Tablet containing telmisartan medicine and preparation method thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, and particularly discloses a tablet containing telmisartan medicine and a preparation method of the tablet. The tablet containing the telmisartan medicine is prepared from the following raw materials in percentage: 11 to 20 percent of telmisartan, 6 to 6.5 percent of basifier, 3 to 7 percent of adhesive, 65 to 76 percent of filler, 0.3 to 1.2 percent of coating agent and 0.4 to 0.6 percent of lubricant, the coating agent is at least one of carnauba wax and beeswax, and the coating process of the tablet containing the telmisartan medicine is a solvent-free dry powder coating process; according to the present invention, the carnauba wax and the beeswax are adopted as the coating materials, and the solvent-free dry powder coating process is combined so as to improve the stability and the moisture-proof and moisture-absorbing effect of the telmisartan tablet, effectively prevent the telmisartan tablet from absorbing moisture, and improve the stability and the dissolution effect of the telmisartan tablet.

Description

Technical Field

[0001] This application relates to the technical field of pharmaceutical preparations, and particularly to a tablet containing telmisartan and its preparation method. Background Art

[0002] Telmisartan is a specific angiotensin II receptor antagonist used to reduce the risk of myocardial infarction, stroke, or death caused by cardiovascular diseases. The existing forms of telmisartan preparations are mainly tablets, capsules, etc. Among them, tablets are more widely used. The stability of telmisartan tablets under packaged conditions in the market is good, but the naked tablets are extremely easy to absorb moisture in a high-humidity environment and are also prone to moisture absorption, softening, deliquescence, etc. during storage and use in a general environment, which brings potential safety hazards to drug use and poor patient compliance.

[0003] In order to improve the moisture-proof performance, moisture-proof materials are currently mostly used for inner packaging during drug packaging, such as double-aluminum packaging, composite film bagging, etc., resulting in high production costs for pharmaceutical companies and high drug use costs for patients. Therefore, conventional coating materials such as hydroxypropyl methylcellulose, polyethylene glycol, titanium dioxide, etc. are usually used for tablet coating, or processes such as wet granule coating followed by tableting are used. However, the phenomenon of moisture absorption and deliquescence of the produced naked telmisartan tablets cannot be isolated under long-term and high-humidity test conditions, which brings potential safety hazards to drug use and poor patient compliance. Summary of the Invention

[0004] In order to improve the moisture-proof, moisture-absorbing and stability of telmisartan preparations, this application provides a tablet containing telmisartan and its preparation method.

[0005] In a first aspect, this application provides a tablet containing telmisartan, adopting the following technical solution: A tablet containing telmisartan comprises the following raw materials in percentage: telmisartan 11 - 20%, alkalizing agent 6 - 6.5%, binder 3 - 7%, filler 65 - 76%, coating agent 0.3 - 1.2%, lubricant 0.4 - 0.6%; the coating agent is at least one of carnauba wax and beeswax, and the coating process of the tablet containing telmisartan is a solvent-free dry powder coating process.

[0006] By adopting the above technical solutions, carnauba wax and beeswax have good hydrophobicity and can form a protective film to effectively prevent the telmisartan tablets from absorbing moisture, improving the stability of the telmisartan tablets and the moisture-proof and moisture-absorbing effect. Carnauba wax and beeswax can delay the release of the drug, thereby achieving the sustained-release effect of the drug, promoting the site-specific release of the drug components in the body, and improving the bioavailability of telmisartan. Using carnauba wax and beeswax as coating agents, a solvent-free dry powder coating process can be adopted, avoiding the use of organic solvents, reducing environmental pollution and production costs, reducing the risk of residual organic solvents in the drug, and at the same time, carnauba wax and beeswax have better biocompatibility, reducing potential toxic and side effects, and improving the safety and dissolution effect of telmisartan tablets.

[0007] Preferably, the coating agent is carnauba wax.

[0008] By adopting the above technical solutions, carnauba wax has better hardness and wear resistance, can effectively protect telmisartan, and reduce the wear and breakage of telmisartan tablets during storage and transportation.

[0009] Preferably, the alkalizing agent is at least one of sodium hydroxide, potassium hydroxide, and meglumine, the binder is at least one of hydroxypropyl cellulose and polyvinylpyrrolidone k30, the filler is at least one of lactose, microcrystalline cellulose, corn starch, pregelatinized starch, sorbitol, and mannitol, and the lubricant is at least one of stearic acid, magnesium stearate, and talc powder.

[0010] By adopting the above technical solutions, sodium hydroxide, potassium hydroxide, and meglumine as alkalizing agents can adjust the pH value of the drug, improve the solubility and dissolution performance of telmisartan, and enhance the bioavailability of telmisartan. Hydroxypropyl cellulose and polyvinylpyrrolidone k30 as binders can increase the adhesion between drug particles, improve the forming effect and stability of telmisartan tablets, improve the hardness and integrity of telmisartan tablets, and reduce the phenomenon of tablet breakage. Stearic acid, magnesium stearate, and talc powder can improve the demoulding property and forming effect of telmisartan tablets, and reduce the friction between telmisartan tablets and the mould.

[0011] Preferably, the filler is lactose and sorbitol, and the mass ratio of lactose to sorbitol is 1:(1 - 1.6).

[0012] By adopting the above technical solutions, lactose and sorbitol have good fluidity and high chemical stability, which helps to maintain the stability and activity of telmisartan drug tablets.

[0013] Preferably, lactose and sorbitol are dried in advance, then mixed with polyvinylpyrrolidone and fatty acids, ball-milled and dried to obtain a composite filler.

[0014] By adopting the above technical solution, polyvinylpyrrolidone and fatty acids can adsorb on the surfaces of fillers lactose and sorbitol, improve the fluidity and compressibility of lactose and sorbitol particles, reduce the hygroscopicity of lactose and sorbitol, and thus improve the moisture-proof performance and stability of telmisartan tablets.

[0015] Preferably, the mass ratio of the total mass of lactose and sorbitol to polyvinylpyrrolidone and fatty acids is 1:(0.5 - 0.8):(0.3 - 0.5).

[0016] By adopting the above technical solution, polyvinylpyrrolidone can enhance the cohesive force between drug particles, improve the forming effect of telmisartan tablets, reduce the degradation of telmisartan drug components at the same time, and maintain the dissolution rate and stability of telmisartan tablets. Fatty acids can reduce the friction between drug particles, improve the fluidity and dissolution performance of drug particles, and improve the bioavailability of telmisartan tablets.

[0017] In a second aspect, the present application provides a method for preparing a tablet containing telmisartan drug, adopting the following technical solution: A method for preparing a tablet containing telmisartan drug, comprising the following specific steps: Pretreatment: Sieve the filler, coating agent, and lubricant respectively to remove coarse powder, and dissolve the alkalizing agent, telmisartan, and binder in an ethanol aqueous solution to form a telmisartan sodium salt solution; Fluidized granulation: Divide the filler into two parts. Under the conditions of an inlet air temperature of 80 - 100 °C, a material temperature of 60 - 80 °C, an air volume of 120 - 180 m 3 / h, and an atomization pressure of 0.1 - 0.3 MPa, spray the telmisartan sodium salt solution on the surface of one part of the filler, with the liquid spraying amount being 25 - 50% of the telmisartan sodium salt solution, and then continue to spray the telmisartan sodium salt solution until it is completely sprayed under the conditions of an inlet air temperature of 80 - 100 °C, a material temperature of 60 - 80 °C, an air volume of 150 - 250 m 3 / h, and an atomization pressure of 0.1 - 0.3 MPa. Finally, under the conditions of an inlet air temperature of 90 - 110 °C, a material temperature of 70 - 90 °C, and an air volume of 150 - 250 m 3 / h, dry for 40 - 80 min to obtain telmisartan particles. When the weight loss of the telmisartan particles is detected to be ≤1%, sieve the dried telmisartan particles; Particle coating: Mix the sieved telmisartan particles with the remaining part of the filler, add the coating agent, and dry by blowing air and heating to make coated telmisartan particles. After sieving, mix the coated telmisartan particles with the lubricant, press into tablets, and package to obtain tablets containing telmisartan drug.

[0018] By adopting the above technical solution, the present application uses a fluidized bed one-step granulation process, taking the filler as the substrate for granulation, and then dry-coating the prepared telmisartan granules with a coating agent, reducing the use of organic solvents in conventional coating materials and reducing the risk of solvent residues in the drug. The solvent-free dry-coating process used in the present application can better isolate the exposure of telmisartan to the external environment, effectively reducing the hygroscopic deliquescence of telmisartan tablets under long-term and high-humidity test conditions, and improving the moisture-proof performance, stability and dissolution effect of telmisartan tablets.

[0019] Preferably, the filler is sieved through a 80-120 mesh sieve, the coating agent is sieved through a 65-100 mesh sieve, and the lubricant is sieved through an 18-24 mesh sieve.

[0020] In summary, the present application has the following beneficial effects: 1. Since the present application uses carnauba wax and beeswax as the coating agent to form a protective film, effectively preventing the telmisartan tablets from absorbing moisture, improving the stability and moisture-proof and moisture-absorbing effects of telmisartan tablets. Instead of using traditional coating materials and organic solvents, a solvent-free dry-coating process is adopted, reducing environmental pollution and production costs, reducing the risk of organic solvent residues in the drug, and improving the stability and dissolution effect of telmisartan tablets.

[0021] 2. In the present application, lactose, microcrystalline cellulose, corn starch, pregelatinized starch, sorbitol, and mannitol are used as fillers. Among them, lactose and sorbitol have good fluidity and high chemical stability, which helps to maintain the stability and activity of telmisartan drug tablets. At the same time, using polyvinylpyrrolidone and fatty acids to mix lactose and sorbitol can reduce the hygroscopicity of lactose and sorbitol, thereby improving the moisture-proof performance and stability of telmisartan drug tablets. Specific Embodiments

[0022] The following further details the present application in conjunction with embodiments.

[0023] All raw materials in the embodiments can be obtained commercially. Embodiments

[0024] Example 1 This example provides a tablet containing telmisartan drug, including the following raw materials: 800 g of telmisartan, 304 g of alkalizing agent, 240 g of binder, 3384 g of filler, 48 g of coating agent, 24 g of lubricant; among them, the coating agent is carnauba wax, the alkalizing agent is 64 g of sodium hydroxide and 240 g of meglumine, the binder is polyvinylpyrrolidone k30, the filler is 1344 g of lactose and 2040 g of sorbitol, and the lubricant is magnesium stearate.

[0025] Preparation method of tablets containing telmisartan drug, comprising the following specific steps: S1 Pretreatment: Pass the filler through a 100-mesh sieve, pass the coating agent through an 80-mesh sieve, and pass the lubricant through a 20-mesh sieve to remove coarse powder.

[0026] S2 Preparation of telmisartan sodium salt solution: Add the alkalizing agent, telmisartan and binder to the ethanol aqueous solution with a mass fraction of 40% while stirring to dissolve, forming a telmisartan sodium salt solution.

[0027] S3 Fluidized granulation: Add lactose in the filler to the fluidized bed granulation and coating machine for preheating. The preheating conditions are an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h. Then, under the conditions of an inlet air temperature of 90 °C, a material temperature of 70 °C, an air volume of 150 m 3 / h, a peristaltic pump speed of 20 rpm, and an atomization pressure of 0.2 MPa, spray the telmisartan sodium salt solution on the surface of the filler lactose. The liquid spraying amount is 38% of the total mass of the telmisartan sodium salt solution. Then, under the conditions of an inlet air temperature of 90 °C, a material temperature of 70 °C, an air volume of 200 m 3 / h, a peristaltic pump speed of 30 rpm, and an atomization pressure of 0.2 MPa, continue to spray the telmisartan sodium salt solution until it is finished. Finally, under the conditions of an inlet air temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, dry for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules is detected to be ≤1%, pass the dried telmisartan granules through a sieve.

[0028] S4 Granule coating: Mix the sieved telmisartan granules with the filler sorbitol at 180 rpm for 5 min, then add the coating agent and mix at 300 rpm for 15 min. Then use air blowing to heat to 80 °C and dry for 30 min to make coated telmisartan granules. After passing through a 40-mesh sieve, mix the coated telmisartan granules with the lubricant at 10 rpm for 5 min, press into tablets, and package them using standard medicinal high-density polyethylene vials to obtain tablets containing telmisartan drug.

[0029] Example 2 The difference between Example 2 and Example 1 is that the usage amount of the coating agent in the raw materials of the tablets containing telmisartan drug is 36 g, and the usage amount of the filler is 3396 g, where the filler is 1344 g of lactose and 2052 g of sorbitol.

[0030] Example 3 The difference between Example 3 and Example 1 is that the usage amount of the coating agent in the raw materials of the tablets containing telmisartan drug is 24 g, and the usage amount of the filler is 3408 g, where the filler is 1344 g of lactose and 2064 g of sorbitol.

[0031] Example 4 The difference between Example 4 and Example 1 is that the tablet containing telmisartan drug comprises raw materials in the following weight ratio: 11 g of telmisartan, 6 g of alkalizing agent, 6.3 g of binder, 76 g of filler, 0.3 g of coating agent, and 0.4 g of lubricant. The filler is lactose and sorbitol, and the mass ratio of lactose to sorbitol is 1:1.

[0032] Example 5 The difference between Example 5 and Example 1 is that the tablet containing telmisartan drug comprises raw materials in the following weight ratio: 20 g of telmisartan, 6.5 g of alkalizing agent, 6.7 g of binder, 65 g of filler, 1.2 g of coating agent, and 0.6 g of lubricant. The filler is lactose and sorbitol, and the mass ratio of lactose to sorbitol is 1:1.5.

[0033] Example 6 The difference between Example 6 and Example 1 is that the coating agent in the raw materials of the tablet containing telmisartan drug is beeswax.

[0034] Example 7 The difference between Example 7 and Example 1 is that the alkalizing agent in the raw materials of the tablet containing telmisartan drug is sodium hydroxide.

[0035] Example 8 The difference between Example 8 and Example 1 is that the binder in the raw materials of the tablet containing telmisartan drug is hydroxypropyl cellulose.

[0036] Example 9 The difference between Example 9 and Example 1 is that the lubricant in the raw materials of the tablet containing telmisartan drug is talc powder.

[0037] Example 10 The difference between Example 10 and Example 1 is that the filler in the raw materials of the tablet containing telmisartan drug is a mixture of microcrystalline cellulose and corn starch. The mass ratio of microcrystalline cellulose to corn starch is 1:1.

[0038] The preparation method of the tablet containing telmisartan drug comprises the following specific steps: S1 Pretreatment: Pass the filler through a 100-mesh sieve, pass the coating agent through an 80-mesh sieve, and pass the lubricant through a 20-mesh sieve to remove coarse powder.

[0039] S2 Preparation of telmisartan sodium salt solution: Add the alkalizing agent, telmisartan, and binder to an ethanol aqueous solution with a mass fraction of 40% while stirring to dissolve, forming a telmisartan sodium salt solution.

[0040] S3 Fluidized Granulation: Divide the filler into two equal parts. Add one part of the filler to the fluidized bed granulator coater for preheating. The preheating conditions are an inlet air temperature of 90°C, a material temperature of 70°C, and an air volume of 150 m 3 / h. Then, under the conditions of an inlet air temperature of 90°C, a material temperature of 70°C, an air volume of 150 m 3 / h, a peristaltic pump speed of 20 rpm, and an atomization pressure of 0.2 MPa, spray the telmisartan sodium salt solution on the surface of the filler. The spraying volume is 38% of the total mass of the telmisartan sodium salt solution. Then, under the conditions of an inlet air temperature of 90°C, a material temperature of 70°C, an air volume of 200 m 3 / h, a peristaltic pump speed of 30 rpm, and an atomization pressure of 0.2 MPa, continue to spray the telmisartan sodium salt solution until it is completely sprayed. Finally, under the conditions of an inlet air temperature of 100°C, a material temperature of 80°C, and an air volume of 200 m 3 / h, dry for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules is detected to be ≤1%, screen the dried telmisartan granules.

[0041] S4 Particle Coating: Mix the sieved telmisartan granules with the remaining part of the filler. Mix at 180 rpm for 5 min, then add the coating agent and mix at 300 rpm for 15 min. Then use air blowing to heat to 80°C and dry for 30 min to make coated telmisartan granules. After screening through a 40-mesh sieve, mix the coated telmisartan granules with the lubricant at 10 rpm for 5 min, press into tablets, and package them in standard medical high-density polyethylene vials to obtain tablets containing telmisartan drugs.

[0042] Example 11 A preparation method of tablets containing telmisartan drugs, comprising the following specific steps: S1 Pretreatment: Screen the filler through a 100-mesh sieve, screen the coating agent through an 80-mesh sieve, and screen the lubricant through a 20-mesh sieve to remove coarse powder.

[0043] S2 Preparation of Telmisartan Sodium Salt Solution: Add the alkalizing agent, telmisartan, and binder to the ethanol aqueous solution with a mass fraction of 40% while stirring to dissolve, forming a telmisartan sodium salt solution.

[0044] S3 Fluidized Granulation: Divide the filler into two equal parts. Add one part of the filler to the fluidized bed granulator coater for preheating. The preheating conditions are an inlet air temperature of 90°C, a material temperature of 70°C, and an air volume of 150 m 3 / h. Then, under the conditions of an inlet air temperature of 90°C, a material temperature of 70°C, an air volume of 150 m 3Under the conditions of an air inlet temperature of 90 °C, a material temperature of 70 °C, and an air volume of 200 m / h, a sodium telmisartan solution was sprayed on the surface of the filler at a peristaltic pump speed of 20 rpm and an atomization pressure of 0.2 MPa. The spraying volume was 38% of the total mass of the sodium telmisartan solution. Then, 3 Under the conditions of an air inlet temperature of 90 °C, a material temperature of 70 °C, and an air volume of 200 m / h, a peristaltic pump speed of 30 rpm, and an atomization pressure of 0.2 MPa, the sodium telmisartan solution was continuously sprayed until completion. Finally, under the conditions of an air inlet temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, it was dried for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules was detected to be ≤1%, the dried telmisartan granules were sieved.

[0045] S4 Granule Coating: The sieved telmisartan granules were mixed with the remaining portion of the filler at 180 rpm for 5 min, then the coating agent was added and mixed at 300 rpm for 15 min. Then, it was dried by blowing air and heating to 80 °C for 30 min to prepare coated telmisartan granules. After passing through a 40-mesh sieve, the coated telmisartan granules were mixed with the lubricant at 10 rpm for 5 min, compressed into tablets, and packaged using standard medicinal high-density polyethylene vials to obtain tablets containing the telmisartan drug.

[0046] Example 12 The difference between Example 12 and Example 11 lies in the preparation method of the tablets containing the telmisartan drug, which includes the following specific steps: S1 Pretreatment: The filler was sieved through a 100-mesh sieve, the coating agent was sieved through an 80-mesh sieve, and the lubricant was sieved through a 20-mesh sieve to remove coarse powder.

[0047] S2 Preparation of Sodium Telmisartan Solution: The alkalizing agent, telmisartan, and binder were added to a 40% ethanol aqueous solution while stirring to dissolve, forming a sodium telmisartan solution.

[0048] S3 Fluidized Granulation: After drying the filler, it was mixed with polyvinylpyrrolidone and fatty acid, ball-milled and then dried. The mass ratio of the total mass of the filler to polyvinylpyrrolidone and fatty acid was 1:0.7:0.4 to obtain a composite filler. The composite filler was evenly divided into two portions. One portion of the composite filler was added to a fluidized bed granulation and coating machine for preheating. The preheating conditions were an air inlet temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h. Then, under the conditions of an air inlet temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h, a peristaltic pump speed of 20 rpm, and an atomization pressure of 0.2 MPa, the sodium telmisartan solution was sprayed on the surface of the composite filler. The spraying volume was 38% of the total mass of the sodium telmisartan solution. Then, under the conditions of an air inlet temperature of 90 °C, a material temperature of 70 °C, and an air volume of 200 m 3Continue to spray the telmisartan sodium salt solution until it is completely sprayed under the conditions of a peristaltic pump speed of 30 rpm and an atomization pressure of 0.2 MPa. Finally, under the conditions of an inlet air temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, dry for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules is detected to be ≤1%, screen the dried telmisartan granules.

[0049] S4 Granule Coating: Mix the sieved telmisartan granules with the remaining portion of the composite filler at 180 rpm for 5 min, then add the coating agent and mix at 300 rpm for 15 min. Then use air blowing to heat to 80 °C and dry for 30 min to make coated telmisartan granules. After screening through a 40-mesh sieve, mix the coated telmisartan granules with the lubricant at 10 rpm for 5 min, press into tablets, and package them in standard medicinal high-density polyethylene vials to obtain tablets containing the telmisartan drug.

[0050] Comparative Example Comparative Example 1 The difference between Comparative Example 1 and Example 1 is that the tablets containing the telmisartan drug include the following raw materials: 800 g of telmisartan, 304 g of alkalizing agent, 240 g of binder, 3240 g of filler, 192 g of coating agent, and 24 g of lubricant; among them, the coating agent is 132 g of hypromellose, 50 g of polyethylene glycol 6000, and 10 g of titanium dioxide, the alkalizing agent is 64 g of sodium hydroxide and 240 g of meglumine, the binder is polyvinylpyrrolidone k30, the filler is 1344 g of lactose and 1896 g of sorbitol, and the lubricant is magnesium stearate.

[0051] Tablets containing the telmisartan drug, preparation method, including the following specific steps: S1 Pretreatment: Screen the filler through a 100-mesh sieve, screen the coating agent through an 80-mesh sieve, and screen the lubricant through a 20-mesh sieve to remove coarse powder.

[0052] S2 Preparation of Telmisartan Sodium Salt Solution: Add the alkalizing agent, telmisartan, and binder to a 40% ethanol aqueous solution while stirring to dissolve, forming a telmisartan sodium salt solution.

[0053] S3 Fluidized Granulation: Add the lactose in the filler to a fluidized bed granulation and coating machine for preheating. The preheating conditions are an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h, and then under the conditions of an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h, a peristaltic pump speed of 20 rpm, and an atomization pressure of 0.2 MPa, spray the telmisartan sodium salt solution on the surface of the filler lactose. The spraying amount is 38% of the total mass of the telmisartan sodium salt solution. Then under the conditions of an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 200 m3 Continue to spray the telmisartan sodium salt solution under the conditions of / h, peristaltic pump speed of 30 rpm, and atomization pressure of 0.2 MPa until it is completely sprayed. Finally, under the conditions of an inlet air temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, dry for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules is detected to be ≤1%, screen the dried telmisartan granules.

[0054] S4: Mix the sieved telmisartan granules with the filler sorbitol at 10 rpm for 10 min, then mix with the lubricant at 10 rpm for 5 min, and press tablets to obtain telmisartan tablets.

[0055] S5 Tablet coating: Dissolve and disperse hypromellose, polyethylene glycol 6000, and titanium dioxide in purified water to prepare a coating solution with a solids content of 15%; place the telmisartan tablets obtained in step S4 in a high-efficiency coating machine for spray coating, with a coating weight gain of approximately 4%, and package them using standard pharmaceutical high-density polyethylene vials to obtain tablets containing the telmisartan drug.

[0056] Comparative Example 2 The difference between Comparative Example 2 and Example 1 is that the tablets containing the telmisartan drug include the following raw materials: 800 g of telmisartan, 304 g of alkalizing agent, 240 g of binder, 3240 g of filler, 192 g of coating agent, and 24 g of lubricant; among them, the coating agent is 132 g of hypromellose, 50 g of polyethylene glycol 6000, and 10 g of titanium dioxide, the alkalizing agent is 64 g of sodium hydroxide and 240 g of meglumine, the binder is polyvinylpyrrolidone k30, the filler is 1344 g of lactose and 1896 g of sorbitol, and the lubricant is magnesium stearate.

[0057] Tablets containing the telmisartan drug, preparation method, including the following specific steps: S1 Pretreatment: Screen the filler through a 100-mesh sieve, screen the coating agent through an 80-mesh sieve, and screen the lubricant through a 20-mesh sieve to remove coarse powder.

[0058] S2 Preparation of telmisartan sodium salt solution: Add the alkalizing agent, telmisartan, and binder to a 40% ethanol aqueous solution while stirring to dissolve, forming a telmisartan sodium salt solution.

[0059] S3 Fluidized granulation: Add lactose in the filler to a fluidized bed granulation and coating machine for preheating. The preheating conditions are an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3 / h, and then at an inlet air temperature of 90 °C, a material temperature of 70 °C, and an air volume of 150 m 3Under the conditions of an air inlet temperature of 90 °C, a material temperature of 70 °C, an air volume of 200 m / h, a peristaltic pump rotation speed of 20 rpm, and an atomization pressure of 0.2 MPa, the telmisartan sodium salt solution was sprayed onto the surface of the filler lactose, and the spraying volume was 38% of the total mass of the telmisartan sodium salt solution. Then, under the conditions of an air inlet temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, a peristaltic pump rotation speed of 30 rpm, and an atomization pressure of 0.2 MPa, the telmisartan sodium salt solution was continuously sprayed until it was completely used up. Finally, under the condition of an air inlet temperature of 100 °C, a material temperature of 80 °C, and an air volume of 200 m 3 / h, it was dried for 60 min to obtain telmisartan granules. When the weight loss of the telmisartan granules was detected to be ≤1%, the dried telmisartan granules were sieved.

[0060] S4 Wet granule coating: Hydroxypropyl methylcellulose, polyethylene glycol 6000, and titanium dioxide were dissolved and dispersed in purified water to prepare a coating solution with a solid content of 15%. The coating solution was added to a fluidized bed granulator and coater, and the coating solution was sprayed onto the surface of the sieved telmisartan granules, and then sieved through a 40-mesh sieve to obtain moisture-proof coated granules.

[0061] S5 Final mixing: The moisture-proof coated granules were mixed with a lubricant at 10 rpm for 5 min, then compressed into tablets, and packaged using standard pharmaceutical high-density polyethylene vials to obtain telmisartan tablets.

[0062] Comparative Example 3 In Comparative Example 3, a reference preparation from Boehringer Ingelheim on the market was used. Performance detection test For the tablets containing telmisartan drugs provided in Examples 1-12 and Comparative Examples 1-3 of the present application, the following performance detections were carried out. The specific detection results are shown in Tables 1, 2, 3, and 4.

[0063] Detection method I. Hygroscopicity The tablets of telmisartan drugs prepared in the examples and comparative examples of the present application were placed continuously for 30 days under the conditions of long-term test (i.e., temperature 25 °C ± 2 °C, relative humidity 60% ± 5%) and stress high humidity test (i.e., temperature 25 °C ± 2 °C, relative humidity 90% ± 5%) respectively, both in the case of naked tablets and with packaging, to investigate the moisture absorption and weight gain of each sample.

[0064] II. Stability The tablets of telmisartan drugs prepared in the examples and comparative examples of the present application were placed continuously for 30 days under the conditions of strong accelerated test (temperature 50 °C ± 2 °C, relative humidity 90% ± 5%) with packaging, to investigate the stability of each sample.

[0065] III. Dissolution effect The dissolution curves of the telmisartan tablets prepared in the examples and comparative examples of this application were measured in the discrimination dissolution conditions, namely, pH 1.0 hydrochloric acid solution and pH 7.5 phosphate buffer medium, respectively.

[0066] Table 1: Data table of hygroscopicity test results It can be seen from the performance test results that under the long-term test conditions for 30 days, the weight gain due to moisture absorption of the telmisartan tablets prepared in the examples of the present invention is all below 5.5%, while the weight gain due to moisture absorption of Comparative Example 1 and Comparative Example 2 is all above 5.5%, and that of the comparative example - reference preparation is above 15%; under the high-humidity test conditions for 30 days, the weight gain due to moisture absorption of the telmisartan tablets prepared in the examples of the present invention, Comparative Example 1 and Comparative Example 2 is all below 40%, while that of the comparative example - reference preparation is above 90%.

[0067] The hygroscopicity test results in Table 1 show that the telmisartan tablets prepared by the film coating material used in this application combined with the non-solvent dry powder film coating process have a significant moisture-proof effect, and the moisture-proof ability is better than that of common film coating materials such as hydroxypropyl methylcellulose, polyethylene glycol 6000, titanium dioxide, and the tablet film coating and wet granule film coating processes. Moreover, it can be seen from Examples 1-3 that the moisture-proof effect of the tablets increases with the increase in the amount of carnauba wax.

[0068] On the other hand, in the case of packaging, under the long-term test conditions for 30 days, the weight gain due to moisture absorption of the examples and Comparative Example 3 - reference preparation in the present invention is all below 3%, while the weight gain due to moisture absorption of Comparative Example 1 and Comparative Example 2 is all below 5%; under the high-humidity test conditions for 30 days, the weight gain due to moisture absorption of the examples and Comparative Examples 1-3 in this application is all below 5%, and the weight gain due to moisture absorption of the examples in this application can be as low as below 3%; further indicating that the telmisartan tablets prepared by the film coating material used in this application combined with the non-solvent dry powder film coating process in HDPE bottles have the same or even better moisture-proof effect compared with the double-aluminum packaging of the comparative example - reference preparation, and the packaging cost of this application is significantly reduced.

[0069] Table 2: Data table of stability test results The stability test results in Table 2 show that in the case of packaging, under the strong accelerated test conditions for 30 days, the content and related substances of the examples and comparative examples in the present invention have no significant changes compared with those at 0 day, and there are no significant differences among the groups, indicating that the stability is good.

[0070] Table 3: Data table of dissolution performance test results with pH 1.0 hydrochloric acid solution (paddle method, 75 rpm) as the dissolution medium Table 4: Data table of dissolution performance test results with pH 7.5 phosphate buffer solution (paddle method, 50 rpm) as the dissolution medium The results show that the dissolution curves of the examples in the present invention in pH 1.0 hydrochloric acid solution and pH 7.5 phosphate buffer solution media are similar to those of Comparative Example 3 - the reference preparation with the similarity factor F2 both greater than 50, and are all similar; while the dissolution curves of Comparative Example 1 and Comparative Example 2 in pH 1.0 hydrochloric acid solution and pH 7.5 phosphate buffer solution media are similar to those of Comparative Example 3 - the reference preparation with the similarity factor F2 both less than 50, and are all dissimilar. It can be seen from this that the telmisartan tablets prepared in this application have good in vitro dissolution performance, are superior to common coating materials and tablet coating and wet granule coating processes, and can provide a guarantee for in vivo bioequivalence.

[0071] This specific embodiment is only an interpretation of this application and is not a limitation of this application. Those skilled in the art can make modifications without creative contributions to this embodiment as needed after reading this specification, but as long as it is within the scope of the claims of this application, it is protected by the patent law.

Claims

1. A tablet containing telmisartan, characterized in that: The raw materials include the following percentages: 11-20% telmisartan, 6-6.5% alkalizer, 3-7% adhesive, 65-76% filler, 0.3-1.2% coating agent, and 0.4-0.6% lubricant; the coating agent is at least one of carnauba wax and beeswax, and the coating process of the tablets containing the telmisartan drug is a solvent-free dry powder coating process.

2. The tablet containing telmisartan according to claim 1, characterized in that: The coating agent is carnauba wax.

3. The tablet containing telmisartan according to claim 1, characterized in that: The alkalizer is at least one of sodium hydroxide, potassium hydroxide, and meglumine; the binder is at least one of hydroxypropyl cellulose and povidone K30; the filler is at least one of lactose, microcrystalline cellulose, corn starch, pregelatinized starch, sorbitol, and mannitol; and the lubricant is at least one of stearic acid, magnesium stearate, and talc.

4. The tablet containing telmisartan according to claim 3, characterized in that: The fillers are lactose and sorbitol, and the mass ratio of the lactose to sorbitol is 1:(1-1.6).

5. The tablet containing telmisartan according to claim 4, characterized in that: Lactose and sorbitol are dried in advance, mixed with polyvinyl pyrrolidone and fatty acid, ball-milled and dried to obtain a composite filler.

6. The tablet containing telmisartan according to claim 5, characterized in that: The mass ratio of the total mass of the lactose and sorbitol to the mass of the polyvinyl pyrrolidone and the fatty acid is 1:(0.5-0.8):(0.3-0.5).

7. A method for preparing a tablet containing telmisartan as claimed in any one of claims 1 to 6, characterized in that: The specific steps include: Pretreatment: sieving the filler, coating agent and lubricant respectively to remove the coarse powder, adding the alkalizer, telmisartan and adhesive into ethanol aqueous solution to dissolve them to form telmisartan sodium salt solution; Fluidized granulation: Divide the filler into two parts, with the air inlet temperature of 80-100℃, material temperature of 60-80℃, air volume of 120-180m 3 / h, atomizing pressure 0.1-0.3 MPa, spray telmisartan sodium salt solution on the surface of a part of the filler, the spraying amount is 25-50% of telmisartan sodium salt solution, and then at an inlet air temperature of 80-100℃, material temperature 60-80℃, air volume 150-250m 3 / h, atomization pressure 0.1-0.3 MPa, continue to spray the telmisartan sodium salt solution, and finally, at the inlet air temperature of 90-110℃, material temperature of 70-90℃, air volume of 150-250m 3 / h, drying for 40-80 min to obtain telmisartan granules, and sieving the dried telmisartan granules when the weight loss of the telmisartan granules is ≤1%; Granule coating: the sieved telmisartan granules are mixed with the remaining filler, and then a coating agent is added, and the mixture is dried by blast heating to prepare coated telmisartan granules. After sieving, the coated telmisartan granules are mixed with a lubricant, and tabletted and packaged to prepare tablets containing the telmisartan drug.

8. The method for preparing a tablet containing telmisartan according to claim 7, characterized in that: The filler is passed through a 80-120 mesh sieve, the coating agent is passed through a 65-100 mesh sieve, and the lubricant is passed through a 18-24 mesh sieve.

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