JP5517327B2 - Composition for orally disintegrating tablets - Google Patents

Description

  The present invention relates to a pharmaceutical composition effective for improving tablet strength and disintegration.

Orally disintegrating tablets disintegrate in the oral cavity with saliva or a small amount of water, and are therefore useful dosage forms that can reduce the burden of taking for those who do not have sufficient swallowing function such as the elderly and children.
For this reason, many orally disintegrating tablets are used in the medical field, but the tablet strength is low compared to ordinary tablets, so cracking and chipping are likely to occur, and the hygroscopic property changes over time (tablet strength) Has been considered unsuitable for automatic packaging.
Therefore, it is desired that sufficient tablet strength is obtained while maintaining rapid disintegration, but it is difficult to achieve a balance between the rapid disintegration property and tablet strength because they conflict.
A tablet having a rapid disintegration property can be obtained by combining a disintegrant with a sugar or sugar alcohol having a property that is extremely soluble in water (Japanese Patent Application Laid-Open No. 2006-77018). I can't get it.
Generally, tablet strength is improved by adding crystalline cellulose (Japanese Patent Laid-Open No. 2006-70046). However, disintegration time is delayed when tableting is performed at a high compression pressure, and tablet strength is improved when tableting is performed at a low compression pressure. It is difficult to manage the conditions at the time of manufacture, such as not expecting much.
Further, if 10% (all in the present specification is mass%) of the tablet mass is not added, a sufficient effect of increasing the hardness cannot be obtained, so that the proportion of water-insoluble components increases. , Leading to a rough feeling in the oral cavity.
A method for improving moldability by granulating using a water-soluble binder is also disclosed (Japanese Patent Laid-Open No. 2008-127320). However, if a water-soluble binder is used, the disintegration time is delayed, so that the moldability is increased. It is not possible to add an amount sufficient to improve the amount.
Furthermore, it is often disadvantageous when handling drugs that are unstable to moisture due to its hygroscopic nature.
Moreover, although the technique which acquires quick disintegration by using starch as a binder is disclosed (WO00 / 47233), granulation proceeds when starch is used as a binder because of its weak binding power. There is a problem that it is difficult, and furthermore, since the binding force is weak, it is not possible to expect an improvement in tablet strength as much as a commonly used cellulose-based binder.
With the techniques described above, it is difficult to complete an orally disintegrating tablet that rapidly disintegrates while maintaining sufficient tablet strength.
Therefore, in most cases, sufficient tablet strength is not obtained, or the disintegrant is forcibly disintegrated by adding a large amount of disintegrant.
However, by adding a large amount of disintegrant, a feeling of dryness due to a large amount of saliva being absorbed, and a disintegrating agent that swells greatly in the oral cavity and feels strongly as an insoluble solid in the oral cavity, the feeling of administration becomes worse .
In addition, there is a problem that the hardness decreases due to humidification.
Therefore, although it has a good feeling of taking (rapid disintegration, most of it dissolves in the oral cavity after disintegration), the oral cavity has sufficient tablet strength and can be used for single-packing without being inferior to ordinary tablets. A technique capable of producing an internally disintegrating tablet is desired.

JP 2006-77018 A JP 2006-70046 A JP 2008-127320 A WO00 / 47233

An object of the present invention is to provide a pharmaceutical composition for an orally disintegrating tablet effective for achieving both strength required for dispensing in an automatic packaging machine and fast disintegration without requiring a special production apparatus. And
Furthermore, it is an object to provide an orally disintegrating tablet using this pharmaceutical composition.

A technique of granulating a polymer by dissolving it in a solvent and using it as a binder is useful for improving tablet hardness.
In general, when trying to improve tablet strength with crystalline cellulose, an addition amount of at least about 10% is required with respect to the total mass of the preparation. However, when the polymer is dissolved in a solvent and granulated, the addition of the polymer A sufficient improvement in tablet strength can be expected when the amount is about 1 to 5%.
Therefore, it is meaningful to improve the tablet strength by using a polymer as a binder, but the water-soluble polymer has a great influence on the disintegration of the tablet, and about 2% of the tablet mass is added. Then, the disintegration time is significantly delayed as compared with the preparation without the binder.

However, as a result of studies by the present inventors, the tablet strength of a preparation in which a granulated powder obtained by granulating with a binder in which a water-insoluble polymer (for example, ethyl cellulose, methacrylic acid copolymer, etc.) is dissolved in a solvent is increased. Was found to have little effect on disintegration.
That is, it was found that tablet strength can be improved while maintaining rapid disintegration.

The contents of the present invention will be specifically described below.
The composition for orally disintegrating tablets according to the present invention is intended to granulate sugar or sugar alcohol with a binder containing a water-insoluble polymer dissolved in a solvent, and disintegrates with sugar or sugar alcohol. Granulated with a binder containing a water-insoluble polymer dissolved in a solvent, or a sugar or sugar alcohol with a binder containing a water-insoluble polymer dissolved in a solvent. It is preferable to use a composition obtained by adding a disintegrant to the granulated product.
Here, the water-insoluble polymer is a polymer corresponding to what is expressed as “almost insoluble in water” in the Japanese Pharmacopoeia.
In addition, since the water-soluble polymer delays the disintegration time of the tablet as described above, it is preferable that the binder does not substantially contain the water-soluble polymer in the present invention.
Here, “substantially free” means that the disintegration time within 60 seconds as the object of the present invention is satisfied as described later, and the water-soluble binder may be contained within a range not affecting this effect. It is meant to be included in the present invention.

Thereby, a tablet can be rapidly disintegrated in an oral cavity with the addition amount of a disintegrant as small as about 1-2%, maintaining sufficient tablet strength.
In the Japanese Pharmacopoeia disintegration test, it was found that a preparation in which only a disintegrant other than a cation-containing disintegrant (for example, crospovidone) was added as a disintegrant swells but does not disintegrate.
On the other hand, disintegrants that do not contain cations also disintegrate in formulations that do not contain a binder.
This indicates that the swelling force of a disintegrant containing no cation such as crospovidone is insufficient to peel off the adhesion between particles due to the binder.
That is, although the said formulation swells when it touches water, it is thought that a certain amount of shear force by a tongue and an upper jaw is required for it to collapse.
Therefore, even in the oral cavity, it is desirable to use a disintegrant containing a cation in order to expect the same disintegration to all people without requiring the shearing force of the tongue and maxilla to disintegrate the tablet. .

Water-insoluble polymers are divided into sustained-release polymers, gastric polymers, enteric polymers and the like.
The sustained-release polymer has a water-insoluble property without being affected by pH, and examples thereof are selected from the group consisting of ethyl cellulose, aminoalkyl methacrylate copolymer RS, vinyl acetate, and combinations thereof. Things.
The gastric polymer is characterized by having a water-insoluble property at a pH of 5 or more, and examples thereof include aminoalkyl methacrylate copolymer E, polyvinyl acetal diethylaminoacetate and the like.
The enteric polymer is characterized by having a water-insoluble property at a pH of 6 or less. Examples thereof include methacrylic acid copolymer L, methacrylic acid copolymer S, hypromellose phthalate, hydroxypropyl methylcellulose acetate succinate. , Carboxymethyl ethyl cellulose, and combinations thereof, and the like.
The water-insoluble polymer shown above is too much to add to the mouth, resulting in a poor feeling of taking a strong sense of the properties of the polymer that does not dissolve in the oral cavity. Disappear.
Therefore, the addition amount of the binder is preferably 1 to 10% of the tablet mass, more preferably 1 to 7%, and further preferably 2 to 6%.
About the addition amount of a disintegrant, when too large, it will swell greatly in an oral cavity and a feeling of taking will worsen, and the fall of the tablet intensity | strength by humidification is worried.
On the other hand, if the addition amount of the disintegrant is too small, the disintegration property of the tablet is deteriorated. Therefore, the addition amount of the disintegrant is preferably 0.5 to 10% of the tablet mass, more preferably 0.5 to 7%, still more preferably 1 to 5%.

In addition, water-soluble polymers eventually dissolve in water, but they have a property of gelation when touched by water, so the gelled polymer blocks the water intrusion route, so that Infiltration is delayed.
Therefore, since it works in the direction of reducing the effect of the present invention that the tablet disintegrates within 60 seconds after touching the water, it is preferably not substantially contained in the present invention as described above.
Examples of the water-soluble polymer include polyvinyl alcohol, povidone, hypromellose, hydroxypropylcellulose, methylcellulose and the like.

  The composition for orally disintegrating tablets according to the present invention may be granulated with medicinal ingredients and other additives as necessary, and the medicinal ingredients and other ingredients as needed in the granulated powder according to the present invention. These additives may be blended.

The medicinal ingredient is not particularly limited as long as it is a drug intended for oral administration. For example, as a drug having high utility value as an orally disintegrating tablet, Alzheimer type dementia therapeutic agent such as donepezil hydrochloride, triazolam, tandospirone citric acid Hypnotic sedatives such as salt, zolpidem tartrate, antipsychotics such as risperidone and milnacipran hydrochloride, antipyretic analgesics and antiphlogistics such as diclofenac sodium and meloxicam, amlodipine besylate, imidapril hydrochloride, enalapril maleate, etc. Antihypertensive agent such as antihypertensive agent, pravastatin sodium, atorvastatin calcium hydrate, antitussive expectorant such as ephedrine hydrochloride, codeine hydrochloride, bronchodilator such as salbutamol sulfate, tulobuterol hydrochloride, dimethylpolysiloxane Antipruritics such as omeprazo Peptic ulcers such as le, lansoprazole, famotidine, diabetic agents such as pioglitazone hydrochloride, voglibose, d-chlorpheniramine maleate, cetirizine hydrochloride, fexofenadine hydrochloride, olopatadine hydrochloride, loratadine, naphthopidyl, etc. Antiallergic agents.
In addition, if there are problems such as poor handling and bitterness with respect to the medicinal component, a medicinal component that has been processed into a raw material (granulation, coating, etc.) to improve it may be used.

As other additives that can be added as necessary, pharmaceutical additives that can be administered orally, such as excipients and lubricants, can be used.
Examples of excipients include sugars such as lactose and mannitol, sugar alcohols, starches such as corn starch, celluloses such as crystalline cellulose, inorganic compounds such as calcium hydrogen phosphate, organic acids such as citric acid, iron oxides, etc. Coloring agents, sweeteners such as aspartame, and fragrances can be mentioned.
Further, examples of the lubricant include magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, hydrogenated oil, talc and the like.

In the present invention, it is possible to produce a pharmaceutical composition for orally disintegrating tablets by a known wet granulation method. For example, fluidized bed granulation method, stirring granulation method, rolling fluidized bed granulation method, extrusion Examples thereof include a granulation method, preferably a fluidized bed granulation method, a stirring granulation method, and a rolling fluidized bed granulation method, and more preferably a fluidized bed granulation method.
For example, when using a fluidized bed granulation method, granulation is performed by spraying a binder solution onto a powder in which medicinal ingredients, excipients, disintegrants and the like are mixed.
Also, medicinal ingredients and disintegrants can be added later.
A target tablet can be obtained by mixing a lubricant, a fragrance, and the like with a pharmaceutical composition obtained by these methods and tableting.

The present invention can balance tablet strength and disintegration by using a binder in which a water-insoluble polymer is dissolved in a solvent.
This reduces the risk of tablet breakage during transportation or removal from the PTP sheet, and makes it easier to handle single-packed preparations, improving handling and compliance.

Examples and comparative examples will be described below in detail.
However, the present invention is not limited to these.
In addition, as a target value for an orally disintegrating tablet that can withstand dispensing in an automatic packaging machine while maintaining rapid disintegration, which is the object of the present invention, tablet hardness of 50 N or more, disintegration time of the JP Disintegration Test Method within 60 seconds Set.

(Example 1 and Comparative Examples 1, 2, 3, 4)
A pharmaceutical composition having the formulation shown in Table 1 was produced by a fluidized bed granulation method (Example 1 and Comparative Examples 1.2 and 3), and the composition was tableted to obtain tablets (Comparative Example 4 was Direct tableting method).
About Example 1 and Comparative Examples 1.2 and 3: D-mannitol (Mannit P, Mitsubishi Corporation Foodtech), croscarmellose sodium (Ac-Di-Sol, FMC) were fluidized bed granulator (FL-mini) In the examples, ethyl cellulose (Etocel Premium 10, Dow Chemical) was dissolved in a solvent (ethanol: water = 7: 3). In the comparative example, hydroxypropyl cellulose (HPC-L, Japan) Soda), or hypromellose 2910 (TC-5R, Shin-Etsu Chemical), or povidone (Kollidon K30, BASF Japan) dissolved in solvent (ethanol: water = 7: 3), sprayed, dried and sized Thus, fluidized bed granulated powder was obtained.
This granulated powder and magnesium stearate (magnesium stearate-S, Japanese fats and oils) were mixed and then tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.
About Comparative Example 4: After mixing D-mannitol for direct compression (Pearritol 200SD, Roquette), croscarmellose sodium and magnesium stearate, the mixture was tableted at 8000 N using a 9.0 mm diameter punch to obtain a tablet.

実施例１及び比較例２，３は比較例４と比較して錠剤硬度が高い。
つまり結合剤を使用することで錠剤硬度が上昇することが確認された。
比較例１はキャッピングが起こって打錠できなかった。
また、実施例１及び比較例４は速やかに崩壊するが、比較例２，３は崩壊が遅い。
したがって、水溶性結合剤は崩壊時間を遅延させる影響を与えるが、水不溶性高分子は崩壊時間にほとんど影響を与えないことが考えられる。
つまり水不溶性高分子で造粒することで、速やかな崩壊時間を維持しつつ錠剤硬度を向上させることができる。 (Experimental example 1)
The tablet physical properties of the tablets produced in Example 1 and Comparative Examples 1, 2, 3, and 4 were evaluated. The results are shown in Table 2.

Example 1 and Comparative Examples 2 and 3 have higher tablet hardness than Comparative Example 4.
That is, it was confirmed that tablet hardness increases by using a binder.
In Comparative Example 1, capping occurred and tableting was not possible.
Moreover, although Example 1 and Comparative Example 4 disintegrate rapidly, Comparative Examples 2 and 3 are slow to disintegrate.
Therefore, it is considered that the water-soluble binder has an effect of delaying the disintegration time, but the water-insoluble polymer hardly affects the disintegration time.
That is, granulation with a water-insoluble polymer can improve tablet hardness while maintaining a rapid disintegration time.

(Example 1 and Comparative Examples 5 and 6)
A pharmaceutical composition having the formulation shown in Table 3 was prepared by a fluidized bed granulation method (Example 1 and Comparative Example 5), and the composition was tableted to obtain a tablet (Comparative Example 5 is a direct tableting method). ).
About Example 1 and Comparative Example 6: D-mannitol and croscarmellose sodium were charged into a fluidized bed granulator, and in Example 1, a solution in which ethylcellulose was dissolved in a solvent (ethanol: water = 7: 3), comparison In Example 6, an aqueous ethylcellulose dispersion (Aquacoat, FMC) was sprayed, dried and sized to obtain a fluidized bed granulated powder.
This granulated powder and magnesium stearate were mixed and then tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.
About Comparative Example 5: D-mannitol for direct compression, croscarmellose sodium, ethyl cellulose, and magnesium stearate were mixed, and then tableted at 8000 N using a 9.0 mm diameter punch to obtain a tablet.

上記の結果から、エチルセルロースを溶媒に溶解させて噴霧するという添加方法が最も硬度を向上させることがわかった。 (Experimental example 2)
The tablet physical properties of the tablets produced in Example 1 and Comparative Examples 5 and 6 were evaluated. The results are shown in Table 4.

From the above results, it has been found that the addition method of dissolving ethyl cellulose in a solvent and spraying it improves the hardness most.

(Examples 2, 3, 4 and Comparative Examples 7, 8, 9, 10)
About Examples 2, 3, 4 and Comparative Examples 7, 8, and 9: Pharmaceutical compositions having the formulations shown in Table 5 were produced by a fluidized bed granulation method.
D-mannitol, disintegrant {croscarmellose sodium, carboxymethyl starch sodium (GLYCOLYS, Roquette), carmellose calcium (ECG505, Gotoku Pharmaceutical), crospovidone (Collidon CL-F, BASF), low substituted hydroxypropylcellulose ( LH-21, Shin-Etsu Chemical), partially pregelatinized starch (PCS, Asahi Kasei)} into a fluid bed granulator and sprayed with a solution in which ethylcellulose was dissolved in a solvent (ethanol: water = 7: 3), Drying and sizing gave a fluidized bed granulated powder.
This granulated powder and magnesium stearate were mixed and then tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.
About Comparative Example 10: Tablets having the formulation shown in Table 6 were produced by the direct tableting method.
After mixing D-mannitol, crospovidone and magnesium stearate, the mixture was tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.

実施例２，３，４（カチオンを含む崩壊剤）では、崩壊試験において速やかに崩壊する錠剤が得られた。
しかしながら比較例７，８，９（カチオンを含まない崩壊剤）では、膨潤はするが６０秒以内に崩壊しないことが確認された。
また、比較例７は崩壊せず比較例１０では崩壊することから、エチルセルロースは水に触れた時の錠剤の膨潤を妨げることはないが、エチルセルロースの結合力によって錠剤の崩壊を妨げていることが考えられる。
さらにその結合を剥がすにはクロスポビドンのようなカチオンを含まない崩壊剤では不十分で、クロスカルメロースナトリウムのようなカチオンを含む崩壊剤が必要であることが確認された。 (Experimental example 3)
The tablet physical properties of the tablets produced in Examples 2, 3, 4 and Comparative Examples 7, 8, 9, and 10 were evaluated. The results are shown in Table 7.

In Examples 2, 3, and 4 (disintegrant containing a cation), tablets that disintegrate rapidly in the disintegration test were obtained.
However, in Comparative Examples 7, 8, and 9 (a disintegrant containing no cation), it was confirmed that it swells but does not disintegrate within 60 seconds.
In addition, since Comparative Example 7 does not disintegrate and disintegrates in Comparative Example 10, ethyl cellulose does not prevent the tablet from swelling when exposed to water, but the binding force of ethyl cellulose may prevent the tablet from collapsing. Conceivable.
Furthermore, it was confirmed that a disintegrant containing no cation such as crospovidone is insufficient to break the bond, and a disintegrant containing a cation such as croscarmellose sodium is necessary.

(Examples 1, 5, 6, 7, 8 and Comparative Example 4)
Examples 1, 5, 6, 7, and 8: Pharmaceutical compositions having the formulations shown in Table 8 were produced by a fluidized bed granulation method.
D-mannitol and croscarmellose sodium were added to a fluidized bed granulator (FL-mini, Freund Sangyo), binder {ethylcellulose, aminoalkyl methacrylate copolymer RS (Eudragit RS, Rohm), aminoalkyl methacrylate copolymer E (Eudragit E, Rohm), methacrylic acid copolymer L (Eudragit L, Rohm), methacrylic acid copolymer S (Eudragit S, Rohm)} in a solvent (ethanol: water = 7: 3) was sprayed. Thereafter, it was dried and sized to obtain a fluidized bed granulated powder.
This granulated powder and magnesium stearate (magnesium stearate-S, Japanese fats and oils) were mixed and then tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.
About Comparative Example 4: Tablets having the formulation shown in Table 9 were produced by the direct compression method.
After mixing D-mannitol (Pearitol 200SD, Roquette), croscarmellose sodium (Ac-Di-Sol, FMC), magnesium stearate (magnesium stearate-S, Japanese fats and oils), using a 9.0 mm diameter bowl Tableting was performed at 8000 N to obtain a tablet.

実施例１，５，６，７，８（水不溶性高分子で造粒）は比較例４（結合剤を含まない）と比べて錠剤硬度が高い。
しかしながら崩壊時間は実施例と比較例でほとんど差は無く、速やかに崩壊する。
したがって、水不溶性高分子で造粒した造粒末を打錠することで、速やかな崩壊時間を保持しつつ錠剤硬度を向上させた口腔内崩壊錠を製造することができる。 (Experimental example 4)
The tablet physical properties of the tablets produced in Examples 1, 5, 6, 7, 8 and Comparative Example 4 were evaluated.
The results are shown in Table 10.

Examples 1, 5, 6, 7, and 8 (granulated with a water-insoluble polymer) have higher tablet hardness than Comparative Example 4 (without binder).
However, the disintegration time is almost the same between the example and the comparative example, and disintegrates quickly.
Therefore, by tableting a granulated powder granulated with a water-insoluble polymer, an orally disintegrating tablet with improved tablet hardness while maintaining a rapid disintegration time can be produced.

(Examples 9 and 10)
About Examples 9 and 10: A pharmaceutical composition having the formulation shown in Table 11 was produced by a fluidized bed granulation method.
A solution in which D-mannitol and croscarmellose sodium are added to a fluid bed granulator, and a binder (aminoalkyl methacrylate copolymer E, methacrylic acid copolymer S) is dissolved in a solvent (ethanol: water = 7: 3). After spraying, it was dried and sized to obtain a fluidized bed granulated powder.
A medicinal component (donepezil hydrochloride) and magnesium stearate were added to the granulated powder and mixed, and the resultant was tableted with 8000 N using a 9.0 mm diameter punch to obtain a tablet.

薬効成分を含んだ場合でも、口腔内崩壊錠として十分な硬度と崩壊性を得られることがわかった。
特に塩酸ドネペジルを使用した場合は良好な硬度が得られる。 (Experimental example 5)
The tablet physical properties of the tablets produced in Examples 9 and 10 were evaluated. The results are shown in Table 12.

It was found that even when a medicinal component was included, sufficient hardness and disintegration could be obtained as an orally disintegrating tablet.
In particular, when donepezil hydrochloride is used, good hardness can be obtained.

(Examples 11 and 12)
About Examples 11 and 12: Pharmaceutical compositions having the formulations shown in Table 13 were produced by a fluidized bed granulation method.
About Example 11: A medicinal ingredient (loratadine), lactose (lactose 200M, DMV), croscarmellose sodium, aspartame (aspartame, Ajinomoto) were charged into a fluid bed granulator, and methacrylic acid copolymer S was used as a solvent (ethanol: After spraying the solution dissolved in water = 7: 3), it was dried and sized to obtain a fluidized bed granulated powder.
A fragrance and magnesium stearate were added to the granulated powder and mixed, and the mixture was tableted at 6000 N using a punch having a diameter of 8.0 mm to obtain a tablet.
About Example 12: Lactose, croscarmellose sodium and aspartame are charged into a fluidized bed granulator, sprayed with a solution in which methacrylic acid copolymer S is dissolved in a solvent (ethanol: water = 7: 3), and then dried. The fluidized bed granulated powder was obtained by sizing.
A medicinal component (loratadine), a fragrance, and magnesium stearate were added to the granulated powder, mixed, and compressed into tablets at 6000 N using a wrinkle with a diameter of 8.0 mm to obtain a tablet.

ロラタジンを含んだ場合でも、口腔内崩壊錠として十分な硬度と崩壊性を得られることがわかった。 (Experimental example 6)
Tablet physical properties of the tablets produced in Examples 11 and 12 were evaluated.
The results are shown in Table 14.

Even when loratadine was included, it was found that sufficient hardness and disintegration can be obtained as an orally disintegrating tablet.

Claims (5)

An orally disintegrating tablet composition comprising a granulated powder obtained by granulating a sugar or sugar alcohol and a disintegrant with a binder containing a water-insoluble polymer dissolved in a solvent,
The water-insoluble polymer is one of a sustained release polymer, a gastric polymer, and an enteric polymer,
The sustained release polymer is selected from the group consisting of ethyl cellulose, aminoalkyl methacrylate copolymer RS, vinyl acetate resin, and combinations thereof,
The gastric polymer is aminoalkyl methacrylate copolymer E or polyvinyl acetal diethylaminoacetate,
The enteric polymer is selected from the group consisting of methacrylic acid copolymer L, methacrylic acid copolymer S, hypromellose phthalate, hydroxypropyl methylcellulose acetate succinate, carboxymethylethylcellulose, and combinations thereof;
The disintegrant is a disintegrant containing a cation,
The composition for orally disintegrating tablets, wherein the disintegrant containing a cation is selected from the group consisting of sodium carboxymethyl starch, carmellose calcium, carmellose sodium, croscarmellose sodium, and combinations thereof .   The composition for orally disintegrating tablets according to claim 1, wherein the granulated powder, a medicinal component and other additives as necessary are blended.   A tablet obtained by tableting using the composition for orally disintegrating tablets according to claim 1 or 2. The tablet according to claim 3, wherein the mixing ratio of the water-insoluble polymer in the tablet is 1 to 10% by mass . The tablet according to claim 3, wherein the mixing ratio of the disintegrant in the tablet is 0.5 to 10% by mass .