Melasartan potassium tablet and preparation method thereof

Abstract

The invention discloses a Melsartan potassium tablet and a preparation method thereof, and relates to the technical field of medicine preparation. The Milsartan potassium tablet is prepared from the following raw materials in parts by mass: 80 to 84.3 parts of Milsartan potassium, 5 to 9 parts of a solid dispersing agent, 180 to 231 parts of a filling agent, 0.05 to 1.7 parts of saccharin sodium salt, 0.13 to 1.7 parts of a stabilizing agent, 0.5 to 1.5 parts of a pH value buffering agent and 0.5 to 1.8 parts of a lubricating agent. The invention solves the problems of difficult storage, poor stability, poor solubility and harsh requirements on industrial production conditions of the Milsartan potassium tablet.

Description

Technical Field

[0001] The present invention relates to the technical field of drug preparation, and particularly relates to an azilsartan medoxomil potassium tablet and a preparation method thereof. Background Art

[0002] Azilsartan Medoxomil Potassium (other name: Azilsartan Potassium) is a prodrug of an angiotensin II receptor blocker (ARB) developed by Takeda Company in Japan. After oral administration, it is rapidly hydrolyzed in vivo into the active ingredient azilsartan, which reduces blood pressure by blocking the action of angiotensin II. The original research drug was approved for marketing in China on January 21, 2021, for the treatment of adult primary hypertension. The recommended starting dose is 40 mg once daily. For patients with poorly controlled blood pressure at lower doses, the maximum dose can be increased to 80 mg once daily. If this product alone cannot adequately control blood pressure, it can be used in combination with other antihypertensive drugs to achieve blood pressure reduction, including diuretics (such as chlorthalidone and hydrochlorothiazide) and calcium channel blockers.

[0003] Azilsartan is a prodrug that can be rapidly converted into the active ingredient azilsartan after oral absorption. Azilsartan can block the action of angiotensin II by selectively blocking the binding of angiotensin II to type 1 receptor (angiotensin type 1 receptor, AT1 receptor) in various tissues. Angiotensin II is the main pressor substance in the renin-angiotensin-aldosterone system (RAAS), and has effects such as vasoconstriction, stimulating the synthesis and release of aldosterone, cardiac excitation, and renal reabsorption of sodium. The affinity of azilsartan for the AT1 receptor is 10,000 times that of the AT2 receptor.

[0004] However, there are many problems with existing azilsartan medoxomil potassium tablets in terms of storage, stability, solubility, and industrial production.

[0005] Specifically:

[0006] 1. Difficult storage and poor stability: Azilsartan medoxomil potassium is an ester salt and is prone to hydrolysis under conditions of moisture or high humidity, resulting in drug failure. Therefore, the inner packaging systems of existing azilsartan medoxomil potassium tablets on the market (such as aluminum-plastic blisters or bottles) usually need to add desiccants to maintain the stability of the product. In addition, even with these measures, the long-term storage of azilsartan medoxomil potassium tablets still faces challenges, and its stability is difficult to guarantee.

[0007] 2. Poor solubility: Both meallasartan potassium and azilsartan are poorly soluble drugs with low solubility, which affects drug absorption and bioavailability. To improve solubility, solubilizers usually need to be added to the formulation or processes such as ultrafine comminution and solid dispersion are employed. However, these methods often increase production costs and complexity.

[0008] 3. Harsh requirements for industrial production conditions: The existing preparation processes for meallasartan potassium tablets have relatively harsh production conditions. For example, the preparation processes disclosed in some patent documents require vacuum drying for up to 16 hours to ensure that the moisture content of the product is at an extremely low level. Such production conditions not only increase production costs but also limit the industrial production scale of meallasartan potassium tablets.

[0009] In view of the above problems, it is particularly important to develop a preparation for improving the stability of meallasartan potassium tablets. Such a formulation should be able to solve the problems of difficult storage or harsh industrial production conditions of current meallasartan potassium tablets, as well as the problem of poor solubility. By optimizing the formulation composition and preparation process, the stability and solubility of meallasartan potassium tablets can be improved, thus meeting the requirements of clinical medication and promoting the industrial production of this drug. Summary of the Invention

[0010] The technical problem to be solved by the present invention is that the existing meallasartan potassium tablets have problems in aspects such as storage. The purpose is to provide a meallasartan potassium tablet and its preparation method, which solve the problems of difficult storage, poor stability, poor solubility, and harsh requirements for industrial production conditions of meallasartan potassium tablets.

[0011] The present invention is achieved through the following technical solutions:

[0012] In the first aspect, the present invention provides a meallasartan potassium tablet, comprising raw materials in the following parts by mass:

[0013] 80 - 84.3 parts of meallasartan potassium, 5 - 9 parts of solid dispersant, 180 - 231 parts of filler, 0.05 - 1.7 parts of sodium saccharin, 0.13 - 1.7 parts of stabilizer, 0.5 - 1.5 parts of pH buffer, and 0.5 - 1.8 parts of lubricant.

[0014] As a possible design, the above solid dispersant includes hydroxypropyl methylcellulose acetate succinate.

[0015] As a possible design, the above filler includes the co-processed product of microcrystalline cellulose and colloidal silicon dioxide, mannitol, and lactose.

[0016] As a possible design, the mass ratio of the co-processed product of microcrystalline cellulose and colloidal silicon dioxide, mannitol, and lactose is 1:(3 - 6):(3 - 5).

[0017] As a possible design, the above stabilizer includes polyvinyl caprolactam-polyvinyl acetate copolymer and L-ascorbic acid palmitate.

[0018] As a possible design, the above pH buffer includes sodium bicarbonate;

[0019] The lubricant includes magnesium stearate or sodium stearyl fumarate.

[0020] In a second aspect, the present invention also provides a method for preparing potassium medoxomil tablets, comprising the following steps:

[0021] Mix potassium medoxomil and saccharin sodium, dissolve in an ethanol solution, then perform ultrasonic treatment and drying to obtain a eutectic product;

[0022] Dissolve the stabilizer in water to obtain a stable solution, add the eutectic product, and perform homogenization treatment to obtain a mixed solution;

[0023] Mix the mixed solution and the solid dispersant evenly, then dry and perform hot melt extrusion. After extrusion, the extrudate is cooled and embrittled by liquid nitrogen, pulverized and sieved to form solid dispersion particles;

[0024] Mix the solid dispersion particles, the filler and the pH buffer evenly, perform roller compaction granulation, screen with a sieve, then add the lubricant and mix evenly. After tableting, potassium medoxomil tablets are obtained.

[0025] As a possible design, the above ultrasonic treatment conditions are ultrasonic treatment at 38 - 42 KHz, 280 - 320 W, and 43 - 47 °C for 20 - 40 min;

[0026] The drying conditions are drying at 35 - 45 °C and -0.1 to -0.05 MPa.

[0027] As a possible design, the above homogenization treatment is specifically carried out by a microfluidic high-pressure homogenizer under the condition of a pressure of 245000 - 255000 psi and circulated 8 - 12 times;

[0028] The hot melt extrusion is carried out by a hot melt extruder, with the feeding section temperature of 75 - 85 °C, the mixing section of 105 - 115 °C, the extrusion section of 85 - 90 °C, and the screw speed of 110 - 130 rpm.

[0029] As a possible design, the above roller compaction granulation conditions are a roll gap of 1 - 1.5 mm and a pressure of 3.8 - 4.2 kN / cm;

[0030] The tableting includes pre-pressing and pressing steps, specifically pre-pressing at a pressure of 2.5 - 2.8 kN first, and then tableting at a pressure of 11 - 12.5 kN;

[0031] The weight variation of the tablets is ±0.15% RSD.

[0032] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0033] By forming a co-crystal of meallasartan potassium and saccharin sodium, the present invention improves its solubility and stability; meanwhile, a solid dispersant is blended with meallasartan potassium. Since the solid dispersant is uniformly distributed in the tablets, it can promote the dissolution of the tablets, thereby enhancing the absorption of meallasartan potassium. In addition, it can also improve the stability of the tablets. Combining with the high-pressure homogenization technology, it can improve the dissolution rate of meallasartan potassium; the filler can improve the flow phase of the powder, promote the preparation efficiency of the tablets, reduce moisture absorption during storage, improve stability, and can also promote the rapid disintegration of the tablets when swallowed; the stabilizer can be connected to meallasartan potassium to improve the stability of meallasartan potassium; the pH buffer can create a suitable pH value for the dissolution of the solid dispersant to promote the dissolution of the tablets. Through the comprehensive action, the problems of difficult storage, poor stability and poor solubility of meallasartan potassium tablets are jointly solved.

[0034] By simplifying the process flow and complexity, the present invention reduces the production cost and facilitates the industrial production of meallasartan potassium tablets. Detailed implementation mode

[0035] To make the objectives, technical solutions and advantages of the present invention clearer and more understandable, the present invention will be further described in detail below with reference to the embodiments. The illustrative implementation modes and descriptions of the present invention are only used to explain the present invention and are not intended to limit the present invention. For those conditions not specified in the embodiments, they are carried out according to the conventional conditions or the conditions recommended by the manufacturer. For the reagents or instruments whose manufacturers are not specified, they are all conventional products that can be obtained through commercial purchase.

[0036] A meallasartan potassium tablet, comprising raw materials in the following parts by mass:

[0037] 80 - 84.3 parts of meallasartan potassium, 5 - 9 parts of solid dispersant, 180 - 231 parts of filler, 0.05 - 1.7 parts of saccharin sodium, 0.13 - 1.7 parts of stabilizer, 0.5 - 1.5 parts of pH buffer and 0.5 - 1.8 parts of lubricant.

[0038] The above saccharin sodium forms a co-crystal with azilsartan medoxomil to reconstruct the API crystal field, improving solubility and chemical stability. Specifically, it can reduce the logP value and increase the solubility of azilsartan medoxomil in water. In the co-crystal, a complex hydrogen bond network can be formed between azilsartan medoxomil and saccharin sodium, which not only stabilizes the co-crystal structure but also inhibits hydrolysis degradation by stabilizing the conformation of the drug molecule and reducing its interaction with water molecules. This helps to extend the shelf life of the drug and ensure its stability during storage and use.

[0039] Preferably, the dosage of the above azilsartan medoxomil is 80 - 84.3 mg / tablet.

[0040] In some embodiments of the present invention, the above solid dispersant includes hypromellose acetate succinate (HPMCAS-LF). Hypromellose acetate succinate is easily soluble at a pH value of about 5.5 to 7.5, and the pH value of the human intestine is between 6.0 and 7.5. Wrapping azilsartan medoxomil with it can promote the dissolution effect of the tablet and enable the drug to be released in a nano-suspension state. At the same time, HPMCAS-LF has a good ultraviolet light barrier effect (UV-cutoff 300 nm), which can improve the storage stability of the tablet.

[0041] In some embodiments of the present invention, the above filler includes co-processed microcrystalline cellulose and colloidal silicon dioxide (abbreviated as SMCC), mannitol, and lactose. Co-processed microcrystalline cellulose and colloidal silicon dioxide is prepared by co-blending microcrystalline cellulose (MCC) and colloidal silicon dioxide (CSD) in a specific ratio (98:2) through a spray drying process. It can improve the powder flowability and has good compressibility. The colloidal silicon dioxide on the surface can build a nano-scale hydrophobic barrier (the contact angle is increased to 110°) to prevent microcrystalline cellulose from absorbing moisture, thereby maintaining the stability of the tablet. It has a large specific surface area and can carry more drugs. At the same time, the combined use of co-processed microcrystalline cellulose and colloidal silicon dioxide, mannitol, and lactose can optimize solubility, promote the rapid disintegration of the tablet, thereby improving the dissolution rate of the drug and enhancing the bioavailability.

[0042] In some embodiments of the present invention, the mass ratio of the above co-processed microcrystalline cellulose and colloidal silicon dioxide, mannitol, and lactose is 1:(3 - 6):(3 - 5). Preferably, the mass ratio of co-processed microcrystalline cellulose and colloidal silicon dioxide, mannitol, and lactose is 1:(4 - 5.2):(3 - 3.9).

[0043] In some embodiments of the present invention, the above stabilizer includes polyvinylcaprolactam-polyvinyl acetate copolymer (Soluplus) and L-ascorbyl palmitate. Soluplus fixes the mearspirin molecules through hydrogen bonds, effectively inhibits hydrolysis, and improves the stability of the tablets. L-ascorbyl palmitate has high oxygen scavenging ability, which can improve the stability of the tablets and extend the shelf life. In addition, the two can play a synergistic role in stabilizing the drug. On the one hand, Soluplus fixes the mearspirin molecules and effectively inhibits hydrolysis; on the other hand, L-ascorbyl palmitate scavenges free radicals and oxygen. Overall, it can achieve a good effect of stabilizing the drug.

[0044] Preferably, the mass ratio of the above polyvinylcaprolactam-polyvinyl acetate copolymer to L-ascorbyl palmitate is 10:(0.5 - 0.8).

[0045] In some embodiments of the present invention, the above pH buffer includes sodium bicarbonate. By adjusting the overall pH value between 5.8 and 6.2, the pH buffer can create an environment with this pH value after being dissolved in water after the tablets are taken, promoting the dissolution of the solid dispersant, and then enabling the drug to be released in a nano-suspension state for easy absorption. This makes it unnecessary for the whole tablets to be absorbed in a specific in-vivo environment, increasing the absorption effect of the tablets. Before the pH buffer is dissolved, it exists in a solid form and does not promote the dissolution of HPMCAS-LF.

[0046] In some embodiments of the present invention, the above lubricant includes magnesium stearate or sodium stearoyl fumarate.

[0047] The present invention also provides a method for preparing mearspirin potassium tablets, which includes the following steps:

[0048] S1. Mix mearspirin potassium and saccharin sodium, dissolve them in an ethanol solution, then perform ultrasonic treatment, and dry to obtain a co-crystal product.

[0049] Preferably, the volume concentration of the above ethanol solution is 70%.

[0050] In some embodiments of the present invention, the above ultrasonic treatment conditions are ultrasonic treatment for 20 - 40 min at 38 - 42 KHz, 280 - 320 W, and 43 - 47 °C.

[0051] In some embodiments of the present invention, the above drying conditions are drying at 35 - 45 °C and -0.1 to -0.05 MPa.

[0052] S2. Dissolve the stabilizer in water to obtain a stable solution, add the co-crystal product, and perform homogenization treatment to obtain a mixed solution.

[0053] Through homogenization treatment with a microfluidic high-pressure homogenizer, the particle size of API is reduced by shear force and cavitation effect, improving its dissolution rate.

[0054] The particle size of the active pharmaceutical ingredient (API) in the above-mentioned mixed solution is ≤200 nm. Within this range, the specific surface area is larger and the dissolution rate is faster, thereby improving the solubility and bioavailability of the drug.

[0055] The concentration of the above-mentioned mixed solution is 0.05 - 0.15%.

[0056] The above homogenization treatment is specifically carried out by a microfluidic high-pressure homogenizer under the condition of a pressure of 245000 - 255000 psi for 8 - 12 cycles.

[0057] S3. Mix the mixed solution and the solid dispersant evenly, then dry and carry out hot melt extrusion. After extrusion, the extrudate is cooled and embrittled by liquid nitrogen, pulverized and sieved to form solid dispersion particles.

[0058] During the hot melt extrusion process, API is dispersed in the polymer matrix in an amorphous state, further reducing the dissolution energy barrier.

[0059] The above drying is spray drying or vacuum drying.

[0060] The above hot melt extrusion is carried out by a hot melt extruder. The temperature of the feeding section is 75 - 85 °C, the mixing section is 105 - 115 °C, the extrusion section is 85 - 90 °C, and the screw speed is 110 - 130 rpm.

[0061] By controlling the extrusion temperature within this range, degradation can be avoided. Specifically, the low temperature of the feeding section can prevent the raw materials from softening prematurely, the high temperature in the mixing section is conducive to their uniform mixing, and finally cooling and extrusion are carried out to avoid its degradation.

[0062] The size of the above sieving is 30 mesh.

[0063] S4. Mix the solid dispersion particles, filler and pH buffer evenly, carry out roller compaction granulation, screen with a sieve, then add a lubricant and mix evenly. After tabletting, potassium medoxomil tablets are obtained.

[0064] In some embodiments of the present invention, the above roller compaction granulation conditions are a roll gap of 1 - 1.5 mm and a pressure of 3.8 - 4.2 kN / cm.

[0065] Preferably, the pore size of the above sieve is 20 mesh.

[0066] In some embodiments of the present invention, the above tabletting includes pre-pressing and pressing steps. Specifically, it is first pre-pressed under a pressure of 2.5 - 2.8 kN, and then tabletted under a pressure of 11 - 12.5 kN.

[0067] In some embodiments of the present invention, the weight deviation of the above tablets is ±0.15% RSD.

[0068] Example 1

[0069] A method for preparing potassium medoxomil tablets, comprising the following steps:

[0070]

[0071] Mix potassium medoxomil and saccharin sodium, dissolve in 70% ethanol solution, then ultrasonically treat for 20 min at 38 KHz, 280 W, and 43 °C, and then dry at 35 °C and -0.05 MPa to obtain a eutectic product;

[0072] Dissolve the stabilizer in water to obtain a stabilizing solution with a concentration of 0.1%, add the eutectic product, and homogenize at a pressure of 245000 psi for 8 cycles to obtain a mixed solution;

[0073] Mix the mixed solution and the solid dispersant evenly, then dry and perform hot melt extrusion. After extrusion, the extrudate is cooled and embrittled with liquid nitrogen, pulverized, and sieved through a 30-mesh sieve to form solid dispersion particles. Among them, the temperature of the feeding section of the hot melt extruder is 75 - 85 °C, the mixing section is 105 °C, the extrusion section is 85 °C, and the screw speed is 110 rpm;

[0074] Mix the solid dispersion particles, filler, and pH buffer evenly, granulate by roller pressing at a roll gap of 1 mm and a pressure of 3.8 kN / cm, screen with a sieve, then add a lubricant and mix evenly. First pre-press at a pressure of 2.5 kN, and then press into tablets at a pressure of 11 kN. After pressing, potassium medoxomil tablets are obtained.

[0075] Example 2

[0076] A method for preparing potassium medoxomil tablets, comprising the following steps:

[0077]

[0078]

[0079] Mix potassium medoxomil and saccharin sodium, dissolve in 70% ethanol solution, then ultrasonically treat for 30 min at 40 KHz, 300 W, and 43 - 47 °C, and then dry at 40 °C and -0.08 MPa to obtain a eutectic product;

[0080] Dissolve the stabilizer in water to obtain a stabilizing solution with a concentration of 0.1%, add the eutectic product, and homogenize at a pressure of 250000 psi for 10 cycles to obtain a mixed solution;

[0081] The mixture is uniformly mixed with a solid dispersant, dried and then subjected to hot melt extrusion. After extrusion, the extrudate is cooled and embrittled by liquid nitrogen, pulverized and sieved through a 30-mesh sieve to form solid dispersion particles. Among them, the temperature of the feeding section of the hot melt extruder is 80 °C, the mixing section is 110 °C, the extrusion section is 88 °C, and the screw speed is 120 rpm;

[0082] The solid dispersion particles are uniformly mixed with a filler and a pH buffer, granulated by roll pressing under a roll gap of 1.2 mm and a pressure of 4 N / cm, screened with a 20-mesh sieve, and then uniformly mixed with a lubricant. First, pre-pressed under a pressure of 2.6 kN, and then tabletted under a pressure of 12 kN. After tabletting, potassium medoxomil tablets are obtained.

[0083] Example 3

[0084] A preparation method of potassium medoxomil tablets, comprising the following steps:

[0085]

[0086] Potassium medoxomil and saccharin sodium are mixed, dissolved in a 70% ethanol solution, ultrasonically treated for 40 min under the conditions of 42 KHz, 320 W, and 47 °C, and then dried under the conditions of 45 °C and -0.1 MPa to obtain a eutectic product;

[0087] The stabilizer is dissolved in water to obtain a stabilizing solution with a concentration of 0.1%, added to the eutectic product, and homogenized under a pressure of 255000 psi for 12 cycles to obtain a mixture;

[0088] The mixture is uniformly mixed with a solid dispersant, dried and then subjected to hot melt extrusion. After extrusion, the extrudate is cooled and embrittled by liquid nitrogen, pulverized and sieved through a 30-mesh sieve to form solid dispersion particles. Among them, the temperature of the feeding section of the hot melt extruder is 85 °C, the mixing section is 115 °C, the extrusion section is 90 °C, and the screw speed is 130 rpm;

[0089] The solid dispersion particles are uniformly mixed with a filler and a pH buffer, granulated by roll pressing under a roll gap of 1.5 mm and a pressure of 4.2 kN / cm, screened with a 20-mesh sieve, and then uniformly mixed with a lubricant. First, pre-pressed under a pressure of 2.8 kN, and then tabletted under a pressure of 12.5 kN. After tabletting, potassium medoxomil tablets are obtained.

[0090] Comparative Example 1

[0091] This comparative example is basically the same as Example 2, the difference is that: the raw material does not contain saccharin sodium.

[0092] Comparative Example 2

[0093] This comparative example is basically the same as Example 2, the difference is that: in the filler, there is no SMCC, and mannitol is 103.2 mg / tablet.

[0094] Comparative Example 3

[0095] This comparative example is basically the same as Example 2, except that: the raw material has no solid dispersant (HPMCAS-LF).

[0096] Comparative Example 4

[0097] This comparative example is basically the same as Example 2, except that: the raw material has no solid dispersant (HPMCAS-LF) and pH buffer (sodium bicarbonate).

[0098] Comparative Example 5

[0099] This comparative example is basically the same as Example 2, except that: no homogenization treatment is carried out. After the eutectic product is added with the stabilizing solution, it is stirred evenly, and after drying, hot melt extrusion is carried out.

[0100] Comparative Example 6

[0101] This comparative example is basically the same as Example 2, except that: no hot melt extrusion is carried out. After the mixed solution is mixed evenly with the solid dispersant and then dried, it is mixed evenly with the filler and pH buffer, and roller compaction granulation is carried out under the same conditions.

[0102] Experimental Example

[0103] (1). The tablets of Examples 1-3 and Comparative Examples 1-6 were subjected to an accelerated stability test of potassium medoxomil tablets at 60 °C for 10 days using the HPLC method, and the results are shown in Table 1.

[0104] Table 1

[0105]

[0106]

[0107] (2). The dissolution curves of the samples of Example 2 and Comparative Examples 1-6 were investigated in pH 7.8 phosphate buffer solution (37 °C, rotation speed 50 rpm, medium 900 ml). According to the ultraviolet-visible spectrophotometry (General Principles 0401, Volume IV, Chinese Pharmacopoeia 2020 Edition), the absorbance was measured at a wavelength of 290 nm, and the dissolution amount of each tablet was calculated.

[0108] Table 2

[0109]

[0110]

[0111] Observing Tables 1-2, it can be seen that the tablets of Example 2 have the smallest change in related substances and the best stability in the accelerated test; and the tablets of Example 2 have the largest dissolution amount and high dissolution efficiency.

[0112] The specific embodiments described above further elaborate on the purpose, technical solutions, and beneficial effects of the present invention. It should be understood that the above description is only for the specific embodiments of the present invention and is not used to limit the protection scope of the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A mesartan potassium tablet, characterized in that: The invention comprises the following raw materials in parts by weight: 80-84.3 parts of asartan potassium, 5-9 parts of solid dispersant, 180-231 parts of filler, 0.05-1.7 parts of saccharin sodium, 0.13-1.7 parts of stabilizer, 0.5-1.5 parts of pH buffer and 0.5-1.8 parts of lubricant.

2. A mesartan potassium tablet according to claim 1, characterized in that: The solid dispersant includes hydroxypropyl methylcellulose acetate succinate.

3. A mesartan potassium tablet according to claim 1, characterized in that: The fillers include microcrystalline cellulose co-processed with colloidal silicon dioxide, mannitol and lactose.

4. A mesartan potassium tablet according to claim 3, characterized in that: The mass ratio of the microcrystalline cellulose and colloidal silicon dioxide co-processed product, mannitol and lactose is 1:(3-6):(3-5).

5. The asartan potassium tablet according to claim 1, characterized in that: The stabilizer includes polyethylene caprolactam-polyvinyl acetate copolymer and L-ascorbyl palmitate.

6. The asartan potassium tablet according to claim 1, characterized in that: The pH buffer comprises sodium bicarbonate; The lubricant includes magnesium stearate or sodium stearyl fumarate.

7. The method for preparing a mesartan potassium tablet according to any one of claims 1 to 6, characterized in that: The steps include: Mixing mesartan potassium and saccharin sodium, dissolving in an ethanol solution, ultrasonically treating, and drying to obtain a cocrystal product; Dissolving a stabilizer in water to obtain a stabilized solution, adding the eutectic product, and homogenizing to obtain a mixed solution; The mixed liquid and the solid dispersant are mixed evenly, and then dried and hot-melt extruded. After extrusion, the extrudate is cooled and embrittled by liquid nitrogen, crushed and sieved to form solid dispersion particles; The solid dispersion particles are mixed evenly with the filler and the pH buffer, and the granules are roller-pressed. After screening with a sieve, a lubricant is added and mixed evenly. After tableting, the mesartan potassium tablets are obtained.

8. The method for preparing a mesartan potassium tablet according to claim 7, characterized in that: The ultrasonic treatment conditions are: ultrasonic treatment at 38-42KHz, 280-320W, 43-47°C for 20-40min; The drying conditions are as follows: drying at 35 to 45° C. and -0.1 to -0.05 MPa.

9. The method for preparing a mesartan potassium tablet according to claim 7, characterized in that: The homogenization treatment is specifically carried out by homogenizing with a microfluidizer at a pressure of 245,000 to 255,000 psi, for 8 to 12 cycles; The hot melt extrusion is carried out by a hot melt extruder, with a feeding section temperature of 75-85° C., a mixing section temperature of 105-115° C., an extrusion section temperature of 85-90° C., and a screw speed of 110-130 rpm.

10. The method for preparing a potassium sartan tablet according to claim 7, characterized in that: The roller pressing granulation conditions are as follows: roller gap 1-1.5 mm, pressure 3.8-4.2 kN / cm; The tableting process includes pre-pressing and pressing steps, specifically, pre-pressing at a pressure of 2.5 to 2.8 kN, and then tableting at a pressure of 11 to 12.5 kN; The weight deviation of the tablets was ± 0.15% RSD.

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