JP7322474B2 - Tablets containing azilsartan - Google Patents

Description

The present invention relates to tablets containing azilsartan.

Since azilsartan suppresses vasoconstriction and shows antihypertensive action, it is used as a therapeutic drug for hypertension.
However, it is known that its form and/or various additives may induce decomposition over time (for example, Patent Document 1).

JP 2018-154596 A

Under such circumstances, a pharmaceutical composition containing azilsartan is required to have a tablet capable of maintaining stable physical properties regardless of its form.
In addition, in order to meet a wide variety of dosage forms of patients, there is a demand for a tablet that can be taken without water and that can be easily prepared in the form of enteral nutrition such as a suspension.
An object of the present invention is to provide a tablet that has excellent disintegration properties and tablet hardness and that can maintain stable physical properties during production and long-term storage.

The present application includes the following inventions.
A stabilized tablet comprising azilsartan and at least one selected from the group consisting of magnesium aluminometasilicate, light anhydrous silicic acid and anhydrous calcium hydrogen phosphate.

The azilsartan-containing tablet of the present invention has excellent disintegration properties and tablet hardness, and can maintain stable physical properties during production and long-term storage.

It is a flow chart which shows a manufacturing method of a tablet of the present invention. Fig. 10 is a graph showing changes over time in the proportion of azilsartan-derived related substances on days 7 and 14 of a severe test (60°C, 75% RH) of the tablet of the present invention and a comparative example. It is a graph which shows the disintegration time of the tablet which is a tablet of this invention, and a comparative example. 4 is a graph showing the hardness of tablets of the present invention and comparative examples on day 7 of a severe test (60° C., 75% RH). FIG. 10 is a graph showing the residual hardness of tablets of the present invention and comparative examples after 7 days of a severe test (60° C., 75% RH). In the tablet of the present invention, change over time in the ratio of related substances derived from azilsartan on days 7 and 14 of the severe test of tablets with different amounts of specific additives and comparative examples without specific additives It is a graph showing. 1 is a graph showing the disintegration time depending on the amount of specific excipients in the tablet of the present invention. Fig. 3 is a graph showing the hardness of tablets of the present invention depending on the amount of specific excipients on day 7 of a stress test (60°C, 75% RH). Fig. 10 is a graph showing the residual hardness of the tablets of the present invention depending on the amount of specific excipients after 7 days of a stress test (60°C, 75% RH).

The tablet of the present invention contains azilsartan as an active ingredient. The tablet of the present invention contains, in addition to azilsartan, at least one porous inorganic material selected from the group consisting of magnesium aluminometasilicate, light anhydrous silicic acid and anhydrous calcium hydrogen phosphate, that is, an additive. In this way, by combining azilsartan with specific excipients, it is possible to obtain a tablet that is easy to take while suppressing the destabilization of azilsartan as described above, and has excellent disintegration and tablet hardness. Azilsartan-containing tablets shown can be obtained. In particular, there is a trade-off relationship between disintegration and tablet hardness. As disintegration improves, tablet hardness decreases, and during the manufacturing process, distribution process, and personal storage and use, it tends to crumble, resulting in defective products in the manufacturing process. can lead to an increase in However, the tablet of the present invention can maintain its shape even during the manufacturing process, distribution process, storage at home, etc. While maintaining stable physical properties and shape during storage, it disintegrates quickly in the mouth or in a suspension, etc., when taken, can be easily swallowed without water, and can be used as a suspension agent. Tablets can be provided that are easy to prepare during enteral nutrition.

Azilsartan has the chemical name of (2-ethoxy-1-[[2′-(4,5-dihydro-5-oxo-1,2,4-oxadiazol-3-yl)biphenyl-4-yl] methyl]benzimidazole-7-carboxylic acid), which is a therapeutic agent for hypertension that inhibits vasoconstriction by antagonizing angiotensin II to exhibit a hypotensive effect.
Azilsartan in the tablet is contained in an amount of 5 w/w% to 35 w/w% based on the weight of the tablet. From another point of view, it can be composed so that the single dose is 10 mg to 40 mg.

Magnesium aluminometasilicate, light anhydrous silicic acid, and anhydrous calcium hydrogen phosphate are usually additives that can impart functions such as fluidizing agents and anti-adhesion agents. The tablet of the present invention may be used in combination with a fluidizing agent commonly used in the field as long as these functions are not inhibited. Fluidizing agents include, for example, hydrated silicon dioxide, magnesium trisilicate, titanium oxide, and magnesium stearate. The fluidizing agents can be used singly or in combination of two or more.
The content of magnesium aluminometasilicate and/or light anhydrous silicic acid can be contained at 0.001 w/w% to 10 w/w%, based on the weight of the tablet, and 0.001 w/w% to 8 w /w%, more preferably 0.001w/w% to 5w/w%, more preferably 0.001w/w% to 3w/w%, 1w/w% or less, for example, 0.001w/w% ~1 w/w% is even more preferred. In addition, when other fluidizing agents are included, their total content can be 0.001 w/w% to 10 w/w%, preferably 0.001 w/w% to 5 w/w%. and more preferably 0.001 w/w% to 3 w/w%. In addition, the content of anhydrous calcium hydrogen phosphate, based on the weight of the tablet, can be contained in 0.001w / w% ~ 30w / w%, preferably 1w / w% ~ 20w / w%, 5w /w% to 15w/w%, more preferably 8w/w% to 10w/w%.
By setting such a content, it is possible to shorten the tablet disintegration time while maintaining an appropriate tablet hardness.

The tablet of the present invention can contain other additives that are commonly used in the field of pharmaceutical formulations other than the above, as long as they do not affect the effects described above. For example, binders, excipients, binders, disintegrants, lubricants, lubricants, wetting agents, surfactants, sweeteners, corrigents, organic acids, flavoring agents/perfumes, coloring agents, stabilizers , coating agents, and the like. These can be used singly or in combination of two or more.
As the binder, those commonly used in the art, such as polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer, polyvinyl alcohol/polyethylene glycol/graft copolymer, polyvinyl alcohol, hydroxypropyl cellulose (HPC), povidone (polyvinyl pyrrolidone (PVP)), hydroxypropylmethylcellulose (hypromellose, HPMC), carmellose sodium, polyvinyl alcohol, pregelatinized starch, agar, gelatin, sodium carboxymethylcellulose, dextrin, ethylcellulose, guar gum and polyethylene oxide. These can be used singly or in combination of two or more.
The polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer is a polymer compound obtained by copolymerizing partially saponified polyvinyl alcohol with acrylic acid and methyl methacrylate. Examples include those marketed as POVACOAT®. Polyvinyl alcohol/polyethylene glycol/graft copolymers include those commercially available as Kollicoat (registered trademark) IR.
The binder content is 0.01 w/w% to 10 w/w%, preferably 0.1 w/w% to 5 w/w%, based on the weight of the tablet. Among them, the binder is preferably a polyvinyl alcohol/acrylic acid/methyl methacrylate copolymer. As a result, it is possible to obtain an azilsartan-containing tablet that is easy to take, such as ingestion or swallowing, while suppressing destabilization of azilsartan, and that exhibits excellent disintegration and tablet hardness.

Examples of excipients include D-mannitol, anhydrous lactose, lactose hydrate, refined sucrose, sucrose, sucrose, fructose, fructooligosaccharide, glucose, maltose, reduced maltose, powdered sugar, powdered candy, reduced lactose and the like. Sugars, sugar alcohols such as erythritol, sorbitol, maltitol and xylitol, kaolin, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, starch (for example, natural starch such as potato starch, rice starch, wheat starch, corn starch), etc. is mentioned. These can be used singly or in combination of two or more.
The content of excipients is 10 w/w% to 85 w/w% based on the weight of the tablet, preferably 15 w/w% to 80 w/w%, more preferably 20 w/w% to 80 w/w%. preferable.

Stabilizers include, for example, crystalline cellulose, macrogol (eg, average molecular weight of 200 to 20,000, particularly preferably 6,000), stearic acid, triethyl citrate, carnauba wax, and the like. These can be used singly or in combination of two or more. Among them, it is preferable to use stearic acid. For example, in order to obtain good disintegration and dissolution properties as a tablet, it is necessary that the tablet is wetted with the test liquid, absorbs moisture and disintegrates, and the contained drug dissolves in the test liquid. On the other hand, since stearic acid is almost insoluble in water, the wettability of the tablet itself is poorer than when macrogol, which is easily soluble in water, causes poor disintegration, and it is thought that the contained drug will be difficult to elute. be done. However, by including stearic acid in the tablet in combination with the above-mentioned specific fluidizing agent, the effects of these additives are combined, and the stabilization of azilsartan can be further maintained, and disintegration and the like can be improved. can be improved.
The content of the stabilizer is 0.1 w/w% to 5 w/w%, preferably 1 w/w% to 3 w/w%, based on the weight of the tablet.

Examples of lubricants include calcium stearate, sodium lauryl sulfate, glyceryl monostearate, glyceryl palmitostearate, sodium stearyl fumarate, magnesium stearate, sucrose fatty acid ester, zinc stearate, talc, carnauba wax, L- Examples include leucine and macrogol. These can be used singly or in combination of two or more.
The content of the lubricant is 0.01 w/w% to 5 w/w%, preferably 0.01 w/w% to 4 w/w%, based on the weight of the tablet.

Examples of disintegrants include crospovidone, povidone, low-substituted hydroxypropyl cellulose (L-HPC), crystalline cellulose, carmellose calcium, carmellose, croscarmellose sodium, alginic acid, sodium carboxymethyl starch, sodium starch glycolate, talc and the like. These can be used singly or in combination of two or more.
The content of the disintegrant is 1 w/w% to 25 w/w% based on the weight of the tablet.

Lubricants include, for example, calcium stearate, sodium stearate, hydrous silicon dioxide, light anhydrous silicic acid, magnesium carbonate, corn starch, mineral oil, polyethylene glycol, sesame oil and the like. These can be used singly or in combination of two or more.
The lubricant content is 0.5 w/w% to 2 w/w% based on the weight of the tablet.
Wetting agents include sodium lauryl sulfate, macrogol and the like.

Examples of surfactants include ionic surfactants such as sodium lauryl sulfate; polysorbates, sucrose fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene hydrogenated castor oil and poloxamers (polyoxyethylene polyoxypropylene glycol) and other nonionic surfactants. These can be used singly or in combination of two or more.
The content of the surfactant is 2 w/w% or less based on the weight of the tablet.

Sweeteners include, for example, aspartame, mannitol, saccharin and the like. These can be used singly or in combination of two or more.
Flavoring agents include, for example, menthol, artificial or natural fruit flavors, and the like. These can be used singly or in combination of two or more.
Examples of coloring agents include caramel, iron oxide (yellow or black), iron sesquioxide, yellow iron sesquioxide, black iron sesquioxide, natural or synthetic organic pigments, lakes, and the like. These can be used singly or in combination of two or more.

Coating agents include, for example, carboxymethylcellulose sodium, cellulose acetate, methylcellulose, polyethylene glycol, hypromellose and the like. These can be used singly or in combination of two or more.
The content of the coating agent is 0.1 w/w% to 3 w/w% based on the weight of the tablet.

In one embodiment of the present invention, for example, at least one additive selected from the group consisting of magnesium aluminometasilicate, light anhydrous silicic acid, and anhydrous calcium hydrogen phosphate is added to the granule containing azilsartan. preferably. At least one additive selected from the group consisting of magnesium aluminometasilicate, light anhydrous silicic acid and anhydrous calcium hydrogen phosphate may be added to the granulated material containing azilsartan and stearic acid. However, other additives may be combined without being limited to these descriptions.

The tablet of the present invention can be made into various dosage forms including tablets by undergoing further steps. Examples include fine granules, granules, powders, tablets, capsules, pills, chewables, lozenges and the like. Among these, tablets, particularly orally disintegrating tablets, are preferred. These dosage forms may be those defined in the Japanese Pharmacopoeia General Rules for Pharmaceutical Preparations. Moreover, a score line, an identification mark, or the like may be attached to the tablet or the like. The tablet may be of any shape such as a round tablet, a round R tablet, a round corner tablet, a round two-step R tablet, various irregularly shaped tablets, etc., or may be divided tablets. The tablet may be an uncoated tablet or may be coated.
In the present invention, formulation using specific excipients, particularly tableting, can achieve good stability, that is, reduction in generation of related substances, degradation products, impurities, and the like. In particular, compared with commercially available azilsartan-containing tablets, that is, azilva tablets (registered trademark), it is possible to achieve marked stabilization. In addition, even after tableting, it is possible to shorten the disintegration time while maintaining appropriate tablet hardness. This is unexpected because the disintegration time can be remarkably shortened despite the high hardness compared to tablets using hydroxypropyl cellulose, which is often used as a binder. can be effective.

When producing the tablet of the present invention, conventional formulation methods can be used.
Among others, the tablet of the present invention comprises, for example, azilsartan, as shown in FIG. is preferred) is added to a mixer or granulator and mixed.
Then, while stirring these mixtures, a binder is added and granulated. At that time, the binder is preferably added after being dissolved in purified water, but may be added after being dissolved in a mixture of an organic solvent and water, an organic solvent, or the like.
After that, the granules are preferably dried and optionally sized.
It is preferable to add excipients/fluidizers/disintegrants/lubricants and the like to the obtained granules and add the above-mentioned additives peculiar to the present application and mix them.
Subsequently, as shown in FIG. 1, the granulated product or mixture of azilsartan obtained above is tableted.

The mixer or granulator to be used is not particularly limited as long as it can mix powders and the like, and any machine may be used.
The granulator is preferably a device capable of wet granulation. Wet granulation can be performed using an extrusion granulator, a tumbling granulator, a stirring granulator, a wet crushing granulator, a fluid bed granulator, or the like. Among them, it is preferable to use a stirring granulator and a fluidized bed granulator, and it is particularly preferable to use a stirring granulator. When using an agitation granulator, for example, the rotation of the blade and/or screw may be set at an arbitrary number of rotations. When a fluidized bed granulator is used, for example, a method of granulating while spraying a binder solution or the like at an air supply temperature of 30°C to 90°C and an exhaust temperature of 20°C to 80°C can be mentioned. The dry granulation method includes, for example, a method in which a roller compactor (Freund Corporation) is used and granulation is performed at a roll rotation speed of 1 rpm to 50 rpm.
It is preferable to add a binder when granulating azilsartan or the like. It is preferable to add the binder at the timing when it is uniformly mixed with azilsartan. It is preferable to add the binder together with purified water or by dispersing/dissolving it in purified water. Thereby, the binder adheres to the granules containing azilsartan and is in the form of granules together with azilsartan, or partly adheres to the granules containing azilsartan and another part will be contained in the form contained in the granules together with azilsartan.

The resulting granules are preferably dried and sieved (for example, several hundred micrometers to several millimeters) to size them. Drying may be carried out, for example, at a temperature from room temperature to 90° C. for 1 minute to 12 hours, preferably several hours.
During or after sizing, the above-described additives including the above-described additives specific to the present invention are optionally added to the granulated material and mixed.
Any tableting machine known in the art may be used for tableting. For example, a single tableting machine, a rotary tableting machine and the like can be mentioned. For tabletting, it is preferable to add a lubricant such as sodium stearyl fumarate to the tableting mixture. For example, the pressure in the case of compression tableting may be such that the tablet has sufficient hardness, and is preferably 1 kN or more, more preferably 3 kN or more. The hardness of the resulting tablet is preferably 20N or higher, more preferably 30N or higher, 35N or higher, or 40N or higher. The "hardness" of a tablet can be measured with a tablet hardness tester (eg MultiTest 50 from Dr. Schleuniger Pharmatron).
In addition to the above, in order to prepare a suitable solid form, for example, grinding, crushing, mixing, sugar coating, film coating, capsule filling, etc. can be further performed by methods and conditions known in the art.

The tablets containing azilsartan of the present invention, particularly the orally disintegrating agent, showed a total similarity after 1 week (7 days) and 2 weeks (14 days) of storage in a severe test (60°C, 75% RH). The mass of decomposed products, impurities, etc. caused by the substance and each active ingredient can be extremely reduced, and stability can be achieved over a long period of time. In addition, in the manufacturing process, the distribution process, and personal storage, it is possible to secure an appropriate hardness that does not cause inconvenience such as not crumbling or increasing the number of defective products in the manufacturing process. The disintegration time can be shortened to the extent that it disintegrates rapidly in a turbid liquid or the like, and can be easily ingested or swallowed.

まず、アジルサルタン、賦形剤１及び安定化剤を撹拌造粒機（岡田精工社製）に投入し、混合した。
ブレード回転（回転数：８００ｒｐｍ～１０００ｒｐｍ）で攪拌しながら、精製水と結合剤との混合した溶液を添加し、攪拌造粒した。その後、棚乾燥にて５０℃で１．５時間乾燥した。
篩（８５０μｍ）で整粒した顆粒に、賦形剤２、多孔質性無機物、崩壊剤、滑沢剤を添加し、混合した。
得られた混合物を、ロータリー打錠機（菊水製作所製）にて、打錠圧３．５ｋＮでの錠剤とした。 Examples 1-3
Each component below was weighed at the ratio shown in Table 1, and tablets were prepared by the following method shown in FIG.

First, azilsartan, excipient 1 and stabilizer were placed in a stirring granulator (manufactured by Okada Seiko Co., Ltd.) and mixed.
A mixed solution of purified water and a binder was added while stirring with blade rotation (rotation speed: 800 rpm to 1000 rpm), followed by stirring and granulation. After that, it was dried at 50° C. for 1.5 hours in a shelf drying.
Excipient 2, a porous inorganic substance, a disintegrant and a lubricant were added to granules sieved with a sieve (850 μm) and mixed.
The obtained mixture was made into tablets with a tableting pressure of 3.5 kN using a rotary tableting machine (manufactured by Kikusui Seisakusho).

Comparative example 1
In the manufacturing method of Example 1, tablets were manufactured in the same manner as in Example 1, except that the porous inorganic material was not added to the stirring granulator.

図２及び表２から明らかなように、本願実施例１、２及び３では、特定の添加剤を含むことから、錠剤とした場合であっても、苛酷試験開始後の７日目及び１４日目において、アジルサルタン由来の類縁物質及び不純物が、市販品に比較して、低減することが確認された。 Test example 1
The tablets of Examples 1, 2 and 3, and 20 mg of the commercially available Azilva tablet were each stored without packaging under the conditions of 60° C. and 75% RH for 14 days, and the stability was evaluated as follows.
A purity test (related substances, that is, degradation products caused by azilsartan) was performed for stability evaluation on the tablets before, during, and after storage by the following method.
One tablet was taken and 2 mL of water was added to disintegrate the tablet. Subsequently, methanol was added to make 50 mL. This liquid was filtered through a membrane filter (Milex LH) with a pore size of 0.45 μm or less. The first filtrate (3 mL) was removed, and the next filtrate was used as the sample solution. Accurately 5 μL of each sample solution was taken and tested by liquid chromatography under the following conditions, and the peak area of each liquid was measured by an automatic integration method. The amounts of individual analogues and the total amount of analogues were determined by the following formula.
Amount (%) of each analogue = A _T1 /A _S
Total amount of related substances (%) = A _T2 /A _S
(Wherein, A _S : the peak area of azilsartan in the standard solution,
A _T1 : Individual peak area other than azilsartan of sample solution A _T2 : Total area of peaks other than azilsartan of sample solution.
Test conditions Detector: UV absorption photometer (measurement wavelength: 210 nm)
Column: A stainless steel tube having an inner diameter of 4.6 mm and a length of 25 cm was packed with 5 μm octadecylsilylated silica gel for liquid chromatography. (Inertsil ODS-3C/N)
Column temperature: Constant temperature around 35° C. Mobile phase A: About 3.67 g of potassium dihydrogen phosphate was dissolved in water to make 2700 mL, and 0.42 ml of phosphoric acid was added (pH 3.0). A mobile phase A was prepared by adding 300 mL of acetonitrile to this liquid.
Mobile phase B: acetonitrile Feeding of mobile phase: The concentration gradient was controlled by changing the mixing ratio of mobile phase A and mobile phase B as follows.
Mobile phase A was 78 vol % and mobile phase B was 22 vol % 0-3 minutes after injection.
3-30 minutes after injection, mobile phase A was 78→22 vol% and mobile phase B was 22→78 vol%.
30-40 minutes after injection, mobile phase A was 22 vol% and mobile phase B was 78 vol%.
40-41 minutes after injection, mobile phase A was 22→78 vol% and mobile phase B was 78→22 vol%.
41-46 minutes after injection, mobile phase A was 22 vol % and mobile phase B was 22 vol %.
Flow rate: 1 mL per minute
Planimetric range: from after solvent peak to 40 minutes after injection The results are shown in FIG.

As is clear from FIG. 2 and Table 2, in Examples 1, 2 and 3 of the present application, since the specific additives are included, even if it is made into tablets, 7 days and 14 days after the start of the stress test In eyes, it was confirmed that azilsartan-derived related substances and impurities were reduced compared to the commercial product.

Test Example 2: Disintegration Test The disintegration time (seconds) of the tablets obtained in Examples 1, 2 and 3 and Comparative Example 1 was measured using a tricoop tester (manufactured by Okada Seiko Co., Ltd.). The results are shown in FIG.
In the disintegration test, a liquid containing 1.47 g / L of KCl, 1.44 g / L of NaCl and 0.3% of TWEEN 80 was used as an artificial saliva raw material, and the ejection speed (liquid speed) was set to 6.0 mL / min. set and measured.
As is clear from FIG. 3, in Examples 1, 2 and 3 of the present application, the disintegration time was significantly shortened compared to Comparative Example 1, even in the case of tablets, by containing specific additives. It was confirmed that

Test Example 3: Hardness The hardness and hardness retention rate of the tablets of Examples 1, 2 and 3 and Comparative Example 1 were measured. The hardness was measured by a hardness tester (MultiTest 50, manufactured by Dr. Schleuniger Pharmatron) immediately after production (day 0) and after storage for 7 days under the conditions of 60°C and 75% RH without packaging (7 days). It was measured. The hardness retention rate was expressed as the ratio of the hardness after 7 days to the hardness at 0 days. These results are shown in Figures 4A, 4B and Table 3, respectively.
As is clear from FIG. 4A, the tablets of Examples 1, 2 and 3 using the specific excipients were comparable to Comparative Example 1 immediately after the tablets were manufactured. This result is unexpected considering that the tablets of Examples 1, 2 and 3 had a significantly shorter disintegration time compared to the tablet of Comparative Example 1 in the disintegration test described above. In addition, as is clear from FIG. 4B, the tablets of Examples 1, 2 and 3 have a better hardness retention rate than the tablet of Comparative Example 1, that is, the hardness is maintained over a long period of time. was confirmed.

Examples 4-6
Each component below was weighed at the ratio shown in Table 4, and a tablet was produced by the following method shown in FIG.

Test example 4
The tablets of Examples 4, 5 and 6 and 20 mg of the commercially available Azilva tablet were each stored without packaging under the conditions of 60°C and 75% RH for 7 days, and the stability was evaluated in the same manner as in Test Example 1. did
The results are shown in FIG. 5 and Table 5.
As is clear from FIG. 5 and Table 5, in Examples 4, 5 and 6 of the present application, since the specific excipients were included, even when tablets were made, analogues and impurities derived from azilsartan were not found on the market. It was confirmed that it was reduced compared to the product.

Test Example 5: Disintegration Test The tablets obtained in Examples 4, 5 and 6 and Comparative Example 1 were measured for disintegration time (seconds) according to Test Example 2 using a Tricorp Tester (manufactured by Okada Seiko Co., Ltd.). The results are shown in FIG.
As is clear from FIG. 6, in Examples 4, 5 and 6 of the present application, the disintegration time is significantly shortened compared to Comparative Example 1, even in the case of tablets, by containing specific additives. It was confirmed that

Test Example 6: Hardness The hardness and hardness retention rate of the tablets of Examples 4, 5 and 6 and Comparative Example 1 were measured. Hardness was measured in the same manner as in Test Example 3. The hardness retention rate was expressed as the ratio of the hardness after 7 days to the hardness after 0 days after the severe test (stored at 60° C. and 75% RH without packaging). These results are shown in Figures 7A, 7B and Table 6, respectively.
As is clear from FIG. 7A, the tablets of Examples 4, 5 and 6 were equivalent to Comparative Example 1 immediately after the tablets were manufactured. This result is unexpected considering that the tablets of Examples 4, 5 and 6 had a significantly shorter disintegration time compared to the tablet of Comparative Example 1 in the disintegration test described above. In addition, as is clear from FIG. 7B, the tablets of Examples 4, 5 and 6 have a better hardness retention rate than the tablet of Comparative Example 1, that is, the hardness is maintained over a long period of time. was confirmed.

INDUSTRIAL APPLICABILITY The tablet of the present invention can ensure long-term stability during manufacturing, storage, and distribution processes. Moreover, it was confirmed that the disintegration time can be shortened while maintaining appropriate hardness.

Claims (3)

azilsartan and magnesium aluminometasilicate and
A stabilized tablet containing stearic acid . 2. The tablet according to claim 1, wherein the magnesium aluminometasilicate is contained at 1 w/w% or less based on the weight of the tablet. 3. The tablet according to claim 1 or 2, which is an orally disintegrating tablet .

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