JP2016183195A - Irbesartan-containing pharmaceutical composition with excellent elution property and orally disintegrable tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an irbesartan-containing pharmaceutical composition which shows excellent elution properties, and to provide an irbesartan-containing orally disintegrable tablet having excellent characteristics such that it (1) can be easily produced in general facilities without requiring any special formulation technology, (2) has moderate strength for preventing disintegration during distribution, (3) shows rapid disintegration in oral cavity, (4) shows good elution properties and (5) exerts good organoleptic properties at taking.SOLUTION: There are provided an irbesartan-containing pharmaceutical composition comprising at least one binder selected from hydroxypropyl cellulose and polyvinyl alcohol. An orally disintegrable tablet comprises (1) D-mannitol, (2) irbesartan, (3) at least one disintegrant chosen from crospovidone and carmellose, (4) at least one binder selected from hydroxypropyl cellulose and polyvinyl alcohol and (5) at least one lubricant selected from sodium stearyl fumarate and sucrose fatty acid ester.SELECTED DRAWING: None

Description

  The present invention relates to an oral pharmaceutical composition containing irbesartan and having good dissolution properties, particularly a tablet. The present invention also relates to a rapidly disintegrating tablet containing irbesartan that has good dissolution properties and has rapid disintegration or solubility even in the oral cavity without a small amount of water or water.

  Irbesartan, 2-Butyl-3- {4- [2- (1H-tetrazol-5-yl) phenyl] -benzyl} -1,3-diazaspiro [4.4] non-1-en-4-one, It is a long-acting angiotensin II receptor antagonist useful for the treatment of diseases. Irbesartan has the formula:

(Patent Document 1). Irbesartan generally needs to be administered in a relatively large amount, for example, 50 to 300 mg for the treatment of the above diseases. From the viewpoint of ease of administration, etc., a small-sized preparation is desired, but irbesartan has a low affinity with water, so it has good tablet formulation characteristics, particularly good dissolution properties, while miniaturizing tablets. Thus, there has been a problem to be solved regarding the high concentration of irbesartan. As preparations for the purpose of solving this problem, Patent Documents 2 and 3 contain about 20 to about 70% by weight and more than 70% by weight of irbesartan, respectively. 0.1N heated to
An oral irbesartan formulation is shown that exhibits dissolution behavior of about 80% or more eluting within 30 minutes when the dissolution test is performed with 1000 mL of hydrochloric acid and a paddle speed of 50 rpm.

  On the other hand, various pharmaceutical dosage forms for oral use have been known, but there are few dosage forms that take into consideration the ease of swallowing patients and are particularly suitable for elderly people, children, and severely ill patients who have trouble taking drugs. A new dosage form is desired. For example, tablets and capsules are the most widely used dosage forms due to their fixed dose or physicochemical stability and manufacturing cost. However, they are difficult to swallow and can be used for throat use. Many patients dislike it. Powders and granules remain in the mouth and are difficult to swallow, leaving discomfort in the mouth. Although liquid preparations such as syrups have been in dosage forms suitable for the elderly and children, taking by metering is difficult for the elderly, children and severely ill patients, and the correct amount cannot be expected. Also, there was a problem with physicochemical stability. Recently, many technologies relating to formulations that rapidly disintegrate in the oral cavity have been disclosed as dosage forms that retain the fixed dose properties and physicochemical stability of tablets and capsules and that are easy to swallow like syrups. ing.

  However, the above technique uses a relatively large amount of water, so that the drug is likely to be unstable, the drug does not have the appropriate strength, and may be damaged in the distribution process. When tableting, it has difficulty in handling such as causing tableting troubles such as sticking and capping, and has various problems. In order to solve the above-mentioned problems, various combinations of additives and manufacturing methods have been studied. For example, the manufacturing method is complicated, such as a method of humidifying and drying a molded tablet or an external lubrication method. Many of them required a lot of equipment.

  Patent Document 4, Patent Document 5 and the like are relatively versatile techniques, both of which exhibit rapid disintegration in the oral cavity, have appropriate strength, and do not depend on a special manufacturing method. Further consideration was necessary to provide the tablets.

  Patent Document 6 discloses a tablet that exhibits a rapid disintegration property and good dosing feeling in the oral cavity and has an appropriate strength that does not collapse during the distribution process. Patent Document 7 discloses a tablet that rapidly disintegrates (disintegrates) in the mouth using a soluble diluent used in the form of a directly compressible product. However, these techniques have problems such as degradation in the oral cavity when the content of the pharmaceutically active ingredient in the preparation is high.

  Patent Document 8 discloses an orally disintegrating tablet containing 125 mg of irbesartan in one tablet weight of 500 mg. The preparation is large as a tablet, and even if it is an orally disintegrating tablet, it cannot be said that the dosage is good. Furthermore, the breaking force (tablet hardness) of 2.5 kp cannot be said to be a sufficient strength in handling the preparation.

  Furthermore, as described above, a poorly water-soluble pharmaceutically active ingredient such as irbesartan has a low affinity with water, and therefore, it is generally not easy to produce a preparation with good dissolution property. In addition, when the preparation is contained at a high concentration in order to reduce the size of the preparation, the affinity with water is further reduced. Therefore, it is very difficult to produce an orally disintegrating tablet containing irbesartan at a high concentration and having good dissolution properties.

US Pat. No. 5,270,317 US Pat. No. 6,342,247 JP 2008-501680 A Japanese Patent Laid-Open No. 10-182436 Japanese Patent Laid-Open No. 9-71523 International Publication No. 00/47233 Pamphlet JP-A-11-35450 JP 2001-302499 A

  An object of the present invention is to provide a pharmaceutical composition of irbesartan that exhibits good dissolution properties. Further, another problem of the present invention is that (1) it can be easily manufactured with general equipment without requiring special formulation technology, (2) has an appropriate strength that does not collapse in the distribution process, (3) An object of the present invention is to provide an orally disintegrating tablet containing irbesartan having excellent characteristics such as rapid disintegration in the oral cavity and (4) good dissolution properties.

As a result of intensive studies to solve such problems, the present inventors can obtain a tablet containing irbesartan exhibiting good dissolution properties when hydroxypropylcellulose and / or polyvinyl alcohol is used as a binder. I found.
Further, the inventors have (1) D-mannitol, (2) irbesartan, (3) crospovidone and / or carmellose, (4) hydroxypropylcellulose and / or polyvinyl alcohol, and (5) sodium stearyl fumarate. In combination with sucrose fatty acid ester, it disintegrates within 1 minute, more preferably within 45 seconds in the oral cavity, which is considered difficult to prepare with a conventional compression molding machine, and has practical hardness. Furthermore, it was found that a tablet containing irbesartan showing better dissolution properties can be obtained.

That is, the present invention is as follows.
[1] An irbesartan-containing pharmaceutical composition comprising one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol (hereinafter also referred to as “irbesartan-containing pharmaceutical composition of the present invention” or “the present invention composition”).
[2] Contains (1) an excipient, (2) irbesartan, (3) a disintegrant, (4) one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol, and (5) a lubricant. The pharmaceutical composition according to [1] above.
[3] The pharmaceutical composition according to [2] above, wherein the excipient is one or more compounds selected from lactose hydrate, anhydrous lactose and D-mannitol.
[4] The lubricant is one or more compounds selected from calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, sodium stearyl fumarate, zinc stearate, stearic acid and talc. The pharmaceutical composition according to [2] or [3].
[5] (1) D-mannitol, (2) irbesartan, (3) one or more disintegrants selected from crospovidone and carmellose, (4) one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol And (5) an orally disintegrating tablet containing at least one lubricant selected from sodium stearyl fumarate and a sucrose fatty acid ester (hereinafter also referred to as “orally disintegrating tablet of the present invention”).
[6] The orally disintegrating tablet according to [5], wherein the disintegrant is crospovidone.
[7] The orally disintegrating tablet according to [5] or [6] above, wherein the binder is hydroxypropylcellulose.
[8] The orally disintegrating tablet according to any one of the above [5] to [7], wherein the hydroxypropylcellulose has a viscosity of 2 to 10 mPa · s.
[9] The orally disintegrating tablet according to any one of the above [5] to [8], wherein the lubricant is sodium stearyl fumarate.
[10] The orally disintegrating tablet according to any one of [5] to [9], wherein the content of one or more disintegrants selected from crospovidone and carmellose is 1 w / w% to 20 w / w%.
[11] The oral cavity according to any one of [5] to [10] above, wherein the content of one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol is 0.01 w / w% to 2 w / w%. Inner disintegrating tablet.
[12] Any one of [5] to [11] above, wherein the content of one or more lubricants selected from sodium stearyl fumarate and sucrose fatty acid ester is 0.01 w / w% to 5 w / w% Orally disintegrating tablets.
[13] The orally disintegrating tablet according to any one of [5] to [12], wherein an average particle diameter of D-mannitol is greater than 30 μm and not greater than 150 μm.
[14] The orally disintegrating tablet according to any one of [5] to [13], wherein D-mannitol is a β-type crystal.
[15] The orally disintegrating tablet according to any one of [5] to [14], further comprising starch.
[16] The orally disintegrating tablet according to the above [15], wherein the starch is at least one selected from corn starch, potato starch, rice starch, and wheat starch.
[17] The orally disintegrating tablet according to any one of [5] to [16], further comprising a surfactant.
[18] An orally disintegrating tablet produced by mixing a granule containing irbesartan and a surfactant and a lubricant, wherein the surfactant is sodium lauryl sulfate, polysorbates, sucrose fatty acid ester, The orally disintegrating tablet according to [17], which is at least one selected from polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, and poloxamers (polyoxyethylene polyoxypropylene glycol).
[19] The orally disintegrating tablet according to the above [18], wherein the surfactant is at least one selected from polysorbates and poloxamers.
[20] The orally disintegrating tablet according to any one of [5] to [19], further comprising a taste-masking agent.
[21] The orally disintegrating tablet according to [20] above, wherein the corrigent is at least one selected from aspartame, thaumatin, sucralose, acesulfame K and neotame.
[22] The orally disintegrating tablet according to [21], wherein the corrigent is sucralose.
[23] The orally disintegrating tablet according to any one of the above [5] to [22], further comprising an organic acid or a salt thereof or a solvate thereof.
[24] The orally disintegrating tablet according to the above [23], wherein the organic acid is at least one selected from malic acid, citric acid, tartaric acid and ascorbic acid.
[25] The orally disintegrating tablet according to any one of [5] to [24], further including a fragrance. [26] The orally disintegrating tablet according to the above [25], wherein the flavor is at least one selected from coffee flavor, grapefruit flavor and cherry flavor.
[27] (1) D-mannitol having an average particle size of more than 30 μm and not more than 150 μm, (2) Irbesartan of 20 w / w% to 60 w / w%, (3) 1 w / w% to 20 w / w% Crospovidone and / or carmellose, (4) hydroxypropylcellulose that is 2 w / w% or less, (5) starch that is 5 w / w% to 20 w / w%, and (6) 0.1 w / w% to 5 w The orally disintegrating tablet according to any one of the above [5] to [26], comprising / w% sodium stearyl fumarate.
[28] The orally disintegrating tablet according to any one of the above [5] to [27], further comprising 0.01 w / w% to 0.5 w / w% of polysorbate 80.
[29] The orally disintegrating tablet according to any one of [5] to [28], wherein the tablet disintegrates within 60 seconds and has an absolute hardness of 1.0 N / mm ² or more.
[30] The orally disintegrating tablet according to any one of the above [5] to [29], which disintegrates within 45 seconds in the oral cavity and has an absolute hardness of 1.5 N / mm ² or more.
[31] The orally disintegrating tablet according to any one of the above [5] to [30], which is produced using granules obtained by wet granulation of a mixture containing irbesartan.
[32] The orally disintegrating tablet according to [31] above, which is produced using granules obtained by wet granulation of a mixture containing D-mannitol, irbesartan and a disintegrant.
[33] The method described in [31] or [32] above, which comprises a step of mixing a granule obtained by wet granulation of a mixture containing irbesartan and a granule containing sucralose. Orally disintegrating tablets.
[34] The above [31] or [32, characterized by being produced by mixing a granule obtained by wet granulation of a mixture containing irbesartan and a granule containing sucralose and an organic acid. Orally disintegrating tablets.
[35] The method according to [31] or [32] above, wherein the granule obtained by wet granulation of a mixture containing irbesartan is mixed with a mixture containing sucralose. Orally disintegrating tablets.
[36] The pharmaceutical composition or oral cavity according to any one of [1] to [35] above, wherein as a result of the dissolution test in the second dissolution solution of the 15th revised Japanese Pharmacopoeia, irbesartan is eluted at 70% or more in 15 minutes Inner disintegrating tablet.

The irbesartan-containing pharmaceutical composition of the present invention is obtained by using one or two binders selected from the group consisting of hydroxypropylcellulose and polyvinyl alcohol.
1) High irbesartan content and miniaturized tablets can be produced, thereby increasing patient compliance, and (2) having excellent characteristics (good dissolution properties) in the release of irbesartan.
Furthermore, (1) one or more disintegrants selected from D-mannitol, (2) irbesartan, (3) crospovidone and carmellose, (4) one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol, And (5) The orally disintegrating tablet of the present invention containing one or more lubricants selected from sodium stearyl fumarate and sucrose fatty acid ester exhibits rapid disintegration in the oral cavity and collapses in the distribution process Even when irbesartan is contained at a high concentration, it exhibits good elution properties. Moreover, the orally disintegrating tablet of the present invention does not require a special device and can be easily produced.

Hereinafter, the present invention will be described in more detail.
In the present invention, as irbesartan which is an active ingredient, a pulverized product or a pulverized product may be used as necessary for improving handling property or dissolution property. Further, for the purpose of bitterness masking, elution control, stabilization, etc., part or all of the surface may be coated with a binder or coating agent such as a water-soluble polymer.
The content of irbesartan in the composition of the present invention is usually 65 w / w% or less, preferably 60 w / w% or less. Although the minimum of content is not specifically limited, Usually, it is 20 w / w% or more, Preferably the quantity exceeding 30 w / w% is mentioned. More preferably, it is 20 w / w% or more and 60 w / w% or less, More preferably, it exceeds 30 w / w% and 60 w / w% or less is mentioned.

The composition of the present invention contains one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol.
The binder used in the composition of the present invention not only promotes granulation of granules containing irbesartan, but also promotes dissolution of irbesartan. The hydroxypropyl cellulose used as the binder of the composition of the present invention preferably has a viscosity of 2 to 10 mPa · s at 20 ° C. in a 2% aqueous solution.
Although the content in the composition of the present invention of one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol is not particularly limited, it may be 10 w / w% or less. Preferably 5 w / w% or less is mentioned, More preferably, 3 w / w% or less is mentioned. Moreover, 0.01 w / w% or more, Preferably 0.05 w / w% or more is mentioned. More preferably, 0.01 w / w%-3 w / w% are mentioned, More preferably, 0.05 w / w%-3 w / w% are mentioned. When hydroxypropyl cellulose and polyvinyl alcohol are used in combination, the above range is exemplified as the total content thereof.

  As long as the composition of the present invention does not affect the effects of the present invention, non-toxic and inert additives usually used in the pharmaceutical field other than the above can be added. The additive to be used may be any pharmaceutically acceptable, for example, excipients, disintegrants, lubricants, binders other than hydroxypropylcellulose and polyvinyl alcohol, surfactants, sweeteners, Examples include flavoring agents, organic acids, flavoring agents / fragrances, fluidizing agents, coloring agents, stabilizers, coating agents, and starches.

  Examples of the composition of the present invention include (1) an excipient, (2) irbesartan, (3) a disintegrant, (4) one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol, and (5) A pharmaceutical composition containing a lubricant is exemplified.

Excipients used in the composition of the present invention include, for example, lactose (lactose hydrate, anhydrous lactose), sucrose, sucrose, fructose, fructooligosaccharide, glucose, maltose, reduced maltose, powdered sugar, powdered koji, reduced lactose, etc. Sugars such as erythritol, sorbitol, maltitol, xylitol, D-mannitol, kaolin, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, starch (eg, corn starch, potato starch, rice starch, wheat starch, etc.) Natural starch), crystalline cellulose and the like. Preferably, sugars such as lactose hydrate and anhydrous lactose, sugar alcohols such as D-mannitol, starch, and crystalline cellulose are used.
The content of the excipient in the composition of the present invention is not particularly limited, and is usually 20 w / w% to 75 w / w%, preferably 25 w / w% to 50 w / w%. The content in the composition of the present invention of the total amount of the excipient when two or more excipients are used is also the same as described above.

Examples of the disintegrant used in the composition of the present invention include croscarmellose sodium, carmellose calcium, carboxymethyl starch sodium, low-substituted hydroxypropylcellulose, crospovidone, carmellose and the like.
The content of the disintegrant in the composition of the present invention is not particularly limited, but is usually 1 to 20 w / w%, preferably 1 w / w% to 15 w / w%. The content in the composition of the present invention of the total amount of disintegrant when two or more disintegrants are used is also the same as described above.

Lubricants used in the present composition are calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, zinc stearate, stearic acid, talc, carnauba wax, Examples thereof include L-leucine and macrogol.
The content of the lubricant in the composition of the present invention is not particularly limited, but is usually 0.01 w / w% to 5 w / w%, preferably 0.01 w / w% to 4 w / w%. The content of the lubricant in the composition of the present invention when two or more lubricants are used is also the same as described above.

In the composition of the present invention, a binder usually used in the pharmaceutical field other than hydroxypropylcellulose and polyvinyl alcohol can be added as long as the effect of the present invention is not affected. Examples of the binder include pregelatinized starch, povidone (polyvinylpyrrolidone), hydroxypropylmethylcellulose (hypromellose), agar, and gelatin. The binder can be used alone or in combination of two or more.
The content of the binder other than hydroxypropylcellulose and polyvinyl alcohol in the composition of the present invention is not particularly limited as long as it does not affect the effects of the present invention.

In the composition of the present invention, more preferable dissolution property can be obtained by further containing a surfactant. Surfactants include ionic surfactants such as sodium lauryl sulfate, or polysorbates, sucrose fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene hydrogenated castor oil and poloxamers (polyoxyethylene polyoxypropylene). Nonionic surfactants such as glycol), preferably nonionic surfactants such as polysorbates, sucrose fatty acid esters, polyglycerin fatty acid esters, polyoxyethylene hydrogenated castor oil and poloxamers. More preferred are polysorbates and poloxamers, and most preferred are polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and poloxamer 188. Surfactant can be used 1 type or in combination of 2 or more types.
The content of the surfactant in the composition of the present invention is preferably 0.01 w / w% to 2 w / w%, more preferably 0.01 w / w% to 0.5 w / w%.

Examples of the fluidizing agent used in the composition of the present invention include light anhydrous silicic acid and magnesium aluminate metasilicate. A fluidizing agent can be used 1 type or in combination of 2 or more types.
The content of the fluidizing agent in the composition of the present invention is preferably 3 w / w% or less, more preferably 2 w / w% or less.

  Examples of the colorant used in the composition of the present invention include iron sesquioxide, yellow iron sesquioxide, and black iron sesquioxide. An appropriate amount of the colorant can be appropriately added in combination of one or two or more.

  The composition of the present invention (particularly the orally disintegrating tablet of the present invention described in detail below) has good dissolution properties. Specifically, in the dissolution test using the second solution of dissolution test according to the 15th revised Japanese Pharmacopoeia dissolution test method (paddle method), the dissolution rate of irbesartan at 15 minutes is usually 65% or more, preferably 70%. That's it.

  Examples of the dosage form of the composition of the present invention include tablets such as uncoated tablets, chewable tablets, and film-coated tablets. From the viewpoint of ease of taking, orally disintegrating tablets are preferred.

When the composition of the present invention is an orally disintegrating tablet, D-mannitol is preferred as an excipient. D-mannitol has a tendency that if the particle size is too small, the compression moldability is improved, but the disintegration property tends to be remarkably lowered. There is also a feeling of roughness in the oral cavity, and the feeling of taking worsens. The average particle diameter of D-mannitol used in the present invention is from 10 μm to 500 μm, more preferably from 30 μm to 200 μm, and still more preferably from 30 μm to 150 μm.
Here, in this specification, an average particle diameter means the median diameter by volume basis calculated from the particle size distribution measured by the dry method with the laser diffraction type particle size distribution meter.

  In addition, D-mannitol is known to have α, β, and δ crystal polymorphs, and in the present application, the crystal form is not particularly limited, but α and δ are relatively different depending on temperature and humidity. Since the crystal form easily changes, it is preferable to use the β type which is the most stable form. The content of D-mannitol in the preparation is not particularly limited, but is preferably 20 w / w% or more, and more preferably 25 w / w% or more. Although the upper limit of content is not specifically limited, 75 w / w% or less is mentioned, Preferably 50 w / w% or less is mentioned.

When the composition of the present invention is an orally disintegrating tablet, the content in the preparation of one or more binders selected from hydroxypropylcellulose and polyvinyl alcohol is preferably 2 w / w% or less, more preferably 1 w / w% or less is mentioned, More preferably, 0.5 w / w% or less is mentioned. Moreover, Preferably it is 0.01 w / w% or more, More preferably, 0.05 w / w% or more is mentioned. Preferably 0.01 w / w% to 2 w / w% is mentioned, More preferably, 0.01 w / w% to 1 w / w% is mentioned, More preferably, 0.05 w / w% to 0.5 w / w %. When hydroxypropyl cellulose and polyvinyl alcohol are used in combination, the above range is exemplified as the total content thereof.
When the composition of the present invention is an orally disintegrating tablet, it is preferable to use a hydroxypropyl cellulose having a 2% aqueous solution viscosity at 20 ° C. of 2 to 10 mPa · s.

  When the composition of the present invention is an orally disintegrating tablet, a binder other than hydroxypropylcellulose and polyvinyl alcohol can be added as long as the effect of the present invention is not affected. Examples of the binder are the same as those described above for the composition of the present invention. The content of the binder other than hydroxypropylcellulose and polyvinyl alcohol in the preparation of the present invention is not particularly limited as long as it does not affect the effects of the present invention.

  When the composition of the present invention is an orally disintegrating tablet, examples of the disintegrant include crospovidone and carmellose, and particularly preferably crospovidone. The content in the preparation of one or more disintegrants selected from crospovidone and carmellose is not particularly limited, but preferably 1 to 20 w / w%, more preferably 1 w / w% to 15 w / w%. . When crospovidone and carmellose are used in combination, the above range is exemplified as their total content.

In addition, the orally disintegrating tablet of the present invention can be added with a disintegrating agent usually used in the pharmaceutical field other than the above as long as it does not affect the effects of the present invention. Examples of the disintegrant include croscarmellose sodium, carboxymethylcellulose calcium, carboxymethyl starch sodium, and low-substituted hydroxypropylcellulose.
The disintegrant content other than crospovidone and carmellose is not particularly limited as long as it does not affect the effect of the present invention.

  When the composition of the present invention is used as an orally disintegrating tablet, more preferable disintegration can be obtained by further containing starch. Examples of the starch include natural starches such as corn starch, potato starch, rice starch, and wheat starch. The content of starch in the preparation is not particularly limited, but examples include 1 w / w% to 50 w / w%, preferably 5 w / w% to 30 w / w%, more preferably 5 w / w% to 20 w / w%. Is mentioned.

When the composition of the present invention is an orally disintegrating tablet, the lubricant preferably includes sodium stearyl fumarate and sucrose fatty acid ester, more preferably sodium stearyl fumarate. The content in the preparation of one or more lubricants selected from sodium stearyl fumarate and sucrose fatty acid ester is not particularly limited, but is usually used in the range of 0.01 w / w% to 5 w / w%, preferably The range of 0.01-4 w / w% is mentioned. Moreover, when using an external lubrication apparatus, the range of 0.01 w / w%-0.5 w / w% is preferable, and when mixing with the composition for compression, 0.5 w / w%-4 w / w % Range is preferred. When using a combination of sodium stearyl fumarate and a sucrose fatty acid ester, the above range is exemplified as the total content thereof. Further, in the case of sodium stearyl fumarate, 0.1 w / w% to 5 w / w% is preferable, and 1.5 w / w% to 4 w / w% is more preferable.
When the composition of the present invention is an orally disintegrating tablet, the lubricant is a granule (preferably a granule obtained by wet granulation) containing irbesartan and an optional additive (for example, a surfactant). It is preferable to use it after mixing.

  In addition, the orally disintegrating tablet of the present invention can be added with a lubricant usually used in the pharmaceutical field other than the above as long as it does not affect the effects of the present invention. Examples of the lubricant include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, zinc stearate, stearic acid, talc, carnauba wax, L-leucine, and macrogol. The content of the lubricant in the preparation other than sodium stearyl fumarate and sucrose fatty acid ester is not particularly limited as long as it does not affect the effect of the present invention.

  When the composition of the present invention is an orally disintegrating tablet, a more preferable dissolution property can be obtained by further containing a surfactant. Examples of the surfactant include the same as those described above for the composition of the present invention, and the surfactant content includes the range described above for the composition of the present invention.

When making this invention composition into an orally disintegrating tablet, it is preferable to contain an organic acid or its salt, or those solvates. Examples of the organic acid include malic acid, citric acid, tartaric acid, ascorbic acid and the like, and preferably citric acid and malic acid. The salt of the organic acid is not particularly limited as long as it is a pharmaceutically acceptable salt, and examples thereof include sodium salt, potassium salt, calcium salt, magnesium salt, or a double salt thereof, and acidic hydrogen remains. It may be an acidic salt (for example, disodium citrate). Examples of organic acids or solvates thereof include hydrates. The organic acid or a salt thereof or a solvate thereof can be used alone or in combination of two or more.
The content of the organic acid or a salt thereof or a solvate thereof in the preparation is preferably 0.025 w / w% to 7.5 w / w%, more preferably 0.25 w / w% to 2.5 w / w%. Is mentioned.

  When making this invention composition into an orally disintegrating tablet, it is preferable to contain a sweetener and a corrigent. Examples of the sweetener and flavoring agent include high-intensity sweeteners such as aspartame, saccharin, sodium saccharin, dipotassium glycyrrhizinate, stevia, thaumatin, sucralose, acesulfame K, and neotame. Preferred high-intensity sweeteners include aspartame, thaumatin, sucralose, acesulfame K, and neotame, and particularly preferred high-intensity sweeteners include sucralose. The sweetener and the corrigent can be appropriately added in an appropriate amount by combining one or more kinds.

  When making this invention composition into an orally disintegrating tablet, it is preferable to contain a flavoring agent and a fragrance | flavor. Examples of the flavoring agent / fragrance include citrus flavors such as lemon, orange, grapefruit, peppermint, spearmint, menthol, pine, cherry, fruit, yogurt, coffee, etc. Preferred flavoring agents / fragrances include Examples include citrus flavors such as lemon, orange and grapefruit, cherry, and coffee. There may be a case where a more preferable feeling is obtained by blending the sweetener, the flavoring agent, and the flavoring agent / fragrance. Flavoring agents and fragrances can be appropriately added in an appropriate amount by combining one kind or two or more kinds.

When the composition of the present invention is an orally disintegrating tablet, (1) one or more disintegrating agents selected from (1) D-mannitol, (2) irbesartan, (3) crospovidone and carmellose, (4) hydroxypropylcellulose Orally disintegrating tablets containing one or more binders selected from polyvinyl alcohol and (5) one or more lubricants selected from sodium stearyl fumarate and sucrose fatty acid esters are preferred.
The orally disintegrating tablet of the present invention containing the above components (1) to (5) not only has the good dissolution properties described above for the composition of the present invention, but also has a rapid disintegrating property in the oral cavity, And it has an appropriate strength that does not collapse during the distribution process. Specifically, the orally disintegrating tablet of the present invention usually disintegrates within 60 seconds (preferably within 45 seconds) in the oral cavity, and usually has an absolute hardness of 1.0 N / mm ² or more (preferably 1.5 N). / Mm ² or more). The upper limit of the absolute hardness is not particularly limited, but is usually 4 N / mm ² or less.
The orally disintegrating tablet of the present invention has the above-mentioned good dissolution property, disintegration property and appropriate strength even when irbesartan is contained at a high concentration of 20 w / w% or more, preferably more than 30 w / w%. It is useful in.

As the orally disintegrating tablet of the present invention, (1) D-mannitol having an average particle size of more than 30 μm and 150 μm or less, (2) 20 w / w% to 60 w / w% (preferably 30 w / w%) Irbesartan that is greater than or equal to 60 w / w%), (3) crospovidone and / or carmellose that is between 1 w / w% and 20 w / w%, (4) hydroxypropylcellulose that is less than or equal to 2 w / w%, (5) Orally disintegrating tablets containing 5 w / w% to 20 w / w% starch and (6) 0.1 w / w% to 5 w / w% sodium stearyl fumarate are preferred.
As the orally disintegrating tablet of the present invention, an orally disintegrating tablet containing 0.01 w / w% to 0.5 w / w% of polysorbate 80 is further preferable.

The composition of the present invention may be formulated by a method known per se in the pharmaceutical field.
Although the manufacturing method of a tablet in this invention is not specifically limited, For example, it can manufacture with the following method.
Irbesartan and optional additives [eg excipients (eg D-mannitol, crystalline cellulose), disintegrants (eg crospovidone, carmellose, croscarmellose sodium), starch (eg corn starch), colorants ( For example, yellow ferric oxide) and the like, and the resulting mixture is selected from binders (hydroxypropylcellulose and polyvinyl alcohol) containing a surfactant (eg, polysorbate 80, polysorbate 188) as necessary. Granulated with an aqueous solution of one or more binders) and dried. In the obtained granule containing irbesartan, any additive [for example, lubricant (for example, sodium stearyl fumarate, magnesium stearate), fluidizing agent (for example, light anhydrous silicic acid), sweetener or taste masking Agent (eg, sucralose), flavor or flavoring (eg, coffee flavor, cherry flavor, grapefruit flavor), organic acid (eg, citric acid, malic acid), starch (eg, corn starch), etc.] A tablet can be obtained by compression molding. The granulated product containing irbesartan may contain any additive [for example, sweetener or flavoring agent (for example, sucralose), flavoring or flavoring (for example, coffee flavoring, cherry flavoring, grapefruit flavoring), organic acid Granules (eg, citric acid, malic acid), starch (eg, corn starch, etc.), and lubricants (eg, sodium stearyl fumarate, magnesium stearate, sucrose fatty acid esters), fluidizing agents ( For example, light anhydrous silicic acid) or the like may be mixed and compression-formed.
Irbesartan may be used by coating part or all of its surface with a binder or coating agent such as a water-soluble polymer for the purpose of bitterness masking, elution control, stabilization, and the like.

  As the granulation method, wet granulation is preferred. Examples of the wet granulation method include a fluidized bed granulation method, a stirring granulation method, an extrusion granulation method, a kneading granulation method, and a spray granulation method. Of these, the stirring granulation method and the kneading granulation method are preferable. When there is a possibility of inhibiting the uniformity of the content of medicinal ingredients, such as when each component used is agglomerated or crystals or granulated products are large, each component may be ground before or after mixing. It is desirable to use a method to adjust the particle size so as to ensure content uniformity.

The method for forming the tablet (orally disintegrating tablet) is not particularly limited, but in the case of commercial production, a compression molding method using a rotary tableting machine or a single tableting machine is used.
The tablet of the present invention (orally disintegrating tablet) can be compression-molded without using an external lubrication method, but can of course be molded using an external lubrication method. In this case, after mixing the ingredients excluding the lubricant, the tableting is performed while spraying the lubricant on the tooling, or a part of the lubricant is mixed in advance, and then the remaining lubricant is mixed. Tablet while spraying on the tool.
The compression molding force is not particularly limited as long as it gives a tablet (orally disintegrating tablet) with sufficient strength, but a compression force of 1 kN (about 100 kgf) or more is preferable. The shape of the tablet (orally disintegrating tablet) obtained in the present invention is not particularly limited, and may be any shape such as a circular tablet, a circular R tablet, a circular corner tablet, a circular two-stage R tablet, and various irregular tablets. It may be a split tablet.

When the composition of the present invention is used as an orally disintegrating tablet, although not particularly limited, granules obtained by wet granulation of a mixture containing irbesartan (preferably a mixture containing irbesartan, D-mannitol and a disintegrant) It is preferable to manufacture using.
In the present invention, the method for producing an orally disintegrating tablet preferably includes the following steps.
(1) Step of obtaining granules by wet granulating a mixture containing irbesartan (2) Granules obtained in (1) above and granules containing sucralose (preferably granules containing sucralose and an organic acid) Or the process of mixing the mixture containing sucralose (3) The process of shape | molding the mixture obtained by said (2)

  In the present invention, the “orally disintegrating tablet” means a tablet that disintegrates within 60 seconds, preferably within 45 seconds with only saliva in the oral cavity, and can be taken in the oral cavity without ingesting water. To do. The time for disintegration in the oral cavity can be measured with good reproducibility by using an orally disintegrating tablet tester (model ODT-101, Toyama Sangyo Co., Ltd.).

In the present invention, the “absolute hardness” indicates a value obtained by dividing the tablet hardness by the fracture area. In addition, the practical hardness means not only that the tablet is not broken when it is taken out from the PTP, but also has a strength that can be applied to the tablet automatic packaging machine during manufacturing and distribution process, and also at the time of dispensing, Specifically, usually 1.0 N / mm ² or more as an absolute hardness, preferably 1.5 N / mm ² or more, more preferably include 2.0 N / mm ² or more strength. “Tablet hardness” can be measured by a tablet hardness meter (for example, model TH-203MP, Toyama Sangyo Co., Ltd.). In the present invention, the “breaking area” is a value calculated from the tablet shape and tablet thickness.

The irbesartan-containing pharmaceutical composition of the present invention and the orally disintegrating tablet of the present invention are useful for the treatment of hypertension and the like as an angiotensin II receptor antagonist.
The irbesartan-containing pharmaceutical composition of the present invention and the orally disintegrating tablet of the present invention can be safely orally administered to mammals such as humans.
The dose can be appropriately selected depending on the age, body weight, severity of the disease, etc. For example, 50 to 300 mg per day is administered to an adult.

  EXAMPLES Hereinafter, although an Example, a comparative example, and a test example are given and this invention is demonstrated in more detail, this invention is not limited.

[Example 1]
In accordance with the following formulation, irbesartan, D-mannitol, crystalline cellulose (Theolas PH-101, manufactured by Asahi Kasei Kogyo Co., Ltd.), croscarmellose sodium (Ac-Di-Sol, manufactured by FMC Co., Ltd.), a small universal mixer (dispensing mixer, Shinagawa Co., Ltd.) After being prepared and mixed in (manufactured by Kogyosho), an aqueous solution of hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda) was added and kneaded. The kneaded product was dried and sized. After mixing magnesium stearate into the obtained granulated product, using a single tableting machine (EK0, manufactured by KORSCH), a compressive force of about 4 kN with a circular tablet die having a diameter of 8 mm and a curvature radius of 12 mm. To obtain tablets.

[Example 2]
In accordance with the following formulation, irbesartan, D-mannitol, crystalline cellulose (Theolas PH-101, manufactured by Asahi Kasei Kogyo Co., Ltd.), croscarmellose sodium (Ac-Di-Sol, manufactured by FMC Co., Ltd.), a small universal mixer (dispensing mixer, Shinagawa Co., Ltd.) After being prepared and mixed, the aqueous solution of polyvinyl alcohol (GOHSENOL EG-05, manufactured by Nippon Synthetic Chemical) was added and kneaded. The kneaded product was dried and sized. After mixing magnesium stearate into the obtained granulated product, using a single tableting machine (EK0, manufactured by KORSCH), a compressive force of about 4 kN with a circular tablet die having a diameter of 8 mm and a curvature radius of 12 mm. To obtain tablets.

[Test Example 1]
The tablets of Examples 1 and 2 were subjected to a dissolution test using the second solution of dissolution test according to the 15th revised Japanese Pharmacopoeia dissolution test method (paddle method), and the dissolution rate at 15 minutes was determined. It was 70% or more (Table 3).

[Example 3]
In accordance with the following formulation, irbesartan, D-mannitol, corn starch, crospovidone (Polyplastone XL-10, manufactured by ISP) were charged into a small universal mixer (dispensing mixer, manufactured by Shinagawa Kogyo Co., Ltd.) and mixed. Hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda) aqueous solution was added and kneaded. The kneaded product was dried and sized. After mixing light anhydrous silicic acid (ADSOLIDER 101, manufactured by Freund Sangyo) and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) with the obtained granulated product, a single tableting machine (EK0, manufactured by KORSCH) was used. Then, the tablet was obtained by molding with a compression force of about 6 kN in a circular tablet die having a diameter of 9 mm and a curvature radius of 14 mm.

[Example 4]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed and then a small universal mixer (dispensing mixer) together with irbesartan, D-mannitol, crospovidone (Polyplastidone XL-10, manufactured by ISP) , Manufactured by Shinagawa Kogyo Co., Ltd.), and after mixing, an aqueous solution of hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda) was added and kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), coffee flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine (EK0, KORSCH) Was used to form tablets with a compression force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm.

[Example 5]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed and then a small universal mixer (dispensing mixer) together with irbesartan, D-mannitol, crospovidone (Polyplastidone XL-10, manufactured by ISP) , Manufactured by Shinagawa Kogyo Co., Ltd.), and after mixing, an aqueous solution of hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda) was added and kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), citric acid, cherry flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine ( EK0, manufactured by KORSCH) was molded with a compressive force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm to obtain tablets.

[Example 6]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed and then a small universal mixer (dispensing mixer) together with irbesartan, D-mannitol, crospovidone (Polyplastidone XL-10, manufactured by ISP) , Manufactured by Shinagawa Kogyo Co., Ltd.), mixed, and then added a solution of hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda) and polysorbate 80 (NIKKOL TO-10MV, manufactured by Nikko Chemicals) in water. Kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), malic acid, grapefruit fragrance, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) into the obtained granulated product, a single tableting machine ( EK0, manufactured by KORSCH) was molded with a compressive force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm to obtain tablets.

[Example 7]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed, and then irbesartan, D-mannitol, crospovidone (Polyplastone XL-10, manufactured by ISP Co., Ltd.) is a small universal mixer (dispensing mixer) , Manufactured by Shinagawa Kogyo Co., Ltd.), mixed, and then mixed with a solution of hydroxypropylcellulose (HPC-L, manufactured by Nippon Soda) and Poloxamer 188 (Pluronic F68, manufactured by ADEKA) in water. Combined. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), malic acid, grapefruit fragrance, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) into the obtained granulated product, a single tableting machine ( EK0, manufactured by KORSCH) was molded with a compressive force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm to obtain tablets.

[Example 8]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed, and then irbesartan, D-mannitol, crospovidone (Polyplastone XL-10, manufactured by ISP Co., Ltd.) is a small universal mixer (dispensing mixer) , Shinagawa Kogyo Co., Ltd.), and after mixing, a solution obtained by dissolving polyvinyl alcohol (GOHSENOL EG-05, Nippon Synthetic Chemical) and polysorbate 80 (NIKKOL TO-10MV, Nikko Chemicals) in water is added. And kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), coffee flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine (EK0, KORSCH) Was used to form tablets with a compression force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm.

[Example 9]
After pre-mixing corn starch (for granulation) and yellow ferric oxide according to the following formulation, irbesartan, D-mannitol, carmellose (NS-300, manufactured by Gotoku Pharmaceutical) is a small universal mixer (dispensing mixer, Shinagawa Co., Ltd.) After being prepared and mixed, a solution obtained by dissolving hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda) and polysorbate 80 (NIKKOL TO-10MV, manufactured by Nikko Chemicals) in water was added and kneaded. . The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), coffee flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine (EK0, KORSCH) Was used to form tablets with a compression force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm.

[Example 10]
After charging and mixing irbesartan, D-mannitol, corn starch, croscarmellose sodium (Ac-Di-Sol, manufactured by FMC) into a small universal mixer (dispensing mixer, manufactured by Shinagawa Kogyo Co., Ltd.) according to the following formulation Hydroxypropyl cellulose (HPC-L, manufactured by Nippon Soda) aqueous solution was added and kneaded. The kneaded product was dried and sized. The resulting granulated product was mixed with light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA), and then used a single tableting machine (EK0, manufactured by KORSCH) with a diameter of 9 mm and a radius of curvature of 14 mm. Were molded with a compressive force of about 6 kN in a circular tablet mold to obtain tablets.

[Comparative Example 1]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed and then a small universal mixer (dispensing mixer) together with irbesartan, D-mannitol, crospovidone (Polyplastidone XL-10, manufactured by ISP) , Manufactured by Shinagawa Kogyo Co., Ltd.), and after mixing, water was added and kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), coffee flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine (EK0, KORSCH) Was used to form tablets with a compression force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm.

[Comparative Example 2]
In accordance with the following formulation, corn starch (for granulation) and yellow ferric oxide are premixed, and then irbesartan, D-mannitol, crospovidone (Polyplastone XL-10, manufactured by ISP Co., Ltd.) is a small universal mixer (dispensing mixer) , Manufactured by Shinagawa Kogyo Co., Ltd.) and mixed, and then an aqueous solution of methyl cellulose (Metroses SM-15, manufactured by Shin-Etsu Chemical) was added and kneaded. The kneaded product was dried and sized. After mixing sucralose, corn starch (for powder mixing), citric acid, cherry flavor, light anhydrous silicic acid and sodium stearyl fumarate (PRUV, manufactured by JRS PHARMA) to the obtained granulated product, a single tableting machine ( EK0, manufactured by KORSCH) was molded with a compressive force of about 4 kN in a circular tablet mold having a diameter of 8 mm and a curvature radius of 12 mm to obtain tablets.

[Test Example 2]
For the tablets of Examples 3 to 10 and Comparative Examples 1 and 2, using an orally disintegrating tablet tester (Toyama Sangyo Co., Ltd., model ODT-101), test solution: water (37 ± 1 ° C.), weight mass: 15 g The disintegration time was measured under the condition of rotation speed: 25 rpm. Moreover, the hardness was measured using a tablet hardness meter (Toyama Sangyo Co., Ltd. TH-203MP), and the value obtained by dividing the obtained hardness by the area of the fracture surface of the tablet was expressed as absolute hardness. Furthermore, in accordance with the 15th revised Japanese Pharmacopoeia dissolution test method (paddle method), a dissolution test was conducted with the second dissolution test solution, and the dissolution rate at 15 minutes was determined. Moreover, the feeling of administration when the tablet was contained in the mouth and completely disintegrated was determined. These results are shown in Table 14.
All of the preparations of Examples 3 to 10 were good with a 15-minute dissolution rate of 70% or more. The preparations of Examples 3 to 9 containing crospovidone or carmellose as a disintegrant have an absolute hardness of 2.0 N / mm ² or more and a disintegration time of 45 seconds or less, and have sufficient disintegrability as an orally disintegrating tablet. It was. Moreover, the bitterness of the preparations of Examples 4 to 9 containing sucralose was reduced to a level at which it can be taken and had a good feeling of taking.
Although the disintegration time of the preparation of Comparative Example 1 was as fast as 27 seconds, the 15-minute dissolution rate was 61%, which was not good dissolution. The preparation of Comparative Example 2 had a disintegration time as slow as 95 seconds and a 15-minute dissolution rate of 62%, and both disintegration and dissolution were insufficient.

  According to the present invention, an irbesartan-containing pharmaceutical composition exhibiting good dissolution properties, and (1) it can be easily produced by general equipment without requiring a special preparation technique, and (2) an appropriate amount that does not collapse in the distribution process It is possible to provide an orally disintegrating tablet containing irbesartan having strength, (3) having rapid disintegration property in the oral cavity, and (4) having excellent dissolution properties.

Claims (22)

  (1) an excipient containing D-mannitol, (2) irbesartan, (3) one or more disintegrants selected from the group consisting of croscarmellose sodium, crospovidone, and carmellose, (4) hydroxypropylcellulose And one or more binders selected from polyvinyl alcohol, and (5) a lubricant (excluding magnesium stearate and sodium stearyl fumarate).   The excipient is selected from the group consisting of D-mannitol and sugars, sugar alcohols (excluding D-mannitol), kaolin, calcium hydrogen phosphate, calcium sulfate, calcium carbonate, starch, and crystalline cellulose. The pharmaceutical composition according to claim 1, optionally comprising more than one species.   The pharmaceutical composition according to claim 1 or 2, wherein the binder is polyvinyl alcohol.   The pharmaceutical composition according to claim 1 or 2, wherein the binder is hydroxypropylcellulose.   The lubricant is at least one selected from the group consisting of calcium stearate, glyceryl monostearate, glyceryl palmitostearate, sucrose fatty acid ester, zinc stearate, stearic acid, talc, carnauba wax, L-leucine, and macrogol. The pharmaceutical composition according to any one of claims 1 to 4, which is a species or more.   The pharmaceutical composition according to any one of claims 1 to 5, wherein the content of irbesartan is 20 w / w% to 65 w / w%.   The pharmaceutical composition according to any one of claims 1 to 5, wherein the content of irbesartan is 20 w / w% to 60 w / w%.   The pharmaceutical composition according to any one of claims 1 to 5, wherein the content of irbesartan is 30 w / w% to 65 w / w%.   The pharmaceutical composition according to claim 8, wherein the content of irbesartan is 30 w / w% to 60 w / w%.   The pharmaceutical composition according to any one of claims 1 to 9, wherein the content of the excipient is 20 w / w% to 75 w / w%.   The pharmaceutical composition according to any one of claims 1 to 10, wherein the content of the disintegrant is 1 w / w% to 20 w / w%.   The pharmaceutical composition according to any one of claims 1 to 11, wherein the content of the binder is 0.01 w / w% to 10 w / w%.   The pharmaceutical composition according to claim 12, wherein the content of the binder is 0.01 w / w% to 5 w / w%.   The pharmaceutical composition according to claim 13, wherein the content of the binder is 0.01 w / w% to 2 w / w%.   The pharmaceutical composition according to any one of claims 1 to 14, wherein the content of the lubricant is 0.01 w / w% to 5 w / w%.   The pharmaceutical composition according to any one of claims 1 to 15, wherein the pharmaceutical composition is a tablet.   The pharmaceutical composition according to any one of claims 1 to 15, wherein the pharmaceutical composition is an orally disintegrating tablet.   The orally disintegrating tablet according to claim 17, further comprising starch.   The orally disintegrating tablet according to claim 17 or 18, further comprising a surfactant.   Furthermore, the orally disintegrating tablet as described in any one of Claims 17-19 containing a flavoring agent.   The orally disintegrating tablet according to any one of claims 17 to 20, further comprising an organic acid or a salt thereof or a solvate thereof.   Furthermore, the orally disintegrating tablet as described in any one of Claims 17-21 containing a fragrance | flavor.