 2 shown.

[0034] This application first mixes a filler and water, and dries them to obtain a blank pellet core. In some specific implementation manners, the filler includes but is not limited to microcrystalline cellulose, and this application has no special requirements for the selection of the filler.

[0035] This application mixes ibuprofen solution, starch-based resin and microcrystalline cellulose, and sprays them on the surface of blank pellets using a fluidized bed or a centrifugal granulator, followed by drying and curing to obtain drug-loaded pellets with a sustained-release layer. In some specific implementation manners, the preparation method of the ibuprofen solution includes: mixing ibuprofen, a solvent and a solubilizer to obtain an ibuprofen solution; the solvent includes but is not limited to water; the solubilizer includes but is not limited to Tween-80. This application has no special requirements for the selection of the solvent and the solubilizer. In some specific implementation manners, the curing method is gradient drying, and the temperature of the gradient drying is 40°C in the first stage, 32°C in the second stage, and 25°C in the third stage.

[0036] This application mixes ibuprofen solution, mannitol, cross-linked carboxymethyl cellulose sodium, and polyvinylpyrrolidone k30, sprays them on the surface of drug-loaded pellets containing a drug-loaded sustained-release layer, and cures them to obtain ibuprofen pellets with a double-layer film structure. In some specific implementation manners, the curing method is gradient drying.

[0037] This application coats a flavoring agent to obtain ibuprofen pellets with a double-layer film structure.

[0038] The following further elaborates on this application in conjunction with embodiments. The protection scope of this application is not limited by the following embodiments.

[0039] Example 1

[0040] This example provides ibuprofen pellets with a double-layer film structure, including a blank pellet core and a drug-loaded sustained-release layer, a drug-loaded immediate-release layer, and a coating sequentially coated on the blank pellet core. The components are shown in Table 1:

[0041] Table 1

[0042]

[0043] The preparation method of the ibuprofen pellets with the double-layer film structure includes:

[0044] Preparation of blank pellets: Wet microcrystalline cellulose (MCC) with pure water, prepare blank pellet cores using a centrifugal granulator, dry them, and sieve them through a screen;

[0045] Preparation of ibuprofen solution: After micronizing ibuprofen, add an appropriate amount of pure water to prepare an ibuprofen solution with a suitable concentration. If a higher concentration of ibuprofen solution is required, add the solubilizer Tween-80 when necessary.

[0046] Preparation of starch-based resin: Physically mix 3-5 parts of carboxymethyl starch and 2-3 parts of glycerol.

[0047] Preparation of drug-loaded sustained-release layer: Mix ibuprofen fine powder, starch-based resin, microcrystalline cellulose and pure water, and evenly spray it on blank pellets using equipment such as fluidized bed or centrifugal granulator. Gradually dry to volatilize the solvent and cure to obtain drug-loaded pellets containing the drug-loaded sustained-release layer. After the inner layer film is completed, mix the pellets with 2 parts of talcum powder and store temporarily to avoid adhesion;

[0048] Preparation of drug-loaded rapid-release layer: Take an appropriate amount of ibuprofen fine powder, add mannitol, croscarmellose sodium, polyvinylpyrrolidone k30 and pure water and mix evenly. Spray it on the pellets containing the drug-loaded sustained-release layer and dry and cure;

[0049] External coating: After performing side spray sugar coating in a fluidized bed, dry and cure to obtain ibuprofen pellets with a double-layer film structure.

[0050] Example 2

[0051] This example provides ibuprofen pellets with a double-layer film structure, which is different from Example 1 in that the components of the ibuprofen pellets with the double-layer film structure are different, and the components are shown in Table 2:

[0052] Table 2

[0053]

[0054] Example 3

[0055] This example provides ibuprofen pellets with a double-layer film structure, which is different from Example 1 in that the components of the ibuprofen pellets with the double-layer film structure are different, and the components are shown in Table 3:

[0056] Table 3

[0057]

[0058] Comparative Example 1

[0059] Comparative Example 1 is a commercially available reference preparation, the trade name is ibuprofen sustained-release capsule, the specification is 0.3 g, the batch number is 16100542, and the manufacturer is GlaxoSmithKline Tianjin Pharmaceutical Co., Ltd.

[0060] Comparative Example 2

[0061] This comparative example provides ibuprofen pellets with a double-layer film structure without starch-based resin, which is different from Example 1 in that the components of the ibuprofen pellets with the double-layer film structure are different, and the components are shown in Table 4:

[0062] Table 4

[0063]

[0064] Perform performance tests on the ibuprofen pellets with the double-layer film structure provided in Examples 1-3 and Comparative Examples 1-2. The test methods are as follows:

[0065] Three media, namely pH 5.5 acetate buffer, pH 6.0 phosphate buffer, and pH 6.8 phosphate buffer, were selected to investigate the dissolution of ibuprofen sustained-release capsules. The preparations prepared in Examples 1, 2, and 3 and Comparative Example 1 were used as per the general rule 0931 (Method 1) in the 2020 Edition of the Chinese Pharmacopoeia (Volume IV). Using pH 5.5 acetate buffer, pH 6.0 phosphate buffer, and pH 6.8 phosphate buffer as dissolution media respectively, with a media volume of 900 mL, a temperature of 37°C ± 0.5°C, and a rotation speed of 30 rpm, sampling was carried out according to the specified time list to determine the cumulative dissolution percentage (%) of each preparation at different times. The 2020 Edition of the Pharmacopoeia requires a release standard of pH 6.0 ± 0.05: 10 - 35% at 1 h; 25 - 55% at 2 h; 50 - 80% at 4 h; > 75% at 7 h. The in vitro dissolution curves of Examples 1 - 3 and Comparative Example 1 at pH 5.5 are as shown in Figure 3 shown, and the cumulative release degrees are shown in Table 5; the in vitro dissolution curves of Examples 1 - 3 and Comparative Example 1 at pH 6 are as shown in Figure 4 shown, and the cumulative release degrees are shown in Table 6; the in vitro dissolution curves of Examples 1 - 3 and Comparative Example 1 at pH 6.8 are as shown in Figure 5 shown, and the cumulative release degrees are shown in Table 7;

[0066] Table 5

[0067]

[0068] Table 6

[0069]

[0070] Table 7

[0071]

[0072] From Tables 5 - 7 and Figures 3 - 5 it can be seen that compared with the commercially available Comparative Example 1, under the conditions of pH 5.5, 6.0, and 6.8, the initial drug release rates of Examples 1 - 3 are faster than those of the commercially available product. After the dissolution degree reaches 40% - 50%, the drug is released continuously and steadily, and the connection between the drug-loaded rapid-release layer and the drug-loaded sustained-release layer is stable, effectively avoiding the appearance of the "peak-valley" phenomenon. Compared with Comparative Example 2, the starch-based resin in the sustained-release layer is different in composition for Examples 1 - 3. After the release degree exceeds 40%, Comparative Example 2 still releases the drug relatively fast, and the sustained-release effect of Examples 1 - 3 is better than that of Comparative Example 2. The results show that the three-dimensional network structure formed by hydrophilic starch-based resin and hydrophobic microcrystalline cellulose enhances the stable drug release.

[0073] As described above, it is only the preferred specific implementation manner of the present application, but the protection scope of the present application is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present application, according to the technical solution and the application concept of the present application, making equivalent substitutions or changes, shall be covered by the protection scope of the present application.

Claims

1. An ibuprofen pellet with a double-layer film structure, characterized in that, It includes a blank pellet core and a drug-loaded sustained-release layer and a drug-loaded immediate-release layer successively coated on the outer surface of the blank pellet core; the drug-loaded sustained-release layer includes 20-40 parts by mass of ibuprofen, 5-7 parts by mass of microcrystalline cellulose and 5-7 parts by mass of starch-based resin.

2. The ibuprofen pellets with a double-layer film structure according to claim 1, characterized in that, The starch-based resin includes 3-5 parts by mass of carboxymethyl starch and 2-3 parts by mass of glycerol.

3. The ibuprofen pellets with a bilayer membrane structure according to claim 1, characterized in that, The drug-loaded immediate-release layer includes, by mass: 20-40 parts of ibuprofen, 5-6 parts of mannitol, 3-6 parts of croscarmellose sodium and 1-2 parts of povidone k30.

4. The ibuprofen pellets with a double-layer film structure according to claim 1, wherein, The thickness of the drug-loaded sustained-release layer is 2-3 mm; the thickness of the drug-loaded immediate-release layer is 1-2 mm; The mass ratio of the blank pellet core to the drug-loaded sustained-release layer is (1-2):(5-6); The mass ratio of the blank pellet core to the drug-loaded immediate-release layer is (1-2):(3-5).

5. The ibuprofen pellets with a bilayer membrane structure according to claim 1, characterized in that, The drug-loaded sustained-release layer further includes 1 to 2 parts by mass of a lubricant; the lubricant includes talc powder and / or microcrystalline cellulose.

6. The ibuprofen pellets with a bilayer membrane structure according to claim 1, characterized in that, An enteric coating layer is further included outside the drug-loaded immediate-release layer; the mass ratio of the blank pellet core to the enteric coating layer is 1:(0.5-2).

7. The ibuprofen pellets with a double-layer film structure according to claim 1, wherein All of the ibuprofen is micronized.

8. A preparation method of ibuprofen pellets with a double-layer film structure, characterized in that, It includes: Forming a drug-loaded sustained-release layer on the surface of the blank pellet core, and forming a drug-loaded immediate-release layer on the surface of the drug-loaded sustained-release layer to obtain ibuprofen pellets with a bilayer film structure.

9. The preparation method according to claim 8, wherein The step of forming the drug-loaded sustained-release layer on the surface of the blank pellet core includes: mixing an ibuprofen solution, a starch-based resin and microcrystalline cellulose, coating on the surface of the blank pellet core, and curing to form the drug-loaded sustained-release layer; The preparation method of the ibuprofen solution includes: micronizing ibuprofen and then mixing it with water to obtain the ibuprofen solution.

10. The preparation method according to claim 8, characterized in that, The step of forming the drug-loaded immediate-release layer includes: mixing an ibuprofen solution, mannitol, croscarmellose sodium and povidone k30, adding the drug by fluidized bed spraying on the surface of the drug-loaded sustained-release layer, drying by gradient, and curing to form the drug-loaded immediate-release layer.

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