JP7437039B2 - tablet - Google Patents

Description

The present invention provides (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or its pharmaceutical The present invention relates to tablets containing a legally acceptable salt.

(2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile (hereinafter referred to as "Compound A") ) is a dipeptidyl peptidase-4 (DPP-4) inhibitor, and tablets used for the treatment of type 2 diabetes are commercially available (Non-Patent Document 1).
It is known that impurities in Compound A increase when it comes into contact with moisture or specific additives (Patent Documents 1 and 2).

Patent Document 1 contains Compound A and at least one selected from the group consisting of mannitol, lactose, and cornstarch, and the total content of at least one selected from the group consisting of mannitol, lactose, and cornstarch. A pharmaceutical composition containing Compound A is described, which is characterized in that the amount of Compound A is 50% by mass or more.

Patent Document 2 describes a solid preparation containing Compound A and a binder, wherein the binder is selected from pregelatinized starch, hydroxypropylcellulose, and carmellose sodium. .

US Pat. No. 5,002,001 describes (a) 5-60% by weight of a DPP-IV inhibitor in free or acid addition salt form on a dry weight basis; (b) 40-95% by weight of a pharmaceutically acceptable drug on a dry weight basis. (c) 0-20% by weight on a dry weight basis of a pharmaceutically acceptable disintegrant; and optionally (d) 0.1-10% by weight on a dry weight basis of a pharmaceutically acceptable disintegrant. Pharmaceutical compositions containing lubricants are described. The examples describe tablets containing Compound A that are manufactured by a direct compression method in which Compound A does not come into contact with moisture.

Patent Document 4 describes (a) Compound A or a pharmaceutically acceptable salt thereof, (b) hydroxypropyl methylcellulose having an apparent viscosity of 80,000 cP to 120,000 cP when present in a 1% solution; ) microcrystalline cellulose, and (d) magnesium stearate. The examples describe tablets containing Compound A that are manufactured by a direct compression method in which Compound A does not come into contact with moisture.

US Pat. No. 5,001,201 discloses that the active ingredients consist of Compound A and metformin or in each case a pharmaceutically acceptable salt thereof, between 50 and 98% by weight, between 60 and 98% by weight, based on dry weight; Pharmaceutical compositions containing between 70 and 98% or 80 and 98% by weight of active ingredient are described. Examples describe tablets obtained by mixing and compressing ungranulated Compound A, granules containing metformin, and additives.

JP 2017-222592 Publication JP2019-182756A Special Publication No. 2007-518760 Special Publication No. 2008-543773 Special Publication No. 2009-510068

Equa (registered trademark) tablet package insert

However, as a result of studies conducted by the present inventor, impurities significantly increase when tablets containing ungranulated Compound A described in Patent Documents 3 to 5 are stored in a high temperature and high humidity environment. I found out that it does.
Next, it was found that when Compound A was wet-granulated into tablets, impurities increased significantly after storage in a high temperature and high humidity environment compared to tablets obtained by direct compression. Ta.

Furthermore, there is a demand for smaller tablets so that they can be easily taken by patients who have difficulty swallowing, such as elderly people. However, the commercially available tablet containing Compound A described in Non-Patent Document 1 has a mass of 200 mg, a diameter of 8.0 mm, and a thickness of 3.6 mm, and is not described in Examples of Patent Documents 1 to 5. Each tablet had a weight of 200 mg or more, and there was room for improvement in ease of taking.
Furthermore, in the direct compression method, it has been found that when the amount of additives contained in the tablet is reduced, tableting problems such as cracking and chipping occur, making it difficult to miniaturize the tablet.
In other words, tablets containing Compound A that do not cause tabletting failures such as cracking or chipping even when miniaturized, have practical hardness, and are excellent in stability under high temperature and high humidity environments are known. It wasn't.

Therefore, the present invention contains Compound A, which does not cause tabletting failures such as cracking or chipping even when miniaturized, has practical hardness, and has excellent stability under high temperature and high humidity environments. The purpose is to provide tablets that

As a result of intensive studies by the present inventors, the additives in the tablet include wet-granulated base granules containing Compound A, a diluent, a binder, and a disintegrant, a molding agent, and a lubricant. By setting the total content of 28 to 50% by mass, tabletting problems such as cracking and chipping do not occur even when miniaturized, and the tablet has practical hardness, and can be used in high temperature and high humidity environments. The present invention has been completed based on the discovery that it is possible to obtain a tablet containing Compound A that has excellent stability in .

Specifically, the present invention is as follows.
(1) (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or its pharmaceutical A tablet comprising an active ingredient containing a salt acceptable to , wet granulated base granules containing a diluent, a binder, a disintegrant, a molding agent, and a lubricant, the tablet comprising:
the binder is hypromellose;
The molding agent is crystalline cellulose,
A tablet in which the content of additives in the tablet is 28 to 50% by mass.
(2) The tablet according to (1) above, wherein the diluent is at least one selected from the group consisting of lactose, mannitol, trehalose, and corn starch.
(3) The tablet according to (1) or (2) above, wherein the content of the diluent is 8 to 30% by mass.
(4) The tablet according to any one of (1) to (3) above, wherein the content of the binder is 0.1 to 3.0% by mass.
(5) The tablet according to any one of (1) to (4) above, wherein the disintegrant is crospovidone.
(6) The tablet according to any one of (1) to (5) above, wherein the content of the disintegrant is 2 to 10% by mass.
(7) The tablet according to any one of (1) to (6) above, wherein the lubricant is magnesium stearate and/or calcium stearate.
(8) The tablet according to any one of (1) to (7) above, wherein the content of the lubricant is 0.5 to 3.0% by mass.
(9) The tablet according to any one of (1) to (8) above, wherein the content of the molding agent is 10 to 27% by mass.
(10) (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or its pharmaceutical A tablet comprising an active ingredient containing a salt acceptable to , wet granulated base granules containing a diluent, a binder, a disintegrant, a molding agent, and a lubricant, the tablet comprising:
The content of additives in the tablet is 28 to 50% by mass,
8 to 30% by mass of at least one diluent selected from the group consisting of lactose, mannitol, and trehalose;
0.1 to 3.0% by mass of a binder that is hypromellose;
2 to 10% by mass of a disintegrant, which is crospovidone;
A tablet comprising 0.5 to 3.0% by mass of a lubricant which is magnesium stearate and/or calcium stearate, and 10 to 27% by mass of a molding agent which is crystalline cellulose.
(11) The tablet according to any one of (1) to (10) above, each having a mass of 70 to 100 mg.
(12) The tablet according to any one of (1) to (11) above, which does not contain any active ingredients other than vildagliptin or a pharmaceutically acceptable salt thereof.
(13) (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile per tablet The tablet according to any one of (1) to (12) above, having a content of 25 to 50 mg.

According to the present invention, tableting failures such as cracking and chipping do not occur, the increase in impurities after storage in high temperature and high humidity environments can be suppressed, and the present invention is small and has practical hardness. , a tablet containing Compound A can be provided.

One embodiment of the tablet of the present invention comprises wet-granulated main drug granules containing an active ingredient containing Compound A or a pharmaceutically acceptable salt thereof, a diluent, a binder, and a disintegrant. , a tablet comprising a molding agent and a lubricant, the binder is hypromellose, the molding agent is crystalline cellulose, and the content of additives in the tablet is 28 to 50% by mass. .
Examples of tablets include ordinary tablets and orally disintegrating tablets. In the present invention, regular tablets are preferred because they can be miniaturized and are easy to take without disintegrating in the oral cavity.

[Active ingredient]
Compound A is a DPP-4 inhibitor described in Non-Patent Document 1 and is used for the treatment of type 2 diabetes.

The content of Compound A in the oral solid preparation of the present invention is not particularly limited and can be set appropriately depending on the therapeutic use and target patient, but when used for the treatment of type 2 diabetes, it is 25 mg per tablet. It is preferably 50 mg, more preferably 50 mg.

One preferred embodiment of the tablet of the present invention is that it does not contain any active ingredients other than Compound A or a pharmaceutically acceptable salt thereof, but it may contain other active ingredients without departing from the purpose of the present invention. Components can be used as appropriate.
Other active ingredients include, for example, antidiabetic drugs such as biguanides, thiazolidines, α-glucosidase inhibitors, SGLT2 inhibitors, sulfonylureas, and fast-acting insulin secretagogues, and preferably biguanides, Preferred is metformin hydrochloride.

[Additive]
The additives used in the present invention are not particularly limited as long as they are additives used in pharmaceuticals other than active ingredients, and preferably include diluents, binders, disintegrants, molding agents, and lubricants described below. These additives may be contained in the main drug granules or used outside the main drug granules, but it is preferable that the diluent, binder, and disintegrant be contained in the main drug granules, and the forming agent and The lubricant is preferably contained outside the main drug granules.

The tablets of the present invention do not cause tableting problems because the total content of all additives excluding the active ingredient (excluding water and solvents used during manufacturing) is 28 to 50% by mass. , it is possible to suppress the increase in impurities after storage in a high temperature and high humidity environment, and it is possible to obtain tablets that are small and have a practical hardness. From the viewpoint of tablet hardness, the content of the additive is preferably 40 to 50% by mass, more preferably 45 to 50% by mass. In addition, the content of the additive is preferably 28 to 45% by mass, more preferably 28 to 40% by mass from the viewpoint of stability when stored in a high temperature and high humidity environment and miniaturization. It is.

(diluent)
Diluents are additives that are added for the purpose of increasing or diluting the volume, and examples include rice starch, corn starch, potato starch, pregelatinized starch, trehalose, magnesium aluminate metasilicate, anhydrous calcium phosphate, precipitated calcium carbonate, and silicic acid. Examples include calcium, calcium lactate, lactose, fructose, mannitol, erythritol, xylitol, maltose, sorbitol, maltitol, and the like. Preferred are lactose, mannitol, trehalose, and corn starch, and more preferred is mannitol.

The content of the diluent is not particularly limited, but is 8 to 30% by mass from the viewpoint of stability when stored in a high temperature and high humidity environment, miniaturization of tablets, tableting properties, hardness, etc. The content is preferably from 12 to 25% by weight, even more preferably from 15 to 20% by weight.

(molding agent)
The molding agent is an additive added for the purpose of improving moldability, and in the present invention, crystalline cellulose can be used.
The content of the molding agent is preferably 10 to 27% by mass, and preferably 14 to 25% by mass, from the viewpoint of stability, tablet hardness, etc. when stored in a high temperature and high humidity environment. The amount is more preferably 20 to 25% by mass.

(disintegrant)
Examples of the disintegrant include low-substituted hydroxypropylcellulose, croscarmellose sodium, carmellose calcium, carmellose sodium, sodium starch glycolate, carmellose, partially pregelatinized starch, crospovidone, etc., and preferably starch Examples include sodium glycolate and crospovidone, and more preferably crospovidone.

The content of the disintegrant is not particularly limited, but is preferably 2 to 10% by mass in terms of disintegration, stability when stored in a high temperature and high humidity environment, miniaturization of tablets, etc. , more preferably 3 to 8% by mass, and still more preferably 4 to 7% by mass.

(lubricant)
Examples of the lubricant include magnesium stearate, calcium stearate, stearic acid, talc, light silicic anhydride, sucrose fatty acid ester, sodium stearyl fumarate, polyethylene glycol, glyceryl monostearate, etc., and preferably stearate. Examples include magnesium acid and calcium stearate.

The content of the lubricant is not particularly limited, but from the viewpoint of tableting properties, content uniformity, stability when stored in high temperature and high humidity environments, and miniaturization of tablets, it is 0.5 to 0.5. The content is preferably 3.0% by weight, more preferably 0.6-2.5% by weight, and even more preferably 0.7-2.0% by weight.

(Binder)
As a binder, hypromellose can be used in the present invention.

The content of the binder is not particularly limited, but from the viewpoint of strength, dissolution, stability when stored in high temperature and high humidity environments, miniaturization of tablets, etc., it is 0.1 to 3.0 mass. %, more preferably 0.2 to 2.0% by mass, even more preferably 0.3 to 1.0% by mass.

(Other additives)
In addition to the above-mentioned components, the tablets of the present invention may contain additives such as coloring agents, acidulants, and flavoring agents as appropriate, without departing from the object of the present invention. These additives may be included in the main drug granules or used outside the main drug granules.

Examples of colorants include iron sesquioxide, yellow iron sesquioxide, yellow iron oxide, brown iron oxide, food yellow No. 4, food yellow No. 5, food yellow No. 4 aluminum lake, food red No. 2, and food red No. 3. , Food Red No. 102, carmine, riboflavin, etc.

Examples of the acidulant include citric acid, tartaric acid, malic acid, and ascorbic acid.

Examples of the flavoring agent include L-aspartic acid, sodium chloride, magnesium chloride, sodium citrate, calcium citrate, sodium L-glutamate, and sodium hydrogen carbonate.

A preferred embodiment of the tablet of the present invention is wet-granulated main drug granules containing an active ingredient containing Compound A or a pharmaceutically acceptable salt thereof, a diluent, a binder, and a disintegrant. , a molding agent, and a lubricant, wherein the content of additives in the tablet is 28 to 50% by mass, and at least one selected from the group consisting of lactose, mannitol, trehalose, and corn starch. 8-30% by weight of one diluent, 0.1-3.0% by weight of a binder which is hypromellose, 2-10% by weight of a disintegrant which is crospovidone, magnesium stearate and/or calcium stearate. It is a tablet containing 0.5-3.0% by weight of a certain lubricant and 10-27% by weight of a molding agent which is crystalline cellulose.

(Manufacturing method, etc.)
The main drug granules are preferably produced by a wet granulation method. A preferred method for manufacturing the tablets of the present invention is to mix an active ingredient including Compound A or a pharmaceutically acceptable salt thereof and additives including a diluent, a binder, and a disintegrant, and prepare a granulation liquid containing water. The method includes a step of adding and granulating to obtain main drug granules, and a step of mixing the obtained main drug granules, excipients including a molding agent and a lubricant, and tableting.
As the wet granulation method, stirring granulation method, fluidized bed granulation method, etc. can be used.

The mass of each tablet of the present invention is preferably 70 to 100 mg, from the viewpoint of stability when stored in a high temperature and high humidity environment, tablet miniaturization, tablet hardness, etc. More preferably, the amount is between 100 mg and 100 mg.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples, but the scope of the present invention is not limited by the Examples below.

[Tablet physical properties]
Immediately after production, the diameter and thickness of each of the following tablets (round plain tablets without score lines) were measured, and the hardness was measured using a hardness meter.

[Tabletability]
In addition, the presence or absence of tableting failures such as cracks and chips in the tablets during sample manufacture (tableting) was confirmed.

[Purity test]
Each of the following tablets was tested using liquid chromatography at the start (immediately after manufacture) and after being sealed in a glass bottle and stored at 60°C for 14 days, and the area of each peak was measured using automatic integration method. Then, the total amount of impurities in Compound A (by area percentage method) was determined.
Note that when the tablets are placed in a glass bottle, sealed and stored at 60°C, the interior of the container becomes a high temperature and high humidity environment due to the moisture contained in the tablets.

[Comparative Examples 1 to 3 Direct compression method; Verification of additive amount]
With reference to Example 2 of Patent Document 3, Compound A and additives were mixed in the ratio shown in Table 1 below, and then tableted using a single-shot tablet machine to obtain tablets of Comparative Example 1.
In addition, the comparative examples except that the amounts of crystalline cellulose and magnesium stearate were reduced to the amounts shown in Table 1 below (Comparative Example 2 is half the amount of Comparative Example 1, Comparative Example 3 is 1/4 the amount of Comparative Example 1) Tablets were obtained in the same manner as in 1.
For the tablets of Comparative Examples 1 to 3 obtained, the physical properties of the tablets, the purity test results, and the presence or absence of tableting failure are shown in Table 1 below.

In the tablet of Comparative Example 1 manufactured by the direct compression method, after 14 days of being sealed at 60° C., impurities were significantly increased compared to the beginning.
In the tablet of Comparative Example 2, in which the amounts of crystalline cellulose and magnesium stearate were reduced to half of those in Comparative Example 1, impurities were significantly increased, although not as much as in Comparative Example 1. Furthermore, tableting failure occurred and the yield decreased.
The tablet of Comparative Example 3, in which the amount of crystalline cellulose and magnesium stearate was reduced to 1/4 of that of Comparative Example 1, was able to significantly suppress the increase in impurities compared to Comparative Example 1, but the tablet Failures occurred, yields decreased significantly, and hardness also decreased.

[Comparative Examples 4 and 5, Reference Example 1 Wet granulation; verification of additive amount]
Tablets of Comparative Example 4 were prepared using the same types and amounts of additives as in Comparative Example 1 by wet granulation.
Specifically, Compound A, lactose hydrate, and sodium starch glycolate were mixed in a mortar in the ratio shown in Table 2 below, purified water was added thereto, and the mixture was granulated and dried to obtain main drug granules. Next, the obtained main drug granules, crystalline cellulose, and magnesium stearate were mixed and then tableted using a single-shot tableting machine to obtain tablets of Comparative Example 4.

Further, a tablet of Comparative Example 5 was obtained in the same manner as Comparative Example 4, except that the amounts of crystalline cellulose and magnesium stearate were reduced to the amounts shown in Table 2 below (half the amount of Comparative Example 4).
In addition, the same procedure as Comparative Example 5 was carried out except that the amounts of lactose hydrate, sodium starch glycolate, purified water, crystalline cellulose, and magnesium stearate were reduced to the amounts shown in Table 2 below (half the amount of Comparative Example 5). , a tablet of Reference Example 1 was obtained.
Regarding the tablets of Comparative Examples 4 to 5 and Reference Example 1, the physical properties of the tablets, the purity test results, and the presence or absence of tableting problems are shown in Table 2 below.

The tablet of Comparative Example 4, which was manufactured by wet granulation using the same types and amounts of additives as Comparative Example 1, had an increased amount of impurities compared to Comparative Example 1 after 14 days of being sealed at 60°C.
In the tablet of Comparative Example 5, in which the amounts of crystalline cellulose and magnesium stearate were reduced to half of those in Comparative Example 4, impurities were significantly increased, although not as much as in Comparative Example 4.
The tablet of Reference Example 1, in which the amounts of lactose hydrate, sodium starch glycolate, purified water, crystalline cellulose, and magnesium stearate were reduced to half of that of Comparative Example 5, suppressed the increase in impurities compared to Comparative Examples 4 and 5. We were able to. Furthermore, the mass per tablet could be reduced from 200 mg in Comparative Example 4 to 100 mg, the tablets could be made smaller, and the hardness was also good. Furthermore, no tableting failure occurred.

[Reference Example 2, Example 1, Reference Example 3 Wet granulation; Verification of binder]
Tablets of Reference Example 2 were prepared by adding hydroxypropyl cellulose as a binder to the main drug granules of Reference Example 1, finely adjusting the type and amount of additives, and setting each tablet weight to 100 mg.
Specifically, Compound A, lactose hydrate, sodium starch glycolate, and hydroxypropylcellulose are mixed in a mortar in the ratio shown in Table 3 below, and purified water is added thereto, granulated, and dried to form main drug granules. I got it. Next, the obtained main drug granules, crystalline cellulose, and magnesium stearate were mixed and then tableted using a single-shot tableting machine to obtain tablets of Reference Example 2.

Further, tablets of Example 1 and Reference Example 3 were obtained in the same manner as Reference Example 2 except that hydroxypropylcellulose was changed to hypromellose or polyvinyl alcohol.
For the obtained tablets of Reference Example 2, Example 1, and Reference Example 3, the tablet physical properties, purity test results, and presence or absence of tableting failure are shown in Table 3 below.

Reference Example 2 containing hydroxypropylcellulose as a binder, Example 1 containing hypromellose, and Reference Example 3 containing polyvinyl alcohol were all able to suppress the increase in impurities. Furthermore, the mass per tablet could be reduced to 100 mg, the tablets could be made smaller, and the hardness was also good. Furthermore, no tableting failure occurred.
These results show that whichever binder is used, the stability of Compound A can be improved when stored under high temperature and high humidity environments, and it is also compact, easy to take, and has low hardness. It has been found that tablets containing good Compound A can be provided. Particularly when hypromellose was used, the hardness was good.

[Example 2 and 3 Wet granulation; Verification of diluent]
Tablets of Example 2 were prepared in the same manner as in Example 1, except that the diluent was changed from lactose hydrate to D-mannitol.
Specifically, Compound A, D-mannitol, sodium starch glycolate, and hypromellose were mixed in a mortar in the ratio shown in Table 4 below, and purified water was added thereto, followed by granulation and drying to obtain main drug granules. . Next, the obtained main drug granules, crystalline cellulose, and magnesium stearate were mixed and then tableted using a single-shot tableting machine to obtain the tablets of Example 2.

Further, a tablet of Example 3 was obtained in the same manner as in Example 2 except that D-mannitol was changed to trehalose.
Table 4 below shows the tablet physical properties, purity test results, and presence or absence of tableting failure for the tablets of Examples 2 and 3 obtained.

As a diluent, Example 1 containing lactose hydrate, Example 2 containing D-mannitol, and Example 3 containing trehalose were all able to significantly suppress the increase in impurities. Furthermore, the mass per tablet could be reduced to 100 mg, the tablets could be made smaller, and the hardness was also good. Furthermore, no tableting failure occurred.
These results show that whichever diluent is used, the stability of Compound A can be improved when stored under high temperature and high humidity environments, and it is also possible to improve the stability of Compound A when stored in a high temperature and high humidity environment. It was found that it is possible to provide a tablet containing Compound A that has good properties and hardness.

[Example 4 Wet granulation; Verification of disintegrant]
Tablets of Example 4 were prepared in the same manner as in Example 2, except that the disintegrant was changed from sodium starch glycolate to crospovidone.
Table 5 below shows the tablet physical properties, purity test results, and presence or absence of tableting failure for the obtained tablets of Example 4.

Both Example 2 containing sodium starch glycolate and Example 4 containing crospovidone as a disintegrant were able to significantly suppress the increase in impurities. Furthermore, the mass per tablet could be reduced to 100 mg, the tablets could be made smaller, and the hardness was also good. Furthermore, no tableting failure occurred.
These results show that whichever disintegrant is used, the stability of Compound A can be improved when stored in high temperature and high humidity environments, and it is also small, easy to take, and hard. It has been found that tablets containing Compound A with good quality can be provided.
In particular, the tablet of Example 4 using crospovidone as a disintegrant was able to significantly improve the stability of Compound A when stored in a high temperature and high humidity environment.

[Examples 5 to 7 Wet granulation; Verification of additive amount]
Tablets of Examples 5 to 7 were obtained in the same manner as in Example 4, except that the amount of the additive used in Example 4 was reduced to the amount shown in Table 6 below.
Table 6 below shows the tablet physical properties, purity test results, and presence or absence of tableting failure for the tablets of Examples 5 to 7 obtained.

In the tablets of Examples 5 to 7, in which the amount of each additive was reduced, as in Example 4, the increase in impurities could be significantly suppressed. Furthermore, the tablets could be made smaller and tableting problems did not occur. Although the tablets of Examples 5 to 7 had a slightly low tablet hardness, the hardness was within a sufficiently practical range (20N or more).

Claims (11)

(2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or a pharmaceutically acceptable thereof A tablet comprising an active ingredient containing only a salt, wet-granulated main drug granules containing a diluent, a binder, and a disintegrant, a molding agent, and a lubricant,
the binder is hypromellose;
The molding agent is crystalline cellulose,
The content of the molding agent is 10 to 27% by mass,
The content of additives in the tablet is 28 to 50% by mass,
Tablets with a mass of 70 to 100 mg per tablet . The tablet according to claim 1, wherein the diluent is at least one selected from the group consisting of lactose, mannitol, trehalose, and corn starch. The tablet according to claim 1 or 2, wherein the content of the diluent is 8 to 30% by mass. The tablet according to any one of claims 1 to 3, wherein the content of the binder is 0.1 to 3.0% by mass. The tablet according to any one of claims 1 to 4, wherein the disintegrant is crospovidone. The tablet according to any one of claims 1 to 5, wherein the content of the disintegrant is 2 to 10% by mass. The tablet according to any one of claims 1 to 6, wherein the lubricant is magnesium stearate and/or calcium stearate. The tablet according to any one of claims 1 to 7, wherein the content of the lubricant is 0.5 to 3.0% by mass. (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or a pharmaceutically acceptable thereof A tablet comprising an active ingredient containing only a salt, wet-granulated main drug granules containing a diluent, a binder, and a disintegrant, a molding agent, and a lubricant,
The content of additives in the tablet is 28 to 50% by mass,
8 to 30% by mass of at least one diluent selected from the group consisting of lactose, mannitol, trehalose and corn starch;
0.1 to 3.0% by mass of a binder that is hypromellose;
2 to 10% by mass of a disintegrant, which is crospovidone;
Contains 0.5 to 3.0% by mass of a lubricant that is magnesium stearate and/or calcium stearate, and 10 to 27% by mass of a molding agent that is crystalline cellulose,
Tablets with a mass of 70 to 100 mg per tablet . Content of (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile per tablet The tablet according to any one of claims 1 to 9, wherein the tablet is 50 mg. (2S)-1-{[(3-hydroxytricyclo[3.3.1.1 ^3,7 ]Dec-1-yl)amino]acetyl}-pyrrolidine-2-carbonitrile or a pharmaceutically acceptable salt thereof; active ingredient granules containing a diluent; a binder; and a disintegrant. A method for manufacturing a tablet, comprising a step of manufacturing by a wet granulation method, and a step of mixing the main drug granules, a molding agent, and a lubricant,
the binder is hypromellose;
The molding agent is crystalline cellulose,
The content of the molding agent is 10 to 27% by mass,
The content of additives in the tablet is 28 to 50% by mass,
A method for producing tablets with a mass of 70 to 100 mg per tablet.