Preparation method of novel irbesartan composition

Abstract

The invention provides a novel preparation method of an irbesartan composition, and belongs to the technical field of pharmaceutical preparations, the irbesartan composition comprises irbesartan and silicon dioxide, the irbesartan and the silicon dioxide are subjected to wet grinding in a planetary ball mill, and the mass ratio of the irbesartan to the silicon dioxide is (50: 1)-(100: 1); the particle size of irbesartan is not greater than 50 microns; the composition can also comprise one or more of a filler, a disintegrating agent, an adhesive, a lubricant and a flow aid. According to the irbesartan composition, amorphous silicon dioxide is used as a hydrophilic porous carrier to increase the specific surface area of a medicine and promote the wettability of the medicine, and irbesartan is ground into nano-scale particle size by adopting a wet grinding process and is embedded into silicon dioxide, so that the irbesartan composition is prepared. According to the irbesartan tablet, the dissolution rate and oral bioavailability of irbesartan under a low-acid condition can be remarkably improved, an organic solvent and a solubilizer do not need to be used, the medicine storage stability can be improved, the raw material cost is low, the compatibility of existing production equipment is good, and the irbesartan tablet is suitable for industrial mass production.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of pharmaceutical preparations, in particular to a preparation method of a new irbesartan composition. BACKGROUND

[0002] Irbesartan is the third generation product of angiotensin II receptor blockers (ARB) antihypertensive drugs, with a long half-life of about 11-15 hours and good tissue penetration, becoming the dominant product in clinical once-daily administration, and is widely used in the treatment of primary hypertension and diabetic nephropathy-related hypertension complications. The demand for this kind of long-acting antihypertensive drugs in the elderly patient population continues to increase, and its clinical application scenario is constantly expanding, becoming an important drug selection in the field of hypertension treatment.

[0003] Irbesartan is classified as a BCS II drug, with low solubility and high permeability, and the solubility shows obvious pH dependence. In pure water, it is only about 0.01 mg / mL, in simulated gastric juice (pH 1.2), it is 0.49 mg / mL, and in simulated intestinal juice (pH 6.8), it is 0.3 mg / mL. This pH-dependent limited dissolution behavior leads to its in vivo absorption being easily affected by the gastrointestinal environment. When patients have gastric acid deficiency (such as long-term use of PPIs or old atrophic gastritis), the dissolution rate decreases significantly, thereby reducing the bioavailability. In addition, the solubility of the drug in commonly used organic solvents (such as ethanol, propylene glycol) is also low, limiting the development and application of liquid formulations. Given that irbesartan formulations in clinical application are more likely to be used by elderly patients, who generally have gastric acid deficiency, it is necessary to improve its dissolution in low-acid gastrointestinal environment.

[0004] To improve the dissolution and bioavailability of poorly soluble drugs, various means have been developed in the prior art, including drug micronization, addition of solubilizers or cosolvents, use of cyclodextrin inclusion technology, and preparation of solid dispersions. These methods have been applied to some extent in different poorly soluble drug formulations.

[0005] However, the prior art still has significant defects: the commonly used solubilizers or cosolvents have strong irritation or serious adverse reactions, reducing the patient's long-term medication compliance; simple micronization technology cannot achieve the desired solubilization effect; the cyclodextrin inclusion technology and the solid dispersion technology generally have the problems of multiple process steps and complex operation, which are not conducive to industrial scale-up production. For example, the preparation method of irbesartan tablets disclosed in CN115721620A uses 2A carcinogen dichloromethane as a solvent, which not only increases the production cost, but also has the risks of steam safety hazards and formulation residues. SUMMARY

[0006] To overcome the shortcomings of the prior art, the purpose of this invention is to provide a new method for preparing irbesartan compositions. This invention can significantly improve the dissolution rate and oral bioavailability of irbesartan under low acid conditions, eliminates the need for organic solvents and solubilizers, improves drug storage stability, and has low raw material costs and good compatibility with existing production equipment, making it suitable for large-scale industrial production.

[0007] To achieve the above objectives, the present invention provides the following solution: On one hand, the present invention provides a novel method for preparing an irbesartan composition, comprising the following steps: S1. Irbesartan and silica are suspended in an aqueous solution to form a suspension; S2. Add the suspension to the planetary ball mill and perform wet co-milling, then remove the solvent from the milling system to obtain a solid product; S3. The solid product is mechanically pulverized to obtain a co-ground material of irbesartan and silica, which is the irbesartan composition.

[0008] Preferably, in S1, the mass ratio of irbesartan to silica is 50:1 to 100:1, the particle size of irbesartan is not greater than 50 μm, and the silica is pharmaceutical-grade micron-sized amorphous silica.

[0009] Preferably, the mass ratio of irbesartan to silica is 55:1 to 80:1, the particle size of irbesartan is no greater than 30 μm, and the surface area of ​​the pharmaceutical-grade micron-sized amorphous silica is no less than 500 m². 2 / g.

[0010] Preferably, in S2, the planetary ball mill has a revolution speed of not less than 250 rpm and a rotation speed of not less than 450 rpm, the number of ball mill jars is not less than 4, and the ratio of the revolution speed to the rotation speed of the planetary ball mill is 1:1.2 to 1:2.

[0011] Preferably, in S2, the solvent removal process from the grinding system includes one or more of rotary evaporation, hot air circulation drying, and vacuum drying.

[0012] Preferably, in S3, the mechanical crushing adopts a hammer mill or a cone mill, and the particle size of the crushed solid product is controlled by a sieve with an aperture of 1.0~1.2mm.

[0013] Secondly, the present invention also provides an irbesartan composition prepared by the above-mentioned method for preparing the novel irbesartan composition, wherein the irbesartan composition comprises a co-ground material of irbesartan and silica.

[0014] In addition, the present invention also provides an oral solid dosage form prepared using the above-mentioned irbesartan composition, comprising: adding excipients to the co-ground material of irbesartan and silica, mixing evenly to prepare an oral solid dosage form; wherein the excipients are selected from one or more of fillers, disintegrants, binders, and lubricants, and the preparation process of the oral solid dosage form is a direct mixing process or a dry granulation process.

[0015] Preferably, the oral solid dosage form is a tablet or capsule, and the irbesartan composition has a dissolution rate of not less than 85% in a pH 6.8 buffer solution for 30 minutes.

[0016] Preferably, the filler is selected from one or more of lactose, microcrystalline cellulose, mannitol, corn starch, pregelatinized starch, dextrin, calcium sulfate, calcium hydrogen phosphate dihydrate, and calcium carbonate; the disintegrant is selected from one or more of croscarmellose sodium, carboxymethyl starch sodium, croscarmellose, low-substituted hydroxypropyl cellulose, and starch; the binder is selected from one or more of povidone K30, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, and methylcellulose; and the lubricant is selected from one or more of magnesium stearate, magnesium dodecyl sulfate, polyethylene glycol, stearic acid, and sodium lauryl sulfate.

[0017] According to specific embodiments provided by the present invention, the present invention discloses the following technical effects: (1) This invention can significantly improve the clinical efficacy and stability of irbesartan. The silanol groups on the surface of amorphous silica can form a hydrogen bond network with water molecules, actively guiding water to penetrate into the particle interior. At the same time, the high porosity of amorphous silica can uniformly disperse irbesartan on the carrier surface or in the pores at the nanoscale, greatly increasing the specific surface area and wettability of the drug. The wet grinding of the planetary ball mill destroys the drug crystallization zone through the mechanochemical effect, forming an amorphous or metastable crystal form, further accelerating the dissolution kinetics process, which significantly improves the dissolution rate and oral bioavailability of irbesartan in simulated intestinal fluid (pH 6.8 buffer solution). In addition, the shell-core structure formed by amorphous silica encapsulating drug microcrystals can effectively block oxygen and inhibit drug recrystallization. After being stored for 6 months under accelerated conditions of 40℃ / 75% RH, the drug content did not change significantly and the dissolution behavior was stable, effectively ensuring the medication effect for patients with low gastric acid (such as long-term PPIs or elderly patients with atrophic gastritis).

[0018] (2) The present invention uses an aqueous solution as the dispersion medium and does not require the use of any organic solvents throughout the process, thus avoiding the potential health risks of solvent residues to patients from the source. At the same time, by taking advantage of the hydrophilic carrier effect of amorphous silica and the control of irbesartan particle size by wet milling, efficient drug dissolution can be achieved without the need to add additional solubilizers. This is because the porous structure of amorphous silica and the nanoscale dispersion of the drug together break through the inherent solubility limitation of irbesartan, replacing the solubilizing function of traditional solubilizers, which not only reduces adverse drug reactions, but also conforms to the trend of green pharmaceutical manufacturing, and significantly improves the safety and environmental protection of the production process.

[0019] (3) The present invention has significant cost advantages and good industrial adaptability. In terms of raw material cost, the pharmaceutical-grade micron-sized amorphous silica used in the present invention has a cost reduction of about 60% compared with high-end carriers such as liposomes or polymer nanoparticles. Because pharmaceutical-grade micron-sized amorphous silica does not require complex chemical modification or structural design, it can achieve the carrier function through physical adsorption and dispersion, which greatly controls the raw material cost.

[0020] (4) In terms of industrial production adaptability, the planetary ball mill, rotary evaporation / hot air circulation drying / vacuum drying, mechanical pulverization and subsequent direct mixing and dry granulation processes adopted in this invention are all conventional equipment in the pharmaceutical industry. There is no need to introduce special high-end equipment. The process parameters can be adjusted through existing equipment. Generic drug companies can quickly adapt to existing production lines, reduce equipment modification costs, and thus achieve large-scale industrial production. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1 This is a flowchart of a method for preparing a novel irbesartan composition according to the present invention; Figure 2 This is a scanning electron microscope image of the co-ground irbesartan and silica provided in Example 1 of the present invention; Figure 3 This is a comparison curve of in vitro dissolution in pH 6.8 medium between Example 2 and Comparative Example 1 of the present invention; Figure 4 Mean plasma drug concentration-time curves for oral administration of the co-ground compound of Example 1 and other control groups to mice with gastric acid deficiency. Detailed Implementation

[0023] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0024] To make the above-mentioned objects, features and advantages of the present invention more apparent and understandable, the present invention will be further described in detail below with reference to the accompanying drawings and specific embodiments.

[0025] like Figure 1 As shown, the present invention provides a new method for preparing an irbesartan composition, comprising the following steps: S1. Irbesartan and silica are suspended in an aqueous solution to form a suspension.

[0026] In the above, the silanol groups (Si-OH) on the surface of silica can form a hydrogen bond network with water molecules, improving the spreading ability of hydrophobic drugs in aqueous media. Hydrophilic carriers can actively guide water into the particle interior, improving the wettability of irbesartan and thus enhancing oral bioavailability.

[0027] Specifically, the mass ratio of irbesartan to silica is 50:1 to 100:1, preferably 55:1 to 80:1; the particle size of irbesartan is no greater than 50 μm, preferably no greater than 30 μm; the silica is pharmaceutical-grade micron-sized amorphous silica with a surface area of ​​no less than 500 m². 2 / g. Among them, amorphous silica possesses extremely high porosity and surface active sites, enabling irbesartan molecules to be uniformly dispersed at the nanoscale on the carrier surface or within the pores. This physical adsorption significantly increases the effective contact area of ​​the drug, thereby overcoming its inherent solubility limitations.

[0028] S2. Add the suspension to the planetary ball mill for wet co-milling, and then remove the solvent from the milling system to obtain a solid product.

[0029] In the above description, the irbesartan and silica co-grind is prepared by wet grinding in a planetary ball mill. Through mechanochemical effects, the shear force generated during the grinding process further destroys the drug crystallization zone, forming an amorphous or metastable crystal form, and accelerating the dissolution kinetics process.

[0030] Specifically, the planetary ball mill has a revolution speed of not less than 250 rpm and a rotation speed of not less than 450 rpm; further, the revolution speed is 250~400 rpm and the rotation speed is 450~720 rpm; the number of milling jars is not less than 4, and the ratio of the revolution speed to the rotation speed of the planetary ball mill is 1:1.2~1:2, preferably 1:1.5~1:1.8. In addition, the solvent removal process from the grinding system includes one or more of rotary evaporation, hot air circulation drying, and vacuum drying methods.

[0031] S3. The solid product is mechanically pulverized to obtain a co-ground material of irbesartan and silica, which is the irbesartan composition.

[0032] Specifically, mechanical crushing uses a hammer mill or a cone mill, and the particle size of the crushed solid product is controlled by a sieve with an aperture of 1.0~1.2mm.

[0033] In addition, the present invention also provides an oral solid dosage form prepared using the above-mentioned irbesartan composition, comprising: adding excipients to the co-ground material of irbesartan and silica, mixing evenly to prepare an oral solid dosage form; wherein the excipients are selected from one or more of fillers, disintegrants, binders, and lubricants, and the preparation process of the oral solid dosage form is a direct mixing process or a dry granulation process.

[0034] The filler is selected from one or more of lactose, microcrystalline cellulose, mannitol, corn starch, pregelatinized starch, dextrin, calcium sulfate, calcium hydrogen phosphate dihydrate, and calcium carbonate; the disintegrant is selected from one or more of croscarmellose sodium, carboxymethyl starch sodium, croscarmellose, low-substituted hydroxypropyl cellulose, and starch; the binder is selected from one or more of povidone K30, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, and methylcellulose; and the lubricant is selected from one or more of magnesium stearate, magnesium dodecyl sulfate, polyethylene glycol, stearic acid, and sodium lauryl sulfate.

[0035] The oral solid dosage form prepared according to the above content is a tablet or capsule, and the irbesartan composition has a dissolution rate of not less than 85% in a pH 6.8 buffer solution for 30 minutes.

[0036] The above content will be further explained below through specific implementation methods, wherein the described embodiments are only some embodiments of the present invention.

[0037] Example 1 This embodiment provides a process for preparing a co-ground material of irbesartan and silica, wherein the raw materials include, by weight, 60 parts irbesartan, 1 part silica, and 30 parts purified water.

[0038] The specific preparation process includes: irbesartan and silica with a particle size of 17.3 μm are suspended in an aqueous solution. The suspension is then added to a ball mill, which is set to a revolution speed of 300 rpm and a rotation speed of 500 rpm, using four ball mill jars for grinding. The homogenized solution after grinding is dried in a vacuum drying oven at 50-55℃ with a vacuum degree above 8 Pa for 8 hours. The dried solid is then granulated using a hammer mill with a 1.0 mm aperture. The resulting solid product is the irbesartan and silica co-ground material. Figure 2 As shown, in the irbesartan and silica co-grinding material prepared in Example 1, the irbesartan active pharmaceutical ingredient is uniformly embedded in the silica pores.

[0039] Example 2 This embodiment provides the preparation of irbesartan tablets, the raw material composition of which, by weight, includes: 60 parts of irbesartan and silica co-ground material, 11 parts of microcrystalline cellulose, 19 parts of lactose, 5 parts of croscarmellose sodium, 3 parts of hydroxypropyl methylcellulose, and 1 part of magnesium stearate. The specific preparation process is as follows: the irbesartan and silica co-ground material prepared in Example 1 is added to the other excipients except magnesium stearate and mixed evenly, then magnesium stearate is added and mixed evenly, and finally compressed into tablets to obtain irbesartan tablets.

[0040] The performance was then determined according to the given experimental methods and materials, as follows: I. Dissolution determination method in simulated intestinal fluid (pH 6.8 phosphate buffer) Take the test sample and perform the dissolution test according to the method (Chinese Pharmacopoeia 2025 Edition, Part IV, Method 0931, Method 2), using 900 ml of pH 6.8 phosphate buffer as solvent, rotating at 50 rpm. After 5, 10, 15, 20, 30, 45, and 60 minutes, collect samples and filter them through a filter membrane. Determine the dissolution rate according to the high-performance liquid chromatography (High-Performance Liquid Chromatography, Chinese Pharmacopoeia 2025 Edition, Part IV, Method 0512). Inject 50 μL each of the reference solution and the test solution into the liquid chromatograph, and calculate the dissolution amount per tablet based on peak area using the external standard method.

[0041] II. Methods for determining content and dissolution during stability testing The samples were stored at 40℃ / 75%RH for 6 months under accelerated stability conditions. The irbesartan content was determined by high performance liquid chromatography, and the dissolution rate in simulated intestinal fluid (pH 6.8 phosphate buffer) was measured for 30 minutes.

[0042] The dissolution curves at 0 days and the content and dissolution rate during the accelerated stability process were determined according to Experiments I and II above.

[0043] Comparative Example 1 This comparative example provides the preparation of irbesartan tablets. Compared with Example 2, the raw material composition of this comparative example includes, by weight, 60 parts of irbesartan, 1 part of silica, 11 parts of microcrystalline cellulose, 19 parts of lactose, 5 parts of croscarmellose sodium, 3 parts of hydroxypropyl methylcellulose, and 1 part of magnesium stearate.

[0044] The specific preparation process is as follows: Irbesartan and silica are mixed evenly and then dry granulated. After granulation through a 1.0mm aperture granulator, other excipients except magnesium stearate are added and mixed evenly. Then magnesium stearate is added, mixed evenly, and tableted to obtain the final product.

[0045] The dissolution curves at day 0 and the content and dissolution rate during the accelerated stability process were determined according to Experiments I and II provided in Example 2. The results measured in Comparative Example 1 and Example 2 are summarized as shown in Tables 1 and 2.

[0046] Table 1. Dissolution rates of Example 2 and Comparative Example 1 in pH 6.8 phosphate buffer.

[0047] Table 2. Accelerated stability results of Example 2 and Comparative Example 1

[0048] In addition, a comparison graph of the in vitro dissolution of Example 2 and Comparative Example 1 in pH 6.8 medium is shown below. Figure 3 In Example 2, the saturation rate reached over 85% within 30 minutes, which was significantly higher than that of Comparative Example 1.

[0049] Example 3 This embodiment provides a process for preparing a co-ground material of irbesartan and silica, wherein the raw materials include, by weight, 80 parts irbesartan, 1 part silica, and 40 parts purified water.

[0050] The specific preparation process includes: irbesartan and silica with a particle size of 10.5 μm are suspended in an aqueous solution. The suspension is then added to a ball mill, which is set to a revolution speed of 250 rpm and a rotation speed of 500 rpm, using five ball mill jars for grinding. The homogenized solution after grinding is dried in a 60℃ hot air circulating drying oven for 12 hours. The dried solid is then granulated using a hammer mill with a 1.0 mm aperture. The resulting solid product is the irbesartan and silica co-ground material.

[0051] Example 4 This embodiment provides the preparation of irbesartan tablets, the raw material composition of which includes, by weight: 81 parts of irbesartan and silica co-ground material, 13 parts of mannitol, 2 parts of sodium carboxymethyl starch Type A, 3 parts of povidone K30, and 1 part of magnesium stearate.

[0052] The specific preparation process is as follows: Irbesartan prepared in Example 3 and silica co-ground material are added to other excipients except magnesium stearate and mixed evenly. Then magnesium stearate is added and mixed evenly, and tablets are compressed to obtain irbesartan tablets. The dissolution curve at 0 days and the content and dissolution rate during the accelerated stability process are determined according to Experiment I and Experiment II provided in Example 2.

[0053] Example 5 This embodiment provides the preparation of irbesartan capsules, the raw material composition of which, by weight, includes: 61 parts of irbesartan and silica co-ground material, 23 parts of lactose, 9 parts of corn starch, 4 parts of crospovidone, 2 parts of ethyl cellulose, and 1 part of magnesium stearate.

[0054] The preparation process is as follows: Irbesartan and silica co-ground material prepared in Example 1 are mixed evenly with other excipients except magnesium stearate, magnesium stearate is then added and mixed evenly, and the mixture is filled into capsules.

[0055] Example 6 This embodiment provides a process for preparing a co-ground material of irbesartan and silica, wherein the raw materials include, by weight, 70 parts irbesartan, 1 part silica, and 30 parts purified water.

[0056] The specific preparation process includes: irbesartan and silica with a particle size of 27.8 μm are suspended in an aqueous solution. The suspension is then added to a ball mill, which is set to a revolution speed of 300 rpm and a rotation speed of 500 rpm, using five ball mill jars for grinding. The homogenized solution after grinding is dried in a 60℃ hot air circulating drying oven for 12 hours. The dried solid is then granulated using a hammer mill with a 1.2 mm aperture. The resulting solid product is the irbesartan and silica co-ground material.

[0057] The following is a pharmacokinetic study in mice based on the above-described implementation method. Specifically, C57BL / 6 male mice (n=40) were first randomly divided into 4 groups (n=10 per group). These included: Group A: Normal control group (saline gavage); Group B: Irbesartan-only administration group; Group C: Irbesartan + silica physical mixture administration group; Group D: Irbesartan-silica co-ground compound administration group (Example 3).

[0058] Except for group A, mice in the other groups were pre-administered with intraperitoneal injection of omeprazole (20 mg / kg / d) for 3 consecutive days to establish a mouse model of gastric acid deficiency. Irbesartan suspension (equivalent to 0.2 ml / 10 g), irbesartan + silica physical mixture suspension, and the ground powder suspension from Example 1 were administered orally as single doses. Orbital venous blood samples were collected at 0.5, 1, 2, 4, and 6 hours after administration, and plasma irbesartan concentrations were determined by LC-MS / MS. Figure 4 As shown in Table 3, the pharmacokinetic parameters were calculated.

[0059] Table 3 Pharmacokinetic Parameter Results

[0060] It can be observed that group D of the present invention exhibits a higher AUC (0-∞), approximately 1.7 times that of the irbesartan B group alone (p<0.05), and a earlier time to peak (T0). max (Shortened by ≥30%), with a significant increase in relative bioavailability.

[0061] Therefore, by adopting the above-mentioned new method for preparing irbesartan composition, the present invention can significantly improve the dissolution rate and oral bioavailability of irbesartan under low acid conditions, eliminate the need for organic solvents and solubilizers, improve drug storage stability, and has low raw material costs and good compatibility with existing production equipment, making it suitable for large-scale industrial production.

[0062] The various embodiments in this specification are described in a progressive manner, with each embodiment focusing on the differences from other embodiments. The same or similar parts between the various embodiments can be referred to each other.

[0063] This document uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of the above embodiments are only for the purpose of helping to understand the method and core ideas of the present invention. Furthermore, those skilled in the art will recognize that, based on the ideas of the present invention, there will be changes in the specific implementation methods and application scope. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A method for preparing a novel irbesartan composition, characterized in that, Includes the following steps: S1. Irbesartan and silica are suspended in an aqueous solution to form a suspension; S2. Add the suspension to the planetary ball mill and perform wet co-milling, then remove the solvent from the milling system to obtain a solid product; S3. The solid product is mechanically pulverized to obtain a co-ground material of irbesartan and silica, which is the irbesartan composition.

2. The method for preparing a novel irbesartan composition according to claim 1, characterized in that, In S1, the mass ratio of irbesartan to silica is 50:1 to 100:1, the particle size of irbesartan is no greater than 50 μm, and the silica is pharmaceutical-grade micron-sized amorphous silica.

3. The method for preparing a novel irbesartan composition according to claim 2, characterized in that, The mass ratio of irbesartan to silica is 55:1 to 80:1, the particle size of irbesartan is no greater than 30 μm, and the surface area of ​​the pharmaceutical-grade micron-sized amorphous silica is no less than 500 m². 2 / g.

4. The method for preparing a novel irbesartan composition according to claim 1, characterized in that, In S2, the planetary ball mill has a revolution speed of not less than 250 rpm and a rotation speed of not less than 450 rpm, the number of ball mill jars is not less than 4, and the speed ratio of the revolution speed to the rotation speed of the planetary ball mill is 1:1.2 to 1:

2.

5. A method for preparing a novel irbesartan composition according to claim 1, characterized in that, In S2, the solvent removal process from the grinding system includes one or more of rotary evaporation, hot air circulation drying, and vacuum drying.

6. A method for preparing a novel irbesartan composition according to claim 1, characterized in that, In S3, the mechanical crushing adopts a hammer mill or a cone mill, and the particle size of the crushed solid product is controlled by a sieve with an aperture of 1.0~1.2mm.

7. An irbesartan composition prepared by the method for preparing a novel irbesartan composition according to any one of claims 1 to 6, characterized in that, The irbesartan composition comprises a co-milled mixture of irbesartan and silica.

8. An oral solid dosage form prepared using the irbesartan composition as described in claim 7, characterized in that, include: Add excipients to the co-ground material of irbesartan and silica, mix thoroughly, and prepare an oral solid dosage form; the excipients are selected from one or more of fillers, disintegrants, binders, and lubricants, and the preparation process of the oral solid dosage form is a direct mixing process or a dry granulation process.

9. An oral solid dosage form prepared using an irbesartan composition according to claim 8, characterized in that, The oral solid dosage form is a tablet or capsule, and the irbesartan composition has a dissolution rate of not less than 85% in a pH 6.8 buffer solution for 30 minutes.

10. An oral solid dosage form prepared using an irbesartan composition according to claim 8, characterized in that, The filler is selected from one or more of lactose, microcrystalline cellulose, mannitol, corn starch, pregelatinized starch, dextrin, calcium sulfate, calcium hydrogen phosphate dihydrate, and calcium carbonate; the disintegrant is selected from one or more of croscarmellose sodium, carboxymethyl starch sodium, croscarmellose, low-substituted hydroxypropyl cellulose, and starch; the binder is selected from one or more of povidone K30, hydroxypropyl methylcellulose, hydroxypropyl cellulose, ethyl cellulose, and methylcellulose; and the lubricant is selected from one or more of magnesium stearate, magnesium dodecyl sulfate, polyethylene glycol, stearic acid, and sodium lauryl sulfate.

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