Azilsartan tablet and preparation method thereof

Abstract

The present application relates to the technical field of pharmaceutical preparations, and specifically discloses a kind of azilsartan tablet and its preparation method. A kind of azilsartan tablet, the raw material of the tablet includes 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, 0.39-1.04 parts of carnauba wax; The particle size D90 of the azilsartan is 50-80um. In this application, azilsartan, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc having a particle size D90 of 50-80um are first used to press into tablets, and then carnauba wax is used to form a coating on the tablet surface, which not only improves the dissolution rate and dissolution uniformity of the tablet, but also greatly improves the stability of the tablet.

Description

Technical Field

[0001] The present application relates to the technical field of pharmaceutical preparations, and in particular to an azilsartan tablet and a preparation method thereof. Background Art

[0002] Azilsartan is a non-peptide angiotensin II receptor antagonist developed by Takeda Pharmaceuticals of Japan. It selectively blocks angiotensin II receptor 1 (AT1-R). Currently, two forms are available: acesartan potassium and azilsartan. Azilsartan potassium is a prodrug of azilsartan that is hydrolyzed in the gastrointestinal tract to form the active metabolite, azilsartan. Azilsartan potassium was approved by the FDA in 2011, and azilsartan was launched in Japan in 2012. As a new-generation selective AT1 subtype angiotensin II receptor antagonist, azilsartan offers a stronger and more sustained antihypertensive effect than ACE inhibitors, without causing a dry cough. However, the commonly used azilsartan has difficulty maintaining high dissolution rates while maintaining good stability and uniformity. Summary of the Invention

[0003] In order to improve the dissolution rate of azilsartan while ensuring uniform dissolution and good stability, the present application provides an azilsartan tablet and a preparation method thereof.

[0004] In the first aspect, the present application provides an azilsartan tablet, which adopts the following technical solution:

[0005] Disclosed is an azilsartan tablet. 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.

[0006] By adopting the above technical solution, azilsartan with a particle size D90 of 50-80 μm, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc are pressed into tablets, and then carnauba wax is used to form a coating on the surface of the tablets. This not only improves the dissolution rate and dissolution uniformity of the tablets, but also greatly improves the stability of the tablets.

[0007] In a specific embodiment, the particle size D90 of the carnauba wax is 200-230 μm.

[0008] In a specific embodiment, the particle size D90 of the silicified microcrystalline cellulose is 300-330 μm.

[0009] In a specific embodiment, the particle size D90 of the low-substituted hydroxypropyl cellulose is 200-230 μm.

[0010] In a specific embodiment, the particle size D90 of the talc powder is 10-30 μm.

[0011] By adopting the above technical solution, the particle sizes of carnauba wax, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc are further limited, so that the obtained tablets have better dissolution rate and dissolution uniformity.

[0012] In a second aspect, the present application provides a method for preparing an azilsartan tablet, which adopts the following technical solution. The method for preparing an azilsartan tablet comprises the following steps:

[0013] 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 powder and pressed into tablets to obtain azilsartan tablets; surface treatment: Azilsartan tablets are first preheated, then carnauba wax is sieved and slowly and continuously poured into the azilsartan tablets, mixed and rubbed with the azilsartan tablets, and cooled to obtain azilsartan tablets.

[0014] By adopting the above technical solution, azilsartan, low-substituted hydroxypropyl cellulose, silicified microcrystalline cellulose and talc are first mixed and tableted to obtain azilsartan tablets, and then the azilsartan tablets are coated with carnauba wax to obtain azilsartan tablets with high dissolution rate, uniform dissolution and good stability.

[0015] In a specific embodiment, the tableting step is: mixing azilsartan with low-substituted hydroxypropyl cellulose and passing the mixture through a 60-mesh sieve to obtain premix A; mixing premix A with silicified microcrystalline cellulose and passing the mixture through a 40-mesh sieve to obtain premix B; mixing premix B with talc and pressing the mixture into tablets to obtain azilsartan tablets.

[0016] In a specific embodiment, the surface treatment step is: first preheating the azilsartan tablets at 40°C, then passing the carnauba wax through a 60-mesh sieve and slowly and continuously pouring it into the azilsartan tablets, stopping heating, mixing the carnauba wax and the azilsartan tablets and rubbing them for 25-35 minutes, and cooling to obtain azilsartan tablets.

[0017] By adopting the above technical solution, the preheating temperature and the mixing friction time are further limited, so that the carnauba wax can better coat the azilsartan tablets.

[0018] In summary, this application includes at least one of the following beneficial technical effects:

[0019] 1. In this application, azilsartan with a particle size D90 of 50-80 μm, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc are compressed into tablets, and carnauba wax is then used to form a coating on the tablet surface. This not only improves the dissolution rate and dissolution uniformity of the tablets, but also greatly enhances the stability of the tablets.

[0020] 2. This application further defines the particle sizes of carnauba wax, silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc, so that the resulting tablets have a good dissolution rate and dissolution uniformity;

[0021] 3. The method of the present application first mixes azilsartan, low-substituted hydroxypropyl cellulose, silicified microcrystalline cellulose, and talc and compresses them into tablets to obtain azilsartan tablets, and then coats the azilsartan tablets with carnauba wax to obtain azilsartan tablets with high dissolution rate, good dissolution uniformity, and good stability. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 This is a graph used in this application to reflect the dissolution curves of the drugs in Examples 1-3 and the control example in a phosphate medium with a pH of 6.8.

[0023] Figure 2 This is a graph used in this application to reflect the dissolution curves of the drugs in Comparative Examples 1-2, Comparative Examples 4-5 and the control example in a phosphate medium with a pH of 6.8. DETAILED DESCRIPTION

[0024] The present application is further described in detail below with reference to the embodiments.

[0025] All raw materials in the examples are commercially available.

[0026] Example

[0027] Example 1

[0028] Example 1 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0029] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 50 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0030] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.65 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0031] Example 2

[0032] Example 2 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0033] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0034] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.65 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0035] Example 3

[0036] Example 3 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0037] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 80 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0038] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.65 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0039] Example 4

[0040] Example 4 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0041] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0042] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.39 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0043] Example 5

[0044] Example 5 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0045] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0046] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 1.04 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0047] Example 6

[0048] Example 6 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0049] Tablet preparation: 35g of azilsartan and 10g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 72g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 3g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130mg; wherein the particle size D90 of azilsartan is 65μm; the particle size D90 of silicified microcrystalline cellulose is 320μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220μm; and the particle size D90 of talc is 20μm.

[0050] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.39 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0051] Example 7

[0052] Example 7 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0053] Tablet preparation: 45 g of azilsartan and 12 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 76 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 7 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0054] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 1.04 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0055] Comparative Example

[0056] Comparative Example 1

[0057] Comparative Example 1 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0058] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 45 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0059] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.65 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0060] Comparative Example 2

[0061] Comparative Example 2 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0062] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 90 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0063] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.65 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0064] Comparative Example 3

[0065] Comparative Example 3 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0066] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0067] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 0.26 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0068] Comparative Example 4

[0069] Comparative Example 4 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0070] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose were uniformly mixed, and the mixture was passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A was uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture was passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B was uniformly mixed with 5 g of talc, and the mixture was compressed using a rotary tablet press to obtain azilsartan tablets weighing approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0071] Surface treatment: First, add the Azilsartan tablets into the coating equipment, set the heating temperature to 45℃ and the air volume to 1000m 3 / h, speed 4 rpm, preheat to 40 ° C, then pass 1.17 g of carnauba wax through a 60-mesh sieve, slowly and continuously pour it into the azilsartan tablets, stop heating, increase the speed to 6 rpm, continue mixing and rubbing for 30 minutes, and after cooling to room temperature, obtain azilsartan tablets.

[0072] Comparative Example 5

[0073] Comparative Example 5 provides a method for preparing an azilsartan tablet, comprising the following steps:

[0074] Tablet preparation: 40 g of azilsartan and 11 g of low-substituted hydroxypropyl cellulose are uniformly mixed, and the mixture is passed through a 60-mesh sieve using an oscillating granulator to obtain premix A; premix A is uniformly mixed with 74 g of silicified microcrystalline cellulose, and the mixture is passed through a 40-mesh sieve using an oscillating granulator to obtain premix B; premix B is uniformly mixed with 5 g of talc, and the mixture is compressed using a rotary tablet press to obtain azilsartan tablets with a tablet weight of approximately 130 mg; wherein the particle size D90 of azilsartan is 65 μm; the particle size D90 of silicified microcrystalline cellulose is 320 μm; the particle size D90 of low-substituted hydroxypropyl cellulose is 220 μm; and the particle size D90 of talc is 20 μm.

[0075] Control Example

[0076] The control example is Azilsartan original drug

[0077] Performance test Dissolution performance: The dissolution of the drugs in each example and comparative example was tested in a phosphate buffer medium with a pH of 6.8. The test method was a paddle method, the medium volume was 900 mL, the water bath temperature was 37±0.5°C, and the stirring paddle speed was 50 r / min. The dissolution curve was obtained. See Figure 1 and Figure 2 .

[0078] Stability: The drugs in the Examples and Comparative Examples were subjected to accelerated tests and high humidity tests. The samples were placed for 30 consecutive days to examine changes in related substances in the samples. The accelerated test conditions were: temperature of 40°C ± 2°C and relative humidity of 75% ± 5%; the high humidity test conditions were: temperature of 25°C ± 2°C and relative humidity of 90% ± 5%.

[0079] Table 1 Drug dissolution performance test results

[0080]

[0081]

[0082] Table 2 Drug stability test results

[0083]

[0084] Combined with Table 1, Figure 1 , Examples 1-3 and the control example, the dissolution curves of the drugs in Examples 1-3 in a phosphate buffer medium at pH 6.8 are similar to those of the control example. Therefore, the azilsartan tablets of the present invention use azilsartan with a particle size D90 of 50 to 80 μm, and then use silicified microcrystalline cellulose, low-substituted hydroxypropyl cellulose, and talc to press into tablets, and finally use carnauba wax to form a coating on the surface of the tablets, which can improve the dissolution performance of the tablets.

[0085] Combined with Table 1, Figure 1-2 , Example 1 and Comparative Examples 1-2, it can be seen that in Comparative Example 1, azilsartan is too finely ground. Although its solubility is high, it is too high compared with the original drug, and the similarity factor F2 value is lower than 50, which poses a greater risk of in vivo bioequivalence; when the particle size of azilsartan in Comparative Example 2 is too large, its solubility is low, so the particle size of azilsartan is preferably 50-80 μm.

[0086] Combined with Table 1, Figure 1-2 , Example 1 and Comparative Example 4, it can be seen that when the amount of carnauba wax coating is 0.9%, it will hinder the dissolution and cause the dissolution to be slow. Therefore, when the amount of carnauba wax is too large, it will affect the dissolution of the tablet.

[0087] Combined with Table 1, Figure 1 Comparing Example 5 with the control example, it can be seen that the dissolution uniformity is poor and the RSD is large when the carnauba wax coating is not used. From the dissolution phenomenon, the applicant discovered that the coated drug immediately slides to the center of the dissolution cup bottom, while the uncoated drug becomes sticky due to dissolution and adheres to other locations on the cup bottom, causing some dissolution to be faster and some to be slower, resulting in different dissolution uniformity.

[0088] In combination with Table 2, Examples 1-3, Comparative Example 5 and the control example, it can be seen that under accelerated test conditions for 30 days, the 30-day related substances and the increase in the drug in Examples 1-3 were all less than 0.5%, while the 30-day related substances and the increase in the drug in Comparative Examples 5-6 were all above 0.5%; under high humidity test conditions for 30 days, the 30-day related substances and the increase in the drug in Examples 1-3 were all less than 0.5%, while the 30-day related substances and the increase in the drug in Comparative Examples 5-6 were all above 0.5%; it can be seen that the use of carnauba wax to coat azilsartan in this application has a significant barrier protection effect, thereby improving the stability of the obtained azilsartan tablets.

[0089] Combining Table 2, Example 3 and Comparative Example 4, it can be seen that when using carnauba wax to coat azilsartan, if the dosage is too low, the coating effect is poor, thereby affecting the stability of the obtained azilsartan tablets.

[0090] This specific embodiment is merely an explanation of the present application and is not a limitation of the present application. After reading this specification, those skilled in the art may make non-creative modifications to the present embodiment as needed, but as long as they are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. An azilsartan tablet, characterized in that: The raw materials of the tablets 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; and the preparation method of the tablets includes the following steps: tableting: mixing azilsartan and low-substituted hydroxypropyl cellulose and sieving to obtain a premix A; mixing premix A and silicified microcrystalline cellulose and sieving to obtain a premix B; mixing premix B and talc, pressing into tablets, and obtaining azilsartan tablets; and surface treatment: first preheating the azilsartan tablets, then sieving the carnauba wax, slowly and continuously pouring it into the azilsartan tablets, mixing and rubbing the azilsartan tablets, and cooling to obtain the azilsartan tablets.

2. An azilsartan tablet according to claim 1, characterized in that: The particle size D90 of the carnauba wax is 200-230 μm.

3. An azilsartan tablet according to claim 1, characterized in that: The particle size D90 of the silicified microcrystalline cellulose is 300-330 μm.

4. An azilsartan tablet according to claim 1, characterized in that: The particle size D90 of the low-substituted hydroxypropyl cellulose is 200-230 μm.

5. An azilsartan tablet according to claim 1, characterized in that: The particle size D90 of the talcum powder is 10-30 μm.

6. A method for preparing the azilsartan tablet according to any one of claims 1 to 5, characterized in that: The following steps are involved: Tablet preparation: Azilsartan and low-substituted hydroxypropyl cellulose are mixed and sieved to obtain premix A; premix A is mixed and sieved with silicified microcrystalline cellulose to obtain premix B; premix B is mixed with talc and compressed into tablets to obtain azilsartan tablets; 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, and cool to obtain azilsartan tablets.

7. The method for preparing an azilsartan tablet according to claim 6, wherein: The tableting steps are: mixing azilsartan and low-substituted hydroxypropyl cellulose and passing the mixture through a 60-mesh sieve to obtain a premix A; mixing the premix A and silicified microcrystalline cellulose and passing the mixture through a 40-mesh sieve to obtain a premix B; and mixing the premix B with talc powder and pressing the mixture into tablets to obtain azilsartan tablets.

8. The method for preparing an azilsartan tablet according to claim 6, wherein: The surface treatment step comprises: preheating the azilsartan tablets at 40° C., passing the carnauba wax through a 60-mesh sieve, slowly and continuously pouring the wax into the azilsartan tablets, stopping heating, mixing and rubbing the carnauba wax and the azilsartan tablets for 25-35 minutes, and cooling to obtain the azilsartan tablets.

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