JP7129957B2 - Orally disintegrating tablet composition, method for producing the same, and orally disintegrating tablet using the same and method for producing the same - Google Patents

Description

The present invention relates to an orally disintegrating tablet composition for producing an orally disintegrating tablet having excellent oral disintegrability, a method for producing the same, an orally disintegrating tablet using the same, and a method for producing the same.

Many pharmaceutical preparations and health foods are taken orally as tablets. Tablets are usually taken with water. However, it is difficult to take tablets with water in an emergency or when a patient with severe disease takes the drug while lying down. Furthermore, children with immature swallowing functions and elderly people with reduced swallowing functions may find it difficult to swallow tablets, and there is a demand for improvements in the ease of taking tablets.

Orally disintegrating tablets that can be taken without water are known as tablets with improved ingestibility. Orally disintegrating tablets are characterized by containing drug-containing particles containing a drug, water-soluble polymer and sugar or sugar alcohol, and spray-dried particles containing mannitol or mannitol and xylitol, carboxymethylcellulose and a disintegrant. An orally disintegrating tablet has been proposed (Patent Document 1).

International Publication No. 2011/019043 Pamphlet

However, the orally disintegrating tablet described in Patent Document 1 is manufactured by granulating one raw material to obtain drug-containing particles, dispersing the other raw material in a dispersion solvent, and then spray-drying it. The manufacturing process up to tableting is cumbersome, including obtaining dry particles and then mixing and tableting the obtained drug-containing particles and spray-dried particles.

In addition, since orally disintegrating tablets are tablets having both moderate tablet strength and excellent disintegration properties, formulation design is difficult. Moreover, since carboxymethylcellulose used in Patent Document 1 is an ionic disintegrant, it may interact with active ingredients.

Therefore, in view of the above circumstances, the present invention provides an orally disintegrating tablet for producing an orally disintegrating tablet that can be produced without adopting a complicated process and has an appropriate tablet strength and excellent disintegrability. It is an object of the present invention to provide a tablet composition and a method for producing the same. Another object of the present invention is to provide the orally disintegrating tablet and a method for producing the same.

The inventors of the present invention, as a result of intensive studies to achieve the above object, surprisingly produced by using a composition obtained by mixing raw materials containing water-soluble cellulose ether, catechin and sugar. It has been found that an orally disintegrating tablet can exhibit excellent disintegrability in the oral cavity while having appropriate hardness.

Finally, based on the above findings, a composition for an orally disintegrating tablet containing a water-soluble cellulose ether, a catechin, and a sugar, which can solve the problems of the present invention; an orally disintegrating tablet that is a tableted product of the orally disintegrating tablet composition; and a method for producing the orally disintegrating tablet. The present invention has been completed based on the findings and successful examples first discovered by the present inventors.

Accordingly, the present invention provides an orally disintegrating tablet composition, a method for producing an orally disintegrating tablet composition, an orally disintegrating tablet, and a method for producing an orally disintegrating tablet in the following aspects.
[1] A composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar.
[2] The composition for an orally disintegrating tablet according to [1], which further contains a sugar alcohol.
[3] The orally disintegrating tablet according to [1] or [2], wherein the mass ratio of the water-soluble cellulose ether to the catechin (water-soluble cellulose ether/catechin) is 1.0/1 to 7.5/1. composition.
[4] The composition for an orally disintegrating tablet according to any one of [1] to [3], further comprising an active ingredient.
[5] The water-soluble cellulose ether according to any one of [1] to [4], wherein the water-soluble cellulose ether is at least one water-soluble cellulose ether selected from the group consisting of alkylcellulose, hydroxyalkylcellulose and hydroxyalkylalkylcellulose. A composition for an orally disintegrating tablet.
[6] An orally disintegrating tablet, which is a tableted product of the composition for orally disintegrating tablet according to any one of [1] to [5].
[7] A step of dry-mixing powder raw materials containing water-soluble cellulose ether, catechin, and sugar to obtain an orally disintegrating tablet composition containing water-soluble cellulose ether, catechin, and sugar. A method for producing an orally disintegrating tablet composition.
[8] A powder raw material containing water-soluble cellulose ether, catechin, and sugar is added with an aqueous raw material containing water and granulated, thereby containing water-soluble cellulose ether, catechin, and sugar. A method for producing an orally disintegrating tablet composition, comprising a step of obtaining an orally disintegrating tablet composition.
[9] A step of obtaining an extrudate containing water-soluble cellulose ether and catechin by heat-melt extruding a powder raw material containing water-soluble cellulose ether and catechin, and pulverizing the extrudate. and obtaining an orally disintegrating tablet composition containing a water-soluble cellulose ether, catechins, and sugar by mixing the pulverized product and a raw material containing sugar. A method for producing a disintegrating tablet composition.
[10] The method for producing an orally disintegrating tablet composition according to any one of [7] to [9], wherein the powder raw material further contains an active ingredient.
[11] A method for producing an orally disintegrating tablet, comprising a step of obtaining an orally disintegrating tablet by tableting the composition for an orally disintegrating tablet according to any one of [7] to [10].

ADVANTAGE OF THE INVENTION According to this invention, the orally disintegrating tablet which has sufficient hardness and shows the outstanding disintegration property can be obtained, without adopting a complicated process.

Hereinafter, a composition for an orally disintegrating tablet, a method for producing an orally disintegrating tablet composition, an orally disintegrating tablet, and a method for producing an orally disintegrating tablet, which are one aspect of the present invention, will be described in detail. Various aspects can be adopted as long as the object is achieved.

Each term used herein has the meaning commonly used by those skilled in the art, unless otherwise specified, and should not be construed as having an unduly restrictive meaning. In addition, the speculations and theories made in the present specification are based on the knowledge and experience of the present inventors, so the present invention is not bound solely by such speculations and theories. do not have.

The term "composition" is not particularly limited in its commonly used meaning, but is, for example, a combination of two or more components. "Ingredients" means one ingredient or combination of two or more ingredients to make up the composition.
“Orally disintegrating tablet” means a tablet that disintegrates in the oral cavity only with saliva in the oral cavity or a small amount of water in a short period of time (generally within 1 minute, preferably within 30 seconds).
The term "and/or" means any one, or any or all combinations of two or more of the associated listed items.
"Content" is synonymous with concentration and means the ratio of the amount of an ingredient to the total amount of the composition. In this specification, the unit of content means "mass % (wt%)" unless otherwise specified. However, the total content of the components does not exceed 100% by mass.
The numerical range "to" is a range including the numerical values before and after it, for example, "0% by mass to 100% by mass" means a range of 0% by mass or more and 100% by mass or less. .
"Contains" means that it can add elements other than those specifically stated to be included (synonymous with "including at least"), but includes "consisting of" and "consisting essentially of" do. That is, "comprising" can mean including the specified element and any one or more elements, consisting of, or consisting essentially of the specified element. . Factors include limitations such as components, steps, conditions, parameters, and the like.

The number of digits in the integer value and the number of significant digits are the same. For example, 1 has 1 significant digit and 10 has 2 significant digits. Also, for decimal values, the number of digits after the decimal point and the number of significant digits are the same. For example, 0.1 has one significant digit and 0.10 has two significant digits.

<Composition for Orally Disintegrating Tablets>
A composition for an orally disintegrating tablet according to one aspect of the present invention contains water-soluble cellulose ether, catechin, and sugar.

A water-soluble cellulose ether is a nonionic polymer obtained by etherifying a portion of the hydroxyl groups of cellulose. In the composition for orally disintegrating tablets, the water-soluble cellulose ether functions as a binder and also functions as a disintegrant by swelling upon hydration.

The water-soluble cellulose ether is not particularly limited as long as it is a cellulose ether exhibiting water solubility, and the organic group constituting the ether is not particularly limited. Examples thereof include alkylcellulose, hydroxyalkylcellulose, and hydroxyalkylalkylcellulose.

Examples of alkyl cellulose include methyl cellulose and ethyl cellulose, and methyl cellulose, which is readily water-soluble, is preferred.

The methoxy group content in methylcellulose is preferably 26.0% by mass to 33.0% by mass, more preferably 27.5% by mass to 31.5% by mass, from the viewpoint of solubility in water. The methoxy group content in methylcellulose is a value measured by the quantitative method described in the Japanese Pharmacopoeia 17th Edition, "Methylcellulose".

Examples of hydroxyalkyl cellulose include hydroxypropyl cellulose and hydroxyethyl cellulose, and hydroxypropyl cellulose is preferred from the viewpoint of solubility.

The hydroxypropoxy group content in hydroxypropylcellulose is preferably 53.4% by mass to 77.5% by mass, more preferably 60.0% by mass to 70.0% by mass, from the viewpoint of solubility. The hydroxypropoxy group content in hydroxypropyl cellulose is a value measured by the quantitative method described in the Japanese Pharmacopoeia 17th Edition, "Hydroxypropyl cellulose".

Examples of hydroxyalkylalkylcellulose include hypromellose (hydroxypropylmethylcellulose; hereinafter also referred to as "HPMC"), hydroxyethylmethylcellulose, hydroxyethylethylcellulose, etc. However, from the viewpoint of moldability and disintegration, HPMC is preferred. preferable.

The methoxy group content in HPMC is preferably 16.5% by mass to 30.0% by mass, more preferably 19.0% by mass to 30.0% by mass, from the viewpoint of solubility in water, More preferably, it is 19.0% by mass to 29.0% by mass. In addition, the hydroxypropoxy group content in HPMC is preferably 3.0% by mass to 32.0% by mass, more preferably 3.0% by mass to 12.0% by mass, from the viewpoint of solubility in water. and more preferably 4.0% by mass to 12.0% by mass. The hydroxypropoxy group content and the methoxy group content in HPMC are values measured by the quantitative method described in the section "Hypromellose" in the Japanese Pharmacopoeia 17th Edition.

The average particle size of the water-soluble cellulose ether is preferably 50 μm or more, more preferably 55 μm to 500 μm, still more preferably 60 μm to 300 μm, from the viewpoint of hardness and disintegration properties of the orally disintegrating tablet. The average particle size of the water-soluble cellulose ether is a value (50% cumulative value of a volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

The viscosity of the 2% by mass aqueous solution of the water-soluble cellulose ether at 20° C. is preferably 1.0 mPa s to 150,000 mPa s, more preferably 2.0 mPa s, from the viewpoint of the hardness of the orally disintegrating tablet. 120,000 mPa·s, more preferably 2.5 mPa·s to 6,000 mPa·s. The viscosity at 20° C. of a 2% by mass aqueous solution of water-soluble cellulose ether is a value measured by the method described in Examples below.

As for the water-soluble cellulose ethers, one of the above-mentioned ones may be used alone, or two or more of them may be used in combination. The water-soluble cellulose ether may be commercially available or may be produced by a known method.

Catechin is a kind of polyphenols, as is generally known, and is not particularly limited as long as it is a tea (tea) extract. In addition to epicatechin and epigallocatechin, catechins include epigallocatechin gallate and epicatechin gallate having a gallate group.

The catechin preferably contains any two, three or all four of epicatechin, epigallocatechin, epigallocatechin gallate and epicatechin gallate.

Catechin may be used alone or in combination of two or more. A commercially available catechin may be used, or a catechin obtained by extracting from tea leaves according to a conventional method may be used.

According to the findings of the present inventors, catechin forms an insoluble swollen substance together with water-soluble cellulose ether in the presence of water. Furthermore, the formed insoluble swollen matter contributes to the disintegrability in the composition for orally disintegrating tablets.

According to the knowledge found by the present inventors, by using an orally disintegrating tablet composition having a large mass ratio of water-soluble cellulose ether to catechin (water-soluble cellulose ether/catechin), oral cavity with excellent hardness and disintegration Disintegrating tablets tend to be obtained. Therefore, the mass ratio of water-soluble cellulose ether to catechin (water-soluble cellulose ether/catechin) is preferably 0.5/1 to 7.5/1 from the viewpoint of formation of insoluble matter by water-soluble cellulose ether and catechin. Yes, more preferably 1.0/1 to 7.5/1, still more preferably 1.0/1 to 5.0/1.

From the viewpoint of hardness and disintegration of the resulting orally disintegrating tablet, the content of water-soluble cellulose ether and catechin is preferably 1.0% by mass to 10% by mass, and 1.5% by mass. and/or the catechin content is preferably 0.1% to 10% by mass, more preferably 0.5% to 5.0% by mass.

Sugar functions as a medium that promotes water conduction to the inside of the orally disintegrating tablet.
Sugars include, for example, lactose, maltose, sucrose, pullulan, trehalose, isomaltose, turanose, cellobiose, etc. Monosaccharides and disaccharides are preferred from the viewpoint of water solubility. The average particle size of the sugar is preferably 5 μm to 100 μm, more preferably 10 μm to 50 μm, from the viewpoint of hardness and disintegration of the orally disintegrating tablet. The average particle size of sugar is a value (50% cumulative value of volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

The content of sugar in the composition for orally disintegrating tablets is preferably 500 parts by mass to 2,500 parts by mass with respect to 100 parts by mass as the total mass of the water-soluble cellulose ether and catechins, from the viewpoint of water conductivity in the orally disintegrating tablet. parts by mass, more preferably 800 to 2,200 parts by mass.

As for the sugars, one of the above-described sugars may be used alone, or two or more of them may be used in combination. Moreover, a commercially available sugar can be used.

The composition for orally disintegrating tablets preferably further contains a sugar alcohol. When the composition for an orally disintegrating tablet contains a sugar alcohol, the water conductivity of the obtained orally disintegrating tablet is increased, and the disintegrability of the orally disintegrating tablet can be improved.

Examples of sugar alcohols include erythritol, D/L(-/+)-mannitol, xylitol, isomalt, sorbitol and the like. The average particle size of the sugar alcohol is preferably 5 μm to 500 μm, more preferably 10 μm to 100 μm, from the viewpoint of hardness and disintegration of the orally disintegrating tablet. The average particle size of the sugar alcohol is a value (50% cumulative value of a volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

The content of the sugar alcohol in the composition for an orally disintegrating tablet is preferably 200 parts by mass to 2 parts by mass with respect to 100 parts by mass as the total mass of the water-soluble cellulose ether and catechins, from the viewpoint of disintegrating properties of the orally disintegrating tablet. 000 parts by mass, more preferably 300 to 1,600 parts by mass.

As for the sugar alcohols, one of the above-described ones may be used alone, or two or more may be used in combination. Moreover, a commercially available sugar alcohol can be used.

The composition for orally disintegrating tablets can contain additives, for example, additives commonly used for producing orally disintegrating tablets. Such additives include, for example, lubricants, flavoring agents, flavoring agents, stabilizers, flow agents, coloring agents, cooling agents, preservatives, chelating agents, pH adjusters, antioxidants, thickeners and the like. The amount of the additive used is not particularly limited as long as it does not interfere with the solution of the problems of the present invention, and can be set as appropriate. Some of the additives are listed below by way of example only and not by way of limitation.

Lubricants include, for example, magnesium stearate, calcium stearate, talc, sodium stearyl fumarate, sucrose fatty acid ester and the like. Examples of flavoring agents include citric acid, tartaric acid, and malic acid. Flavoring agents include, for example, menthol, peppermint oil, vanillin and the like.

In addition to the water-soluble cellulose ethers, catechins and sugars, the orally disintegrating tablet composition contains any other disintegrant, binder and/or excipient, as long as it does not interfere with the solution of the problems of the present invention. may include Disintegrants include, for example, low-substituted hydroxypropyl cellulose, corn starch, partially pregelatinized starch, carboxymethyl starch sodium, croscarmellose, croscarmellose sodium, crystalline cellulose, crospovidone and the like. Binders include, for example, polyvinylpyrrolidone and polyvinyl alcohol. Excipients include, for example, crystalline cellulose, powdered cellulose, calcium phosphate, calcium sulfate and the like.

For example, when a granulation process and a hot-melt extrusion process are employed, solvents, plasticizers, surfactants, and the like can be used as additives depending on the manufacturing process employed.

Examples of the solvent include water such as purified water, and lower alcohols having 1 to 3 carbon atoms such as ethanol and isopropanol. Examples of plasticizers include higher alcohols preferably having 10 to 20 carbon atoms such as acetone, cetyl alcohol and stearyl alcohol, preferably dihydric to hexahydric alcohols such as glycerin, beeswax, triethyl citrate and polyethylene glycol. or alkylene glycol of propylene glycol sugar, triacetin, dibutyl sebacate, glycerin monostearate, monoglycerin acetate and the like. Surfactants include, for example, anionic surfactants such as sodium lauryl sulfate; Natural surfactants such as ionic surfactants, lecithin, and sodium taurocholate are included.

Additives such as those described above may be used singly or in combination of two or more. In addition, commercially available additives can be used.

The content of additives in the composition for orally disintegrating tablets is not particularly limited as long as it does not interfere with the solution of the problems of the present invention. It is preferably 0 to 10,000 parts by mass, more preferably 50 to 1,000 parts by mass, based on 100 parts by mass of the total mass.

The orally disintegrating tablet composition preferably further contains an active ingredient. The active ingredient is not particularly limited as long as it is an active ingredient that can be orally administered. etc.

Drugs used in pharmaceuticals include, for example, central nervous system drugs, circulatory system drugs, respiratory system drugs, digestive system drugs, antibiotics, antitussives and expectorants, antihistamines, antipyretic analgesic antiphlogistic agents, diuretics, Nerve active agents, antimalarial agents, antiparasitic agents, psychotropic agents, vitamins and derivatives thereof, and the like.

Central nervous system drugs include, for example, diazepam, idebenone, naproxen, piroxicam, indomethacin, sulindac, lorazepam, nitrazepam, phenytoin, acetaminophen, ethenzamide, ketoprofen and chlordiazepoxide.

Cardiovascular drugs include, for example, molsidomine, vinpocetine, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedibin, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbitol nitrate, delapril hydrochloride, meclofenoxate hydrochloride, diltiazem hydrochloride, etilephrine hydrochloride, digitoxin and alprenolol hydrochloride.

Respiratory drugs include, for example, amlexanox, dextromethorphan, theophylline, pseudoephedrine, salbutamol and guaifenesin.

Examples of digestive drugs include 2-[[3-methyl-4-(2,2,2-trifluoroethoxy)-2-pyridyl]methylsulfinyl]benzimidazole and 5-methoxy-2-[(4 -Methoxy-3,5-dimethyl-2-pyridyl)methylsulfinyl]benzimidazole, cimetidine, ranitidine, pirenzepine hydrochloride, pancreatin, bisacodyl, 5-aminosalicylic acid, etc. .

Antibiotics include, for example, talampicillin hydrochloride, bacampicillin hydrochloride, cefaclor and erythromycin.

Antitussives/expectants include, for example, noscapine hydrochloride, carbetapentane citrate, isoaminyl citrate, and dimemorphan phosphate.

Antihistamines include, for example, chlorpheniramine maleate, diphenhydramine hydrochloride and promethazine hydrochloride.

Examples of antipyretic analgesic antiphlogistic agents include ibuprofen, diclofenac sodium, flufenamic acid, sulpyrine, aspirin and ketoprofen.

Diuretics include, for example, caffeine.

Examples of autonomic drugs include dihydrocodeine phosphate and dl-methylephedrine hydrochloride, atropine sulfate, acetylcholine chloride, neostigmine and the like.

Antimalarial agents include, for example, quinine hydrochloride. Antistatic agents include, for example, loperamide hydrochloride. Examples of psychotropic agents include chlorpromazine and the like.

Examples of vitamins and derivatives thereof include vitamin A, vitamin _B1 , fursultiamine, vitamin B2, vitamin _B6 , vitamin _B12 , vitamin _C , vitamin D, vitamin E, vitamin K, calcium pantothenate and tranexam. acid and the like.

Active ingredients used in health foods include, for example, vitamins and their derivatives, minerals, carotenoids, amino acids and their derivatives, plant extracts and health food ingredients.

Minerals include, for example, calcium, magnesium, manganese, zinc, iron, copper, selenium, chromium, sulfur, iodine, and the like.

Examples of carotenoids include β-carotene, α-carotene, lutein, cryptoxanthin, zeaxanthin, lycopene, astaxanthin, multicarotene and the like.

Amino acids include, for example, acidic amino acids, basic amino acids, neutral amino acids, acidic amino acid amides, and the like.

Acidic amino acids include, for example, aspartic acid and glutamic acid. Basic amino acids include, for example, lysine, arginine and histidine.

Examples of neutral amino acids include linear aliphatic amino acids such as alanine and glycine, branched aliphatic amino acids such as valine, leucine and isoleucine, hydroxy amino acids such as serine and threonine, and sulfur-containing amino acids such as cysteine and methionine. Examples include amino acids, aromatic amino acids such as phenylalanine and tyrosine, heterocyclic amino acids such as tryptophan, and imino acids such as proline.

Acidic amino acid amides include, for example, asparagine and glutamine.

Examples of amino acid derivatives include acetylglutamine, acetylcysteine, carboxymethylcysteine, acetyltyrosine, acetylhydroxyproline, 5-hydroxyproline, glutathione, creatine, S-adenosylmethionine, glycylglycine, glycylglutamine, dopa, ara Nylglutamine, carnitine, γ-aminobutyric acid and the like.

Plant extracts include, for example, aloe, propolis, agaricus, ginseng, ginkgo biloba, turmeric, curcumin, sprouted brown rice, shiitake mushroom mycelia, sweet tea, sweet tea, Korean mushroom, sesame, garlic, maca, cordyceps, chamomile and hot pepper. be done.

Examples of health food materials include royal jelly, dietary fiber, protein, bifidobacteria, lactic acid bacteria, chitosan, yeast, glucosamine, lecithin, polyphenol, animal cartilage, soft-shelled turtle, lactoferrin, clam, eicosapentaenoic acid, germanium, enzymes, creatine, carnitine, citric acid, raspberry ketones, coenzyme Q10, methylsulfonylmethane and phospholipid-bound soybean peptides;

The content of the active ingredient can be appropriately determined depending on the desired pharmacological action or functionality. It is preferably 200 parts by mass to 1,100 parts by mass with respect to 100 parts by mass.

As for the active ingredient, one of the above-described active ingredients may be used alone, or two or more thereof may be used in combination. In addition, commercially available active ingredients can be used.

<Method for producing composition for orally disintegrating tablet>
A composition for an orally disintegrating tablet contains water-soluble cellulose ether, catechin and sugar, and is produced so as to obtain an orally disintegrating tablet by subjecting it to a tableting process. The method for producing an orally disintegrating tablet composition is not particularly limited, and examples thereof include a method including steps such as dry mixing, granulation, hot-melt extrusion, and the like.

[Dry mixing]
In a method employing dry blending, a composition for an orally disintegrating tablet containing a water-soluble cellulose ether, a catechin, and a sugar is obtained by dry-blending powder raw materials containing a water-soluble cellulose ether, a catechin, and a sugar. including the step of obtaining

The method of dry mixing is not particularly limited. The powder raw materials subjected to dry mixing may contain sugar alcohols and optional additives. The powdered raw material preferably contains an active ingredient.

When dry blending is employed, it is preferable to use a water-soluble cellulose ether having an average particle size of 100 μm or more from the viewpoint of disintegrating properties of an orally disintegrating tablet produced from the composition for an orally disintegrating tablet. It is more preferred to use a water-soluble cellulose ether having a .DELTA. By containing the water-soluble cellulose ether having such an average particle size, the orally disintegrating tablet composition contains a certain amount of water-soluble cellulose ether in the orally disintegrating tablet even after tableting. Since it can be used, it is more excellent in disintegration. The average particle size of the water-soluble cellulose ether is a value (50% cumulative value of volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

[Granulation]
In the method employing granulation, an aqueous raw material containing water is added to a powdery raw material containing water-soluble cellulose ether, catechin, and sugar, and granulated to obtain water-soluble cellulose ether and catechin. and a step of obtaining an orally disintegrating tablet composition containing sugar.

Granulation can be performed by using a granulator. Examples of granulators include, but are not limited to, fluidized bed granulators, stirring granulators, tumbling fluidized bed granulators, and spray drying granulators.

When granulation is performed using a fluidized bed granulator, the intake air temperature is preferably 50° C. to 100° C. from the viewpoint of the progress efficiency of granulation and the quality of the granules; and/or the exhaust temperature is preferably is between 25°C and 80°C.

Although the content of water in the aqueous raw material is not particularly limited, it is preferably 20% by mass to 100% by mass. The aqueous source may include an aqueous solution of binder. In addition, the aqueous raw material preferably contains a lower alcohol having 1 to 3 carbon atoms in order to increase the solubility of the components. The content of the lower alcohol having 1 to 3 carbon atoms in the aqueous raw material is preferably 10% by mass to 80% by mass from the viewpoint of solubility of the binder. The powdered ingredients and/or aqueous ingredients may also optionally contain sugar alcohols and other additives. The powdered raw material preferably contains an active ingredient.

The average particle size of the granules is preferably 120 μm to 500 μm, more preferably 150 μm to 250 μm, from the viewpoint of hardness and disintegration properties of an orally disintegrating tablet produced from the composition for an orally disintegrating tablet. The average particle size of the granules is a value (50% cumulative value of a volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

Granules are preferably subjected to a drying treatment. However, this is not the case when using a fluidized bed granulator or the like that can simultaneously carry out spraying and drying. Drying of the granules can be carried out using a known method such as a fluidized bed dryer, a tray dryer and the like. Although the drying temperature is not particularly limited, it is preferably 40°C to 80°C.

The water content of the granules is preferably 5% by mass or less, more preferably 0.2% by mass to 1% by mass, from the viewpoint of stability of the formulation. The water content of the granules is measured by the method described in Examples below.

When a composition for an orally disintegrating tablet is produced by granulation, a water-soluble cellulose ether having a viscosity of 1.0 mPa·s to 100 mPa·s at 20° C. in a 2% by mass aqueous solution is used from the viewpoint of productivity. More preferably, a water-soluble cellulose ether having a viscosity of 2.0 mPa·s to 10.0 mPa·s at 20° C. in a 2% by weight aqueous solution is used.

An orally disintegrating tablet composition containing granules containing water-soluble cellulose ether, catechin, and sugar can be obtained by a method employing granulation.

[Hot Melt Extrusion]
A method employing hot-melt extrusion includes a step of hot-melt extruding a powder raw material containing water-soluble cellulose ether and catechin to obtain an extrudate containing water-soluble cellulose ether and catechin, and pulverizing the extrudate. a step of obtaining a pulverized product by mixing the pulverized product with a sugar-containing raw material to obtain an orally disintegrating tablet composition containing a water-soluble cellulose ether, catechins, and sugar; including.

Hot-melt extrusion can be performed using a hot-melt extruder. Examples of heat-melting extruders include a single-screw piston type extruder such as Capilograph (manufactured by Toyo Seiki Co., Ltd.), "Nano-16" (manufactured by Leistritz), and "Mini Lab" (Thermo Fisher Scientific ( (manufactured by Thermo Fisher Scientific) and "Pharma Lab" (manufactured by Thermo Fisher Scientific).

The conditions for hot-melt extrusion can be appropriately set depending on the equipment used. For example, the barrel temperature in hot-melt extrusion is preferably 100° C. to 220° C. from the viewpoint of screw kneading and extrudability. The screw rotation speed in hot-melt extrusion is preferably 20 rpm to 500 rpm from the viewpoint of productivity and melt stability.

The powder raw material to be subjected to hot-melt extrusion is not particularly limited as long as it contains water-soluble cellulose ether and catechin. For example, additives such as plasticizers and surfactants may optionally be added. The powdered raw material preferably contains an active ingredient. From the viewpoint of storage stability, the amount of the plasticizer to be used is preferably 30 parts by mass or less with respect to 100 parts by mass of the water-soluble cellulose ether. From the viewpoint of storage stability, the amount of the surfactant used is preferably 10 parts by mass or less per 100 parts by mass of the water-soluble cellulose ether. The lower limit of the amount of plasticizer and surfactant used is not particularly limited, and is typically 0 parts by mass.

The method employing hot-melt extrusion can improve the miscibility of the water-soluble cellulose ether and catechin compared to the method employing dry mixing or granulation, and the resulting orally disintegrating tablet has improved disintegration properties. can be made better.

A pulverized product is obtained by pulverizing the extruded product obtained by hot-melt extrusion. Since the extrudate is usually a stranded product, a grinding process is employed to produce an orally disintegrating tablet using the extrudate.

Pulverization of the extrudate is not particularly limited, but can be performed using, for example, a pulverizer. Examples of pulverizers include coffee mills, hammer mills, pin mills, jet mills and the like. It can be pulverized to any particle size by using a pulverizer. The average particle size of the pulverized product is preferably 50 μm to 350 μm, more preferably 100 μm to 200 μm, from the viewpoint of hardness and disintegration properties of the orally disintegrating tablet, and mixing uniformity with the sugar and sugar alcohol used later. be. The average particle size of the pulverized product is a value (50% cumulative value of a volume-based cumulative particle size distribution curve) measured by the method described in Examples below.

By mixing the resulting pulverized product (pulverized extrudate) with raw materials containing sugar, a composition for orally disintegrating tablets containing water-soluble cellulose ether, catechin and sugar is obtained. The raw material containing sugar preferably contains a sugar alcohol. Mixing of the pulverized material and raw material containing sugar is not particularly limited as long as a uniform mixture can be obtained.

In the case of producing an orally disintegrating tablet composition by hot-melt extrusion, from the viewpoint of productivity, a water-soluble cellulose ether having a viscosity of 1.0 mPa s to 100 mPa s in a 2% by weight aqueous solution at 20°C is used. It is preferable to use a water-soluble cellulose ether having a viscosity of 2.0 mPa·s to 10.0 mPa·s at 20° C. in a 2 mass % aqueous solution.

An orally disintegrating tablet composition containing sugar and a hot melt extrudate containing water-soluble cellulose ether and catechin can be obtained by a method employing hot melt extrusion.

<orally disintegrating tablet>
An orally disintegrating tablet is obtained by tableting the composition for an orally disintegrating tablet. The orally disintegrating tablet is not particularly limited in physical properties such as hardness and disintegrating property, as long as it is obtained from the composition for an orally disintegrating tablet that is one aspect of the present invention.

The hardness of the orally disintegrating tablet is preferably 40 N or more, more preferably 40 N to 250 N, from the viewpoint of preventing cracking, chipping, etc. during filling, transportation and/or removal of the orally disintegrating tablet from the PTP sheet. and more preferably 40N to 100N. Hardness is measured by the method described in Examples below.

The disintegration property of an orally disintegrating tablet is measured by the amount of displacement of the probe when a load of 0.1 N is applied to the orally disintegrating tablet for 200 seconds using a tensile compression tester (displacement value after 200 seconds) and/or the disintegration rate. Evaluated by

The disintegration property of the orally disintegrating tablet is preferably −0.1 mm to −5.0 mm, and more preferably −0.4 mm to − for the displacement value after 200 seconds in order to achieve preferable dosability. 3.5 mm, more preferably −0.6 mm to −3.0 mm; and/or the disintegration rate is preferably −0.5×10 ⁻² mm/s to −5.0×10 ^{− 2} mm/s, more preferably −0.5×10 ⁻² mm/s to −3.5×10 ⁻² mm/s, still more preferably −0.8×10 ⁻² mm/s ˜−3.0×10 ⁻² mm/s. The displacement value and disintegration rate after 200 seconds of the orally disintegrating tablet are measured according to the method detailed in the examples described later.

<Method for producing orally disintegrating tablet>
A method for producing an orally disintegrating tablet includes a step of obtaining an orally disintegrating tablet by tableting the composition for an orally disintegrating tablet of one embodiment of the present invention. Orally disintegrating tablets contain water-soluble cellulose ethers, catechins, sugars, and optionally sugar alcohols and additives. Orally disintegrating tablets preferably contain an active ingredient.

Compression can be performed using a tablet press. The tableting machine includes, for example, a rotary tableting machine and a single-shot tableting machine. The tableting pressure during tableting is preferably 2 kN to 40 kN from the viewpoint of tablet hardness and tableting trouble.

Formulation design such as the size and weight of the orally disintegrating tablet after compression can be appropriately set as desired. For example, the diameter of the orally disintegrating tablet (the diameter of the orally disintegrating tablet) is preferably 6 mm to 12 mm from the viewpoint of handling and administration. The mass of the orally disintegrating tablet is not particularly limited, and is preferably 70 mg to 700 mg per tablet.

EXAMPLES The present invention will be described in more detail below with reference to Examples and Comparative Examples, but the present invention is not limited to these Examples.

<Materials used>
As water-soluble cellulose ethers, hypromellose (HPMC-1 to HPMC-4) and methylcellulose (MC-1), which were produced according to conventional methods, were used. Table 1 shows the physical properties of the water-soluble cellulose ether used.

As catechin, "Sunfood 100" (manufactured by Mitsubishi Chemical Foods; total amount of epigallocatechin gallate and epicatechin gallate: 25% by mass or more) was used.

Lactose (“Pharmatose 200M”; manufactured by DFE Pharma; average particle size: 40 μm) and maltose (“Sanmaruto Midori”; manufactured by Hayashibara Co., Ltd.; average particle size: 49 μm) were used as sugars.

Erythritol (“Erythritol 50M”; manufactured by Bussan Food Science; average particle size: 50 μm) and D(−)-mannitol (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.; average particle size: 40 μm) were used as sugar alcohols.

Riboflavin (“vitamin B ₂ ”; manufactured by Kyowa Pharma Chemical Co., Ltd.) was used as the active ingredient.

<Physical property evaluation>
[Average particle size]
The average particle diameter (d ₅₀ ) is determined by a dry method using a laser diffraction particle size distribution analyzer (“Mastersizer 3000”; manufactured by Malvern) according to the Fraunhofer diffraction theory, with a dispersion pressure of 1.5 bar and a scattering intensity of 2. % to 10%, it was measured by the 50% cumulative value of the volume-based cumulative particle size distribution curve.

[viscosity]
An amount corresponding to 6 g of dried water-soluble cellulose ether was accurately weighed into a wide-mouth bottle (diameter 65 mm; height 120 mm; volume 350 ml), and hot water at 98° C. was added to make 300.0 g. After the jar was capped, the mixture was stirred at 350-500 rpm for 20 minutes using a stirrer until a uniform dispersion was obtained. After that, the mixture was stirred in a water bath at 0° C. to 5° C. for 40 minutes to dissolve the water-soluble cellulose ether, thereby obtaining a 2 mass % aqueous solution of the water-soluble cellulose ether as a sample solution.

The viscosity of a 2% by mass aqueous solution of water-soluble cellulose ether at 20° C. was measured using an Ubbelohde viscometer according to the capillary viscometer method of the viscosity measurement method of the general test method described in the 17th edition of the Japanese Pharmacopoeia.

[Methoxy group content and hydroxypropoxy group content]
It was measured according to the quantitative method described in the Japanese Pharmacopoeia 17th Edition, “Hypromellose” and “Methylcellulose”.

[moisture]
1 g of the granulated material was weighed into a weighing bottle, left to stand in a dryer set at 105° C. for 3 hours, and the water content (loss on drying) was calculated from the weight change rate.

[Tablet hardness]
For the orally disintegrating tablet produced as follows, load is applied in the diameter direction of the tablet at the following constant speed and pressure using a tablet hardness tester ("TBH125"; manufactured by ERWEKA Co., Ltd.) under the following measurement conditions. It was measured as the maximum breaking strength when the tablet broke. Three tests were performed, and the average value was taken as the hardness of the tablet.

Hardness measurement conditions:
Constant velocity: 2.3mm/s
Equal pressure: 20N/s

[Tablet disintegration]
The orally disintegrating tablets produced were evaluated for disintegration by the following procedure using a tensile compression tester (“SDT-503NB”; manufactured by Imada Seisakusho Co., Ltd.).

An orally disintegrating tablet produced as described below was placed in the center of a petri dish having a diameter of 95 mm and a depth of 15 mm, and compression measurement was started under the following conditions. A probe (diameter: 11.28 mm, cylindrical) was brought into contact with the surface of the orally disintegrating tablet, and 15 ml of purified water was added 5 seconds after the time when the starting point detection load value was reached was taken as the measurement start time.

A load of about 0.1 N was applied to the orally disintegrating tablet for 200 seconds, and the amount of displacement of the probe accompanying the disintegration of the orally disintegrating tablet was used as an index of disintegration. With the position of the probe when the load reaches the starting point detection load value as the origin, the larger the negative displacement value, the higher the disintegrability of the orally disintegrating tablet.

In addition, the displacement speed of the probe per 5 seconds (based on formula 1) was calculated from the obtained collapse profile, and the point at which the displacement speed became -0.002 or less after the start of the test was defined as the collapse start point. The point at which the displacement rate became -0.002 or higher was defined as the collapse end point. The slope of a straight line obtained from two points, the collapse start point and the collapse end point, was defined as the collapse rate (based on Equation 2). A larger negative disintegration rate indicates higher disintegrability of the orally disintegrating tablet.

Specifically, according to Equation 1, the amount of change (displacement value) of the probe in 5 seconds from 0 (measurement start) to 5 seconds, 1 to 6 seconds, and 2 to 7 seconds is obtained in order, and the displacement speed is determined in order. Calculation was carried out one by one, the starting point of collapse and the end point of collapse were determined, and the collapse rate was calculated according to Equation (2).

(Formula 1)
Displacement speed (mm/s) = Probe change amount (displacement value) in 5 seconds/5
(Formula 2)
Collapse speed (mm/s) = (Displacement value at collapse end point - Displacement value at collapse start point) / (Time at collapse end point - Time at collapse start point)

Measurement conditions of SDT-503NB type tensile compression tester:
Start point detection: 0.1N
Load: 0.1N
Load width: 0.05 to 0.15N
Test speed: 5.0mm/min
Maintenance speed: 10mm/min
Adjustment speed: 1.0mm/min
Switching load: 0.05N

<Orally disintegrating tablet composition and production of orally disintegrating tablet>
[Example 1]
HPMC-1, catechin and lactose were weighed and mixed so as to have the mass ratio shown in Table 2 to produce an orally disintegrating tablet composition.

350 mg of the orally disintegrating tablet composition thus produced was tableted using a tableting machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 15 kN, and each tablet had a diameter of 10 mm. , a radius of curvature of 14.0 mm and a tablet weight of 350 mg.

[Example 2]
A composition for an orally disintegrating tablet was produced in the same manner as in Example 1, except that maltose was used as sugar instead of lactose.

350 mg of the orally disintegrating tablet composition thus produced was compressed using a tableting machine ("HAND TAB-200"; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 1 so that the tablet hardness was approximately the same as in Example 1. An orally disintegrating tablet was produced by tableting at 0 kN.

[Example 3]
A composition for an orally disintegrating tablet and an orally disintegrating tablet were produced in the same manner as in Example 1, except that HPMC-2 was used instead of HPMC-1 as the water-soluble cellulose ether.

[Example 4]
HPMC-1, catechin, lactose and erythritol were weighed and mixed so as to have the mass ratio shown in Table 2 to produce an orally disintegrating tablet composition. An orally disintegrating tablet was produced in the same manner as in Example 1 using the produced composition for an orally disintegrating tablet.

[Example 5]
HPMC-1, catechin, maltose and erythritol were weighed and mixed in the mass ratios shown in Table 2 to produce an orally disintegrating tablet composition.

350 mg of the orally disintegrating tablet composition thus produced was pressed using a tableting machine ("HAND TAB-200"; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 2 so that the tablet hardness was approximately the same as in Example 2. Orally disintegrating tablets were produced by tableting at 5 kN.

[Example 6]
A composition for an orally disintegrating tablet and an orally disintegrating tablet were prepared in the same manner as in Example 4, except that the mass ratio of HPMC-1 to catechin (water-soluble cellulose ether/catechin) was 2.3. manufactured.

[Example 7]
A composition for orally disintegrating tablets and an orally disintegrating tablet were prepared in the same manner as in Example 4, except that the mass ratio of HPMC-1 and catechin (water-soluble cellulose ether/catechin) was 1.0. manufactured.

[Example 8]
A composition for an orally disintegrating tablet and an orally disintegrating tablet were produced in the same manner as in Example 4, except that HPMC-2 was used instead of HPMC-1 as the water-soluble cellulose ether.

[Example 9]
A composition for orally disintegrating tablets and an orally disintegrating tablet were produced in the same manner as in Example 8, except that D-mannitol was used instead of erythritol as the sugar alcohol.

[Example 10]
A composition for an orally disintegrating tablet and an orally disintegrating tablet were produced in the same manner as in Example 4, except that HPMC-3 was used instead of HPMC-1 as the water-soluble cellulose ether.

[Example 11]
A composition for orally disintegrating tablets and an orally disintegrating tablet were produced in the same manner as in Example 4, except that MC-1 was used instead of HPMC-1 as the water-soluble cellulose ether.

[Example 12]
HPMC-4 (7.6 g), catechin (1.6 g), lactose (160 g) and erythritol (30.8 g) were charged into a fluid bed granulator, and a mixture of ethanol and purified water (ethanol/purified water = 7/3 (mass ratio), 300 g) was granulated under the following conditions to obtain an orally disintegrating tablet composition as a granule having an average particle size of 173 μm. The water content (loss on drying) of the granules was 0.5% by mass.

An orally disintegrating tablet was produced in the same manner as in Example 1 using the obtained granules (orally disintegrating tablet composition).

<Equipment used>
Fluid bed granulator "Flowcoater FZ-LABO" (Freund Corporation)
<Granulation conditions>
Intake temperature: 60°C
Exhaust temperature: 27-32°C
Fluid air volume: 45L/min
Spray rate: 10-12g/min
Spray air pressure: 0.10 MPa

[Example 13]
Using HPMC-4 (5.3 g) and catechin (1.1 g), an extrudate was obtained by hot-melt extrusion under the following conditions. The extrudate was pulverized for 3 seconds using a "Wonder Blender" (Osaka Chemical Co., Ltd.), and a pulverized material having an average particle size of 143 µm was recovered. The resulting pulverized product (2 g), lactose (34.8 g) and erythritol (6.7 g) were mixed at the mass ratio shown in Table 2 to produce an orally disintegrating tablet composition.

An orally disintegrating tablet was produced in the same manner as in Example 1 using the produced composition for an orally disintegrating tablet.

<Equipment used>
Compounding extruder "HAAKE MiniLab II" (manufactured by Thermo Fisher Scientific Co., Ltd.)
<Extrusion conditions>
Barrel temperature: 180°C
Screw rotation speed: 70 rpm
Input time: 5min
Circulation time: 5min

[Example 14]
HPMC-2, catechin, lactose and erythritol, and riboflavin (VB2) as an active ingredient were added, weighed and mixed to achieve the mass ratio shown in Table 2, to produce an orally disintegrating tablet composition.

350 mg of the orally disintegrating tablet composition thus produced was compressed using a tableting machine ("HAND TAB-200"; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 7 so that the tablet hardness was approximately the same as in Example 3. An orally disintegrating tablet was produced by tableting at 0 kN.

[Comparative Example 1]
Without adding catechin, HPMC-1 and lactose were weighed and mixed in the mass ratio shown in Table 2 to produce a tablet composition. Tablets were obtained in the same manner as in Example 1 using the manufactured composition for tablets.

In Comparative Example 1, the tablet did not disintegrate and the displacement rate (mm/s) did not fall below -0.002, so the disintegration rate could not be calculated.

[Comparative Example 2]
Without adding water-soluble cellulose ether, catechin and lactose were weighed and mixed in the mass ratio shown in Table 2 to produce a tablet composition. Tablets were obtained in the same manner as in Example 1 using the manufactured composition for tablets.

In Comparative Example 2, the tablet did not disintegrate and the displacement rate (mm/s) did not fall below -0.002, so the disintegration rate could not be calculated.

[Comparative Example 3]
Without adding sugar, HPMC-1 and catechin were weighed and mixed at the mass ratios shown in Table 2 to produce a tablet composition.

350 mg of the manufactured tablet composition was compressed using a tableting machine ("HAND TAB-200"; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 2.0 kN so that the tablet hardness was about the same as in Example 1. Tablets were produced by compression.

In Comparative Example 3, the tablet did not disintegrate and the displacement rate (mm/s) did not fall below -0.002, so the disintegration rate could not be calculated.

<Evaluation of Orally Disintegrating Tablets>
A comparison between Example 1 and Comparative Examples 1 to 3 shows that the orally disintegrating tablet produced from the orally disintegrating tablet composition containing water-soluble cellulose ether, catechin, and sugar has sufficient hardness and excellent disintegration. It was found to exhibit sexuality. Moreover, from the results of Examples 1 and 2, it was confirmed that an orally disintegrating tablet exhibiting sufficient hardness and excellent disintegration properties can be obtained regardless of the type of sugar such as lactose or maltose.

From the results of Examples 1 and 3, in the case of producing an orally disintegrating tablet composition by dry mixing, the larger the average particle size of the water-soluble cellulose ether used, the better the disintegrating properties of the resulting orally disintegrating tablet. was found to be superior.

From the results of Examples 1 and 4, and Examples 2 and 5, it was found that when the composition for orally disintegrating tablets contains a sugar alcohol, orally disintegrating tablets with better disintegration properties can be obtained. was done.

From the results of Examples 4, 6 and 7, when the mass ratio of water-soluble cellulose ether to catechin in the composition for orally disintegrating tablets is increased, the obtained orally disintegrating tablets are more excellent in hardness and disintegration properties. It was found that

From the results of Examples 4 and 8, when producing an orally disintegrating tablet composition containing a sugar alcohol by dry mixing, the larger the average particle size of the water-soluble cellulose ether, the more the orally disintegrating tablet obtained. It was found to be excellent in disintegration.

From the results of Examples 8 and 9, it was confirmed that an orally disintegrating tablet exhibiting sufficient hardness and excellent disintegration properties can be obtained regardless of the type of sugar alcohol such as erythritol or D-mannitol.

From the results of Examples 4, 10 and 11, regardless of the types of water-soluble cellulose ethers such as HPMC and MC with various particle sizes, orally disintegrating tablets exhibiting sufficient hardness and excellent disintegration properties were obtained. confirmed to be obtained.

From the results of Examples 10, 12, and 13, sufficient hardness and excellent disintegration are demonstrated regardless of the method for producing an orally disintegrating tablet composition such as dry mixing, granulation, and hot-melt extrusion. It was confirmed that an orally disintegrating tablet was obtained. However, for reasons such as the disintegration behavior of the obtained orally disintegrating tablet differing depending on the manufacturing method of the orally disintegrating tablet composition, an orally disintegrating tablet with excellent displacement value and disintegration rate after 200 seconds by hot melt extrusion is available. It was found to be obtained.

From the results of Examples 3 and 14, it was confirmed that an orally disintegrating tablet exhibiting sufficient hardness and excellent disintegrability was obtained even when an active ingredient was contained.

INDUSTRIAL APPLICABILITY According to the present invention, an orally disintegrating tablet having sufficient hardness and excellent disintegrability can be produced on a general-purpose, industrial scale without adopting complicated steps.

Claims (11)

A composition for an orally disintegrating tablet, comprising water-soluble cellulose ether, at least one catechin selected from the group consisting of epigallocatechin gallate and epicatechin gallate, and sugar. The composition for an orally disintegrating tablet according to claim 1, further comprising a sugar alcohol. The composition for an orally disintegrating tablet according to claim 1 or 2, wherein the mass ratio of the water-soluble cellulose ether to the catechin (water-soluble cellulose ether/catechin) is 1.0/1 to 7.5/1. . The composition for an orally disintegrating tablet according to any one of claims 1 to 3, further comprising an active ingredient. The orally disintegrating material according to any one of claims 1 to 4, wherein the water-soluble cellulose ether is at least one water-soluble cellulose ether selected from the group consisting of alkylcellulose, hydroxyalkylcellulose and hydroxyalkylalkylcellulose. Composition for tablets. An orally disintegrating tablet, which is a tableted product of the composition for an orally disintegrating tablet according to any one of claims 1 to 5. Orally disintegrating comprising a step of dry-mixing powder raw materials containing water-soluble cellulose ether, catechin and sugar to obtain an orally disintegrating tablet composition containing water-soluble cellulose ether, catechin and sugar. A method for producing a tablet composition, wherein the catechin is at least one catechin selected from the group consisting of epigallocatechin gallate and epicatechin gallate . A powder raw material containing water-soluble cellulose ether, catechin and sugar is granulated by adding an aqueous raw material containing water to produce an oral cavity containing water-soluble cellulose ether, catechin and sugar. A method for producing an orally disintegrating tablet composition comprising a step of obtaining a disintegrating tablet composition, wherein the catechin is at least one catechin selected from the group consisting of epigallocatechin gallate and epicatechin gallate. the aforementioned method . obtaining an extrudate containing the water-soluble cellulose ether and the catechins by heat-melt extruding a powder raw material containing the water-soluble cellulose ethers and the catechins;
a step of pulverizing the extrudate to obtain a pulverized product;
A composition for an orally disintegrating tablet comprising a step of mixing the pulverized product and a raw material containing a sugar to obtain a composition for an orally disintegrating tablet containing a water-soluble cellulose ether, catechins, and sugar. A production method , wherein the catechin is at least one catechin selected from the group consisting of epigallocatechin gallate and epicatechin gallate . The method for producing an orally disintegrating tablet composition according to any one of claims 7 to 9, wherein the powder raw material further contains an active ingredient. A method for producing an orally disintegrating tablet, comprising a step of obtaining an orally disintegrating tablet by tableting the composition for an orally disintegrating tablet according to any one of claims 7 to 10.