JP2016098190A - Oral pharmaceutical composition containing telmisartan - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an oral pharmaceutical composition containing telmisartan improving a feeling of dosing.SOLUTION: There is provided an oral pharmaceutical composition containing telmisartan-containing granules which has a layer (b)containing an acid and a layer (b) containing telmisartan and a basic compound outside of a nuclear particle.SELECTED DRAWING: None

Description

  The present invention relates to an oral pharmaceutical composition comprising telmisartan.

  Telmisartan (chemical name: 4 ′-{[4-methyl-6- (1-methyl-1H-benzimidazol-2-yl) -2-propyl-1H-benzimidazol-1-yl] methyl} biphenyl-2- Carboxylic acid) is one of angiotensin II receptor antagonists and is mainly used for the treatment of hypertension.

  As an oral medicine containing telmisartan, for example, a pharmaceutical composition in which a basic reagent and a poloxamer are blended with telmisartan is described (Patent Document 1).

International Publication No. 2004/028505

  In the pharmaceutical composition disclosed in Patent Document 1, when the telmisartan elutes in the body after taking the substance, various basic studies are simultaneously dissolved in the pharmaceutical composition of Patent Document 1 during various studies for improving the dosage of telmisartan. Thus, it has been found that there is a problem that the surrounding pH becomes high. The pH value reaches 10 and there is a concern that the digestive tract may be damaged (for example, esophagitis) when taking continuously. In particular, when it is taken as an orally disintegrating tablet, there is also a concern that the patient feels pain in the oral mucosa due to the high pH in the oral cavity, and the dosage is significantly reduced.

  An object of the present invention is to provide an oral pharmaceutical composition containing telmisartan that can solve the above-mentioned problems.

  As a result of intensive studies, the inventors of the present invention have an oral pharmaceutical composition comprising a telmisartan-containing granule having a layer containing telmisartan and a basic compound, and further comprising a layer containing an acid. As a result, the present inventors have found that the above-mentioned problems can be solved without affecting the elution characteristics of telmisartan, and have further studied and completed the present invention.

That is, the present invention
[1] An oral pharmaceutical composition comprising telmisartan-containing granules having a layer (a) containing telmisartan and a basic compound and a layer (b) containing an acid outside the core particles,
[2] The oral pharmaceutical composition according to the above [1], wherein the acid is at least one selected from pharmaceutically acceptable inorganic acids and organic acids,
[3] The above [1], wherein the basic compound is at least one selected from the group consisting of an alkali metal hydroxide, an alkali metal hydrogen carbonate, an alkali metal carbonate, an alkali metal monohydrogen phosphate, a basic amino acid, and meglumine. Or an oral pharmaceutical composition according to [2],
[4] The above-mentioned [1] to [3], wherein the acid content is such that the pH becomes 6.5 to 8.5 when the oral pharmaceutical composition is dissolved in about 5 times the mass of purified water. An oral pharmaceutical composition according to any one of
[5] The oral pharmaceutical composition according to any one of the above [1] to [4], wherein the layer (a) is located outside the layer (b),
[6] The oral pharmaceutical composition according to any one of the above [1] to [5], which is in the form of an orally disintegrating tablet,
[7] Orally disintegrating tablets
(1) A granulated product obtained by dry granulating a mixture containing telmisartan-containing granules and at least one selected from the group consisting of sodium stearyl fumarate, magnesium stearate and calcium stearate,
(2) at least one selected from the group consisting of sodium stearyl fumarate, magnesium stearate and calcium stearate, and
(3) The oral pharmaceutical composition according to the above [6], which is obtained by tableting a mixture containing crystalline cellulose.
[8] The oral pharmaceutical composition according to the above [7], wherein the content of crystalline cellulose is 20 to 60% by mass with respect to the total mass of the oral pharmaceutical composition,
About.

  According to the oral pharmaceutical composition of the present invention, in the oral pharmaceutical composition comprising a telmisartan-containing granule having a layer containing telmisartan and a basic compound, the granule has a layer containing an acid. Thus, it is possible to suppress an increase in pH when telmisartan is eluted together with the basic compound. Therefore, it is possible to effectively prevent the gastrointestinal tract from being damaged (for example, esophagitis). In particular, when the oral pharmaceutical composition is an orally disintegrating tablet, the development of pain in the oral mucosa due to an increase in pH in the oral cavity can also be suppressed. Telmisartan is a therapeutic agent for hypertension, and is taken continuously by patients for a long period of time. Therefore, such improvement in dosage is therapeutically significant.

[Oral pharmaceutical composition]
One embodiment of the present invention is an oral pharmaceutical composition comprising a telmisartan-containing granule having a layer (a) containing telmisartan and a basic compound and a layer (b) containing an acid outside the core particle. It is. For telmisartan-containing granules, a layer (a) containing telmisartan and a basic compound and a layer (b) containing an acid are provided outside the core particles by a granulation method usually used in this field, for example, wet granulation. Can be obtained.

<Nuclear particles>
The core particle is not particularly limited as long as it functions as a granulated core, and any of those normally used in this field, for example, a core particle made of an excipient can be suitably used. Here, the excipient constituting the core particles is not particularly limited, and examples thereof include celluloses (crystalline cellulose, ethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose (hypromellose), etc. ) And derivatives thereof, starch (corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, hydroxypropyl starch, etc.) and derivatives thereof, sugar (glucose, lactose, sucrose, refined sucrose, powdered sugar, trehalose, dextran) , Dextrin, etc.), sugar alcohol (D-mannitol, xylitol, sorbitol, erythritol, etc.), glycerin fatty acid ester, inorganic powder (magnesium aluminate metasilicate, synthesis) Hydrotalcite), anhydrous calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium hydrogen hydrate phosphoric acid, inorganic salts such as sodium hydrogen carbonate. Preferred are celluloses, starches, sugars and sugar alcohols. These may be used alone or in combination of two or more. The size of the core particles is usually 500 μm or less, and in this case, a large number are in the range of several tens of μm to 300 μm.

<Layer (a) and Layer (b)>
The order of the layer (a) and the layer (b) provided on the outer side of the core particle is not limited, and the order of the layers (a) and the layer (b) may be integrated. Thus, for example, when these layers are formed by fluidized bed granulation, the granulation liquid (a) for forming the layer (a) and the granulation liquid (b) for forming the layer (b) Either one may be sprayed first and then the other may be sprayed, or the granulating liquid (a) and the granulating liquid (b) may be sprayed simultaneously.

  For example, the layer (a) and the layer (b) are preferably formed such that the layer (b) is on the inside and the layer (a) is on the outside. In this case, the granulating liquid (a) is sprayed after the granulating liquid (b) is sprayed. Thereby, the fluidity | liquidity of the granulated particle in a granulation process improves, and there exists a tendency which becomes easy to manufacture.

  Telmisartan is in solution to form layer (a). Here, since telmisartan has low solubility at a pH of neutral or lower, it is necessary to include a basic compound. On the other hand, the reason why the layer (b) contains an acid is to neutralize the alkalinity caused by elution of the basic compound from the layer (a). That is, when the basic compound is eluted together with telmisartan in the gastrointestinal tract, the pH in the vicinity of the basic compound is greatly inclined toward the alkali side. For this reason, since the surrounding mucous membrane is injured and there is a concern that inflammation (for example, esophagitis etc.) may develop in some cases, this is prevented by neutralization with acid.

(Basic compound)
As the basic compound contained in the layer (a), various compounds can be used as long as they are pharmaceutically acceptable. Specific examples thereof include alkalis such as sodium hydroxide and potassium hydroxide. Metal hydroxides; alkali hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; alkali metal carbonates such as sodium carbonate and potassium carbonate; alkali metal monohydrogen phosphates such as sodium monohydrogen phosphate and potassium monohydrogen phosphate; And basic amino acids such as arginine; and meglumine (N-methyl-D-glucamine). Among these, meglumine and sodium hydroxide are preferable, and sodium hydroxide is more preferable. One or more basic compounds can be used in combination.

  The basic compound is added to improve the solubility of telmisartan, and the blending amount of the basic compound for achieving such purpose varies depending on the type of the basic compound. For example, when sodium hydroxide is used as the basic compound, the molar ratio of telmisartan to the basic compound is preferably telmisartan: basic compound is 1: 1 to 1:10.

(acid)
As the acid contained in the layer (b), various acids can be used as long as they are pharmaceutically acceptable. Specific examples thereof include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, and phosphoric acid. And inorganic acids such as lactic acid, acetic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, malic acid, methanesulfonic acid, benzoic acid, and toluenesulfonic acid. Of these, hydrochloric acid, phosphoric acid, lactic acid, and citric acid are preferred. The acid can be used alone or in combination of two or more. The acid content is preferably an amount that can neutralize the alkalinity due to the basic compound, that is, when the oral pharmaceutical composition that is the final product form is dissolved in about 5 times the amount of water by mass ratio. PH is about 6.5 to 8.5, preferably about 7 (in terms of pH, “about” in “about 7” means within ± 5%, preferably within ± 3%) This is the amount.
<Wet granulation>
In the wet granulation, a granulation liquid is sprayed on the core particles. When wet granulation is applied to the present embodiment, as a granulation liquid, a granulation liquid (a) and a layer (b) containing telmisartan and a basic compound for forming the layer (a) are formed. A granulating liquid (b) containing an acid is used. The wet granulation can be performed using a conventional apparatus used in this field, such as a rolling granulator, a fluidized bed granulator, and a stirring granulator. Among these, it is preferable to use a fluidized bed granulator. Various conditions for granulation can be appropriately determined according to the type of apparatus, the type of granulation liquid, and the like.

(Granulating liquid)
In the granulation liquids (a) and (b), an aqueous solvent can be used as the solvent. As the aqueous solvent, in addition to water, one or more selected from water and ethanol, methanol, dichloromethane and propanol And a mixed solution with an organic solvent. When the aqueous solvent is composed of water and an organic solvent, the water content varies depending on the type of the organic solvent, but is usually preferably 50% by mass or more. As the aqueous solvent, water is preferable.

  The content of telmisartan in the granulating liquid (a) is usually preferably 20 to 60% by mass with respect to the total amount of the granulating liquid (a).

  Additives usually used in this field can be blended with the granulation liquid. Examples of such additives include surfactants and emulsifiers.

  Surfactants and / or emulsifiers may be either ionic or nonionic. Specifically, poloxamer or Pluronic (registered trademark), polyethylene glycol, polyethylene glycol monostearate, polysorbate, or the like can be used.

<Telmisartan-containing granules>
The particle size distribution of the telmisartan-containing granules obtained above can be adjusted by adjusting the size as necessary. The sizing can be performed, for example, by sieving the granulated product with a sieve having a predetermined size (for example, an opening of 500 μm).

<Oral pharmaceutical composition>
Telmisartan-containing granules can be made into various oral pharmaceutical compositions comprising the telmisartan-containing granules by a conventional method. Here, “comprising telmisartan-containing granules” means an oral pharmaceutical composition obtained by using telmisartan-containing granules and encapsulating them without giving a chemical change. The oral pharmaceutical composition is a granule or fine granule containing telmisartan-containing granules; a capsule filled with telmisartan-containing granules; a pill further granulated with telmisartan-containing granules; It means that the tablet is obtained by tableting a tableting raw material containing granules. Therefore, the oral pharmaceutical composition thus obtained can be various oral dosage forms such as tablets, granules, fine granules, hard capsules, caplets, soft capsules, pills, orally disintegrating tablets.

[Orally disintegrating tablets]
In another embodiment of the present invention, the oral pharmaceutical composition is in the form of an orally disintegrating tablet. The orally disintegrating tablet is obtained by subjecting a dry granulation raw material containing telmisartan-containing granules (first granulated product) to dry granulation to obtain a dry granulated product (second granulated product). It can be produced by tableting a tableting raw material containing the granulated product.

<Dry granulation process>
Dry granulation is a granulation method in which granulation is performed by increasing the cohesive strength of raw materials without using a liquid component during granulation. For example, the compression granulation which compresses powder with the pressure of a roll etc. corresponds. In the present embodiment, dry granulation can be carried out using an apparatus for dry granulation, and any of those known in this field can be suitably used as such an apparatus. Examples of such devices include a roller compactor (Freund Sangyo Co., Ltd.), Pharmapactor (Hosokawa Micron Co., Ltd.), Chilsonator (Dalton Co., Ltd.), rotary press (Daishin Kiko Co., Ltd.), etc. .

  Dry granulation can be carried out under suitable conditions depending on each device. For example, when a roller compactor is used, the roll rotation speed is 0.1 to 10 rpm, preferably 1 to 5 rpm.

(Dry granulation raw material)
In addition to the telmisartan-containing granule (first granulated product), the dry granulation raw material can contain additives usually used in this field, such as lubricants and excipients.

  The lubricant is not particularly limited. For example, stearic acid, sodium stearyl fumarate, magnesium stearate, calcium stearate, sucrose fatty acid ester, polyethylene glycol, light anhydrous silicic acid, hydrogenated oil, glycerin fatty acid ester And talc. Preferably sodium stearyl fumarate, magnesium stearate or calcium stearate is used. The lubricants may be used alone or in combination of two or more.

  The excipient is not particularly limited, and examples thereof include celluloses (crystalline cellulose, ethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methylcellulose (hypromellose), etc.) and derivatives thereof, starch (corn Starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, hydroxypropyl starch, etc.) and derivatives thereof, sugar (glucose, lactose, saccharose, refined sucrose, powdered sugar, trehalose, dextran, dextrin, etc.), sugar alcohol ( D-mannitol, xylitol, sorbitol, erythritol, etc.), glycerin fatty acid ester, inorganic powder (magnesium aluminate metasilicate, synthetic hydrotalcite), anhydrous Calcium acid, precipitated calcium carbonate, calcium silicate, calcium hydrogen hydrate phosphoric acid, inorganic salts such as sodium hydrogen carbonate. Preferred are crystalline cellulose and low-substituted hydroxypropylcellulose. An excipient | filler may be used independently and may be used in mixture of 2 or more types.

(Dry granulated product)
The dry granulated product (second granulated product) obtained by dry granulation can be subjected to sizing as desired. For the sizing, for example, the granulated product is sieved with a sieve of a predetermined size (for example, openings 710 to 850 μm), or a sizing device (for example, a com mill manufactured by POWREC Co., Ltd.) is used. Can be implemented. Furthermore, fine powder can be removed from the powder after sizing by passing through a sieve of a predetermined size (for example, an opening of 75 to 180 μm).

<Tabletting process>
The tableting step is a step of tableting a tableting raw material including a dry granulated product (second granulated product) to obtain an orally disintegrating tablet.

(Tablet raw materials)
The raw materials for tableting include additives such as excipients, disintegrants, fluidizers, binders, sweeteners, lubricants in addition to dry granulated products (second granulated products). It's okay.

  The excipient is not particularly limited, and any of the excipients described in the section of the raw material for dry granulation can be suitably used. Preferred are celluloses. An excipient | filler may be used independently and may use 2 or more types together.

  Disintegrants are roughly classified into Wicking type disintegrants and Welling type disintegrants. The Wicking type disintegrant has a property that the infiltration rate of water is high because the contact angle is small, and water is taken into the entire voids of the disintegrant. Due to this good wettability, water penetrates instantly into the tablet, and the force breaks the bonding force between the particles and disperses the composition in the tablet in water. On the other hand, the disintegrating agent of the Welling type has the property that the disintegrating agent itself is insoluble in water, but swells by taking in a larger amount of water than the voids of the disintegrating agent and breaks the tablet by its swelling power.

  The disintegrant of Wicking type is not particularly limited, for example, carmellose, carmellose sodium, crystalline cellulose carmellose sodium, cellulose acetate phthalate, wheat starch, rice starch, corn starch, potato starch, pregelatinized starch, partial α It is a modified starch. Carmellose is preferable. These may be used alone or in combination of two or more.

  The swelling type disintegrant is not particularly limited, and examples thereof include hydroxypropyl starch, low-substituted hydroxypropylcellulose, sodium carboxymethyl starch, croscarmellose, croscarmellose sodium, and crospovidone. Preferably, crospovidone is used. These may be used alone or in combination of two or more.

  The total content of the Wicking type disintegrant and the Swelling type disintegrant is not particularly limited. For example, when the total mass of the orally disintegrating tablet is 100%, it is 1 to 20% by mass, preferably 5 to 15% by mass. %. The mass ratio of the Wicking type disintegrant to the Welling type disintegrant is preferably Wicking type disintegrant: Swelling type disintegrant = 1: 1.

  The binder is not particularly limited. Partially pregelatinized starch is mentioned. Preferred are hydroxypropylcellulose, hypromellose, and polyvinylpyrrolidone. These may be used alone or in combination of two or more.

  The sweetening agent is not particularly limited, and examples thereof include aspartame, stevia, sugar alcohol, saccharin sodium, dipotassium glycyrrhizin, thaumatin, acesulfame potassium, and sucralose. Aspartame, thaumatin and acesulfame potassium are preferred. These may be used alone or in combination of two or more.

  The lubricant is not particularly limited, and examples thereof include stearic acid, sodium stearyl fumarate, magnesium stearate, calcium stearate, sucrose fatty acid ester, polyethylene glycol, light anhydrous silicic acid, hydrogenated oil, glycerin fatty acid ester, and talc. Can be mentioned. Preferred is sodium stearyl fumarate, magnesium stearate or calcium stearate. These may be used alone or in combination of two or more.

(Tabletting of orally disintegrating tablets)
If desired, the second granulated product is tableted as a tableting raw material to which the above additives are added and mixed. The tableting method is not particularly limited. For example, using a tableting die, an upper punch and a lower punch, a hydraulic hand press machine, a single-punch tableting machine, a rotary tableting machine, etc. A method is mentioned. Tableting is performed by adjusting so that the resulting tablet has an appropriate hardness and rapidly disintegrates as an orally disintegrating tablet. The tableting pressure is appropriately adjusted according to the tableting method, the device used for tableting, the size of the tablet, and the like, but is usually 1 to 20 kN, preferably 3 to 20 kN.

(Orally disintegrating tablets)
The shape of the orally disintegrating tablet is not particularly limited, and may be, for example, a disk shape, a donut shape, a polygonal plate shape, a spherical shape, an oval shape, a caplet shape, or the like. The size is preferably small, preferably about 7 to 10 mm in diameter and about 3.8 to 4.2 mm in thickness. The mass is preferably about 310 to 350 mg. The hardness is 40N or more, preferably 50N or more. When taken without water, the disintegration time is within 60 seconds, preferably within 30 seconds, in the oral cavity.

  EXAMPLES Hereinafter, although this invention is demonstrated concretely based on an Example, this invention is not intended to be limited to these Examples.

(Reagent used)
D-mannitol: JP XVI
Citric acid hydrate: JP XVI
Phosphate: JP XVI
Sodium hydroxide (NaOH): JP XVI
Sodium stearyl fumarate (SSF): JP XVI
Low-substituted hydroxypropyl cellulose (L-HPC): JP XVI
Crospovidone: Carmellose (Carboxymethylcellulose (CMC)): JP XVI
Crystalline cellulose: JP XVI
Aspartame: JP XVI
Acesulfame potassium (Ace K): JP XVI

  In the above, JP XVI represents the 16th revised Japanese Pharmacopoeia, and supplementary regulations represent Pharmaceutical Additive Standard 2003 and its supplements.

  Hereafter, it implemented according to description of Table 1.

(A) Preparation of granulation liquid For each example, a predetermined acid was added to purified water (30 g) and dissolved by stirring to prepare a first granulation liquid.

  For each example, telmisartan and sodium hydroxide (NaOH) were added to purified water (220 g) and dissolved by stirring to prepare a second granulated liquid.

(B) Fluidized bed granulation After sieving D-mannitol with a 500 μm sieve, it was put into a fluidized bed granulator (MP-01, manufactured by POWREC Co., Ltd.) as a granulation core. While the fluidized bed granulator was started to fluidize the granulation core, the first granulating liquid was sprayed, and then the second granulating liquid was sprayed to perform fluidized bed granulation. The conditions for fluidized bed granulation were an intake air temperature of 75 ° C. and an air pressure of 60 L / min. Then, it dried at 80 degreeC for 10 minute (s), and cooled until the exhaust_gas | exhaustion temperature became 35 degreeC with the intake temperature of 25 degreeC. The obtained granulated product was sieved with a 500 μm sieve and sized.

(C) Dry granulation After mixing the granulated granule obtained above with sodium stearyl fumarate (SSF) as an additional component, the mixture is obtained with a roller compactor (TF-MINI type, manufactured by Freund Sangyo Co., Ltd.). Dry granulation (roll rotation speed: 2 rpm) was performed. The granulated powder was sized with a power mill (using a screen of 850 μm), and the powder remaining on a 180 μm sieve was used as tableting granules. On the other hand, what passed through the sieve was again subjected to dry granulation with a roller compactor, and thereafter subjected to the same treatment as above to obtain granules for tableting. This operation was repeated once more. Therefore, dry granulation was performed with a roller compactor three times in total.

(D) Tableting The granules for tableting obtained above were mixed with low-substituted hydroxypropylcellulose (L-HPC), crospovidone (PVP), carmellose (CMC), crystalline cellulose, aspartame, acesulfame potassium (Ace K), Sodium stearyl fumarate (SSF) is mixed, the mixture is put into a rotary tableting machine (VIRGO, manufactured by Kikusui Seisakusho Co., Ltd.), and tableted under predetermined conditions (tablet pressure, tablet diameter). Flat tablets (orally disintegrating tablets) were obtained.

  In addition, Example 3 was processed like Example 1 except not having performed the process (c) which concerns on dry granulation. However, the tableting pressure in the step (d) relating to tableting was set to 2.0 kN in order to match the same degree of hardness. Moreover, the comparative example 1 processed like Example 1 except not having performed granulation by the 1st granulation liquid in fluid bed granulation.

<Evaluation>
The following tests were conducted on the tablets of Examples and Comparative Examples obtained above. The results are shown in Table 1.

[Test Example 1]
(PH when the tablet is disintegrated)
The pH when the tablet was disintegrated was determined by measuring the pH when the tablet was completely disintegrated in 5 mL of purified water.

[Test Example 2]
(Texture)
The texture of the tablets was evaluated by a sensory test with three subjects (healthy adult men and women). That is, the subject put a tablet in the oral cavity and evaluated the presence or absence of irritation.

[Test Example 3]
(Tablet hardness)
The hardness of the tablet was measured with a tablet hardness meter (6D type: SCHLEUNIGER). The hardness of the tablet is usually required to be 40N or more, preferably 50N or more.

[Test Example 4]
(Collapse time)
The disintegration time of the tablet was determined by a sensory test with three subjects (healthy adult men and women). That is, the test subject put a tablet in the oral cavity, the time (seconds) until the tablet was completely disintegrated with only saliva in the oral cavity was measured, and the average value was taken as the disintegration time.

[Test Example 5]
(Abrasion resistance)
As an index representing the abrasion resistance of the tablet, a test was conducted according to the abrasion test method of the Japanese Pharmacopoeia of the XVI revision, and the abrasion was measured.

(Test results)
As shown in Table 1, in the tablet of the example, no stimulus was sensed in the texture, whereas in the tablet of the comparative example, the stimulus was sensed.

  ADVANTAGE OF THE INVENTION According to this invention, the oral pharmaceutical composition containing the telmisartan which improved taking feeling can be provided.

Claims (8)

An oral pharmaceutical composition comprising telmisartan-containing granules having a layer (a) containing telmisartan and a basic compound and a layer (b) containing an acid outside the core particle. The oral pharmaceutical composition according to claim 1, wherein the acid is at least one selected from pharmaceutically acceptable inorganic acids and organic acids. The basic compound is at least one selected from the group consisting of an alkali metal hydroxide, an alkali metal hydrogen carbonate, an alkali metal carbonate, an alkali metal monohydrogen phosphate, a basic amino acid, and meglumine. Oral pharmaceutical composition. The acid content is an amount such that the pH becomes 6.5 to 8.5 when the oral pharmaceutical composition is dissolved in 5 times the amount of purified water by mass ratio. Oral pharmaceutical composition. The oral pharmaceutical composition according to any one of claims 1 to 4, wherein the layer (a) is located outside the layer (b). The oral pharmaceutical composition according to any one of claims 1 to 5, which is in the form of an orally disintegrating tablet. Orally disintegrating tablets
(1) A granulated product obtained by dry granulating a mixture containing telmisartan-containing granules and at least one selected from the group consisting of sodium stearyl fumarate, magnesium stearate and calcium stearate,
(2) at least one selected from the group consisting of sodium stearyl fumarate, magnesium stearate and calcium stearate, and
(3) The oral pharmaceutical composition according to claim 6, which is obtained by tableting a mixture containing crystalline cellulose. The oral pharmaceutical composition according to claim 7, wherein the content of crystalline cellulose is 20 to 60% by mass relative to the total mass of the oral pharmaceutical composition.