JP7211136B2 - Tablet and manufacturing method thereof - Google Patents

Description

TECHNICAL FIELD The present invention relates to a tablet containing aripiprazole and a method for producing the same.

A tablet containing aripiprazole, which is a therapeutic agent for schizophrenia and the like, is known (see, for example, Non-Patent Document 1).

There are multiple types of formulations with different aripiprazole contents. Tablets containing 1 mg of aripiprazole per tablet (1-mg tablet) are also available for use in drug therapy.

Several companies, including the applicant, have already marketed generic drugs for 3 mg, 6 mg, 12 mg, and 24 mg tablets of aripiprazole, but not for 1 mg tablets.

The applicant has already obtained the results of bioequivalence tests in clinical trials in order to obtain approval for manufacturing and marketing the 6 mg tablet generic drug. With regard to the 3 mg and 12 mg generic tablets, the dissolution of aripiprazole in the 3 mg and 12 mg tablets is judged to be equivalent to that of the 6 mg tablet (standard formulation) according to the prescribed criteria. By submitting it, approval has been obtained without requiring a clinical trial (see Non-Patent Document 2).

Prescription drug package insert for "ABILIFY (registered trademark) tablets", Pharmaceuticals and Medical Devices Agency, March 2018 revision (19th edition) Prescription Drug Package Insert for “Aripiprazole Tablets “Nipro””, Pharmaceuticals and Medical Devices Agency, Revised April 2018 (4th edition)

In developing a 1mg tablet generic drug for aripiprazole, the present inventors demonstrated that it has the same dissolution properties as 3mg and 12mg tablets, as well as 6mg tablets, and obtained approval without the need for clinical trials. With this in mind, we attempted to design a 1 mg tablet.

The inventors of the present invention first reduced the aripiprazole content of the 3 mg tablet to 1 mg according to the 3 mg tablet, which has the lowest drug content among the already approved aripiprazole tablets, and has the same size as the 3 mg tablet. A 1 mg tablet supplemented with an excipient (lactose hydrate) for the 2 mg reduction in aripiprazole was studied. As a result, it was found that the dissolution of aripiprazole (the dissolution rate after the elapse of a predetermined period of time) was significantly reduced with such a 1 mg tablet, and it could not be said to have the dissolution ability equivalent to that of the 6 mg tablet. Based on this result, the present inventors conducted further studies and found that the dissolution of aripiprazole was enhanced by reducing the content of magnesium stearate contained in the 1 mg tablet as a lubricant.

That is, the amount of magnesium stearate in the 3 mg tablet is the amount necessary for the tablet of the size of the 3 mg tablet to function as a lubricant, and the size of the tablet and the amount of magnesium stearate are the same as those of the 3 mg tablet. Reducing the amount of active ingredient (aripiprazole) to 1 mg while keeping it the same, the ratio of magnesium stearate to active ingredient is tripled. Thus, the present inventors found that in the aripiprazole-containing tablet, the dissolution rate of aripiprazole decreased when the ratio of the amount of magnesium stearate to the amount of aripiprazole increased. Although the reason for this is not clear, it is speculated that, for example, some reaction such as chelate formation occurs between aripiprazole and magnesium stearate (magnesium ions), resulting in a decrease in dissolution. .

Therefore, if the content of magnesium stearate in the tablet (the ratio of the amount of magnesium stearate to the total amount of the tablet) is reduced, the ratio of magnesium stearate to the amount of aripiprazole will decrease, and the decrease in dissolution of aripiprazole can be suppressed. it is conceivable that.

However, if the content of the lubricant magnesium stearate in the tablet becomes low, it will not function as a lubricant sufficiently, and it will easily adhere to the tablet press, making it difficult to manufacture stable tablets. have a nature. Therefore, it is not desirable to reduce the content of magnesium stearate in tablets too much.

Furthermore, by reducing the overall tablet size to match the reduction in aripiprazole content, the ratio of magnesium stearate to the amount of aripiprazole can be reduced while maintaining the ratio of magnesium stearate to the total tablet weight. It is also considered that the decrease in dissolution of aripiprazole can be suppressed.

However, the size of pharmaceutical tablets is required to be within an appropriate range. That is, the lower limit of the size is restricted from the viewpoint of handling by the user, and the upper limit of the size is restricted from the viewpoint of ease of swallowing. For example, a 3 mg tablet of aripiprazole currently on the market has a diameter of 6 mm, and it is not desirable to make the tablet smaller than this size from the viewpoint of ease of handling by the patient. For this reason, the diameter of the currently marketed 1 mg tablet of aripiprazole (innovator product) is 6 mm, the same as the diameter of the 3 mg tablet. Thus, further reduction in tablet size is also undesirable.

In view of the above problems, the present invention provides a tablet containing aripiprazole and magnesium stearate, in which the ratio of magnesium stearate to the content of aripiprazole in the tablet must be set high. It is an object of the present invention to provide a method for suppressing deterioration in dissolution properties and to provide a method for producing tablets in which deterioration in dissolution properties is suppressed.

[1] A tablet containing aripiprazole and magnesium stearate,
The content of aripiprazole in the tablet is less than 3 mg,
The content of magnesium stearate in the tablet is 90 parts by mass or less per 100 parts by mass of aripiprazole,
A tablet, wherein the magnesium stearate has an average particle size of 10 to 50 μm.

[2] A tablet containing aripiprazole and magnesium stearate,
The content of magnesium stearate in the tablet is 34 parts by mass or more per 100 parts by mass of aripiprazole,
Tablets having a dissolution rate of aripiprazole of 20% or more after 180 minutes in 900 mL of water at a paddle rotation speed of 50 rpm in a dissolution test by the paddle method of the dissolution test method of the Japanese Pharmacopoeia General Tests.

[3] the content of magnesium stearate in the tablet is 90 parts by mass or less per 100 parts by mass of aripiprazole;
The tablet of [2], wherein the magnesium stearate has an average particle size of 10 to 50 μm.

[4] The tablet of [2] or [3], wherein the aripiprazole content per tablet is less than 3 mg.

[5] A method for producing a tablet containing aripiprazole and magnesium stearate, comprising:
The content of magnesium stearate in the tablet is 34 parts by mass or more and 90 parts by mass or less with respect to 100 parts by mass of aripiprazole,
A mixing step of mixing raw material powders containing aripiprazole-containing powder and magnesium stearate powder having an average particle size of 10 to 50 μm;
and a tableting step of tableting the mixture obtained in the mixing step.

[6] The method for producing a tablet according to [5], wherein the aripiprazole content in one tablet is less than 3 mg.

According to the present invention, in a tablet containing aripiprazole and magnesium stearate, when the ratio of magnesium stearate to the content of aripiprazole in the tablet is high, the decrease in dissolution of aripiprazole can be suppressed.

1 is a flow chart showing an example embodiment of a tablet manufacturing method. FIG. 1 is a graph showing the relationship between the content (parts by mass) of magnesium stearate with respect to 100 parts by mass of aripiprazole, the average particle size, and the dissolution rate. 2 is a graph showing the relationship between the ratio of magnesium stearate to aripiprazole and dissolution properties, with respect to magnesium stearate having different average particle sizes. It is a graph which shows the relationship between the average particle size of magnesium stearate and the dissolution rate. It is a graph which shows the relationship between the content of magnesium stearate (large particle size) and the dissolution rate.

The tablet of this embodiment is a tablet containing at least aripiprazole and magnesium stearate. Aripiprazole [generic name] is known as a therapeutic drug for schizophrenia, etc., and its chemical name is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4 -dihydro-2(1H)-quinolinone.

The ratio of magnesium stearate to the content of aripiprazole in the tablet is 34 parts by mass or more, preferably 40 parts by mass or more, more preferably 50 parts by mass or more relative to 100 parts by mass of aripiprazole. and more preferably 54 parts by mass or more. Thus, the present invention improves the decrease in aripiprazole dissolution that occurs when the ratio of magnesium stearate to the content of aripiprazole in the tablet is high.

The upper limit of the ratio of magnesium stearate to the content of aripiprazole in the tablet is preferably 90 parts by mass or less, more preferably 70 parts by mass or less, relative to 100 parts by mass of aripiprazole. Yes, more preferably 60 parts by mass or less. If the amount of magnesium stearate is too high, it becomes difficult to suppress the decrease in dissolution of aripiprazole.

The ratio of magnesium stearate to the total weight of the tablet (magnesium stearate content in the tablet) is preferably 0.4 to 1.1% by mass, more preferably 0.5 to 0.8% by mass. , more preferably 0.58 to 0.7% by mass. The content of magnesium stearate in the tablet is preferably 1% by mass or more for stable production, but within this range, the content of magnesium stearate decreases. Also, it is considered that stable production is possible.

The average particle size of magnesium stearate contained in the tablet is preferably 10 μm or more, more preferably 11 μm or more. If the average particle size of magnesium stearate is within this range, even if a certain amount of magnesium stearate is contained, the decrease in dissolution of aripiprazole can be sufficiently suppressed. Although the upper limit of the average particle size of magnesium stearate is not particularly limited, it is usually preferably 50 μm or less, more preferably 20 μm or less. In addition, in this specification, the average particle diameter is a volume-based average particle diameter.

In the dissolution test by the paddle method of the dissolution test method of the Japanese Pharmacopoeia general test method, the tablet of the present embodiment has a dissolution rate of aripiprazole of 20% or more after 180 minutes in 900 mL of water at a paddle rotation speed of 50 rpm. is. In the present invention, by controlling the average particle size of magnesium stearate while maintaining the content of magnesium stearate at a certain level or more, a sufficient dissolution rate can be ensured as described above.

In the tablet of the present embodiment, the content of aripiprazole in one tablet is preferably less than 3 mg, more preferably 0.1 to 2.5 mg, still more preferably 0.5 to 1.5 mg, most Preferably it is 1 mg. When the content of aripiprazole is small in this way, the ratio of magnesium stearate to the content of aripiprazole in the tablet tends to be high, and the effect of the present invention of improving the decrease in dissolution in such a case is significant. can be demonstrated in

In addition to aripiprazole and magnesium stearate, the tablet of the present embodiment contains at least It may contain one component.

As excipients, common pharmaceutically acceptable excipients can be used, for example, crystalline cellulose, glucose, fructose, lactose (including lactose hydrate), sucrose (including refined sucrose) ), reduced maltose, dextran, sugar alcohols (e.g. D-mannitol, xylitol, sorbitol, erythritol, trehalose, maltitol, lactitol), glycerin fatty acid esters, inorganic powders (e.g. magnesium aluminometasilicate, synthetic hydrotal site), starch, partially pregelatinized starch, corn starch, and the like. Only one type of excipient may be used, or two or more types may be used.
The content of the excipient in the tablet (ratio to the total weight of the tablet) is not particularly limited as long as it does not impair the effects of the present invention, but is preferably 62 to 98% by mass, for example.

Common pharmaceutically acceptable binders can be used as binders, such as hydroxypropylcellulose (HPC), hydroxyethylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, partially saponified polyvinyl alcohol, methylcellulose, gelatin, Agar, alginic acid, sodium alginate, dextrin, xanthan gum, gum arabic powder, pullulan and the like. Only one kind of binder may be used, or two or more kinds thereof may be used.
The content of the binder in the tablet (ratio to the total weight of the tablet) is not particularly limited as long as it does not impair the effects of the present invention, but is preferably 0.01 to 10% by mass, for example.

As the disintegrant, general pharmaceutically acceptable disintegrants can be used, for example, crospovidone, sodium carboxystarch, sodium carboxymethylstarch, calcium citrate, light anhydrous silicic acid, synthetic aluminum silicate, Low-substituted hydroxypyropyrcellulose, croscarmellose, croscarmellose sodium, carboxymethylcellulose calcium, carmellose, hydroxypropyl starch and the like. Only one disintegrant may be used, or two or more disintegrants may be used.
The content of the disintegrant in the tablet (ratio to the total weight of the tablet) is not particularly limited as long as it does not impair the effects of the present invention.

As the lubricant, a general pharmaceutically acceptable lubricant can be used, and other than magnesium stearate, for example, calcium stearate, stearic acid, sucrose fatty acid ester, glycerol fatty acid ester, talc, etc. can be used. can be used. Lubricants other than magnesium stearate may be used alone or in combination of two or more.
The content of the lubricant (other than magnesium stearate) in the tablet (ratio to the total amount of the tablet) is not particularly limited as long as it does not impair the effects of the present invention, but is preferably 0.01 to 5% by mass, for example.

The aripiprazole-containing tablet of the present embodiment may contain pharmaceutically or physiologically acceptable additives used in pharmaceuticals and the like other than the above, as long as they do not impair the effects of the present invention. Such additives include coloring agents (e.g., iron sesquioxide, yellow iron sesquioxide, food blue No. 2, etc.), antioxidants, surfactants, thickeners, preservatives, stabilizers, fragrances, Dissolution aids and the like are included.

The tablet is not particularly limited, and may be an uncoated tablet, a coated tablet, or an orally disintegrating tablet.

<Tablet manufacturing method>
The method for producing tablets of the present embodiment is a method for producing tablets containing aripiprazole and magnesium stearate.
The tablet produced by the production method of the present invention has a ratio of magnesium stearate to the content of aripiprazole in the tablet, which is 34 parts by mass or more, preferably 40 parts by mass or more, relative to 100 parts by mass of aripiprazole. , more preferably 50 parts by mass or more, and still more preferably 54 parts by mass or more, according to the production method of the present invention, stearic acid It is possible to improve the decrease in aripiprazole dissolution that occurs in tablets with a high proportion of magnesium.
The manufacturing method of this embodiment includes at least a mixing step and a tableting step.
In the mixing step, raw material powders containing aripiprazole-containing powder and magnesium stearate powder having an average particle size of 10 to 50 μm are mixed.
In the tableting step, the mixture obtained in the mixing step is tableted.

The average particle size of the magnesium stearate powder mixed in the mixing step is preferably 10-50 μm, more preferably 11-20 μm. As a result, even if a certain amount of magnesium stearate is contained, the decrease in dissolution of aripiprazole can be sufficiently suppressed. The average particle size of the magnesium stearate powder can be measured, for example, by laser light scattering/diffraction.

The amount of magnesium stearate in the raw material powder obtained in the mixing step is 90 parts by mass or less, preferably 70 parts by mass or less, more preferably 60 parts by mass or less per 100 parts by mass of aripiprazole. If the amount of magnesium stearate is too high, it becomes difficult to suppress the decrease in dissolution of aripiprazole.

FIG. 1 is a flow chart showing an example of an embodiment of a tablet manufacturing method. In the tablet manufacturing method shown in FIG. 1, first, aripiprazole, lactose hydrate and corn starch are put into a fluid bed granulator. In the fluid bed granulator, a liquid obtained by dissolving hydroxypropyl cellulose (HPC) in purified water and dispersing a coloring agent is sprayed to carry out granulation by a fluid bed granulation method.

Subsequently, the granules are dried in the fluidized bed granulator, and then sieved for sieving. The obtained granulated product is mixed with crystalline cellulose and magnesium stearate (average particle size: 10 to 50 μm) (mixing step), and the mixture is tableted (tabletting step) to give aripiprazole-containing tablets (uncoated tablets). can be obtained.

In the mixing step, for example, it is preferable to use a container rotating mixer such as a horizontal cylindrical mixer, a V-shaped mixer, or a double cone mixer. Mixing conditions may be, for example, a rotational speed of about 3 to 20 rpm and a mixing time of about 0.5 to 30 minutes. By adopting such a mixer and conditions, it is possible to prevent the magnesium stearate particles from being pulverized during mixing and reducing the average particle size.

This embodiment also relates to a tablet obtained by the manufacturing method described above. That is, the tablet contains aripiprazole and magnesium stearate, and the ratio of magnesium stearate to the content of aripiprazole in the tablet is 34 parts by weight or more and 90 parts by weight of magnesium stearate per 100 parts by weight of aripiprazole. parts or less and containing aripiprazole and magnesium stearate powder having an average particle size of 10 to 50 μm are mixed, and the mixed powder obtained by the mixing is tableted. It is a tablet that can be used.

According to the embodiments described above, in the tablet containing aripiprazole and magnesium stearate, even if the ratio of magnesium stearate to the content of aripiprazole in the tablet is a predetermined ratio or more, the dissolution of aripiprazole is reduced. can be suppressed.

Here, the predetermined ratio is 34 parts by mass or more of magnesium stearate with respect to 100 parts by mass of aripiprazole. When the content of the active ingredient (aripiprazole) in the tablet is small (e.g., less than 3 mg), it is often necessary to design the formulation at such a ratio, and in such cases, the dissolution rate of aripiprazole tends to decrease. There is The present invention solves the problem of suppressing this decrease in dissolution rate.

EXAMPLES The present invention will be described in more detail below with reference to Examples, but the present invention is not limited to these.

(Example 1)
In this example, aripiprazole-containing tablets were produced by the above-described tablet production method described with reference to FIG.

Specifically, first, 1 part by mass of aripiprazole, 71.45 parts by mass of lactose hydrate (200M/DFE Pharma) and 10 parts by mass of corn starch (manufactured by Matsutani Chemical Industry) were added to a fluid bed granulator (MP-01). It was put into a mold/manufactured by Powrex). In the fluidized bed granulator, 2 parts by mass of hydroxypropyl cellulose (HPC-L/manufactured by Nippon Soda) was dissolved in purified water to give a 5% by mass solution, and a coloring agent (iron sesquioxide/manufactured by Kishi Kasei) was added to the solution. A liquid in which 0.004 part by mass was dispersed was sprayed, and granulation was carried out by a fluidized bed granulation method at an air supply temperature of 85°C.

Subsequently, the granules were dried in a fluidized bed granulator at an inlet air temperature of 85° C. until the exhaust temperature reached 40° C., and then sieved through a stainless steel sieve with a mesh size of 24 to perform sizing. Next, using a V-type mixer, the total amount of the obtained granulated product, 10 parts by mass of crystalline cellulose (manufactured by Asahi Kasei) and magnesium stearate (average particle size (actual value): 14.24 μm), manufactured by Taihei Kagaku Sangyo "Special" grade) was mixed with 0.55 parts by mass at 6 rpm for 10 minutes, and then the mixture was tableted using a rotary tableting machine (Clean Press Collect 19K / manufactured by Kikusui Seisakusho) to obtain 1 tablet. An uncoated tablet having a total mass of 95 mg (excluding the colorant) and having the formulation shown in Table 1 and having a diameter of 6 mm and a thickness of 2.6 mm was obtained.

(Example 2, Comparative Examples 1 to 6)
In the same manner as in Example 1, except that the average particle size and amount of magnesium stearate and the amount of lactose hydrate and/or crystalline cellulose were changed so as to obtain the formulation shown in Table 1. , Example 2 and Comparative Examples 1-6 were produced.

As the magnesium stearate (StMg) powder, the following three types of magnesium stearate powder having different average particle diameters (measured values) were used.
・ Average particle size 14.24 μm (Taihei Kagaku Sangyo “Special”): Average particle size “large” or “large particle size”
・ Average particle size 9.06 μm (“general” manufactured by Taihei Kagaku Sangyo): average particle size “medium” or “medium particle size”
・ Average particle size 5.94 μm (“Light” manufactured by Taihei Chemical Industry): Average particle size “small” or “small particle size”

<Elution test 1>
Regarding the tablets obtained in Example 1 and Comparative Examples 1 to 3, and the reference product ("Aripiprazole Tablets 6 mg "Nipro"; 6 mg tablets manufactured by Nipro), the paddle method of the Japanese Pharmacopoeia general test method dissolution test method of aripiprazole An elution test was performed. The liquid volume of the test solution (water) was set to 900 mL, and the dissolution rate (%) was measured after a predetermined period of time up to 180 minutes by UV-visible spectrophotometry at a paddle rotation speed of 50 rpm. In addition, in order to compare the dissolution properties with the reference product, six tablets each obtained in Example 1 and Comparative Examples 1 to 3 were placed in 900 mL of water to conduct a dissolution test. Each test was performed three times. The results obtained (average of three times) are shown in FIG.

As shown in FIG. 2, in Comparative Example 1 containing 100 parts by mass of medium particle size magnesium stearate (StMg) per 100 parts by mass of aripiprazole, the dissolution rate was significantly lower than that of the reference product. In Comparative Example 2 in which the content of StMg of medium particle size was reduced to 50 parts by mass, the dissolution rate was higher than in Comparative Example 1, and in Comparative Example 3 containing no StMg, the dissolution rate was higher than that of the standard product. From this, it is considered that the dissolution of aripiprazole can be enhanced by reducing the amount of StMg blended. However, in Comparative Example 3, in which the lubricant StMg was not blended, there were many problems in tableting such as adhesion to punches in the tableting step, and the yield was poor, making it impossible to stably produce tablets. Similarly, when the content of StMg having a medium particle size is further reduced below 50 parts by mass, it may become impossible to stably produce tablets.

On the other hand, in Example 1, by using StMg with a large particle size, the StMg content relative to 100 parts by mass of aripiprazole was maintained at 55 parts by mass (StMg content in the tablet: 0.58% by mass). At the same time, the dissolution rate was able to be raised to a level close to that of the standard product.

FIG. 3 is a graph prepared by plotting the dissolution rate after 180 minutes in the results of dissolution test 1 (FIG. 2). FIG. 3 is a graph showing the relationship between the ratio of magnesium stearate to aripiprazole and dissolution properties for magnesium stearate having different average particle sizes. As can be seen from the graph in FIG. 3, when magnesium stearate with a large average particle size (large particle size) is used, it is possible to increase the dissolution rate of aripiprazole to the required range while maintaining a predetermined amount of magnesium stearate. It can be seen that

From FIG. 3 , if StMg with a large particle size is used, even if the ratio of StMg to aripiprazole is increased to about 37 parts by mass with respect to 100 parts by mass of aripiprazole, the same dissolution rate (about 28%) as the standard product can be obtained. It was found that tablets could be obtained.

<Elution test 2>
The tablets obtained in Examples 1 and 2 and Comparative Examples 1, 4 and 5 and the reference product were subjected to the same dissolution test 1.

Table 2 and FIG. 4 show the results obtained in dissolution test 2 for Example 1, Comparative Examples 4 and 5, and the reference product.

As shown in Table 2 and FIG. 4, when the content of magnesium stearate is 55 parts by mass with respect to 100 parts by mass of aripiprazole, when large particle size magnesium stearate is used (Example 1), Judging that dissolution is biologically equivalent to the reference product, when medium- and small-particle magnesium stearate is used (Comparative Examples 4 and 5), dissolution is biologically equivalent to that of the reference product was determined not to show

Bioequivalence by dissolution test is based on the “Guidelines for Bioequivalence Tests of Solid Oral Drugs with Different Contents” (Notification No. 0229-10 of the Evaluation and Licensing Division, PFSB dated February 29, 2012). It was judged whether the dissolution behavior was considered to be the same when the product was used as the standard formulation. Specifically, when the value of F2 (f2 function shown in the guideline) was 61 or more, it was judged to be equivalent.

Table 3 and FIG. 5 show the results of dissolution test 2 for Examples 1 and 2, Comparative Example 6, and the reference product.

As shown in Table 3 and FIG. 5, when large particle size magnesium stearate was used, for Examples 1 and 2 containing 55 parts by weight and 70 parts by weight of aripiprazole with respect to 100 parts by weight of aripiprazole, It was judged to exhibit bioequivalent dissolution properties to the reference product. Comparative Example 6, in which the content of magnesium stearate was 100 parts by mass with respect to 100 parts by mass of aripiprazole, was judged not to be biologically equivalent to the reference product. The bioequivalence criteria are the same as in Table 2.

It should be considered that the embodiments and examples disclosed this time are illustrative in all respects and not restrictive. The scope of the present invention is indicated by the scope of the claims rather than the above description, and is intended to include all modifications within the meaning and range of equivalents of the scope of the claims.

Claims (5)

A tablet comprising aripiprazole and magnesium stearate,
The content of aripiprazole in the tablet is less than 3 mg,
The content of magnesium stearate in the tablet is 90 parts by mass or less per 100 parts by mass of aripiprazole,
A tablet, wherein the magnesium stearate has an average particle size of 10 to 50 μm. A tablet comprising aripiprazole and magnesium stearate,
The content of magnesium stearate in the tablet is 34 parts by mass or more and 90 parts by mass or less with respect to 100 parts by mass of aripiprazole,
The magnesium stearate has an average particle size of 10 to 50 μm,
Tablets having a dissolution rate of aripiprazole of 20% or more after 180 minutes in 900 mL of water at a paddle rotation speed of 50 rpm in a dissolution test by the paddle method of the dissolution test method of the Japanese Pharmacopoeia General Tests. 3. The tablet according to claim 2 , wherein the aripiprazole content per tablet is less than 3 mg. A method of manufacturing a tablet comprising aripiprazole and magnesium stearate, comprising:
The content of magnesium stearate in the tablet is 34 parts by mass or more and 90 parts by mass or less with respect to 100 parts by mass of aripiprazole,
A mixing step of mixing raw material powders containing aripiprazole-containing powder and magnesium stearate powder having an average particle size of 10 to 50 μm;
and a tableting step of tableting the mixture obtained in the mixing step. 5. The method for producing tablets according to claim 4 , wherein the content of said aripiprazole in one tablet is less than 3 mg.

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