JP2014224086A - Composition for orally quickly disintegrating composition solid formulation - Google Patents

Abstract

An intraoral rapidly disintegrating solid preparation that can be manufactured in a simple process using a simple manufacturing apparatus and has a rapid disintegrating property in the oral cavity and an appropriate moldability to withstand practical use, a manufacturing method thereof, And the composition used as the constituent material of the intraoral quick disintegrating tablet is provided. SOLUTION: (a) a copolymer obtained by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer in a mass ratio of 6: 4 to 9: 1, and (b) an oral cavity containing tannic acid Internally disintegrating composition for solid preparation. An intraoral rapidly disintegrating solid preparation containing this composition. [Selection figure] None

Description

  The present invention relates to a composition for a rapidly disintegrating solid preparation in the oral cavity that disintegrates rapidly and well in the presence of saliva or a small amount of water in the oral cavity, a rapidly disintegrating solid preparation in the oral cavity containing this composition, and The present invention relates to a method for producing an intraoral rapidly disintegrating solid preparation.

  As dosage forms of oral solid preparations, tablets, capsules, granules, powders and the like are generally known. However, few of these dosage forms are easy to handle and easy to take. For example, tablets and capsules have a problem that it becomes difficult to swallow as the shape thereof becomes larger, and granules and powders have a problem that they are peeled off when taken and a problem that they enter between teeth. Further, all of these dosage forms require water at the time of taking, and there is a problem that it is difficult to take while sleeping in an emergency or a serious patient.

  Chewable tablets are known as dosage forms that can be taken without water, but those currently offered are poorly disintegratable and difficult for elderly people and children with low chewing ability to take. There is a problem that.

  Accordingly, there is a demand for the development of an orally rapidly disintegrating tablet that can be easily taken without water and can be taken easily at any time and anywhere.

As a technique for producing such an intraoral rapidly disintegrating tablet, after filling a mold (resin film sheet for PTP packaging) in which an active ingredient and a saccharide are suspended in an agar aqueous solution, it is solidified into a jelly shape, Furthermore, when a method of drying under reduced pressure or ventilation (Patent Document 1), or when a tablet material in a dry state containing a drug, a water-soluble binder, and a water-soluble excipient is transferred to the next manufacturing process as a tablet form A method (Patent Document 2) is known in which a molded tablet is humidified at a minimum pressure required to maintain its form to a hardness that can be maintained, and then the molded tablet is humidified and further dried. Yes.
However, these methods have a problem that a special manufacturing facility is required and the manufacturing process is complicated accordingly.

  Therefore, there is a demand for the development of a solid preparation that exhibits excellent disintegration properties in the oral cavity and has moldability with no practical problems without using special production equipment and without complicating the production process.

Japanese Patent No. 2807346 Japanese Patent No. 29197771

  The present invention relates to an intraoral rapidly disintegrating solid preparation that can be manufactured in a simple process using a simple manufacturing apparatus and has a rapid disintegrating property in the oral cavity and an appropriate moldability that can withstand practical use, and its manufacture It is an object of the present invention to provide a method and a composition that is a constituent material of the intraorally rapidly disintegrating solid preparation.

  As a result of intensive studies to solve the above problems, the present inventors have obtained a copolymer obtained by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer at a mass ratio of 6: 4 to 9: 1. And a composition containing tannic acid, if necessary, by compression molding with a binder and / or a disintegrant in a simple process without using a special production apparatus. It has been found that an intraoral rapidly disintegrating solid preparation that has both a disintegrating property equal to or higher than that of a disintegrating solid preparation and moldability can be produced.

The present invention has been completed based on the above findings, and provides the following intraoral rapidly disintegrating solid preparation composition, intraoral rapidly disintegrating solid preparation, and a method for producing an intraoral rapidly disintegrating solid preparation. .
Item 1.
(a) a copolymer obtained by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer in a mass ratio of 6: 4 to 9: 1, and
(b) An intraoral rapidly disintegrating composition for a solid preparation containing tannic acid.
Item 2.
Item 2. The composition according to Item 1, wherein the solid preparation is a tablet.
Item 3.
Item 3. The composition according to Item 1 or 2, wherein the composition takes the form of a granulated product.
Item 4.
The polymerizable vinyl monomer is a group consisting of unsaturated carboxylic acids, esters of unsaturated carboxylic acids, unsaturated nitriles, unsaturated amides, aromatic vinyls, aliphatic vinyls, and unsaturated heterocyclic rings. Item 4. The composition according to any one of Items 1 to 3, which is at least one selected from the above.
Item 5.
Component (a) is a copolymer of polyvinyl alcohol and two or more polymerizable vinyl monomers, at least one of the polymerizable vinyl monomers is an unsaturated carboxylic acid, and at least one is unsaturated. Item 5. The composition according to any one of Items 1 to 4, which is an ester of carboxylic acid.
Item 6.
The unsaturated carboxylic acid is selected from the group consisting of acrylic acid, methacrylic acid, crotonic acid, fumaric acid, maleic acid, and itaconic acid, and the ester of the unsaturated carboxylic acid is methyl methacrylate or methyl acrylate. , Ethyl methacrylate, ethyl acrylate, butyl methacrylate, butyl acrylate, isobutyl methacrylate, isobutyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate, 2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, hydroxyethyl methacrylate, Item 6. The composition according to Item 5, which is selected from the group consisting of hydroxyethyl acrylate, polyethylene glycol methacrylate, polyethylene glycol acrylate, and polypropylene glycol acrylate.
Item 7.
Item 7. The composition according to item 6, wherein the unsaturated carboxylic acid is acrylic acid, and the ester of the unsaturated carboxylic acid is methyl methacrylate.
Item 8.
Item 8. The composition according to any one of Items 1 to 7, wherein the polyvinyl alcohol is polyvinyl alcohol having an average degree of polymerization of 1300 or less.
Item 9.
Item 9. The composition according to any one of Items 1 to 8, wherein the component (a) is in the form of particles, and the average particle size is 200 μm or less.
Item 10.
Item 10. The composition according to any one of Items 1 to 9, wherein the content of the component (a) is 0.001 to 60% by mass with respect to the total amount of the composition.
Item 11.
Item 11. The composition according to any one of Items 1 to 10, wherein the content of the component (b) is 0.001 to 60% by mass with respect to the total amount of the composition.
Item 12.
Item 12. The composition according to any one of Items 1 to 11, further comprising an excipient.
Item 13.
Item 13. The composition according to Item 12, wherein the excipient is at least one selected from the group consisting of mannitol and lactose hydrate.
Item 14.
Item 14. A solid preparation comprising the composition according to any one of Items 1 to 13.
Item 15.
Item 15. The solid preparation according to Item 14, wherein the solid preparation is a tablet.
Item 16.
Item 16. The solid preparation according to Item 15, further comprising a binder and / or a disintegrant.
Item 17.
Item 18. The solid preparation according to Item 16, wherein the binder is at least one selected from the group consisting of magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate, and crystalline cellulose.
Item 18.
Item 18. The solid preparation according to Item 16 or 17, wherein the disintegrant is at least one selected from the group consisting of crospovidone, croscarmellose sodium, carmellose calcium, carmellose, and low-substituted hydroxypropylcellulose.
Item 19.
Item 19. The solid preparation according to any one of Items 15 to 18, wherein the disintegration time measured by a disintegration test specified in the Japanese Pharmacopoeia is within 30 seconds.
Item 20.
(A) The composition according to any one of Items 1 to 13, or
(B) A method for producing an intraorally rapidly disintegrating solid preparation, which comprises compression-molding a mixture of the composition according to any one of Items 1 to 13 and additives and / or active pharmaceutical ingredients.
Item 21.
Item 21. The method according to Item 20, wherein the solid preparation is a tablet.
Item 22.
Item 22. The method according to Item 20 or 21, wherein the tableting pressure at the time of compression molding is 100 to 1500 kgf / cm ² .
Item 23.
Item 23. The method according to any one of Items 20 to 22, wherein the additive is a binder and / or a disintegrant.

The intraoral rapidly disintegrating solid preparation of the present invention has excellent disintegration properties in the oral cavity and has an appropriate moldability, and therefore has excellent dosing properties.
In addition, the rapidly disintegrating solid preparation in the oral cavity of the present invention is a substance that does not dissolve in the mouth or hardly dissolves in the mouth even after disintegrating in the oral cavity, and is substantially after entering the stomach which is an acidic environment. Elutes. Therefore, the ingredient does not remain in the mouth and is not wasted, the ingredient can be efficiently fed into the body, and even when it contains an ingredient that exhibits an unpleasant taste such as a bitter taste, the taste is masked. .

It is a figure which shows the result of the elution test using water as a test liquid. It is a figure which shows the result of the elution test using the elution test 1st liquid (pH 1.2) as a test liquid.

Hereinafter, the present invention will be described in detail.
(I) Composition for rapidly disintegrating solid preparation in the oral cavity The composition for rapidly disintegrating solid preparation in the oral cavity of the present invention comprises (a) polyvinyl alcohol and a polymerizable vinyl monomer in a mass ratio of 6: 4-9. 1: a copolymer obtained by copolymerization at a ratio of 1: and (b) tannic acid.
In the present invention, “for intraoral rapidly disintegrating solid preparation” means having a use as a constituent material or a production material of an intraoral rapidly disintegrating solid preparation.

(a) Component
The copolymer of component (a) can be produced by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer by a known method. Examples of the method for producing the copolymer of component (a) include methods known per se such as radical polymerization, for example, solution polymerization, suspension polymerization, emulsion polymerization, bulk polymerization and the like. These polymerization reactions are usually carried out in the presence of a polymerization initiator and water, an organic solvent (for example, methanol, ethanol, cellosolve, carbitol) or a mixture thereof, if necessary, for example, a reducing agent (for example, sodium erythorbate). , Sodium metabisulfite, ascorbic acid), chain transfer agent (for example, 2-mercaptoethanol, α-methylstyrene dimer, 2-ethylhexyl thioglycolate, lauryl mercaptan), dispersant (for example, sorbitan ester, lauryl alcohol), etc. Can be added.

Polyvinyl alcohol can be produced by radical polymerization of vinyl acetate and saponification of the obtained polyvinyl acetate.
The average degree of polymerization of polyvinyl alcohol is about 1300 or less, about 200-1300, about 300-1300, about 200-900, about 300-900, about 200-600, about 300-600, about 200-500, about 300. -500 etc. are mentioned.

Polyvinyl alcohol may be completely saponified or partially saponified, but is preferably partially saponified. Examples of the partially saponified polyvinyl alcohol include GOHSENOL EG05 (manufactured by Nippon Synthetic Chemical Industry), GOHSENOL EG25 (manufactured by Nippon Synthetic Chemical Industry), PVA203 (manufactured by Kuraray), PVA204 (manufactured by Kuraray), and PVA205 (Kuraray). Co., Ltd.), JP-04 (manufactured by Nippon Vinegar-Poval), JP-05 (manufactured by Nippon Vinegar-Poval), etc.
As the polyvinyl alcohol, one kind may be used alone, or two or more kinds having different degrees of polymerization and saponification may be used.

  Examples of the polymerizable vinyl monomer include unsaturated carboxylic acids, esters of unsaturated carboxylic acids, unsaturated nitriles, unsaturated amides, aromatic vinyls, aliphatic vinyls, and unsaturated heterocyclic rings. be able to.

Examples of unsaturated carboxylic acids include acrylic acid, methacrylic acid, crotonic acid, fumaric acid, maleic acid, itaconic acid and the like. Among these, acrylic acid and methacrylic acid are preferable, and acrylic acid is more preferable.
Unsaturated carboxylic acid esters include methyl acrylate, ethyl acrylate, butyl acrylate, isobutyl acrylate, cyclohexyl acrylate, 2-ethylhexyl acrylate, hydroxyethyl acrylate, polyethylene glycol acrylate, polypropylene glycol acrylate Acrylic esters such as methyl methacrylate, ethyl methacrylate, butyl methacrylate, isobutyl methacrylate, cyclohexyl methacrylate, 2-ethylhexyl methacrylate, hydroxyethyl methacrylate, and polyethylene glycol methacrylate. Etc. Among these, methacrylic acid esters are preferable, methyl methacrylate and ethyl methacrylate are preferable, and methyl methacrylate is more preferable.

Examples of unsaturated nitriles include acrylonitrile, methacrylonitrile, ethacrylonitrile, and crotonnitrile.
Examples of unsaturated amides include acrylamide, N, N-dimethylacrylamide, and methacrylamide.
Examples of aromatic vinyls include styrene, α-methylstyrene, β-methylstyrene, vinylnaphthalene and the like.
Examples of the aliphatic vinyls include vinyl formate, vinyl acetate, vinyl propionate, vinyl stearate, vinyl pivalate, and vinyl valerate.
Examples of unsaturated heterocycles include N-vinylpyrrolidone and acryloylmorpholine.

  A polymerizable vinyl monomer may be used individually by 1 type, and may use 2 or more types. Among them, it is preferable to use a combination of two or more, more preferably at least one is an unsaturated carboxylic acid, at least one is an ester of an unsaturated carboxylic acid, the unsaturated carboxylic acid is acrylic acid, Even more preferably, the ester of the saturated carboxylic acid is methyl methacrylate.

The mass ratio between the polyvinyl alcohol and the polymerizable vinyl monomer (as a result, the mass ratio of copolymerization) is preferably about 6: 4 to 9: 1, more preferably about 7: 3 to 9: 1, Even more preferred is about 8: 2.
When acrylic acid and methyl methacrylate are used as the polymerizable vinyl monomer, the mass ratio of copolymerization of acrylic acid and methyl methacrylate is preferably about 3: 7 to 0.5: 9.5. About 2: 8 to 1: 9, more preferably about 1.25: 8.75.

The copolymer of component (a) can take the form of particles. The average particle diameter is preferably 200 μm or less, more preferably 150 μm or less, and even more preferably 125 μm or less. If it is the said range, it will be hard to feel roughness at the time of taking, and the tablet of sufficient hardness can be shape | molded with a normal tableting pressure. Moreover, the lower limit value of the average particle diameter can usually be about 1 μm, and within this range, it becomes easy to handle.
The average particle diameter of the copolymer is a value measured by a dynamic light scattering method using a laser diffraction particle size distribution analyzer (LDSA-2400; manufactured by East Japan Computer Co., Ltd.).

  The average degree of polymerization of the component (a) copolymer is preferably 200 or more, more preferably 300 or more, and even more preferably 400 or more. If it is the said range, the solid formulation which has sufficient moldability will be obtained. Moreover, 2000 or less is preferable, 1000 or less is more preferable, and 600 or less is still more preferable. If it is the said range, the solid formulation which has sufficient disintegration will be obtained.

  The copolymer of the component (a) is not particularly limited as long as it can be used in the pharmaceutical field such as pharmaceuticals or foods, but the polyvinyl alcohol having an average polymerization degree of 1300 or less and two kinds of polymerizable vinyl monomers And a copolymer of a mixture of acrylic acid and methyl methacrylate is preferred. Preferable examples of the copolymer of component (a) include, for example, POVACOAT type F (display viscosity 5.5 mPa · s, average particle diameter 1.5 mm), POVACOAT type MP (display viscosity 5.5 mPa · s, average particle) 125μm diameter), POVACOAT type FM (display viscosity 5.5 mPa · s, average particle size 55 μm), POVACOAT type SP (display viscosity 5.5, average particle size 20 μm) (all trade names, manufactured by Daido Kasei Kogyo Co., Ltd.), etc. Is mentioned.

  The content of the component (a) in the composition is preferably about 0.001% by mass or more, more preferably about 0.01% by mass or more, and about 0.1% by mass or more with respect to the total amount of the composition. Even more preferred. If it is this range, solid preparations, such as a tablet manufactured using this composition, will have sufficient moldability. Moreover, about 60 mass% or less is preferable, about 30 mass% or less is more preferable, and about 10 mass% or less is still more preferable. If it is this range, solid preparations, such as a tablet manufactured using this composition, will have sufficient disintegration.

The component (b) tannic acid can be extracted from various plant materials. For example, water or ethanol can be extracted from persimmon fruit, chestnut astringent skin, pentaploid, gallic, cod powder, leguminous tamarind seed skin, or mimosa bark. Preferably, tannic acid extracted from pentaploid or gallic acid listed in the 16th revised Japanese Pharmacopoeia can be used. Tannic acid may be an unpurified product or a purified product, but a purified product is more preferable.

  The content of tannic acid as component (b) in the composition is preferably about 0.001% by mass or more, more preferably about 0.01% by mass or more, and more preferably about 0.1% by mass with respect to the total amount of the composition. Even more preferably, the mass% or more. If it is this range, solid preparations, such as a tablet manufactured using this composition, will have sufficient disintegration. Moreover, 60 mass% or less is preferable, about 30 mass% or less is more preferable, and about 10 mass% or less is still more preferable. If it is this range, solid preparations, such as a tablet manufactured using this composition, will have sufficient moldability.

Ratio of component (a) to component (b) The mass ratio of component (a) component to component (b) content in the composition (component (a): component (b)) is about 1: 0. 0.001 to 1000 is preferred, about 1: 0.01 to 100 is more preferred, and about 1: 0.1 to 10 is even more preferred. If it is this range, it will have sufficient moldability and disintegration.

Other components The composition of the present invention preferably contains an excipient as an additive in addition to the above components (a) and (b), whereby the tablet produced using the composition of the present invention. It becomes possible to further improve the moldability and disintegration property of solid preparations such as.
Excipients include sugar alcohols such as mannitol, sorbitol, xylitol, erythritol, maltitol, isomalt; sugars such as lactose hydrate, fructose, sucrose, glucose, trehalose; corn starch, potato starch, wheat starch, Starches such as rice starch; Amino acids such as glycine and alanine; Light anhydrous silicic acid, Synthetic aluminum silicate, Magnesium aluminate metasilicate, Calcium silicate and other silicic acids; Cellulose such as crystalline cellulose and powdered cellulose; Talc ; Titanium oxide etc. are mentioned. As the excipient, sugar alcohols and saccharides are preferable in that the solid preparation is rapidly disintegrated in the oral cavity, and mannitol and lactose hydrate are particularly preferable.
One type of excipient may be used alone, or two or more types may be used.

In addition, the composition of the present invention can contain an appropriate amount of additives generally used in pharmaceuticals such as lubricants, colorants, flavoring agents, sweeteners, fragrances, and preservatives.
Examples of the lubricant include magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, sodium stearyl fumarate and the like.
Examples of the colorant include food dyes, food lake dyes, iron sesquioxide, and yellow iron sesquioxide.
Examples of the corrigent include citric acid, tartaric acid, malic acid, ascorbic acid and the like.
Examples of the sweetening agent include aspartame, acesulfame potassium, saccharin, sodium saccharin, dipotassium glycyrrhizinate, stevia, thaumatin, sucralose and the like.
Examples of the fragrances include fennel oil, orange oil, chamomile oil, spearmint oil, cinnamon oil, clove oil, mint oil, bergamot oil, eucalyptus oil, lavender oil, lemon oil, rose oil, roman chamomile oil, menthol and the like.
Examples of the preservative include benzoic acid, sodium benzoate, benzyl benzoate, ethyl paraoxybenzoate, butyl paraoxybenzoate, and propyl paraoxybenzoate.
An additive may be used individually by 1 type and may use 2 or more types.

  The composition of the present invention may contain an appropriate amount of a pharmaceutical active ingredient. The pharmaceutical active ingredient is not particularly limited as long as it is a kind and an amount that do not impair the disintegration property and moldability of a solid preparation such as a tablet containing the composition.

Granulation The composition of the present invention containing each of the above components may be in the form of a granulated product such as a granule or may be in the form of an ungranulated powder.
Examples of the granulation treatment of the granulated product include wet granulation treatment, dry granulation treatment, fluidized bed granulation treatment, and the like, and wet granulation treatment is particularly preferable in terms of excellent convenience.
The wet granulation treatment is a treatment in which each component is kneaded with a solvent and then granulated, and if necessary, a method or an apparatus used for production of a general preparation can be used. In addition, as a solvent used in this treatment, alcohols such as ethanol and isopropanol used for production of general preparations and water can be used as a solvent.

The dry granulation treatment is a treatment in which the respective components are mixed uniformly and then granulated, and a method and apparatus used for production of general preparations can be used as necessary.
The fluidized bed granulation process is a process in which each component is granulated while spraying a solvent or a mixed solution of a solvent and a binder, etc., and a method or apparatus used for manufacturing a general preparation as necessary. Can be used.

(II) Orally rapidly disintegrating solid preparation
Although the dosage form of a dosage form solid formulation is not specifically limited, A tablet is mentioned typically. Moreover, a granule is also mentioned as a solid formulation.

When the tableting solid preparation is a tablet, the tableting may be performed by compressing the granulated composition of the present invention or by directly compressing the non-granulated composition of the present invention. Is included. In any case, the composition of the present invention may be mixed with other components such as a binder and a disintegrant as necessary and compression molded.
For the compression molding, a method and an apparatus generally used for tablet formation such as a rotary tableting machine and a single tableting machine can be used. The compression pressure in the compression molding is preferably about 100 kgf / cm ² or more, about 200 kgf / cm ² or more, and preferably from about 400 kgf / cm ² or more and more. Moreover, 1500 kgf / cm ² or less is preferable, about 1200 kgf / cm ² or less is more preferable, and about 1000 kgf / cm ² or less is even more preferable.

  When using a granulated product, prior to the compression molding, the granulated product is dried using a fluidized bed dryer, a shelf-type dryer, etc .; sized using a screen mill, jet mill, hammer mill, pin mill, etc. It may be subjected to operations necessary for the production of tablets such as sieving using a vibrating sieve.

The solid preparation can be substantially composed of only the composition of the present invention described above, but can also contain other components such as a binder and a disintegrant.
When the composition of the present invention contains no excipient, the content of the composition of the present invention in the solid preparation is preferably about 0.1% by mass or more, more preferably 0.5% by mass or more, and about 2 Even more preferably, the mass% or more. Moreover, about 20 mass% or less is preferable, about 15 mass% or less is more preferable, and about 10 mass% or less is still more preferable.
Further, the content of the composition of the present invention in the solid preparation is preferably about 50% by mass or more, more preferably 70% by mass or more, and more preferably about 90% by mass or more when the composition of the present invention contains an excipient. Is even more preferred. Moreover, about 99 mass% or less is preferable, about 96 mass% or less is more preferable, and about 93 mass% or less is still more preferable.
If it is the said range, practically sufficient moldability and disintegration can be obtained.

  In addition, when manufacturing a tablet using a granulated material, since the tablet is manufactured by compression molding, the shape of the granulated material and the shape of the granulated material in the tablet are usually different.

Binder The solid formulation of the present invention can comprise a binder. In the case of producing a solid preparation by direct hitting, the binder has an action of binding each component in the solid preparation to each other. Moreover, when manufacturing a solid formulation by tableting of a granulated material, it has the effect | action which couple | bonds a granulated material mutually.
Binders include povidone, hydroxypropylcellulose, hypromellose phthalate, hydroxypropylmethylcellulose acetate succinate, magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate, carmellose sodium, ethylcellulose , Methylcellulose, hypromellose, gum arabic, sodium alginate, dextrin, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, crystalline cellulose, powdered cellulose, low substituted hydroxypropylcellulose, gelatin, pullulan , Polyvinyl alcohol, carboxyvinyl polymer and the like. Among these, magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate, and crystalline cellulose are preferable.
A binder may be used individually by 1 type and may use 2 or more types.

  The content of the binder is preferably about 0.01% by mass or more, more preferably about 0.1% by mass or more, still more preferably about 1% by mass or more, and further about 30% by mass with respect to the total amount of the solid preparation. % By mass or less is preferable, about 20% by mass or less is more preferable, and about 10% by mass or less is more preferable. If it is the said range, practically sufficient moldability and disintegration can be obtained.

Disintegrant The solid preparation of the present invention may contain a disintegrant. The disintegrant is a component that swells with water or a component that collapses with water.
Disintegrants include crospovidone, carmellose calcium, carmellose, croscarmellose sodium, low-substituted hydroxypropylcellulose, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, carboxymethyl starch Sodium etc. are mentioned. Of these, crospovidone, croscarmellose sodium, carmellose calcium, carmellose, and low-substituted hydroxypropylcellulose are preferred.
A disintegrating agent may be used individually by 1 type, and may use 2 or more types.

  The content of the disintegrant is preferably about 0.01% by mass or more, more preferably about 0.1% by mass or more, still more preferably about 1% by mass or more, and further about 30%, based on the total amount of the solid preparation. % By mass or less is preferable, about 20% by mass or less is more preferable, and about 10% by mass or less is more preferable. If it is the said range, practically sufficient moldability and disintegration can be obtained.

Other Components The solid preparation of the present invention can contain an appropriate amount of additives generally used in pharmaceuticals such as excipients, lubricants, coloring agents, flavoring agents, sweeteners, fragrances, and preservatives. Moreover, a pharmaceutical active ingredient can also be included.
Each of the additive and the active pharmaceutical ingredient may be used alone or in combination of two or more.

  The solid preparation such as the tablet of the present invention obtained in this way has an appropriate moldability with no practical problem, and further has an excellent disintegration property in the oral cavity.

When the solid preparation of the present invention is a tablet, the tablet is disintegrated according to the disintegration test method specified in the 16th revised Japanese Pharmacopoeia Manual (particularly, disintegration time measured using a disintegration tester (manufactured by Toyama Sangyo Co., Ltd.)). ) Is preferably 30 seconds or shorter, more preferably 20 seconds or shorter, and even more preferably 10 seconds or shorter.
When the solid preparation of the present invention is a tablet, the tablet preferably has a hardness (particularly, a hardness measured using a tablet hardness meter (manufactured by Toyama Sangyo Co., Ltd.)) of 40 N or more, more preferably 50 N or more. Preferably, it is still more preferably 60N or more.

EXAMPLES Hereinafter, although an Example and a comparative example are given and this invention is demonstrated in more detail, these do not limit this invention at all.
(1) Evaluation of disintegration and moldability
(1-1) Test method
<Disintegration test>
The test was conducted using a disintegration tester (manufactured by Toyama Sangyo Co., Ltd.) with reference to the disintegration test method specified in the 16th revised Japanese Pharmacopoeia Manual. The number of tests was 6 tablets, and the average disintegration time was used. evaluated.
<Hardness test>
The test was carried out using a tablet hardness meter (manufactured by Toyama Sangyo Co., Ltd.), the number of tests was 10 tablets, and the average value of the hardness was evaluated.

(1-2) Manufacture of tablets
Example 1
Based on the composition shown in Table 1 below, the component (a) and mannitol are put into a stirring granulator and mixed, and then the water / ethanol mixture (17: 3) as the granulating solvent is adjusted to an appropriate amount (b) The liquid in which the components were dissolved was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 1
Based on the composition shown in Table 1 below, the component (a) and mannitol are put into a stirring and mixing granulator and mixed, and then an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent is gradually added. In addition, it was granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 2
Based on the composition shown in Table 1 below, after adding mannitol to the stirring and mixing granulator, the liquid in which the component (b) was dissolved in an appropriate amount of the water / ethanol mixture (17: 3) as the granulating solvent was gradually added. In addition to granulation. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 3
Based on the composition shown in Table 1 below, mannitol was charged into a stirring and mixing granulator, and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 2-5
Based on the composition shown in Table 2 below, the component (a) and mannitol are introduced into a stirring and mixing granulator, mixed, and then adjusted to an appropriate amount of the water / ethanol mixture (17: 3) as the granulating solvent (b ) The solution in which the component was dissolved was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 4
Based on the composition shown in Table 2 below, (a) component and mannitol are put into a stirring and mixing granulator and mixed, and then an appropriate amount of water / ethanol mixture (17: 3) as a granulating solvent is gradually added. In addition, it was granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 6-9
Based on the composition shown in Table 3 below, the component (a) and mannitol are put into a stirring and mixing granulator and mixed, and then the appropriate amount of the water / ethanol mixture (17: 3) as the granulating solvent (b) ) The solution in which the component was dissolved was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 5
Based on the composition shown in Table 3 below, after adding mannitol to the stirring and mixing granulator, the liquid in which the component (b) was dissolved in an appropriate amount of the water / ethanol mixture (17: 3) as the granulating solvent was gradually added. In addition to granulation. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 10-13
Based on the composition shown in Table 4 below, mannitol was introduced into a stirring and mixing granulator, and then a solution in which component (b) was dissolved in an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent was gradually added. In addition to granulation. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Examples 6-9
Based on the composition shown in Table 4 below, mannitol was charged into a stirring and mixing granulator, and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 14-17
Based on the composition shown in Table 5 below, mannitol was introduced into a stirring and mixing granulator, and then a solution in which component (b) was dissolved in an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent was gradually added. In addition to granulation. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Examples 10-13
Based on the composition shown in Table 5 below, mannitol was charged into a stirring and mixing granulator, and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Example 18
Based on the composition shown in Table 6 below, (a) component and lactose hydrate are put into a stirring and mixing granulator, mixed, and then an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. The solution in which the component (b) was dissolved was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 14
Based on the composition shown in Table 6 below, (a) component and lactose hydrate are put into a stirring and mixing granulator, mixed, and then an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. Was gradually added to granulate. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 15
Based on the composition shown in Table 6 below, lactose hydrate was introduced into a stirring and mixing granulator, and then component (b) was dissolved in an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. The liquid was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 16
Based on the composition shown in Table 6 below, lactose hydrate was put into a stirring and mixing granulator and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. . Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 19-22
Based on the composition shown in Table 7 below, lactose hydrate was put into a stirring and mixing granulator, and then component (b) was dissolved in an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. The liquid was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Examples 17-20
Based on the composition shown in Table 7 below, lactose hydrate was put into a stirring and mixing granulator, and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. . Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 23-26
Based on the composition shown in Table 8 below, lactose hydrate was put into a stirring and mixing granulator, and then component (b) was dissolved in an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. The liquid was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Examples 21-24
Based on the composition shown in Table 8 below, lactose hydrate was put into a stirring and mixing granulator, and then granulated by gradually adding an appropriate amount of a water / ethanol mixture (17: 3) as a granulating solvent. . Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Example 27
Based on the composition shown in Table 9 below, the active pharmaceutical ingredient (meclizine hydrochloride), the component (a), and mannitol were put into a stirring and mixing granulator, mixed, and then a water / ethanol mixture (granulation solvent) ( 17: 3) To a suitable amount, a pharmaceutical active ingredient (scopolamine hydrobromide hydrate) and a solution in which component (b) were dissolved were gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Examples 28-30
Based on the composition shown in Table 9 below, the active pharmaceutical ingredient, the component (a), and mannitol are put into a stirring and mixing granulator, mixed, and then a water / ethanol mixture (17: 3) as a granulating solvent. The liquid in which the component (b) was dissolved was gradually added to an appropriate amount and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Example 25
Based on the composition shown in Table 9 below, the active pharmaceutical ingredient (meclizine hydrochloride), the component (a), and mannitol were put into a stirring and mixing granulator, mixed, and then a water / ethanol mixture (granulation solvent) ( A liquid in which an active pharmaceutical ingredient (scopolamine hydrobromide hydrate) was dissolved in an appropriate amount of 17: 3) was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

Comparative Examples 26-28
Based on the composition shown in Table 9 below, the active pharmaceutical ingredient, the component (a), and mannitol are put into a stirring and mixing granulator, mixed, and then a water / ethanol mixture (17: 3) as a granulating solvent. A suitable amount of was gradually added and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

(1-3) Results The results of the composition, disintegration test and hardness test of the tablets of Examples 1 to 30 and Comparative Examples 1 to 28 are shown in Tables 1 to 9 below.

  As is clear from Table 1, the tablet of Example 1 had a disintegration time of 12 seconds and a hardness of 49.3 N, and exhibited excellent disintegration and moldability. On the other hand, the tablet of Comparative Example 1 that does not contain the tannic acid component (b) had a disintegration time of 40 seconds, which was poorer in disintegration than the tablet of Example 1. In addition, the tablet of Comparative Example 2 that does not contain the polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer as the component (a) has a hardness of 41.9 N, and has poor moldability as compared with the tablet of Example 1, A molding defect was observed. Further, the tablet of Comparative Example 3 containing neither the component (a) nor the component (b) had a hardness of 16.5 N, and the moldability was worse than that of the tablet of Example 1, and molding defects were recognized.

  As is apparent from Table 2, the tablets of Examples 2 to 5 have a disintegration time of 9 to 12 seconds and a hardness of 39.7 to 56.9 N, and increase or decrease the blending amount of tannic acid as the component (b). Nevertheless, it showed excellent disintegration and moldability.

  As is apparent from Table 3, the tablets of Examples 6 to 9 have a disintegration time of 11 to 13 seconds and a hardness of 44.8 to 63.1 N, and the polyvinyl alcohol, acrylic acid and methacrylic acid as component (a) Regardless of the increase or decrease in the amount of methyl copolymer, excellent disintegration and moldability were exhibited.

  As is apparent from Table 4, the tablets of Examples 10 to 13 exhibited excellent disintegration and moldability with a disintegration time of 10 to 12 seconds and a hardness of 46.1 to 53.3 N. On the other hand, the tablets of Comparative Examples 6 to 9 containing no tannic acid as the component (b) had a disintegration time of 26 to 40 seconds, and the disintegration was worse than the tablets of Examples 10 to 13.

  As is apparent from Table 5, the tablets of Examples 14 to 17 exhibited excellent disintegration and moldability with a disintegration time of 11 to 20 seconds and a hardness of 37.3 to 50.0 N. On the other hand, the tablets of Comparative Examples 10 to 13 containing no tannic acid as the component (b) had a disintegration time of 40 to 137 seconds and were poor in disintegration as compared with the tablets of Examples 14 to 17.

  As is apparent from Table 6, the tablet of Example 18 had a disintegration time of 14 seconds and a hardness of 40.4 N, and exhibited excellent disintegration and moldability. On the other hand, the tablet of Comparative Example 14 which does not contain the tannic acid of component (b) had a disintegration time of 42 seconds and was not as disintegrating as the tablet of Example 18. In addition, the tablet of Comparative Example 15 that does not contain the polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer as the component (a) has a hardness of 35.2 N, and has poor moldability as compared with the tablet of Example 18, A molding defect was observed. Further, the tablet of Comparative Example 16 containing neither the component (a) nor the component (b) had a hardness of 25.7 N, and the moldability was worse than that of the tablet of Example 18, and molding defects were recognized.

  As is apparent from Table 7, the tablets of Examples 19 to 22 exhibited excellent disintegration and moldability with a disintegration time of 14 to 17 seconds and a hardness of 40.4 to 74.9 N. On the other hand, the tablets of Comparative Examples 17 to 20 containing no tannic acid as the component (b) had a disintegration time of 42 to 47 seconds, which was poorer in disintegration than the tablets of Examples 19 to 22.

  As is apparent from Table 8, the tablets of Examples 23 to 26 exhibited excellent disintegration and moldability with a disintegration time of 13 to 18 seconds and a hardness of 40.4 to 51.9 N. On the other hand, the tablets of Comparative Examples 21 to 24 that did not contain the tannic acid component (b) had a disintegration time of 42 to 94 seconds, which was poorer in disintegration than the tablets of Examples 23 to 26.

  In the present invention, (a) polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer and (b) tannic acid are extremely important in order to obtain an orally rapidly disintegrating tablet having both disintegrating property and moldability. It was shown that.

As is apparent from Table 9, the tablets of Examples 27 to 30 have a disintegration time of 12 to 17 seconds and a hardness of 49.7 to 68.5 N, and excellent disintegration property regardless of the type of pharmaceutically active ingredient. Showed moldability,
On the other hand, the tablets of Comparative Examples 25 to 28 that did not contain the tannic acid of component (b) had a disintegration time of 30 to 49 seconds, which was poorer in disintegration than the tablets of Examples 27 to 30.

  Even when various active pharmaceutical ingredients are contained in the intraoral rapidly disintegrating tablet of the present invention, it is excellent by containing (a) polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer and (b) tannic acid. It was shown that disintegration and moldability can be obtained.

(2) Evaluation of dissolution
(2-1) Test method The test is conducted using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd.) in accordance with dissolution test method method 2 (paddle method), which is a general test method of the Japanese Pharmacopoeia (test solution: Water, paddle rotation speed: 50 rpm, elapsed time: 5 minutes, 10 minutes, 15 minutes, 30 minutes, and 90 minutes), the dissolution amount of ketotifen fumarate from the tablet was determined, and the dissolution rate was calculated from the results. .
Specifically, one tablet was taken, and the test was conducted at 50 rpm by the second dissolution test method (paddle method) using 900 mL of the test solution. After 5 minutes, 10 minutes, 15 minutes, 30 minutes, and 90 minutes from the start of the dissolution test, 10 mL of the dissolution solution was accurately taken, and immediately 10 mL of the test solution heated to 37 ± 0.5 ° C. was replenished with great care. The eluate was filtered through a membrane filter having a pore size of 0.45 μm or less to obtain a sample solution. Separately, about 15 mg of ketotifen fumarate for quantification was accurately weighed and dissolved in methanol to make exactly 100 mL. 1 mL of this solution was accurately weighed and 20 mL of methanol was added, and then water was further added to make exactly 100 mL to obtain a standard solution. The amount of ketotifen fumarate was measured using liquid chromatography.

  Furthermore, the test solution was changed from water to the first solution for dissolution test (pH 1.2), and the same procedure was followed except for the dissolution test.

<Quantitative conditions by liquid chromatography>
Detector: UV absorptiometer (measurement wavelength: 295 nm)
Column: A stainless tube having an inner diameter of 3.0 mm and a length of 15 cm was packed with 5 μm of octadecylsilylated silica gel for liquid chromatography.
Column temperature: Constant temperature mobile phase around 40 ° C .: 2 g of sodium lauryl sulfate dissolved in 1000 mL of acetonitrile / water / phosphoric acid mixture (550: 450: 1) was used as the mobile phase.
Flow rate: Adjusted so that the retention time of ketotifen was about 4 minutes.

(2-2) Manufacture of tablets
Comparative Examples 29-30
Based on the composition shown in Table 10 below, the active pharmaceutical ingredient (ketotifen fumarate), the component (a), and mannitol are put into a stirring and mixing granulator, mixed, and then water / ethanol as a granulating solvent. The liquid in which the component (b) was dissolved was gradually added to an appropriate amount of the mixed liquid (17: 3) and granulated. Next, after this granulated product was dried with a shelf dryer, the dried product was sized. Furthermore, after adding other additives to this sized product and mixing, using a tableting machine, with a tableting pressure of about 800 kgf / cm ² , the diameter of one tablet is 8.5 mm and its mass is 240 mg. Pills were obtained.

(2-3) Results The results when water is used as the test solution are shown in FIG. In Example 29 using a polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer as the component (a), ketotifen fumarate was compared with Comparative Example 29 using povidone and Comparative Example 30 using hydroxypropylcellulose. The elution of the acid salt was suppressed.
Moreover, the result at the time of using the elution test 1st liquid (pH 1.2) as a test liquid is shown in FIG. The elution of ketotifen fumarate was hardly affected by the type of component (a).

When the test solution is water, the state in the oral cavity is assumed, and in the case of the first dissolution test solution (pH 1.2), the state in the stomach is assumed.
From the test results of water, the test solution is effective in the oral cavity when using polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer as component (a) compared to using povidone or hydroxypropyl cellulose. It can be said that the bitterness masking effect with respect to an ingredient is high.
In addition, from the test results of the first dissolution test solution, the drug in the stomach can be used regardless of whether polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, povidone, or hydroxypropylcellulose is used in the stomach. It can be said that there is no difference in absorption of active ingredients.
Therefore, by using the polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer of the present invention, the bitterness to the active pharmaceutical ingredient in the oral cavity is higher than that of other high molecular compounds such as povidone or hydroxypropyl cellulose. It was shown that the masking effect was high and there was no difference in absorption of absorption of the active pharmaceutical ingredient in the stomach.

  The intraoral rapidly disintegrating solid preparation of the present invention can be manufactured without using a complicated manufacturing process or a special manufacturing apparatus, and has excellent disintegration and moldability regardless of the kind of active pharmaceutical ingredient to be contained. Furthermore, it is excellent in taste masking effect of a component having an unpleasant taste. Accordingly, it is suitable for industrial large-scale production, and at the same time, can be widely used as an intraoral rapidly disintegrating solid preparation that can contain various active pharmaceutical ingredients.

Claims (23)

(a) a copolymer obtained by copolymerizing polyvinyl alcohol and a polymerizable vinyl monomer in a mass ratio of 6: 4 to 9: 1, and
(b) An intraoral rapidly disintegrating composition for a solid preparation containing tannic acid.   The composition according to claim 1, wherein the solid preparation is a tablet.   The composition according to claim 1 or 2, wherein the composition takes the form of a granulated product.   The polymerizable vinyl monomer is a group consisting of unsaturated carboxylic acids, esters of unsaturated carboxylic acids, unsaturated nitriles, unsaturated amides, aromatic vinyls, aliphatic vinyls, and unsaturated heterocyclic rings. The composition according to any one of claims 1 to 3, which is at least one selected from the group consisting of more than one.   Component (a) is a copolymer of polyvinyl alcohol and two or more polymerizable vinyl monomers, at least one of the polymerizable vinyl monomers is an unsaturated carboxylic acid, and at least one is unsaturated. The composition according to any one of claims 1 to 4, which is an ester of a carboxylic acid.   The unsaturated carboxylic acid is selected from the group consisting of acrylic acid, methacrylic acid, crotonic acid, fumaric acid, maleic acid, and itaconic acid, and the ester of the unsaturated carboxylic acid is methyl methacrylate or methyl acrylate. , Ethyl methacrylate, ethyl acrylate, butyl methacrylate, butyl acrylate, isobutyl methacrylate, isobutyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate, 2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, hydroxyethyl methacrylate, The composition according to claim 5, wherein the composition is selected from the group consisting of hydroxyethyl acrylate, polyethylene glycol methacrylate, polyethylene glycol acrylate, and polypropylene glycol acrylate.   The composition according to claim 6, wherein the unsaturated carboxylic acid is acrylic acid, and the ester of the unsaturated carboxylic acid is methyl methacrylate.   The composition according to any one of claims 1 to 7, wherein the polyvinyl alcohol is a polyvinyl alcohol having an average degree of polymerization of 1300 or less.   The composition according to any one of claims 1 to 8, wherein the component (a) is in the form of particles, and the average particle size is 200 µm or less.   The composition according to any one of claims 1 to 9, wherein the content of component (a) is 0.001 to 60 mass% with respect to the total amount of the composition.   (b) Content of component is 0.001-60 mass% with respect to the whole quantity of a composition, The composition in any one of Claims 1-10.   Furthermore, the composition in any one of Claims 1-11 containing an excipient | filler.   The composition according to claim 12, wherein the excipient is at least one selected from the group consisting of mannitol and lactose hydrate.   The solid formulation containing the composition in any one of Claims 1-13.   The solid preparation according to claim 14, wherein the solid preparation is a tablet.   Furthermore, the solid formulation of Claim 15 containing a binder and / or a disintegrating agent.   The solid preparation according to claim 16, wherein the binder is at least one selected from the group consisting of magnesium aluminate metasilicate, synthetic aluminum silicate, light anhydrous silicic acid, calcium silicate, and crystalline cellulose.   The solid preparation according to claim 16 or 17, wherein the disintegrant is at least one selected from the group consisting of crospovidone, croscarmellose sodium, carmellose calcium, carmellose, and low-substituted hydroxypropylcellulose.   The solid preparation according to any one of claims 15 to 18, wherein the disintegration time measured by a disintegration test prescribed in the Japanese Pharmacopoeia is within 30 seconds. (A) The composition according to any one of claims 1 to 13, or
(B) A method for producing an intraorally rapidly disintegrating solid preparation comprising compression-molding a mixture of the composition according to any one of claims 1 to 13 and an additive and / or active pharmaceutical ingredient.   The method according to claim 20, wherein the solid preparation is a tablet. The method of claim 20 or 21 tableting pressure during compression molding is 100~1500kgf / cm ^2.   The method according to any one of claims 20 to 22, wherein the additive is a binder and / or a disintegrant.