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CN119818451A - Azilsartan tablet and preparation method thereof - Google Patents

Azilsartan tablet and preparation method thereof Download PDF

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Publication number
CN119818451A
CN119818451A CN202510102115.XA CN202510102115A CN119818451A CN 119818451 A CN119818451 A CN 119818451A CN 202510102115 A CN202510102115 A CN 202510102115A CN 119818451 A CN119818451 A CN 119818451A
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azilsartan
tablets
premix
tablet
particle size
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CN202510102115.XA
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CN119818451B (en
Inventor
梁雷
杨阳
王勇军
张晓明
王彬
庄禾
曹雨
张红娟
张雷
孙苏堂
梅茂峰
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Jiangsu Yabang Aipusen Pharmaceutical Co ltd
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Jiangsu Yabang Aipusen Pharmaceutical Co ltd
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Abstract

The application relates to the technical field of pharmaceutical preparations, and in particular discloses an azilsartan tablet and a preparation method thereof. The azilsartan tablet comprises, by weight, 35-45 parts of azilsartan, 72-76 parts of silicified microcrystalline cellulose, 10-12 parts of low-substituted hydroxypropyl cellulose, 3-7 parts of talcum powder and 0.39-1.04 parts of carnauba wax, wherein the particle size D90 of the azilsartan is 50-80um. According to the application, azilsartan, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose and talcum powder with the particle diameter D90 of 50-80um are pressed into tablets, and then carnauba wax is adopted to form a coating on the surface of the tablets, so that not only are the dissolution rate and dissolution uniformity of the tablets improved, but also the stability of the tablets is greatly improved.

Description

Azilsartan tablet and preparation method thereof
Technical Field
The application relates to the technical field of pharmaceutical preparations, in particular to an azilsartan tablet and a preparation method thereof.
Background
Azilsartan is a non-peptide angiotensin receptor II inhibitor developed by the Japanese Wuta-tsu pharmaceutical company, and can selectively block angiotensin II receptor 1 (AT 1-R), and two forms of metaxartan potassium and azilsartan are currently marketed, wherein the metaxartan potassium is a prodrug of azilsartan and is hydrolyzed into an active metabolite azilsartan in the gastrointestinal tract. Losartan potassium was approved by the FDA for marketing in 2011 and azilsartan was marketed in 2012. Azilsartan is used as a new generation of selective AT1 subtype angiotensin II receptor antagonist, has strong and lasting antihypertensive effect compared with angiotensin converting enzyme inhibitor antihypertensive drugs, and does not cause dry cough. However, the commonly used azilsartan is difficult to have better stability and dissolution uniformity while ensuring higher dissolution rate.
Disclosure of Invention
The application provides an azilsartan tablet and a preparation method thereof in order to improve the dissolution rate of azilsartan and ensure uniform dissolution and good stability.
In a first aspect, the application provides an azilsartan tablet, which adopts the following technical scheme:
The azilsartan tablet comprises, by weight, 35-45 parts of azilsartan, 72-76 parts of silicified microcrystalline cellulose, 10-12 parts of low-substituted hydroxypropyl cellulose, 3-7 parts of talcum powder and 0.39-1.04 parts of carnauba wax, wherein the particle size D90 of the azilsartan is 50-80um.
By adopting the technical scheme, azilsartan, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose and talcum powder with the particle size D90 of 50-80um are pressed into tablets, and then carnauba wax is adopted to form a coating on the surfaces of the tablets, so that the dissolution rate and dissolution uniformity of the tablets are improved, and the stability of the tablets is greatly improved.
In a specific embodiment, the carnauba wax has a particle size D90 of 200 to 230um.
In a specific embodiment, the silicified microcrystalline cellulose has a particle size D90 of 300-330um.
In a specific embodiment, the low substituted hydroxypropylcellulose has a particle size D90 of 200 to 230um.
In a specific embodiment, the talc has a particle size D90 of 10-30um.
By adopting the technical scheme, the particle sizes of the carnauba wax, the silicified microcrystalline cellulose, the low-substituted hydroxypropyl cellulose and the talcum powder are further limited, so that the obtained tablet has good dissolution rate and dissolution uniformity.
In a second aspect, the application provides a preparation method of an azilsartan tablet, which adopts the following technical scheme that the preparation method of the azilsartan tablet comprises the following steps:
The preparation method comprises the steps of tabletting, namely mixing and sieving azilsartan and low-substituted hydroxypropyl cellulose to obtain a premix A, mixing and sieving the premix A and silicified microcrystalline cellulose to obtain a premix B, mixing the premix B and talcum powder, tabletting to obtain azilsartan tablets, and carrying out surface treatment, namely preheating the azilsartan tablets, sieving carnauba wax, slowly and continuously pouring the preheated azilsartan tablets into the azilsartan tablets, mixing and rubbing the azilsartan tablets, and cooling to obtain the azilsartan tablets.
By adopting the technical scheme, the azilsartan, the low-substituted hydroxypropyl cellulose, the silicified microcrystalline cellulose and the talcum powder are mixed and tabletted to obtain the azilsartan medoxomil tablet, and then the azilsartan medoxomil tablet is coated by the carnauba wax to obtain the azilsartan medoxomil tablet with high dissolution rate, uniform dissolution and good stability.
In a specific embodiment, the tabletting step comprises the steps of mixing azilsartan and low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve to obtain a premix A, mixing the premix A and silicified microcrystalline cellulose, sieving with a 40-mesh sieve to obtain a premix B, mixing the premix B and talcum powder, and tabletting to obtain the azilsartan tablet.
In a specific embodiment, the surface treatment step comprises preheating azilsartan medoxomil tablets at 40 ℃, sieving carnauba wax with a 60-mesh sieve, slowly and continuously pouring the preheated azilsartan medoxomil tablets, stopping heating, mixing and rubbing the carnauba wax and the azilsartan medoxomil tablets for 25-35min, and cooling to obtain the azilsartan medoxomil tablets.
By adopting the technical scheme, the preheating temperature and the mixing friction time are further limited, so that the carnauba wax can better coat the azilsartan medoxomil tablet.
In summary, the present application includes at least one of the following beneficial technical effects:
1. According to the application, azilsartan, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose and talcum powder with the particle diameter D90 of 50-80um are pressed into tablets, and then carnauba wax is adopted to form a coating on the surfaces of the tablets, so that not only are the dissolution rate and dissolution uniformity of the tablets improved, but also the stability of the tablets is greatly improved;
2. The particle size of the carnauba wax, the silicified microcrystalline cellulose, the low-substituted hydroxypropyl cellulose and the talcum powder is further limited, so that the obtained tablet has better dissolution rate and dissolution uniformity;
3. according to the method, azilsartan, low-substituted hydroxypropyl cellulose, silicified microcrystalline cellulose and talcum powder are mixed and tabletted to obtain an azilsartan medoxomil tablet, and then the azilsartan medoxomil tablet is coated by carnauba wax to obtain the azilsartan medoxomil tablet with high dissolution rate, good dissolution uniformity and good stability.
Drawings
FIG. 1 is a graph showing the dissolution of the drugs of examples 1-3 and the control in phosphate medium at pH 6.8 according to the present application.
FIG. 2 is a graph showing the dissolution of the drugs of comparative examples 1-2, comparative examples 4-5 and comparative examples in phosphate medium at pH 6.8 according to the present application.
Detailed Description
The present application will be described in further detail with reference to examples.
All the starting materials in the examples are commercially available.
Examples
Example 1
Example 1 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 50um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.65g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 2
Example 2 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.65g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 3
Example 3 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 80um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.65g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 4
Example 4 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.39g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 5
Example 5 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 1.04g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 6
Example 6 provides a process for the preparation of azilsartan tablets comprising the steps of:
the preparation method comprises the steps of uniformly mixing 35g of azilsartan and 10g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A and 72g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B and 3g of talcum powder, and tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.39g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Example 7
Example 7 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 45g of azilsartan with 12g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 76g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 7g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 1.04g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Comparative examples
Comparative example 1
Comparative example 1 provides a process for the preparation of azilsartan tablets comprising the steps of:
tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 45um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.65g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Comparative example 2
Comparative example 2 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 90um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.65g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Comparative example 3
Comparative example 3 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 0.26g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the mixture into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Comparative example 4
Comparative example 4 provides a process for the preparation of azilsartan tablets comprising the steps of:
Tabletting, namely uniformly mixing 40g of azilsartan with 11g of low-substituted hydroxypropyl cellulose, sieving with a 60-mesh sieve through a swinging granulator to obtain a premix A, uniformly mixing the premix A with 74g of silicified microcrystalline cellulose, sieving with a 40-mesh sieve through the swinging granulator to obtain a premix B, uniformly mixing the premix B with 5g of talcum powder, tabletting through a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um;
And (3) surface treatment, namely adding the azilsartan medoxomil tablet into coating equipment, setting the heating temperature to be 45 ℃, setting the air quantity to be 1000m 3/h, setting the rotating speed to be 4rpm, preheating to 40 ℃, then sieving 1.17g of carnauba wax by a 60-mesh sieve, slowly and continuously pouring the 1.17g of carnauba wax into the azilsartan medoxomil tablet, stopping heating, setting the rotating speed to be 6rpm, continuously mixing and rubbing for 30min, and cooling to room temperature to obtain the azilsartan medoxomil tablet.
Comparative example 5
Comparative example 5 provides a process for the preparation of azilsartan tablets comprising the steps of:
The preparation method comprises the steps of uniformly mixing 40g of azilsartan and 11g of low-substituted hydroxypropyl cellulose, sieving the mixture through a 60-mesh sieve by a swinging granulator to obtain a premix A, uniformly mixing the premix A and 74g of silicified microcrystalline cellulose, sieving the mixture through the 40-mesh sieve by the swinging granulator to obtain a premix B, uniformly mixing the premix B and 5g of talcum powder, and tabletting the mixture by a rotary tabletting machine to obtain azilsartan tablets with the tablet weight of about 130mg, wherein the particle size D90 of the azilsartan is 65um, the particle size D90 of the silicified microcrystalline cellulose is 320um, the particle size D90 of the low-substituted hydroxypropyl cellulose is 220um, and the particle size D90 of the talcum powder is 20um.
Comparative example
The reference example is azilsartan crude drug
Performance test dissolution performance of the drugs in each example and comparative example was tested for dissolution in phosphate buffer medium at pH 6.8 by paddle method, medium volume 900mL, water bath temperature 37±0.5 ℃ and stirrer rotation speed 50r/min, and dissolution graphs were obtained as detailed in fig. 1 and 2.
Stability the drugs in each example and comparative example were subjected to an acceleration test under conditions of a temperature of 40.+ -. 2 ℃ and a relative humidity of 75%.+ -. 5% and a high humidity test under conditions of a temperature of 25.+ -. 2 ℃ and a relative humidity of 90%.+ -. 5% for 30 days, respectively, and the samples were examined for changes in the related substances.
TABLE 1 results of drug dissolution test
TABLE 2 stability test results of drugs
In combination with table 1, fig. 1, examples 1-3 and comparative examples, the dissolution curves of the drugs in the phosphate buffer medium with ph of 6.8 in examples 1-3 are similar to those in comparative examples, so that the azilsartan tablets of the invention adopt azilsartan with the particle size D90 of 50-80 um, and are pressed into tablets by silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose and talcum powder, and finally, carnauba wax is adopted to form a coating on the surface of the tablets, thereby improving the dissolution performance of the tablets.
In combination with table 1, fig. 1-2, example 1 and comparative examples 1-2, it can be seen that azilsartan in comparative example 1 is finely pulverized and has a high dissolution rate, but the comparative raw drug is too high, the value of the similarity factor F2 is lower than 50, there is a large risk of bioequivalence in vivo, and the dissolution rate is lower when the particle size of azilsartan in comparative example 2 is too large, so that the particle size of azilsartan is preferably 50-80um.
In combination with Table 1, FIGS. 1-2, example 1 and comparative example 4, it was found that dissolution was hindered when the amount of carnauba wax coating was 0.9%, resulting in slower dissolution, and therefore, dissolution of the tablet was affected when the amount of carnauba wax was too large.
In combination with Table 1, FIG. 1, comparative example 5 and comparative example, it was found that the dissolution uniformity was poor and the RSD was large without the carnauba wax coating. The applicant found that the drug tablet of the coating layer was slid to the central position of the dissolution cup bottom, and the drug without the coating layer was dissolved to generate viscosity, and adhered to other positions of the cup bottom to cause dissolution to be quick and slow, so that uniformity difference was generated.
By combining Table 2, examples 1-3, comparative example 5 and comparative example, it can be seen that the 30-day related substances and the fluctuation range of the medicines in examples 1-3 are all less than 0.5% in 30 days under the accelerated test condition, and the 30-day related substances and the fluctuation range of the medicines in comparative examples 5-6 are all more than 0.5%, the 30-day related substances and the fluctuation range of the medicines in examples 1-3 are all less than 0.5% in 30 days under the high-humidity test condition, and the 30-day related substances and the fluctuation range of the medicines in comparative examples 5-6 are all more than 0.5%, and it can be seen that the azilsartan tablet coated by using the carnauba wax has remarkable barrier protection effect, and the stability of the azilsartan tablet is improved.
In combination with table 2, example 3 and comparative example 4, it can be seen that when azilsartan is coated with carnauba wax, the coating effect is poor if the dosage is too low, thereby affecting the stability of the azilsartan tablets.
The present embodiment is only for explanation of the present application and is not to be construed as limiting the present application, and modifications to the present embodiment, which may not creatively contribute to the present application as required by those skilled in the art after reading the present specification, are all protected by patent laws within the scope of claims of the present application.

Claims (8)

1.一种阿齐沙坦片剂,其特征在于:所述片剂的原料包括如下重量份的组分:阿齐沙坦35~45份、硅化微晶纤维素72~76份、低取代羟丙纤维素10~12份、滑石粉3~7份、巴西棕榈蜡0.39~1.04份;所述阿齐沙坦的粒径D90为50-80um。1. An azilsartan tablet, characterized in that the raw materials of the tablet include the following components in parts by weight: 35-45 parts of azilsartan, 72-76 parts of silicified microcrystalline cellulose, 10-12 parts of low-substituted hydroxypropyl cellulose, 3-7 parts of talc, and 0.39-1.04 parts of carnauba wax; the particle size D90 of the azilsartan is 50-80 μm. 2.根据权利要求1所述的一种阿齐沙坦片剂,其特征在于:所述巴西棕榈蜡的粒径D90为200-230um。2. An azilsartan tablet according to claim 1, characterized in that the particle size D90 of the carnauba wax is 200-230 um. 3.根据权利要求1所述的一种阿齐沙坦片剂,其特征在于:所述硅化微晶纤维素的粒径D90为300-330um。3. An azilsartan tablet according to claim 1, characterized in that the particle size D90 of the silicified microcrystalline cellulose is 300-330 um. 4.根据权利要求1所述的一种阿齐沙坦片剂,其特征在于:所述低取代羟丙纤维素的粒径D90为200-230um。4. The azilsartan tablet according to claim 1, characterized in that the particle size D90 of the low-substituted hydroxypropyl cellulose is 200-230 um. 5.根据权利要求1所述的一种阿齐沙坦片剂,其特征在于:所述滑石粉的粒径D90为10-30um。5. The azilsartan tablet according to claim 1, characterized in that the particle size D90 of the talc is 10-30 um. 6.一种如权利要求1-5任意一项所述的阿齐沙坦片剂的制备方法,其特征在于:包括以下步骤:6. A method for preparing the azilsartan tablet according to any one of claims 1 to 5, characterized in that it comprises the following steps: 制片:将阿齐沙坦与低取代羟丙纤维素混合过筛,得到预混物A;将预混物A与硅化微晶纤维素混合过筛,得到预混物B;将预混物B与滑石粉混合,压制成片,得到阿齐沙坦素片;Tablet preparation: Azilsartan and low-substituted hydroxypropyl cellulose are mixed and sieved to obtain premix A; premix A and silicified microcrystalline cellulose are mixed and sieved to obtain premix B; premix B is mixed with talc and pressed into tablets to obtain azilsartan tablets; 表面处理:先将阿齐沙坦素片进行预热,接着将巴西棕榈蜡过筛,缓慢连续倒入阿齐沙坦素片中,与阿齐沙坦素片混合摩擦,冷却,得到阿齐沙坦片剂。Surface treatment: first preheat the azilsartan tablets, then sieve the carnauba wax, slowly and continuously pour it into the azilsartan tablets, mix and rub with the azilsartan tablets, cool, and obtain azilsartan tablets. 7.根据权利要求6所述的一种阿齐沙坦片剂的制备方法,其特征在于:所述制片步骤为:将阿齐沙坦与低取代羟丙纤维素混合过60目筛,得到预混物A;将预混物A与硅化微晶纤维素混合过40目筛,得到预混物B;将预混物B与滑石粉混合,压制成片,得到阿齐沙坦素片。7. The method for preparing an azilsartan tablet according to claim 6, characterized in that: the tableting step comprises: mixing azilsartan with low-substituted hydroxypropyl cellulose and passing the mixture through a 60-mesh sieve to obtain a premix A; mixing premix A with silicified microcrystalline cellulose and passing the mixture through a 40-mesh sieve to obtain a premix B; mixing premix B with talc and pressing the mixture into tablets to obtain azilsartan tablets. 8.根据权利要求6所述的一种阿齐沙坦片剂的制备方法,其特征在于:所述表面处理步骤为:先将阿齐沙坦素片在40℃下进行预热,接着将巴西棕榈蜡过60目筛,缓慢连续倒入阿齐沙坦素片中,停止加热,将巴西棕榈蜡与阿齐沙坦素片混合摩擦25-35min,冷却,得到阿齐沙坦片剂。8. The method for preparing an azilsartan tablet according to claim 6, characterized in that: the surface treatment step is: first preheating the azilsartan tablet at 40°C, then passing the carnauba wax through a 60-mesh sieve, slowly and continuously pouring it into the azilsartan tablet, stopping heating, mixing and rubbing the carnauba wax and the azilsartan tablet for 25-35 minutes, and cooling to obtain the azilsartan tablet.
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