JP2021031404A - Composition for orally disintegrating tablet and production method thereof as well as orally disintegrating tablet using the same and production method thereof - Google Patents

Abstract

To provide compositions and methods for producing orally disintegrating tablets having moderate tablet strength and excellent disintegration property, by a dry process without adopting a complicated process, as well as to provide the orally disintegrating tablets and production methods thereof.SOLUTION: The above subject is solved by a composition for an orally disintegrating tablet containing at least water-soluble cellulose ether, catechin, and sugar, and a method for producing a composition for an orally disintegrating tablet, and the like, the method comprising a step of obtaining a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar by dry mixing a powder raw material containing water-soluble cellulose ether, catechin, and sugar.SELECTED DRAWING: None

Description

The present invention relates to a composition for an orally disintegrating tablet for producing an orally disintegrating tablet having excellent disintegration property in the oral cavity, a method for producing the same, and 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 when there is an urgent need or when a critically ill patient takes the tablet while lying down. Further, it may be difficult for a child with an immature swallowing function or an elderly person with a deteriorated swallowing function to swallow the tablet, and improvement in the ease of taking the tablet is desired.

Orally disintegrating tablets that can be taken without water are known as those with improved doability. The orally disintegrating tablet is characterized by containing drug-containing particles containing a drug, a water-soluble polymer and a sugar or a sugar alcohol, and spray-dried particles containing mannitol or mannitol and xylitol, carboxymethyl cellulose and a disintegrant. Orally disintegrating tablets have been proposed (Patent Document 1).

International Publication No. 2011/019043 Pamphlet

However, in the manufacturing process of the orally disintegrating tablet described in Patent Document 1, drug-containing particles are obtained by granulating one raw material, the other raw material is dispersed in a dispersion solvent, spray-dried and sprayed. The manufacturing process up to tableting is complicated, including obtaining dried particles and then mixing and tableting the obtained drug-containing particles and spray-dried particles.

Further, since the orally disintegrating tablet is a tablet having both appropriate tablet strength and excellent disintegrating property, it is difficult to design a formulation. Further, since carboxymethyl cellulose used in Patent Document 1 is an ionic disintegrant, an interaction with an active ingredient may occur.

Therefore, in view of the above circumstances, the present invention can be produced without adopting a complicated process, and the oral disintegration for producing an orally disintegrating tablet having appropriate tablet strength and excellent disintegration property. An object of the present invention is 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.

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

Finally, based on the above findings, a composition for an orally disintegrating tablet containing a water-soluble cellulose ether, catechin, and a sugar; a composition for the orally disintegrating tablet, which can solve the problem of the present invention. Method for producing a product; an orally disintegrating tablet which is a tableted product of the composition for an orally disintegrating tablet; succeeded in creating 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.

Therefore, according to the present invention, there are provided a composition for an orally disintegrating tablet, a method for producing a composition for an orally disintegrating tablet, and a method for producing an orally disintegrating tablet and an orally disintegrating tablet according to the following aspects.
[1] A composition for an orally disintegrating tablet containing a 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 for.
[4] The composition for an orally disintegrating tablet according to any one of [1] to [3], which further contains 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 alkyl cellulose, hydroxyalkyl cellulose and hydroxyalkyl alkyl cellulose. Composition for orally disintegrating tablets.
[6] An orally disintegrating tablet which is a lock of the composition for an orally disintegrating tablet according to any one of [1] to [5].
[7] The present invention comprises a step of dry-mixing a powder raw material containing water-soluble cellulose ether, catechin, and sugar to obtain a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar. A method for producing a composition for an orally disintegrating tablet.
[8] A powder raw material containing water-soluble cellulose ether, catechin, and sugar is granulated by adding an aqueous raw material containing water to contain the water-soluble cellulose ether, catechin, and sugar. A method for producing an orally disintegrating tablet composition, which comprises a step of obtaining an orally disintegrating tablet composition.
[9] A step of obtaining an extrusion containing the water-soluble cellulose ether and catechin by heating and melt-extruding a powder raw material containing the water-soluble cellulose ether and catechin, and pulverization by pulverizing the extrusion. Intraoral including a step of obtaining a product and a step of obtaining a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar by mixing the pulverized product with a raw material containing sugar. A method for producing a composition for disintegrating tablets.
[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, which comprises 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].

According to the present invention, it is possible to obtain an orally disintegrating tablet having sufficient hardness and exhibiting excellent disintegration without adopting a complicated process.

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

Unless otherwise specified, each term in the present specification is used in the meaning commonly used by those skilled in the art and should not be construed as having an unreasonably limited meaning. Moreover, since the guesses and theories made in the present specification are based on the knowledge and experience of the present inventors, the present invention is not bound by such guesses and theories alone. Absent.

The "composition" is not particularly limited as having a commonly used meaning, but is, for example, a combination of two or more kinds of components. "Raw material" means one component or a combination of two or more components to form a composition.
"Orally disintegrating tablet" means a tablet that disintegrates in the oral cavity with only saliva in the oral cavity or a small amount of water in a short time (generally within 1 minute, preferably within 30 seconds).
The term "and / or" means any one, or any combination of two or more, or all combinations of a plurality of related items listed.
"Content" is synonymous with concentration and means the ratio of the amount of the component to the total amount of the composition. In the present specification, unless otherwise specified, the unit of content means "mass% (wt%)". However, the total content of the components does not exceed 100% by mass.
"~" In the numerical range is a range including the numerical values before and after that, and for example, "0% by mass to 100% by mass" means a range of 0% by mass or more and 100% by mass or less. ..
"Including" means that elements other than those specified as being included can be added (synonymous with "at least including"), but includes "consisting of" and "essentially consisting of". To do. That is, "contains" can mean that it includes an explicit element and any one or more of the elements, consists of the explicit element, or essentially consists of the explicit element. .. Elements include restrictions such as components, processes, conditions, and parameters.

The number of digits of an integer value and the number of digits of significant figures match. For example, 1 significant digit is 1 digit and 10 significant digit is 2 digits. In addition, the number of digits after the decimal point and the number of significant digits are the same for decimal numbers. For example, 0.1 significant digit is 1 digit and 0.10 significant digit is 2 digits.

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

The water-soluble cellulose ether is a nonionic polymer in which a part of the hydroxyl groups of cellulose is etherified. In the composition for orally disintegrating tablets, the water-soluble cellulose ether functions as a binder and also functions as a disintegrant by hydrating and swelling.

The water-soluble cellulose ether is not particularly limited as long as it is a water-soluble cellulose ether, and the organic group constituting the ether is not particularly limited, and examples thereof include alkyl cellulose, hydroxyalkyl cellulose, and hydroxyalkyl alkyl cellulose.

Examples of the alkyl cellulose include methyl cellulose and ethyl cellulose, but methyl cellulose, which is easily water-soluble, is preferable.

The methoxy group content in methylcellulose is preferably 26.0% by mass to 33.0% by mass, and 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 section "Methylcellulose" of the 17th revised Japanese Pharmacopoeia.

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

The hydroxypropoxy group content in hydroxypropyl cellulose is preferably 53.4% by mass to 77.5% by mass, and 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 section "Hydroxypropyl cellulose" of the 17th revised Japanese Pharmacopoeia.

Examples of the hydroxyalkylalkyl cellulose include hypromellose (hydroxypropylmethyl cellulose; hereinafter, also referred to as “HPMC”), hydroxyethyl methyl cellulose, hydroxyethyl ethyl cellulose and the like, and HPMC is used from the viewpoint of moldability and disintegration. 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. 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. It is 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" of the 17th revised Japanese Pharmacopoeia.

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

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. It is ~ 120,000 mPa · s, more preferably 2.5 mPa · s ~ 6,000 mPa · s. The viscosity of a 2% by mass aqueous solution of water-soluble cellulose ether at 20 ° C. is a value measured by a method as described in Examples described later.

As the water-soluble cellulose ether, one type such as those listed above may be used alone, or two or more types may be used in combination. As the water-soluble cellulose ether, a commercially available one may be used, or one produced by a known method may be used.

Catechin is a kind of polyphenol as is generally known, and is not particularly limited as long as it is a tea extract. In addition to epicatechin and epigallocatechin, catechin includes epigallocatechin galley and epicatechin galade having a garade group.

The catechin preferably contains any two, three or four of epicatechin, epigallocatechin, epigallocatechin galley and epicatechin galade.

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

According to the findings found by the present inventors, catechin forms an insoluble swelling together with water-soluble cellulose ether in the presence of water. Further formed insoluble swelling contributes to disintegration in the orally disintegrating tablet composition.

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

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

Sugar functions as a medium that promotes water conduction into the orally disintegrating tablet.
Examples of the sugar include lactose, maltose, sucrose, pullulan, trehalose, isomaltose, turanose, cellobiose and the like, but monosaccharides and disaccharides are preferable 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 property of the orally disintegrating tablet. The average particle size of the sugar is a value measured by the method described in Examples described later (50% cumulative value of the volume-based cumulative particle size distribution curve).

The sugar content 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 of the total mass of the water-soluble cellulose ether and catechin from the viewpoint of water conductivity in the orally disintegrating tablets. It is by mass, more preferably 800 parts by mass to 2,200 parts by mass.

As the sugar, one kind such as the above-mentioned one may be used alone, or two or more kinds may be used in combination. In addition, 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 enhanced, and the disintegration property 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 property of the orally disintegrating tablet. The average particle size of the sugar alcohol is a value measured by the method described in Examples described later (50% cumulative value of the volume-based cumulative particle size distribution curve).

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

As the sugar alcohol, one kind such as the above-mentioned one may be used alone, or two or more kinds may be used in combination. Further, as the sugar alcohol, a commercially available one can be used.

The composition for an orally disintegrating tablet can contain an additive, for example, an additive usually used for producing an orally disintegrating tablet. Such additives include, for example, lubricants, flavoring agents, fragrances, stabilizers, fluidizing agents, coloring agents, cooling agents, preservatives, chelating agents, pH adjusters, antioxidants, etc. Examples include thickeners. The amount of the additive used is not particularly limited as long as it does not interfere with the solution of the problem of the present invention, and can be set as appropriate. Some of the additives are listed below, but these are examples only and are not limited.

Examples of the lubricant include magnesium stearate, calcium stearate, talc, sodium stearyl fumarate, and sucrose fatty acid ester. Examples of the flavoring agent include citric acid, tartaric acid, malic acid and the like. Examples of the fragrance include menthol, peppermint oil, vanillin and the like.

In addition to the above-mentioned water-soluble cellulose ether, catechin, and sugar, the composition for orally disintegrating tablets may contain any other disintegrant, binder, and / or excipient, as long as it does not interfere with the solution of the problem of the present invention. May include. Examples of the disintegrant include low-degree-of-substitution hydroxypropyl cellulose, corn starch, partially pregelatinized starch, sodium carboxymethyl starch, croscarmellose, croscarmellose sodium, crystalline cellulose, crospovidone and the like. Examples of the binder include polyvinylpyrrolidone, polyvinyl alcohol and the like. Examples of the excipient include crystalline cellulose, powdered cellulose, calcium phosphate, calcium sulfate and the like.

For example, when the granulation step and the heat melt extrusion step are adopted, a solvent, a plasticizer, a surfactant and the like can be used as additives depending on the manufacturing process to be adopted.

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 the plasticizer include higher alcohols having 10 to 20 carbon atoms such as acetone, cetyl alcohol and stearyl alcohol, preferably polyhydric alcohols having 2 to 6 valences such as glycerin, bead wax, triethyl citrate and polyethylene glycol. Alternatively, alkylene glycol, triacetin, dibutyl sevasate, guiserine monostearate, monoglycerine acetate and the like of propylene glycol sugar can be mentioned. Examples of the surfactant include anionic surfactants such as sodium lauryl sulfate, diglycerides, porox summer, polyoxyethylene sorbitan fatty acid esters (twin 20, 60, 80), glycerin fatty acid esters, propylene glycol fatty acid esters and the like. Examples include ionic surfactants, natural surfactants such as lecithin and sodium taurocholate.

As the additive, one kind such as the above-mentioned one may be used alone, or two or more kinds may be used in combination. Further, as the additive, a commercially available one can be used.

The content of the additive in the composition for orally disintegrating tablets is not particularly limited as long as it does not interfere with the solution of the problem of the present invention, but from the viewpoint of hardness and disintegration in the orally disintegrating tablets, water-soluble cellulose ether and catechin It is preferably 0 parts by mass to 10,000 parts by mass, and more preferably 50 parts by mass to 1,000 parts by mass with respect to 100 parts by mass of the total mass.

The composition for orally disintegrating tablets preferably further contains an active ingredient. The active ingredient is not particularly limited as long as it is an orally administrable active ingredient, but is, for example, an active ingredient used in drugs used in pharmaceutical products and health foods such as nutritionally functional foods, foods for specified health uses and foods with functional claims. And so on.

Drugs used in pharmaceuticals include, for example, central nervous system drugs, cardiovascular drugs, respiratory drugs, digestive system drugs, antibiotics, antitussive / expectorant drugs, antihistamines, antipyretic analgesic and anti-inflammatory agents, diuretics, and autonomy. Examples thereof include neuroactive agents, antimalarial agents, antidiarrheal agents, psychotropic agents, vitamins and derivatives thereof.

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

Cardiovascular drugs include, for example, morsidemin, vinposetin, propranolol, methyldopa, dipyridamole, furosemide, triamterene, nifedibin, atenolol, spironolactone, metoprolol, pindolol, captopril, isosorbit nitrate, derapril hydrochloride, meclophenoxate hydrochloride, diltiazem hydrochloride Examples thereof include etilefurin hydrochloride, digitoxin and alprenolol hydrochloride.

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

Examples of gastrointestinal 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 drugs having anti-ulcer activity such as benzimidazole, cimetidine, ranitidine, pirenzepine hydrochloride, pancreatin, bisacodyl, 5-aminosalicylic acid and the like can be mentioned. ..

Examples of the antibiotic include tarampicillin hydrochloride, bacampicillin hydrochloride, cefaclor and erythromycin.

Examples of antitussive / expectorant agents include noscapine hydrochloride, carbetapentane citrate, isoaminile citrate, dimemorfan phosphate and the like.

Examples of the antihistamine include chlorpheniramine maleate, diphenhydramine hydrochloride and promethazine hydrochloride.

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

Examples of the diuretic include caffeine and the like.

Examples of the autonomic nervous agent include dihydrocodein phosphate and dl-methylephedrine hydrochloride, atropine sulfate, acetylcholine chloride, neostigmine and the like.

Examples of the antimalarial agent include quinine hydrochloride and the like. Examples of the antidiarrheal agent include loperamide hydrochloride and the like. Examples of the psychotropic agent include chlorpromazine and the like.

Examples of vitamins and their derivatives include vitamin A, vitamin B ₁ , fursultiamine, vitamin B ₂ , vitamin B ₆ , vitamin B ₁₂ , vitamin C, vitamin D, vitamin E, vitamin K, calcium pantothenate and tranexam. Examples include acids.

Examples of the active ingredient used in health foods include the vitamins and derivatives thereof, minerals, carotenoids, amino acids and derivatives thereof, plant extracts, and health food materials.

Examples of minerals include calcium, magnesium, manganese, zinc, iron, copper, selenium, chromium, sulfur and iodine.

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

Examples of amino acids include acidic amino acids, basic amino acids, neutral amino acids and acidic amino acid amides.

Examples of acidic amino acids include aspartic acid and glutamic acid. Examples of basic amino acids include 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, hydroxyamino acids such as serine and threonine, and sulfurized compounds such as cysteine and methionine. Examples include amino acids, aromatic amino acids such as phenylalanine and tyrosine, heterocyclic amino acids such as tryptophan, and iminoic acid such as proline.

Examples of the acidic amino acid amide include asparagine and glutamine.

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

Examples of plant extracts include aloe, propolis, agaricus, ginseng, ginkgo biloba, turmeric, curcumin, germinated brown rice, shiitake mushroom mycelium, sweet tea, sweet tea, caterpillar fungus, sesame, garlic, maca, caterpillar fungus, chamomile and capsicum. Be done.

Examples of health food materials include royal jelly, dietary fiber, protein, bifidobacteria, lactic acid bacteria, chitosan, yeast, glucosamine, lecithin, polyphenols, animal seafood cartilage, sponge, lactoferrin, shijimi, eikosapentaenoic acid, germanium, enzymes, creatine, etc. Examples thereof include carnithin, citric acid, raspberry ketone, coenzyme Q10, methylsulfonylmethane and phospholipid-bound soybean peptide.

The content of the active ingredient can be appropriately determined according to the desired pharmacological action or functionality, and for example, from the viewpoint of hardness and disintegration of the orally disintegrating tablet, the total mass of the water-soluble cellulose ether and catechin. It is preferably 200 parts by mass to 1,100 parts by mass with respect to 100 parts by mass.

As the active ingredient, one kind such as the above-mentioned one may be used alone, or two or more kinds may be used in combination. Further, as the active ingredient, a commercially available one can be used.

<Manufacturing method of composition for orally disintegrating tablets>
The composition for an orally disintegrating tablet contains water-soluble cellulose ether, catechin, and sugar, and is produced so that an orally disintegrating tablet can be obtained by subjecting it to a tableting step. The method for producing the composition for orally disintegrating tablets is not particularly limited, and examples thereof include methods including steps such as dry mixing, granulation, and heat melt extrusion.

[Dry mixing]
The method of adopting dry mixing is a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar by dry-mixing a powder raw material containing water-soluble cellulose ether, catechin, and sugar. Includes the step of obtaining.

The method of dry mixing is not particularly limited. The powder raw material to be subjected to dry mixing may contain a sugar alcohol and any additive. The powder raw material preferably contains an active ingredient.

When dry mixing is adopted, it is preferable to use a water-soluble cellulose ether having an average particle size of 100 μm or more, and an average particle size is preferable, from the viewpoint of disintegration of the orally disintegrating tablet produced by the composition for orally disintegrating tablets. It is more preferable to use a water-soluble cellulose ether having a size of 100 μm to 300 μm. By containing the water-soluble cellulose ether having such an average particle size in the composition for orally disintegrating tablets, the water-soluble cellulose ether is present in the orally disintegrating tablets in a certain size even after tableting. Because it can be used, it is more resistant to disintegration. The average particle size of the water-soluble cellulose ether is a value measured by the method described in Examples described later (50% cumulative value of the volume-based cumulative particle size distribution curve).

[Granulation]
The method of adopting granulation is to add a water-soluble raw material containing water to a powder raw material containing water-soluble cellulose ether, catechin, and sugar to perform granulation, thereby forming a water-soluble cellulose ether and catechin. A step of obtaining a composition for an orally disintegrating tablet containing sugar and sugar is included.

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

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

The content of water in the aqueous raw material is not particularly limited, but is preferably 20% by mass to 100% by mass. The aqueous raw material may include an aqueous solution of the binder. Further, the aqueous raw material preferably contains a lower alcohol having 1 to 3 carbon atoms in order to enhance the solubility of the component. 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 the solubility of the binder. In addition, the powder raw material and / or the aqueous raw material may optionally contain a sugar alcohol and other additives. The powder raw material preferably contains an active ingredient.

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

The granulated product is preferably subjected to a drying treatment. However, this does not apply when a fluidized bed granulator or the like capable of spraying and drying at the same time is used. The granulated product can be dried by using a known method, for example, a fluidized bed dryer, a shelf dryer, or the like. The drying temperature is not particularly limited, but is preferably 40 ° C to 80 ° C.

From the viewpoint of the stability of the preparation, the water content of the granulated product is preferably 5% by mass or less, more preferably 0.2% by mass to 1% by mass. The water content of the granulated product is measured by the method described in Examples described later.

When producing a composition for orally disintegrating tablets by granulation, a water-soluble cellulose ether having a viscosity of a 2% by mass aqueous solution at 20 ° C. of 1.0 mPa · s to 100 mPa · s is used from the viewpoint of productivity. It is preferable to use a water-soluble cellulose ether having a viscosity of a 2% by mass aqueous solution at 20 ° C. of 2.0 mPa · s to 10.0 mPa · s.

By a method that employs granulation, a composition for an orally disintegrating tablet containing a granulated product containing water-soluble cellulose ether, catechin, and sugar can be obtained.

[Heat melt extrusion]
The method of adopting heat melt extrusion is a step of obtaining an extrusion containing water-soluble cellulose ether and catechin by heat melt extrusion of a powder raw material containing water-soluble cellulose ether and catechin, and pulverizing the extrusion. A step of obtaining a pulverized product, and a step of mixing the pulverized product with a raw material containing sugar to obtain a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar. including.

The heat melt extrusion can be performed using a heat melt extruder. Examples of the heat melt extruder include a uniaxial piston type extruder such as Capillograph (manufactured by Toyo Seiki Co., Ltd.), "Nano-16" (manufactured by Leistritz), and "Mini Lab" (Thermo Fisher Scientific). Biaxial screw type extruders such as (manufactured by Thermo Fisher Scientific) and "Pharma Lab" (manufactured by Thermo Fisher Scientific) and the like can be mentioned.

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

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

By the method adopting heat melt extrusion, the mixing property of the water-soluble cellulose ether and catechin can be enhanced as compared with the method adopting dry mixing or granulation, and the disintegration property of the resulting orally disintegrating tablet can be improved. Can be good.

A pulverized product is obtained by pulverizing the extruded product obtained by heat melt extrusion. Since the extruded product is usually a strand-like product, a pulverization step is adopted to produce an orally disintegrating tablet using the extruded product.

The pulverization of the extruded product is not particularly limited, but can be performed using, for example, a pulverizer. Examples of the crusher include a coffee mill, a hammer mill, a pin mill, a jet mill and the like. It can be crushed to an arbitrary particle size by using a crusher. 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 of the orally disintegrating tablet and mixing uniformity with sugar and sugar alcohol used in the subsequent stage. is there. The average particle size of the pulverized product is a value measured by the method described in Examples described later (50% cumulative value of the volume-based cumulative particle size distribution curve).

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

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

By a method that employs heat melt extrusion, a composition for an orally disintegrating tablet containing a heat melt extrusion containing water-soluble cellulose ether and catechin and sugar can be obtained.

<Orally disintegrating tablet>
By tableting the composition for orally disintegrating tablets, an orally disintegrating tablets can be obtained. The orally disintegrating tablet is not particularly limited in physical properties such as hardness and disintegration as long as it is obtained by the composition for orally disintegrating tablet which is one aspect of the present invention.

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

The disintegration property of the orally disintegrating tablet is the displacement amount (displacement value after 200 seconds) and / or the disintegrating speed 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. Evaluated by.

The disintegration property of the orally disintegrating tablet is preferably -0.1 mm to -5.0 mm, more preferably -0.4 mm to-for the displacement value after 200 seconds, in order to say that it is preferable to take. is 3.5 mm, and more preferably is at -0.6mm~-3.0mm; and / or, for disintegration rate, preferably ^{-0.5 × 10 -2 mm / s~-} 5.0 × 10 - a ² mm / s, more preferably ^{-0.5 × 10 -2 mm / s~-} 3.5 × 10 -2 mm / s, more preferably -0.8 × ¹⁰ -2 mm / s ~ −3.0 × 10 ⁻² mm / s. The displacement value and disintegration rate of the orally disintegrating tablet after 200 seconds are measured according to the method detailed in Examples described later.

<Manufacturing method of orally disintegrating tablets>
The 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 according to one aspect of the present invention. Orally disintegrating tablets include water-soluble cellulose ether, catechin, sugar, and optionally sugar alcohols and additives. The orally disintegrating tablet preferably contains an active ingredient.

Locking can be performed using a locking machine. Examples of the locking machine include a rotary type locking machine and a single-shot locking machine. The tableting pressure at the time of tableting is preferably 2 kN to 40 kN from the viewpoint of tablet hardness and tableting disorder.

The formulation design such as the size and mass of the orally disintegrating tablet after tableting 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 handleability and ease of administration. The mass of the orally disintegrating tablet is not particularly limited, and is preferably 70 mg to 700 mg per tablet.

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

<Material used>
As the water-soluble cellulose ether, hypromellose (HPMC-1 to HPMC-4) and methyl cellulose (MC-1) produced according to a conventional method were used. Table 1 shows the physical characteristics of the water-soluble cellulose ether used.

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

As the sugar, lactose (“Pharmatose 200M”; manufactured by DFE Pharma; average particle size: 40 μm) and maltose (“San Marto Midori”; manufactured by Hayashibara Co., Ltd .; average particle size: 49 μm) were used.

As the sugar alcohol, erythritol (“Erythritol 50M”; manufactured by Bussan Food Science Co., Ltd .; average particle size: 50 μm) and D (-)-mannitol (manufactured by Fuji Film Wako Pure Chemical Industries, Ltd .; average particle size: 40 μm) were used.

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 size (d ₅₀ ) is determined by a dry method using a laser diffraction type particle size distribution measuring device (“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. It was measured by the 50% cumulative value of the volume-based cumulative particle size distribution curve under the condition of% to 10%.

[viscosity]
The amount corresponding to 6 g of the water-soluble cellulose ether in terms of water content was accurately weighed in a wide-mouthed bottle (diameter 65 mm; height 120 mm; volume 350 ml), and boiling water at 98 ° C. was added to make 300.0 g. After covering the wide-mouthed bottle, the mixture was stirred with a stirrer at 350 rpm to 500 rpm for 20 minutes until a uniform dispersion was obtained. Then, the water-soluble cellulose ether was dissolved by stirring in a water bath at 0 ° C. to 5 ° C. for 40 minutes to obtain a 2% by 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 a Ubbelohde viscometer according to the capillary viscometer method of the viscosity measuring method of the general test method described in the 17th revised Japanese Pharmacy.

[Methoxy group content and hydroxypropoxy group content]
The measurement was performed according to the quantitative method described in the "hypromellose" and "methylcellulose" sections of the 17th revised Japanese Pharmacopoeia.

[moisture]
It was calculated by weighing 1 g of the granulated product in a weighing bottle and determining the water content (drying weight loss) from the weight change rate after allowing it to stand in a dryer set at 105 ° C. for 3 hours.

[Tablet hardness]
For orally disintegrating tablets manufactured as follows, a load was applied in the diameter direction of the tablets at the following constant velocity 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 was broken. The number of tests was 3 times, and the average value was taken as the hardness of the tablet.

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

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

The orally disintegrating tablet produced as described later 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. After 5 seconds, 15 ml of purified water was added with the time when the probe (diameter: 11.28 mm, cylindrical) came into contact with the surface of the orally disintegrating tablet and reached the starting point detection load value as the measurement start time.

A load of about 0.1 N was applied to the orally disintegrating tablet for 200 seconds, and the displacement amount of the probe accompanying the disintegration of the orally disintegrating tablet was used as an index of disintegration. It is shown that the larger the displacement value is negative with the position of the probe as the origin when the load reaches the start point detection load value, the higher the disintegration property of the orally disintegrating tablet.

In addition, the displacement velocity of the probe per 5 seconds (based on Equation 1) was calculated from the obtained decay profile, and the point where the displacement velocity became -0.002 or less after the start of the test was defined as the collapse start point, and then. The point where the displacement velocity was -0.002 or more was defined as the collapse end point. The slope of a straight line obtained from the two points of the collapse start point and the collapse end point was defined as the collapse rate (based on Equation 2). The larger the disintegration rate, the higher the disintegration property of the orally disintegrating tablet.

Specifically, according to Equation 1, the amount of change (displacement value) of the probe in 5 seconds such as 0 (measurement start) to 5 seconds, 1 to 6 seconds, and 2 to 7 seconds is sequentially obtained, and the displacement speed is determined in order. The collapse start point and the collapse end point were calculated individually, and the collapse rate was calculated according to Equation 2.

(Equation 1)
Displacement speed (mm / s) = amount of change (displacement value) of probe in 5 seconds / 5
(Equation 2)
Collapse velocity (mm / s) = (displacement value at the end point of collapse-displacement value at the start point of collapse) / (time at the end point of collapse-time at the start point of collapse)

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: 5.0 mm / min
Maintenance speed: 10 mm / min
Adjustment speed: 1.0 mm / min
Switching load: 0.05N

<Manufacturing of composition for orally disintegrating tablets and orally disintegrating tablets>
[Example 1]
HPMC-1, catechin and lactose were weighed and mixed so as to have the mass ratios shown in Table 2 to prepare a composition for orally disintegrating tablets.

The produced composition for orally disintegrating tablets 350 mg was tableted using a tablet molding machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.) at a tableting pressure of 15 kN, and the diameter of one tablet was 10 mm. An orally disintegrating tablet having a radius of curvature of 14.0 mm and a tablet mass of 350 mg was produced.

[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 the sugar instead of lactose.

Using a tablet molding machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.), 350 mg of the produced composition for orally disintegrating tablets was tableted with a tableting pressure of 1 so as to have the same tablet hardness as in Example 1. Orally disintegrating tablets were produced by tableting at 0.0 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 as the water-soluble cellulose ether instead of HPMC-1.

[Example 4]
HPMC-1, catechin, lactose and erythritol were weighed and mixed so as to have the mass ratios shown in Table 2 to prepare a composition for orally disintegrating tablets. Using the produced composition for orally disintegrating tablets, orally disintegrating tablets were produced in the same manner as in Example 1.

[Example 5]
HPMC-1, catechin, maltose and erythritol were weighed and mixed so as to have the mass ratios shown in Table 2 to prepare a composition for orally disintegrating tablets.

Using a tablet molding machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.), 350 mg of the produced composition for orally disintegrating tablets was tableted with a tableting pressure of 2 so as to have the same tablet hardness as in Example 2. Orally disintegrating tablets were produced by tableting at .5 kN.

[Example 6]
The composition for orally disintegrating tablets and the orally disintegrating tablets 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]
The composition for orally disintegrating tablets and the orally disintegrating tablets 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 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 as the water-soluble cellulose ether instead of HPMC-1.

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

[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 as the water-soluble cellulose ether instead of HPMC-1.

[Example 11]
A composition for an orally disintegrating tablet 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 fluidized layer granulator, and a mixed solution of ethanol and purified water (ethanol / purified water =). Granulation was carried out under the following conditions using 7/3 (mass ratio), 300 g) to obtain a composition for orally disintegrating tablets as a granulated product having an average particle diameter of 173 μm. The water content (dry weight loss) of the granulated product was 0.5% by mass.

Using the obtained granulated product (composition for orally disintegrating tablet), an orally disintegrating tablet was produced in the same manner as in Example 1.

<Device used>
Fluidized bed granulator "Flow coater FZ-LABO" (Freund Sangyo Co., Ltd.)
<Granulation conditions>
Intake temperature: 60 ° C
Exhaust temperature: 27-32 ° C
Flowing air amount: 45L / min
Spray speed: 10-12g / min
Spray air pressure: 0.10 MPa

[Example 13]
An extruded product was obtained by heat melt extrusion using HPMC-4 (5.3 g) and catechin (1.1 g) under the following conditions. The extruded product was pulverized using "Wonder Blender" (Osaka Chemical Co., Ltd.) for 3 seconds, and the pulverized product having an average particle size of 143 μm was recovered. The obtained pulverized product (2 g), lactose (34.8 g) and erythritol (6.7 g) were mixed so as to have the mass ratios shown in Table 2 to prepare an orally disintegrating tablet composition.

Using the produced composition for orally disintegrating tablets, an orally disintegrating tablet was produced in the same manner as in Example 1.

<Device 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: 5 min
Circulation time: 5 min

[Example 14]
HPMC-2, catechin, lactose and erythritol, and riboflavin (VB2) as an active ingredient were added and weighed and mixed so as to have the mass ratios shown in Table 2 to prepare a composition for orally disintegrating tablets.

Using a tablet molding machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.), 350 mg of the produced composition for orally disintegrating tablets was tableted with a tableting pressure of 7 so as to have the same tablet hardness as in Example 3. Orally disintegrating tablets were produced by tableting at 0.0 kN.

[Comparative Example 1]
HPMC-1 and lactose were weighed and mixed so as to have the mass ratios shown in Table 2 without adding catechin to prepare a tablet composition. Tablets were obtained in the same manner as in Example 1 using the produced tablet composition.

In Comparative Example 1, the disintegration rate could not be calculated because the tablets did not disintegrate and the displacement rate (mm / s) did not become −0.002 or less.

[Comparative Example 2]
A tablet composition was prepared by weighing and mixing catechin and lactose so as to have the mass ratios shown in Table 2 without adding water-soluble cellulose ether. Tablets were obtained in the same manner as in Example 1 using the produced tablet composition.

In Comparative Example 2, the disintegration rate could not be calculated because the tablets did not disintegrate and the displacement rate (mm / s) did not become −0.002 or less.

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

Using a tablet molding machine (“HAND TAB-200”; manufactured by Ichihashi Seiki Co., Ltd.), 350 mg of the produced tablet composition was used at a tableting pressure of 2.0 kN so as to have the same tablet hardness as in Example 1. Tableting was performed to produce tablets.

In Comparative Example 3, the disintegration rate could not be calculated because the tablets did not disintegrate and the displacement rate (mm / s) did not become −0.002 or less.

<Evaluation of orally disintegrating tablets>
By comparing Example 1 and Comparative Examples 1 to 3, the orally disintegrating tablet produced from the composition for orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar had sufficient hardness and excellent disintegration. It was found to show sex. Further, from the results of Examples 1 and 2, it was confirmed that an orally disintegrating tablet showing sufficient hardness and excellent disintegration property can be obtained regardless of the type of sugar such as lactose and maltose.

From the results of Examples 1 and 3, when the composition for orally disintegrating tablets is produced by dry mixing, the larger the average particle size of the water-soluble cellulose ether used, the more disintegrating the orally disintegrating tablets obtained. Was found to be excellent.

From the results of Examples 1 and 4, and Examples 2 and 5, it was found that when the composition for an orally disintegrating tablet contains a sugar alcohol, an orally disintegrating tablet having more excellent disintegration property can be obtained. Was done.

From the results of Examples 4, 6 and 7, when the mass ratio of the 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. It was found that.

From the results of Examples 4 and 8, when producing a composition for an orally disintegrating tablet containing a sugar alcohol by dry mixing, the larger the average particle size of the water-soluble cellulose ether, the more the obtained orally disintegrating tablet 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 property could be obtained regardless of the type of sugar alcohol such as erythritol and D-mannitol.

From the results of Examples 4, 10 and 11, it is possible to obtain an orally disintegrating tablet that exhibits sufficient hardness and excellent disintegration property regardless of the type of water-soluble cellulose ether such as HPMC and MC having various particle sizes. It was confirmed that it could be obtained.

From the results of Example 10, Example 12, and Example 13, sufficient hardness and excellent disintegration property are exhibited regardless of the method for producing the composition for orally disintegrating tablets such as dry mixing, granulation, and heat melt extrusion. It was confirmed that an orally disintegrating tablet was obtained. However, due to the fact that the disintegration behavior of the obtained orally disintegrating tablet differs depending on the method for producing the composition for the orally disintegrating tablet, the orally disintegrating tablet having an excellent displacement value and disintegration rate after 200 seconds by heat melt extrusion can be obtained. It was found that it was obtained.

From the results of Examples 3 and 14, it was confirmed that an orally disintegrating tablet showing sufficient hardness and excellent disintegration property can be obtained even when the active ingredient is contained.

According to the present invention, it is possible to produce an orally disintegrating tablet having sufficient hardness and exhibiting excellent disintegration property on a general-purpose and industrial scale without adopting a complicated process.

Claims (11)

A composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, 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 oral disintegration 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 alkyl cellulose, hydroxyalkyl cellulose and hydroxyalkyl alkyl cellulose. Composition for tablets. An orally disintegrating tablet which is a lockable product of the composition for an orally disintegrating tablet according to any one of claims 1 to 5. Oral disintegration including a step of obtaining a composition for an orally disintegrating tablet containing water-soluble cellulose ether, catechin, and sugar by dry-mixing a powder raw material containing water-soluble cellulose ether, catechin, and sugar. A method for producing a tablet composition. By adding an aqueous raw material containing water to a powder raw material containing water-soluble cellulose ether, catechin, and sugar to perform granulation, an oral cavity containing water-soluble cellulose ether, catechin, and sugar is performed. A method for producing an orally disintegrating tablet composition, which comprises a step of obtaining a disintegrating tablet composition. A step of obtaining an extruded product containing water-soluble cellulose ether and catechin by heating, melting and extruding a powder raw material containing water-soluble cellulose ether and catechin.
A step of obtaining a pulverized product by pulverizing the extruded product, and
A composition for an orally disintegrating tablet, which comprises a step of obtaining a composition for an orally disintegrating tablet containing the water-soluble cellulose ether, catechin, and sugar by mixing the pulverized product with a raw material containing sugar. Production method. The method for producing a composition for an orally disintegrating tablet 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, which comprises 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.