WO2015115453A1

WO2015115453A1 - Composition for orally rapidly disintegrating solid preparation

Info

Publication number: WO2015115453A1
Application number: PCT/JP2015/052289
Authority: WO
Inventors: 隆夫島谷; 貴博川岸
Original assignee: テイカ製薬株式会社
Priority date: 2014-01-30
Filing date: 2015-01-28
Publication date: 2015-08-06
Also published as: JP6133445B2; JPWO2015115453A1

Abstract

　An orally rapidly disintegrating solid preparation endowed with both disintegrability and moldability equal to or greater than that of conventional orally rapidly disintegrating solid preparations can be produced, without using special production equipment, by compression molding a composition containing polyvinyl alcohol and tannic acid together with a binder and/or disintegrant as needed.

Description

Oral rapidly disintegrating composition for solid preparation

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

As a dosage form of an oral solid preparation, 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 at the time of taking 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 and children with weak chewing ability to take. There is a problem that.

Therefore, 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 an active ingredient and a saccharide suspended in an agar aqueous solution into a mold (resin film sheet for PTP packaging), 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, the development of solid preparations that can be manufactured with a simple manufacturing process using general manufacturing facilities for solid pharmaceutical preparations, exhibit excellent disintegration properties in the oral cavity, and have no practical problems. Is desired.

Japanese Patent No. 2807346 Japanese Patent No. 29197771

The present invention can be produced by a simple process using a production apparatus for a general pharmaceutical solid preparation, has a rapid disintegration property in the oral cavity, and has an appropriate moldability that can withstand practical use. It is an object of the present invention to provide a disintegrating solid preparation, a production method thereof, and a composition that is a constituent material of the intraoral rapidly disintegrating solid preparation.

As a result of intensive investigations to solve the above-mentioned problems, the present inventors have compression-molded a composition containing polyvinyl alcohol and tannic acid together with a binder and / or a disintegrant as necessary. The present inventors have found that an intraoral rapidly disintegrating solid preparation having both the disintegration property and moldability equivalent to or higher than that of a conventional intraoral rapidly disintegrating solid preparation can be produced without using a special production apparatus.

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 method for producing an intraoral rapidly disintegrating solid preparation .
Item 1.
(a) Polyvinyl alcohol
(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.
Item 4. The composition according to any one of Items 1 to 3, wherein the polyvinyl alcohol as the component (a) has an average polymerization degree of 200 to 2500 and a saponification degree of 85 to 89 mol%.
Item 5.
Item 5. The composition according to any one of Items 1 to 4, wherein the content of the component (a) is 0.001 to 60% by mass with respect to the total amount of the composition.
Item 6.
Item 6. The composition according to any one of Items 1 to 5, wherein the content of the component (b) is 0.001 to 60% by mass with respect to the total amount of the composition.
Item 7.
Item 7. The composition according to any one of Items 1 to 6, further comprising an excipient.
Item 8.
Item 8. The composition according to Item 7, wherein the excipient is at least one selected from the group consisting of mannitol and lactose hydrate.
Item 9.
Item 9. A solid preparation comprising the composition according to any one of Items 1 to 8.
Item 10.
Item 10. The solid preparation according to Item 9, wherein the solid preparation is a tablet.
Item 11.
Item 11. The solid preparation according to Item 10, further comprising a binder and / or a disintegrant.
Item 12.
Item 12. The solid preparation according to Item 11, 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 13.
Item 13. The solid preparation according to Item 11 or 12, wherein the disintegrant is crospovidone, croscarmellose sodium, carmellose calcium, carmellose, and low-substituted hydroxypropylcellulose.
Item 14.
Item 14. The solid preparation according to any one of Items 9 to 13, wherein the disintegration time measured by the disintegration test specified in the Japanese Pharmacopoeia is within 30 seconds.
Item 15.
(A) The composition according to any one of Items 1 to 8, or
(B) A method for producing an intraorally rapidly disintegrating solid preparation comprising compression-molding a mixture of the composition and additive according to any one of Items 1 to 8, and / or a pharmaceutically active ingredient.
Item 16.
Item 16. The method according to Item 15, wherein the solid preparation is a tablet.
Item 17.
Item 17. The method according to Item 15 or 16, wherein the tableting pressure at the time of compression molding is 100 to 1500 kgf / cm ² .
Item 18.
Item 18. The method according to any one of Items 15 to 17, 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, when producing tablets in the present invention, even when the tableting pressure is increased, the disintegration is hardly reduced. Therefore, a tableting pressure corresponding to the desired hardness may be employed, and production management is easy. It is.

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 is a composition containing (a) polyvinyl alcohol 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.

Component (a) polyvinyl alcohol can be produced by polymerizing a fatty acid vinyl ester and saponifying the resulting poly fatty acid vinyl ester. Examples of polymerization methods for poly fatty acid vinyl esters include bulk polymerization, solution polymerization, suspension polymerization and emulsion polymerization. Examples of fatty acid vinyl esters include vinyl formate, vinyl acetate, vinyl propionate, vinyl pivalate, and vinyl stearate. Industrially, a method of saponifying polyvinyl acetate obtained by solution polymerization of vinyl acetate using methanol as a solvent with an alkali hydroxide is preferable.
The average degree of polymerization of the polyvinyl alcohol used in the present invention is not limited, but the average degree of polymerization measured by JIS K6726 is preferably 200 to 5000, more preferably 200 to 2500, still more preferably 200 to 2000. is there.
Moreover, there is no restriction | limiting in particular also about a saponification degree, Although fully saponified polyvinyl alcohol or partially saponified polyvinyl alcohol can be used, the saponification degree of polyvinyl alcohol (completely saponified product or partially saponified product) of a pharmaceutical additive specification (2003) is possible. The degree of saponification measured by the measurement method is preferably 75 to 100 mol%, more preferably 78 to 96 mol%, and still more preferably 85 to 89 mol%.

The particle shape of the polyvinyl alcohol (a) component is not particularly limited, but the particle size is that it is miscible with other components when granulating, and it is difficult to feel rough when taking tablets. Is preferably smaller. Specifically, the average particle diameter measured by a dynamic light scattering method using a laser diffraction particle size distribution analyzer (LDSA-2400; manufactured by East Japan Computer Co., Ltd.) is preferably 200 μm or less, and 150 μm. The following is more preferable, and 125 μm or less is further preferable. Moreover, although there is no particular lower limit of the average particle diameter, it is preferably 1 μm or more in view of handling of raw materials.

Examples of polyvinyl alcohol include, but are not limited to, PE-05JPS, PE-04JPS, and PE-18JPS manufactured by Nippon Vinegar Poval. Moreover, polyvinyl alcohol may be used individually by 1 type, and can also be used in combination of 2 or more types from which an average degree of polymerization, a saponification degree, and a particle size differ.

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 further 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), and thereby tablets 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 from the viewpoint of rapidly disintegrating the solid preparation 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 can 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 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 in the case of preparing a granulated product include wet granulation treatment, fluidized bed granulation treatment, and dry granulation treatment, 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.
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.
Moreover, as solvents used in these wet granulation treatment and fluidized bed granulation 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 each component is uniformly mixed and then granulated, and a method and an apparatus used for producing a general preparation can be used as necessary.

(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 at least about 100 kgf / cm ² (about 1 kN), about 200 kgf / cm ² (about 2 kN) or more, and from about 400 kgf / cm ² (about 4 kN) or more preferable. Further, preferably 1500 kgf / cm ² (about 15 kN) or less, more preferably less than about 1200 kgf / cm ² (approximately 12 kN), preferably from about 1000 kgf / cm ² (about 10 kN) or less is more.

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 product, since the tablet is manufactured by compression molding, the shape of the granulated product and the shape of the granulated product 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 And carboxyvinyl polymer. 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 preferable.
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 ingredient of the medicine 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 manner has an appropriate moldability that is not problematic in practice, and also has excellent disintegration properties 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 30 N or more, more preferably 40 N or more. Preferably, it is 50N or more and still more preferable.

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, and the average disintegration time was used. evaluated.
<Hardness test>
The test was carried out using a tablet hardness tester (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, (a) component and D-mannitol are put into a stirring and mixing granulator, mixed, and then an appropriate amount of a water / anhydrous 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, one tablet using five tableting pressures of about 4 kN, about 6 kN, about 8 kN, about 10 kN and about 12 kN using a tableting machine. Obtained a tablet with a diameter of 8.5 mm and a mass of 240 mg.

Comparative Example 1
Based on the composition shown in Table 1 below, (a) component and D-mannitol are put into a stirring and mixing granulator, mixed, and then an appropriate amount of a water / anhydrous 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, one tablet using five tableting pressures of about 4 kN, about 6 kN, about 8 kN, about 10 kN and about 12 kN using a tableting machine. Obtained a tablet with a diameter of 8.5 mm and a mass of 240 mg.

Example 2
Based on the composition shown in Table 1 below, the component (a) and lactose hydrate were introduced into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture (17: 3) as a granulating solvent. A liquid in which the component (b) was dissolved in an appropriate amount 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, one tablet using five tableting pressures of about 4 kN, about 6 kN, about 8 kN, about 10 kN and about 12 kN using a tableting machine. Obtained a tablet with a diameter of 8.5 mm and a mass of 240 mg.

Comparative Example 2
Based on the composition shown in Table 1 below, the component (a) and lactose hydrate were introduced into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture (17: 3) as a granulating solvent. Appropriate amount 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, one tablet using five tableting pressures of about 4 kN, about 6 kN, about 8 kN, about 10 kN and about 12 kN using a tableting machine. Obtained a tablet with a diameter of 8.5 mm and a mass of 240 mg.

Examples 3-5
Based on the composition shown in Table 2 below, the active pharmaceutical ingredient, the component (a), and D-mannitol were charged into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture (17 : The liquid which melt | dissolved the component (b) in the appropriate quantity of 3) was gradually added, and it 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, a tablet with a tableting pressure of about 8 kN and a tablet diameter of 8.5 mm and a mass of 240 mg using a tableting machine. Obtained.

Comparative Examples 3-5
Based on the composition shown in Table 2 below, the active pharmaceutical ingredient, the component (a), and D-mannitol were charged into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture (17 : Appropriate amount of 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, a tablet with a tableting pressure of about 8 kN and a tablet diameter of 8.5 mm and a mass of 240 mg using a tableting machine. Obtained.

Examples 6-8
Based on the composition shown in Table 3 below, the active pharmaceutical ingredient, the component (a), and lactose hydrate are put into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture as a granulating solvent ( The liquid in which the component (b) was dissolved was gradually added to an appropriate amount of 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, a tablet with a tableting pressure of about 8 kN and a tablet diameter of 8.5 mm and a mass of 240 mg using a tableting machine. Obtained.

Comparative Examples 6-8
Based on the composition shown in Table 3 below, the active pharmaceutical ingredient, the component (a), and lactose hydrate are put into a stirring and mixing granulator, mixed, and then mixed with a water / anhydrous ethanol mixture as a granulating solvent ( 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, a tablet with a tableting pressure of about 8 kN and a tablet diameter of 8.5 mm and a mass of 240 mg using a tableting machine. Obtained.

(1-3) Results The results of the composition, hardness test and disintegration test of the tablets of Examples 1 to 8 and Comparative Examples 1 to 8 are shown in Tables 1 to 3 below.

Table 1 shows the case where D-mannitol was used as an excipient. As is apparent from the experimental results, the tablet of Example 1 was compared with the tableting pressure of 8 kN, which is the central value of 5 levels. Exhibited a disintegration time of 14 seconds and a hardness of 49N. On the other hand, the tablet of Example 2 containing no tannic acid had a disintegration time of 38 seconds, and the disintegration property was worse than that of the tablet of Example 1. Furthermore, when the influence of the five levels of tableting pressure on the physical property values of the tablets was confirmed, both tablets of Example 1 and Example 2 showed a clear increase in hardness as the tableting pressure increased. However, the disintegration time was clearly delayed in the formulation of Example 2 as the tableting pressure increased, but only a slight delay was observed in the tablet of Example 1.

Similarly, when lactose hydrate is used as an excipient, it is also shown in Table 1. As is clear from the experimental results, when compared with a tableting pressure of 8 kN, which is the center value of 5 levels, The tablet of Example 3 had a disintegration time of 19 seconds and a hardness of 49N. On the other hand, the tablet of Example 4 containing no tannic acid had a disintegration time of 48 seconds, and the disintegration property was worse than that of the tablet of Example 3. Furthermore, when the influence of the five levels of tableting pressure on the physical properties of the tablets was confirmed, both tablets of Example 3 and Example 4 showed a clear increase in hardness as the tableting pressure increased. However, the disintegration time was clearly delayed in the tablet of Example 4 as the tableting pressure increased, but only a slight delay was observed in the tablet of Example 3.

In order to produce the tablet of the present invention, even when the tableting pressure is increased, the disintegration decrease is extremely small. Therefore, the tableting pressure corresponding to the desired hardness may be employed, and production management is easy. .

When D-mannitol was used as an excipient, as is apparent from Table 2, the tablets of Examples 3 to 5 had a disintegration time of 10 to 14 seconds and a hardness of 40 to 52 N. Regardless of the type, it showed excellent disintegration and moderate moldability,
In contrast, the tablets of Comparative Examples 3 to 5 that do not contain the component (b) tannic acid have a disintegration time of 34 to 46 seconds, which is much worse than the tablets of Examples 3 to 5. It was.

When lactose hydrate was used as an excipient, as is apparent from Table 3, the tablets of Examples 6 to 8 had a disintegration time of 13 to 21 seconds and a hardness of 45 to 57 N. Regardless of the type, it showed excellent disintegration and moderate moldability,
On the other hand, the tablets of Comparative Examples 6 to 8 that do not contain the tannic acid component (b) have a disintegration time of 43 to 57 seconds, which is much worse than the tablets of Examples 6 to 8. It was.

Even if various pharmaceutically active ingredients are contained in the intraoral rapidly disintegrating tablet of the present invention, excellent disintegration and moderate moldability can be obtained by including (a) polyvinyl alcohol and (b) tannic acid. It was shown that.

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

(a) Polyvinyl alcohol
(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 composition according to any one of claims 1 to 3, wherein the polyvinyl alcohol as the component (a) has an average polymerization degree of 200 to 2500 and a saponification degree of 85 to 89 mol%.
The composition according to any one of claims 1 to 4, wherein the content of the component (a) is 0.001 to 60 mass% with respect to the total amount of the composition.
The composition according to any one of claims 1 to 5, wherein the content of the component (b) is 0.001 to 60 mass% with respect to the total amount of the composition.
The composition according to any one of claims 1 to 6, further comprising an excipient.
The composition according to claim 7, wherein the excipient is at least one selected from the group consisting of mannitol and lactose hydrate.
A solid preparation comprising the composition according to any one of claims 1 to 8.
The solid preparation according to claim 9, wherein the solid preparation is a tablet.
The solid preparation according to claim 10, further comprising a binder and / or a disintegrant.
The solid preparation according to claim 11, 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 11 or 12, wherein the disintegrant is crospovidone, croscarmellose sodium, carmellose calcium, carmellose, and low-substituted hydroxypropylcellulose.
The solid preparation according to any one of claims 9 to 13, which has a disintegration time of 30 seconds or less as measured by a disintegration test prescribed in the Japanese Pharmacopoeia.
(A) The composition according to any one of Items 1 to 8, or
(B) A method for producing an intraorally rapidly disintegrating solid preparation comprising compression-molding a mixture of the composition and additive according to any one of Items 1 to 8, and / or a pharmaceutically active ingredient.
The method according to claim 15, wherein the solid preparation is a tablet.
The method according to claim 15 or 16, wherein the tableting pressure at the time of compression molding is 100 to 1500 kgf / cm 2 .
The method according to any one of claims 15 to 17, wherein the additive is a binder and / or a disintegrant.