Prasugrel-containing pharmaceutical composition

Abstract

To provide a pharmaceutical composition that contains prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor, and exhibits superior elution properties.SOLUTION: A pharmaceutical composition contains prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor with a cumulative 90% particle diameter in the particle size distribution of 5 μm or more and 50 μm or less.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a pharmaceutical composition which contains prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor and which exhibits good dissolution properties. [Background technology]

[0002] Prasugrel has the chemical name 2-acetoxy-5-(α-cyclopropylcarbonyl-2-fluorobenzyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine, and tablets containing prasugrel hydrochloride as the active ingredient are known to be an antiplatelet agent and are sold as Efient tablets and Efient OD tablets (Non-Patent Document 1).

[0003] Patent Document 1 describes an invention relating to a solid preparation with excellent content uniformity, which contains prasugrel or a pharmacologically acceptable salt thereof, and mannitol or lactose having a cumulative 90% particle size of a particle size distribution of 80 μm to 300 μm.

[0004] Patent Document 2 describes an invention relating to a method for producing a solid preparation with excellent dissolution properties, which includes a step of mixing a composition containing prasugrel or a pharmacologically acceptable salt thereof by applying mechanical stress using a fixed-container mixer equipped with an agitating blade. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Patent No. 5289975 [Patent Document 2] Patent No. 5433235 [Non-patent literature]

[0006] [Non-Patent Document 1] Package insert "Efient Tablets 2.5mg / 3.75mg / 5mg, Efient OD Tablets 20mg", revised December 2021 (3rd edition) Summary of the Invention [Problem to be solved by the invention]

[0007] An object of the present invention is to provide a pharmaceutical composition which contains prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor and which exhibits good dissolution properties. [Means for solving the problem]

[0008] The inventors of the present invention have found that a pharmaceutical composition comprising prasugrel or a pharmacologically acceptable salt thereof, which has good dissolution properties, can be provided by including a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 5 μm or more and 50 μm or less, and have completed the present invention.

[0009] That is, the present invention provides (1) A pharmaceutical composition comprising prasugrel or a pharmacologically acceptable salt thereof, and a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 5 μm to 50 μm, (2) The pharmaceutical composition according to (1) above, wherein the drug aggregation inhibitor comprises one or more selected from the group consisting of lactose hydrate, D-mannitol, corn starch, partially pregelatinized starch, pregelatinized starch, light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, synthetic aluminum silicate, and magnesium aluminometasilicate. (3) The pharmaceutical composition according to (1) above, comprising a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 20 μm or more and 40 μm or less. (4) The pharmaceutical composition according to any one of (1) to (3), wherein the drug aggregation inhibitor is lactose hydrate. (5) The pharmaceutical composition according to any one of (1) to (3), wherein the drug aggregation inhibitor is D-mannitol. (6) The pharmaceutical composition according to any one of (1) to (3), which is in the form of a powder, fine granules, granules, capsules, or tablets. (7) The pharmaceutical composition according to any one of (1) to (3), which is a tablet. (8) The pharmaceutical composition according to (7), wherein the tablet is a film-coated tablet. (9) The pharmaceutical composition according to (7), wherein the tablet is an orally disintegrating tablet. (10) The pharmaceutical composition according to (9), wherein the orally disintegrating tablet is a film-coated tablet. (11) A method for producing a pharmaceutical composition, comprising a step of mixing prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 5 μm to 50 μm in a stirring mixer. This is regarding. Effect of the Invention

[0010] According to the present invention, it is possible to provide a pharmaceutical composition which contains prasugrel or a pharmacologically acceptable salt thereof and a drug aggregation inhibitor and which exhibits good dissolution properties. [Brief description of the drawings]

[0011] [Figure 1] 1 shows the measurement results of the dissolution tests of Example 1 and Comparative Example 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0012] In the present specification, "good dissolution" means that the dissolution rate is equal to or higher than that of a commercially available preparation. The dissolution rate of prasugrel from the pharmaceutical composition of the present specification can be evaluated, for example, by the dissolution test method described in the Japanese Pharmacopoeia. Specifically, for example, when a dissolution test is performed using the paddle method at 50 revolutions per minute, the dissolution rate of prasugrel in 900 mL of diluted McIlvaine buffer solution at pH 4.0 is 75% or more, 78% or more, or 80% or more in one embodiment at 15 minutes after the start of the dissolution test, and 85% or more, 88% or more, or 90% or more in one embodiment at 30 minutes after the start of the dissolution test.

[0013] In this specification, the "cumulative 90% particle size" refers to a volume-based particle size measured by a laser diffraction particle size distribution measurement method or the like, and can be expressed as d90. In principle, it means the particle size at the time when particles of a certain volume are sieved in ascending order of size and the particles that make up 90% of the volume are separated.

[0014] In this specification, the term "cumulative 50% particle size" refers to a volume-based particle size measured by a laser diffraction particle size distribution measurement method or the like, and can be expressed as d50. In principle, it means the particle size at the time when particles of a certain volume are sieved in ascending order of size and the particles that make up 50% of the volume are separated.

[0015] In this specification, the term "cumulative 10% particle size" refers to a volume-based particle size measured by a laser diffraction particle size distribution measurement method or the like, and can be expressed as d10. In principle, it means the particle size at the time when particles of a certain volume are sieved in ascending order of size and the particles corresponding to 10% of the volume are separated.

[0016] The term "stirred mixture" as used herein refers to a mixture obtained by mixing using external forces such as impact force and shear force in addition to gravity and centrifugal force, as opposed to mixing of powder and granular materials based on gravity and centrifugal force using a V-type mixer or the like.

[0017] In this specification, the term "agitation mixer" refers to a production machine that can obtain an agitated mixture. Specific examples of the machine include a grinder, a granulator, and a high-speed agitation granulator.

[0018] In the present specification, the term "dry manufacturing method" refers to a granulation method that does not use water. Specific examples include melt granulation method, crushing granulation method, and direct compression method, and one embodiment is direct compression method.

[0019]

[0020] The term "direct compression method" as used herein refers to a method in which raw powder containing a drug and / or additives is directly compressed to form a formulation.

[0021] The term "melt granulation method" as used herein means a method of formulating a drug product using granules obtained by mixing a drug, a low melting point substance, and, if necessary, other additives, and melting the mixture at a high temperature.

[0022] The term "crushing granulation method" as used herein refers to a method in which a raw material powder containing a drug and / or additives is compressed into a sheet or slug shape by the roller method or slug method, and then crushed and divided by an appropriate method, specifically, for example, a granulator, to obtain granules, which are then used to prepare a formulation.

[0023] The method for producing the prasugrel-containing pharmaceutical composition of the present invention is described below.

[0024] Prasugrel used in the present invention can be prepared according to the method described in Japanese Patent No. 2683479. Pharmacologically acceptable salts of prasugrel are prepared according to Japanese Patent No. 4001199.

[0025] The indications are "ischemic heart disease for which percutaneous coronary intervention (PCI) is used" and "inhibition of recurrence after ischemic cerebrovascular disease (associated with large vessel atherosclerosis or occlusion of small vessels)." The dosage and administration is as follows: for ischemic heart disease for which percutaneous coronary intervention (PCI) is used, "adults are usually given 20 mg of prasugrel orally once daily on the starting day of administration, followed by a maintenance dose of 3.75 mg orally once daily." For inhibition of recurrence after ischemic cerebrovascular disease (associated with large vessel atherosclerosis or occlusion of small vessels), "adults are usually given 3.75 mg of prasugrel orally once daily."

[0026] The amount of prasugrel is not particularly limited as long as it is the amount of prasugrel in the preparation constituting the dosage of the pharmaceutical preparation. For example, it is 0.1 to 30% by weight in one embodiment, 0.5 to 20% by weight in one embodiment, and 1 to 10% by weight in one embodiment, based on the total weight of one tablet. Also, for example, it is 1 to 20% by weight in one embodiment, and 1.5 to 10% by weight in one embodiment, based on the uncoated tablet portion of one tablet.

[0027] From the viewpoint of manufacturability, the d90 of the prasugrel used in the present invention is in one embodiment 1 μm or more and 200 μm or less, in one embodiment 5 μm or more and 150 μm or less, and in one embodiment 10 μm or more and 100 μm or less.

[0028] From the viewpoint of manufacturability, the d50 of the prasugrel used in the present invention is in one embodiment 0.5 μm or more and 150 μm or less, in one embodiment 1 μm or more and 100 μm or less, and in one embodiment 2 μm or more and 50 μm or less.

[0029] From the viewpoint of manufacturability, d10 of the prasugrel used in the present invention is in one embodiment 0.1 μm or more and 100 μm or less, in one embodiment 0.2 μm or more and 50 μm or less, and in one embodiment 0.3 μm or more and 25 μm or less.

[0030] The drug aggregation inhibitor used in the present invention is not particularly limited as long as it is pharma- ceutical acceptable and improves the dissolution of prasugrel when mixed with a pharmaceutical composition containing prasugrel or a pharmacologically acceptable salt thereof by a stirring mixer.Specific examples of the drug aggregation inhibitor include lactose hydrate, anhydrous lactose, D-mannitol, crystalline cellulose, starch, corn starch, partially pregelatinized starch, pregelatinized starch, potato starch, rice starch, wheat starch, dextrin, trehalose, isomaltulose hydrate, anhydrous calcium hydrogen phosphate, D-sorbitol, white sugar, low-substituted hydroxypropylcellulose, carmellose sodium, gum arabic, pullulan, light anhydrous silicic acid, hydrated silicon dioxide, calcium silicate, synthetic aluminum silicate, magnesium aluminometasilicate, etc. Examples of the drug anti-aggregation agent include lactose hydrate, D-mannitol, corn starch, partially pregelatinized starch, pregelatinized starch, light anhydrous silicic acid, hydrated silicon dioxide, calcium silicate, synthetic aluminum silicate, and magnesium aluminometasilicate. The drug anti-aggregation agent can be formulated in one or more combinations. The drug anti-aggregation agent used in the present invention also functions as a pharmaceutical additive such as an excipient, binder, disintegrant, lubricant, and coating agent. Although the function of the drug anti-aggregation agent has not been specifically elucidated, the inventors of the present invention believe that when the drug anti-aggregation agent and a pharmaceutical composition containing prasugrel or a pharmacologically acceptable salt thereof are mixed with a stirring mixer, the drug anti-aggregation agent breaks down the aggregation of prasugrel or a pharmacologically acceptable salt thereof, and the surface area is increased, improving the solubility of prasugrel or a pharmacologically acceptable salt thereof, thereby achieving the dissolution of prasugrel from the pharmaceutical composition of the present invention.

[0031] Specific examples of lactose hydrates include Lactohale (registered trademark) 210, 220, 230, 300, Lactochem (registered trademark) Microfine (manufactured by DFE Pharma), InhaLac (registered trademark) 400, 500, and SorboLac (registered trademark) 400 (manufactured by Maigret).

[0032] A specific example of D-mannitol is Mannitol C (manufactured by Mitsubishi Corporation Life Sciences).

[0033] Specific examples of corn starch include Pharmacopoeia Corn Starch White (manufactured by Nippon Corn Starch Co., Ltd.) and Nisshoku Pharmacopoeia Corn Starch (manufactured by Nippon Shokuhin Kako Co., Ltd.).

[0034] Specific examples of light anhydrous silicic acid include AEROSIL (registered trademark) 200 (manufactured by EVONIK) and Adsolider (registered trademark)-101 (manufactured by Freund Corporation).

[0035] The cumulative 90% particle size of the drug aggregation inhibitor is, in one embodiment, 5 μm or more and 50 μm or less, in one embodiment, 10 μm or more and 45 μm or less, and in one embodiment, 20 μm or more and 40 μm or less.

[0036] The amount of the drug aggregation inhibitor is not particularly limited as long as it is an amount that can achieve good dissolution of prasugrel from the pharmaceutical preparation. Specifically, for example, the amount is 1.0 to 95.0% in one embodiment, 10.0 to 90.0% in one embodiment, and 30.0 to 85.0% in one embodiment based on the total amount of the pharmaceutical composition.

[0037] The cumulative 90% particle size, cumulative 50% particle size, cumulative 10% particle size and average particle size of the drug aggregation inhibitor used in the present invention can be measured, for example, by a laser diffraction particle size distribution measurement method.

[0038] The pharmaceutical composition of the present invention may contain pharmaceutical additives as necessary, such as excipients, binders, disintegrants, surfactants, lubricants, coating agents, acidulants, foaming agents, sweeteners, flavors, colorants, buffers, antioxidants, etc.

[0039] Examples of excipients include maltitol, xylitol, sucrose fatty acid esters, precipitated calcium carbonate, maltose hydrate, and calcium hydrogen phosphate.

[0040] Examples of binders include hydroxypropyl cellulose, hypromellose, polyvinylpyrrolidone, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, hydroxyethyl cellulose, glyceryl monostearate, macrogol 6000, and polyoxyl 40 stearate.

[0041] Examples of disintegrants include sodium starch glycolate, carmellose, carmellose calcium, hydroxypropyl starch, croscarmellose, croscarmellose sodium, and crospovidone.

[0042] Examples of the surfactant include polysorbate 80, sodium lauryl sulfate, polyoxyethylene hydrogenated castor oil, and the like.

[0043] Examples of lubricants include stearic acid, magnesium stearate, sodium stearate, calcium stearate, talc, sodium stearyl fumarate, hardened oil, and sucrose fatty acid esters.

[0044] Examples of coating agents include hypromellose, hydroxypropyl cellulose, methyl cellulose, polyvinyl alcohol, polyvinyl alcohol-polyethylene glycol graft copolymer, polyvinyl alcohol-acrylic acid-methyl methacrylate copolymer, polyethylene glycol, glycerin monostearate, titanium oxide, and talc.

[0045] Examples of acidulants include citric acid, tartaric acid, malic acid, etc.

[0046] The foaming agent may, for example, be sodium bicarbonate.

[0047] Examples of sweeteners include sucralose, sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, and thaumatin.

[0048] Examples of the flavoring include lemon, lemon-lime, orange, and menthol.

[0049] Examples of coloring agents include ferric oxide, yellow ferric oxide, black ferric oxide, titanium oxide, Food Yellow No. 4, Food Yellow No. 5, Food Red No. 3, Food Red No. 102, Food Blue No. 3, and the like.

[0050] Examples of buffering agents include citric acid, succinic acid, fumaric acid, tartaric acid, ascorbic acid or a salt thereof, glutamic acid, glutamine, glycine, aspartic acid, alanine, arginine or a salt thereof, magnesium oxide, zinc oxide, magnesium hydroxide, phosphoric acid, boric acid or a salt thereof, and the like.

[0051] Examples of the antioxidant include ascorbic acid, dibutylhydroxytoluene, and propyl gallate.

[0052] In the pharmaceutical composition of the present invention, various further pharmaceutical additives may be appropriately used within the range in which the desired effects of the present invention are achieved. The various additional pharmaceutical additives contained in the pharmaceutical composition of the present invention can be combined as appropriate.

[0053] The blending amount is not particularly limited as long as it does not affect the achievement of the desired effects of the present invention.

[0054] The pharmaceutical composition of the present invention includes tablets. The tablets include plain tablets and film-coated tablets. The tablets may be orally disintegrating tablets. The tablets of the present invention can be manufactured by a conventional tablet manufacturing method using a mixture obtained by a predetermined method. More specifically, for example, prasugrel hydrochloride, a drug aggregation inhibitor, and other additives as necessary are charged into a high-speed stirring granulator, and mixed at a blade rotation speed of the stirring impeller (e.g., 10 to 1500 rpm in one embodiment, 100 to 1000 rpm in one embodiment, and 300 to 900 rpm in one embodiment) and a cross screw rotation speed (e.g., 100 to 10000 rpm in one embodiment, 5000 to 7500 rpm in one embodiment, and 1000 to 5000 rpm in one embodiment) for a time period during which the drug aggregation inhibitor eliminates aggregation of prasugrel hydrochloride (e.g., 1 to 60 minutes in one embodiment, 3 to 30 minutes in one embodiment, and 5 to 20 minutes in one embodiment), and then an excipient, a binder, a disintegrant, and a lubricant are mixed with the resulting stirred mixture to obtain a powder for tableting.

[0055] In another embodiment, prasugrel hydrochloride, a drug aggregation inhibitor, a binder, and other additives as necessary are mixed and stirred in a sieving machine, then charged into a fluidized bed granulation dryer, heated while fluidizing to melt the binder, and fluidized for a period of time during which granulation proceeds after the temperature reaches the melting point of the binder or higher (e.g., 1 to 60 minutes in one embodiment, 2 to 20 minutes in one embodiment, and 5 minutes in one embodiment), and cooled until the exhaust temperature reaches a certain temperature (e.g., 45°C or less in one embodiment, 40°C or less in one embodiment, and 35°C or less in one embodiment) to obtain a granulated product. The granulated product is sized in a sieving machine, and a disintegrant, a lubricant, and other additives as necessary are added to the obtained sized product and mixed to obtain a powder for tableting.

[0056] In another embodiment, prasugrel hydrochloride, a drug aggregation inhibitor, a lubricant, and other additives as required are mixed and stirred in a granulator, and then roller-compressed to obtain a granulated product. The granulated product is sized in the granulator, and a disintegrant, a lubricant, and other additives as required are added to the sized product, and the mixture is mixed to obtain a powder for tableting.

[0057] The obtained tableting powder is compressed in a tablet press to obtain uncoated tablets. During tableting, a lubricant may be sprayed onto the tablets using an external lubricating device. If necessary, a film coating liquid is sprayed onto the uncoated tablets to perform film coating. The pharmaceutical composition of the present invention may be packaged using various pharmaceutical packaging materials. EXAMPLES

[0058] The present invention will be described in more detail below with reference to examples, but the present invention is not limited to the following examples in any way. EXAMPLES

[0059] 8.24 g of prasugrel hydrochloride, 137.76 g of lactose hydrate (manufactured by Megret: SorboLac400), and 40 g of crystalline cellulose (manufactured by Asahi Kasei: CEOLUS (registered trademark) UF-702) were mixed for 15 minutes in a high-speed stirring granulator (manufactured by Powrex: VG-01) to obtain a stirred mixture. 5 g of crospovidone (Kollidon (registered trademark) CL-F, manufactured by BASF Japan) and 2 g of magnesium stearate (magnesium stearate (vegetable) manufactured by Taihei Chemical Industry Co., Ltd.) were added to 93 g of the obtained stirred mixture to prepare a tableting powder, which was then compressed into circular plain tablets having a tablet mass of 100 mg and a diameter of 6.5 mm. EXAMPLES

[0060] The plain tablets produced in Example 1 were film-coated with ingredients consisting of hypromellose (Shin-Etsu Chemical Co., Ltd.: TC-5 (registered trademark) R), titanium oxide (Toho Titanium Co., Ltd.: NA-61), talc (Matsumura Sangyo Co., Ltd.: Crown Talc (registered trademark) official PP) and ferric oxide (Kishi Chemical Co., Ltd.: ferric oxide) using a film coating machine (Powrex Co., Ltd.: DRC-300), and then polished with carnauba wax (Freund Sangyo Co., Ltd.: Polishing Wax-105) to obtain film-coated tablets weighing 110 mg each.

[0061] Comparative Example 1 8.24 g of prasugrel hydrochloride, 137.76 g of lactose hydrate (GranuLac230, manufactured by Megre), and 40 g of crystalline cellulose (CEOLUS (registered trademark) UF-702, manufactured by Asahi Kasei) were mixed for 15 minutes in a high-speed stirring granulator (VG-01, manufactured by Powrex) to obtain a stirred mixture. 5 g of crospovidone (Kollidon (registered trademark) CL-F, manufactured by BASF Japan) and 2 g of magnesium stearate (magnesium stearate (vegetable) manufactured by Taihei Chemical Industry Co., Ltd.) were added to 93 g of the obtained stirred mixture to prepare a tableting powder, which was then compressed into circular plain tablets having a tablet mass of 100 mg and a diameter of 6.5 mm.

[0062] Comparative Example 2 The plain tablets produced in Comparative Example 1 were film-coated with ingredients consisting of hypromellose (Shin-Etsu Chemical Co., Ltd.: TC-5 (registered trademark) R), titanium oxide (Toho Titanium Co., Ltd.: NA-61), talc (Matsumura Sangyo Co., Ltd.: Crown Talc (registered trademark) official PP) and ferric oxide (Kishi Chemical Co., Ltd.: ferric oxide) using a film coating machine (Powrex Co., Ltd.: DRC-300), and then polished with carnauba wax (Freund Sangyo Co., Ltd.: Polishing Wax-105) to obtain film-coated tablets weighing 110 mg each.

[0063] [Table 1]

[0064] <Test Example 1: Laser diffraction particle size distribution measurement> The particle size of the lactose hydrate used in the production of the Examples and Comparative Examples was measured under the following conditions using a laser diffraction particle size distribution analyzer Mastersizer 3000 (Spectris Malvern). Three lots of lactose hydrate (Maigret: SorboLac 400) were measured. The results are shown in Table 2. (Measurement conditions) Laser diffraction particle size distribution analyzer: Mastersizer 3000 (Spectris Malvern) Disperser: Aero S, dry dispersion unit Tray: Micro Tray Dispersion pressure: 3.5bar Feed rate: 7

[0065] [Table 2]

[0066] <Test Example 1: Dissolution test> The tablets of Example 1 and Comparative Example 1 were subjected to a dissolution test according to the Japanese Pharmacopoeia Dissolution Test Method, 18th Edition. The tablets were dissolved in 900 mL of diluted McIlvaine buffer solution at pH 4.0 using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd.) by the paddle method. The paddle rotation speed was 50 rpm. 20 mL of the dissolution solution was withdrawn over time from the start of the test until 60 minutes later, and immediately 20 mL of the test solution heated to 37±0.5°C was accurately replenished. The dissolution solution was filtered through a membrane filter with a pore size of 0.45 μm or less, and the dissolution rate of the filtrate was calculated by liquid chromatography. The ultraviolet absorbance of prasugrel was measured at 210 nm. The results are shown in Table 3 and FIG.

[0067] [Table 3]

Claims

1. A pharmaceutical composition comprising prasugrel or a pharmacologically acceptable salt thereof, and a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 5 μm or more and 50 μm or less.

2. 2. The pharmaceutical composition according to claim 1, wherein the drug aggregation inhibitor comprises one or more selected from the group consisting of lactose hydrate, D-mannitol, corn starch, partially pregelatinized starch, pregelatinized starch, light anhydrous silicic acid, hydrous silicon dioxide, calcium silicate, synthetic aluminum silicate, and magnesium aluminometasilicate.

3. 2. The pharmaceutical composition according to claim 1, comprising a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 20 μm or more and 40 μm or less.

4. The pharmaceutical composition according to any one of claims 1 to 3, wherein the drug aggregation inhibitor is lactose hydrate.

5. The pharmaceutical composition according to any one of claims 1 to 3, wherein the drug aggregation inhibitor is D-mannitol.

6. The pharmaceutical composition according to any one of claims 1 to 3, which is in the form of a powder, fine granules, granules, capsules, or tablets.

7. The pharmaceutical composition according to any one of claims 1 to 3, which is in the form of a tablet.

8. The pharmaceutical composition according to claim 7, wherein the tablet is a film-coated tablet.

9. The pharmaceutical composition according to claim 7, wherein the tablet is an orally disintegrating tablet.

10. The pharmaceutical composition according to claim 9, wherein the orally disintegrating tablet is a film-coated tablet.

11. A method for producing a pharmaceutical composition, comprising a step of mixing prasugrel or a pharmacologically acceptable salt thereof, and a drug aggregation inhibitor having a cumulative 90% particle size of particle size distribution of 5 μm to 50 μm inclusive, using a stirring mixer.

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