JP2022102543A - Tablet containing oseltamivir and method for producing the same - Google Patents

Abstract

To provide a tablet containing oseltamivir as an active ingredient, in which the occurrence of binding is inhibited.SOLUTION: A tablet contains sodium stearyl fumarate as a lubricant and also contains, as an active ingredient, oseltamivir or a pharmaceutically acceptable salt thereof or a solvate thereof. The content of the active ingredient is 60 mass% or more and 90 mass% or less relative to the total mass of the tablet.SELECTED DRAWING: Figure 1B

Description

The present invention relates to a tablet containing oseltamivir, a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient, and a method for producing the same. The present invention relates to a method of suppressing the occurrence of binding in compression molding.

Oseltamivir is a compound represented by the following formula (I), and its chemical name is (-)-(3R, 4R, 5S) -4-acetamide-5-amino-3- (1-ethylpropoxy) cyclohexe. -1-En-1-carboxylic acid ethyl ester. Oseltamivir suppresses the growth of the virus by selectively inhibiting neuraminidase of human influenza A and B viruses and inhibiting the release of the newly formed virus from infected cells. Although the oseltamivir preparation currently on the market is a capsule and the oseltamivir tablet is not commercially available, there are some documents describing oseltamivir-containing tablets. For example, in Patent Document 1, pellets containing oseltamivir and starch are mixed with an additive for tablets containing magnesium stearate, and the obtained mixed powder is compression-molded to obtain an orally disintegrating tablet containing oseltamivir. It is stated that it was manufactured.

US Patent Application Publication No. 2016/0120802

The orally disintegrating tablet described in Patent Document 1 has an oseltamivir content of about 10% by mass per tablet, and has a low oseltamivir content. Therefore, the present inventors attempted to produce a tablet in which the content of oseltamivir per tablet was increased by using a general tablet additive, but the binding, which is a kind of tableting disorder during compression molding, was attempted. The outbreak was confirmed. An object of the present invention is to provide an oseltamivir-containing tablet having a composition in which the occurrence of binding is suppressed.

The present inventors have found that the generation of binding during compression molding can be suppressed by producing tablets using stearyl sodium fumarate as a lubricant, and have completed the present invention. Therefore, the present invention contains stearyl sodium fumarate as a lubricant and oseltamivir or a pharmaceutically acceptable salt thereof or a solvate thereof as an active ingredient, and the content of the active ingredient is the total weight of the tablet. Provided are tablets having an amount of 60% by mass or more and 90% by mass or less.

The present invention is a method for producing a tablet containing ocertamivir or a pharmaceutically acceptable salt thereof or a solvent thereof as an active ingredient in an amount of 60% by mass or more and 90% by mass or less of the total mass of the tablet, and contains the active ingredient. A step of obtaining a granulated product, a step of mixing the granulated product with stearyl sodium fumarate as a lubricant to obtain a tableting mixture, and a step of compress-molding the tableting mixture to obtain a tablet. To provide a method for producing a tablet, including.

INDUSTRIAL APPLICABILITY The present invention comprises fumaric acid as a lubricant in the production of tablets containing oseltamivir as an active ingredient, a pharmaceutically acceptable salt thereof, or a solvate thereof in an amount of 60% by mass or more and 90% by mass or less based on the total mass of the tablets. By using stearyl sodium, a method for suppressing the occurrence of binding in compression molding is provided.

According to the present invention, there is provided a tablet containing oseltamivir or a pharmaceutically acceptable salt thereof as an active ingredient or a solvate thereof, in which the occurrence of binding is suppressed, and a method for producing the same.

It is a photograph showing the side surface of a tablet using stearyl fumarate as a lubricant. It is a photograph showing the side surface of a tablet using stearyl fumarate as a lubricant. It is a photograph showing the side surface of a tablet using magnesium stearate (general) as a lubricant. It is a photograph showing the side surface of a tablet using magnesium stearate (general) as a lubricant. It is a photograph showing the side surface of a tablet using magnesium stearate (light) as a lubricant. It is a photograph showing the side surface of a tablet using magnesium stearate (light) as a lubricant. It is a photograph showing the side surface of a tablet using calcium stearate as a lubricant. It is a photograph showing the side surface of a tablet using calcium stearate as a lubricant.

The tablet of the present embodiment contains oseltamivir or a pharmaceutically acceptable salt thereof or a solvate thereof as an active ingredient. Oseltamivir or a pharmaceutically acceptable salt thereof is a salt formed from a compound represented by the above formula (I) and an organic or inorganic acid, which is acceptable for administration to mammals including humans. Say. Examples of such pharmaceutically acceptable salts include phosphates, hydrochlorides, sulfates, acetates and the like. Among them, oseltamivir phosphate is preferable.

The pharmaceutically acceptable solvate of oseltamivir is a compound represented by the above formula (I) or a pharmaceutically acceptable salt thereof, and a solvent that can be administered to mammals including humans. A solid molecule formed from. Examples of such a solvent include water, acetic acid, ethanol and the like.

Hereinafter, the term "oseltamivir" includes compounds represented by the above formula (I), pharmaceutically acceptable salts thereof and solvates thereof, unless otherwise specified. The shape of oseltamivir is not particularly limited, and may be any shape such as powder or crystal.
The particle size of oseltamivir is not particularly limited, but for example, the particle size (D ₅₀ ) of the oseltamivir powder is preferably 5 μm or more and 120 μm or less, and more preferably 15 μm or more and 110 μm or less. In the present specification, this D ₅₀ is based on a volume-based particle size distribution measured using a laser diffraction / scattering type particle size distribution measuring device. Examples of the laser diffraction / scattering type particle size distribution measuring device include "Aerotrack LDSA-SPR" manufactured by Microtrac Bell Co., Ltd. and "Mastersizer 3000" manufactured by Malvern Panalytical Co., Ltd.

In the present embodiment, the content of oseltamivir in the tablet is 60% by mass or more and 90% by mass or less of the total mass of the tablet. The lower limit of the content of oseltamivir in tablets is, for example, 60% by mass, 65% by mass, and 70% by mass. The upper limit of the content of oseltamivir in the tablet is, for example, 90% by mass, 85% by mass, and 80% by mass.

The tablets of this embodiment contain stearyl fumarate as a lubricant. In the present embodiment, by producing a tablet using stearyl fumarate as a lubricant, it is possible to suppress the occurrence of binding during tablet production. Binding refers to a phenomenon in which the side surface of a tablet is scratched when the tablet is beaten.

The particle size of stearyl sodium fumarate to be used is not particularly limited, but for example, the particle size (D ₅₀ ) of the powder of sodium stearyl fumarate is preferably 0.3 μm or more and 10 μm or less, and 0.5 μm or more and 7 μm or less. Is more preferable, and 1 μm or more and 4 μm or less is more preferable.
The content of stearyl fumarate in the tablet is preferably 0.9% by mass or more and 2.0% by mass or less of the total mass of the tablet. The upper limit of the content of stearyl fumarate in the tablet is, for example, 2.0% by mass, 1.9% by mass, 1.8% by mass, 1.7% by mass, and 1.6% by mass. The lower limit of the content of stearyl fumarate in the tablet is, for example, 0.9% by mass, 1.0% by mass, 1.1% by mass, 1.2% by mass, and 1.3% by mass.

In the tablet of the present embodiment, the mass ratio of stearyl fumarate to oseltamivir is, for example, 0.010 or more and 0.030 or less. The lower limit of the mass ratio of stearyl fumarate to oseltamivir in tablets is, for example, 0.010, 0.011, 0.012, 0.013, 0.014, 0.015. The upper limit of the mass ratio of stearyl fumarate to oseltamivir in tablets is, for example, 0.030, 0.029, 0.028, 0.027, 0.026, 0.025, 0.024, 0.023, 0.022, 0.021, 0.020.

In a preferred embodiment, the tablets are substantially free of lubricants other than stearyl fumarate. Here, "substantially free" means that the tablet contains a small amount of a lubricant other than stearyl fumarate, even if it is contained, and the lubricant other than stearyl fumarate is not positively added. To say. Examples of the case where a lubricant other than stearyl fumarate is contained in a small amount include a case where a small amount is mixed as an impurity, a case where a small amount is produced by some chemical reaction or decomposition of a contained component, and the like.

In another embodiment, the tablets may further comprise a pharmaceutically acceptable lubricant other than stearyl fumarate, if desired. Examples of such lubricants include talc, light anhydrous silicic acid, magnesium stearate, calcium stearate and the like. The lubricant other than stearyl fumarate may be used alone or in combination of two or more. In this embodiment, the content of sodium stearyl fumarate in the tablet and the mass ratio of sodium fumarate to oseltamivir are as described above. The upper limit of the content of all lubricants containing stearyl fumarate is preferably 2.0% by mass or less, for example. Further, the upper limit of the mass ratio of all lubricants containing stearyl fumarate to oseltamivir in tablets is preferably 0.030 or less, for example.

In this embodiment, the tablet may further contain a tablet additive. The tablet additive refers to a pharmaceutically acceptable additive used in the manufacture of tablets among pharmaceutical additives. Such additives for tablets can be appropriately selected from pharmaceutically acceptable excipients, disintegrants, binders, sweeteners, colorants and the like.

Pharmaceutically acceptable excipients include, for example, starches, celluloses, sugars, sugar alcohols and the like. Examples of starches include partially pregelatinized starch and corn starch. Examples of celluloses include crystalline cellulose, carmellose, carmellose calcium, carmellose sodium, croscarmellose sodium, and low-degree-of-substitution hydroxypropyl cellulose. Examples of sugars include lactose (also referred to as lactose hydrate) and sucrose. Examples of sugar alcohols include D-sorbitol and D-mannitol. The excipient may be one kind or a combination of two or more kinds.

Pharmaceutically acceptable binders include, for example, hydroxypropyl cellulose, hypromellose, ethyl cellulose, polyvinylpyrrolidone and the like. Among them, it is preferable to use hydroxypropyl cellulose. The binder may be one kind or a combination of two or more kinds.
The viscosity of hydroxypropyl cellulose when hydroxypropyl cellulose is used as a binder is not particularly limited, but is preferably 2 mPa · s or more and 10 mPa · s or less. Here, the viscosity of hydroxypropyl cellulose in the present specification refers to a value obtained by measuring the viscosity of an aqueous solution of hydroxypropyl cellulose at 20 ° C. and 2% by mass based on the viscosity measuring method described in the Japanese Pharmacopoeia. As the hydroxypropyl cellulose, for example, those having a viscosity of 2 mPa · s or more and 2.9 mPa · s or less may be used, or those having a viscosity of 3 mPa · s or more and 5.9 mPa · s or less may be used. Those having 6 mPa · s or more and 10 mPa · s or less may be used.

Pharmaceutically acceptable sweeteners include, for example, acesulfame potassium, sucralose, aspartame, saccharin sodium and the like. The sweetener may be one kind or a combination of two or more kinds.

Examples of the pharmaceutically acceptable colorant include iron sesquioxide, yellow iron sesquioxide, and the like. The colorant may be one kind or a combination of two or more kinds.

Pharmaceutically acceptable disintegrants include crospovidone, carmellose calcium, croscarmellose sodium, low degree of substitution hydroxypropyl cellulose, corn starch and the like. The disintegrant may be one kind or a combination of two or more kinds.

The tablets may be further coated, if desired. As the coating, a known coating method can be used. For example, a pan coating method, a fluidized bed coating method, or the like can be used. By coating the tablets, the bitterness of oseltamivir can be suppressed. Examples of the coating agent include hypromellose, ethyl cellulose, talc, titanium oxide, silicic acid, hydroxypropyl cellulose, polyvinylpyrrolidone, aminoalkyl methacrylate copolymer, polyvinyl alcohol, polyvinyl alcohol diethylaminoacetate, polyvinyl alcohol acetate phthalate, cellulose acetate phthalate and hypromellose. Examples thereof include phthalate, a copolymer of methacrylic acid, a copolymer of methyl methacrylate and butyl methacrylate, and a copolymer of dimethylaminoethyl methacrylate. The coating agent may be one kind or a combination of two or more kinds.
When hypromellose is used as the coating agent, the viscosity of hypromellose is not particularly limited, but is preferably 3 mPa · s or more and 10 mPa · s or less. Here, the viscosity of hypromellose in the present specification refers to a value obtained by measuring the viscosity of an aqueous solution of hypromellose at 20 ° C. and 2% by mass based on the viscosity measuring method described in the Japanese Pharmacopoeia. As the hypromellose, for example, one having a viscosity of 4.8 mPa · s or more and 7.2 mPa · s or less may be used.

The tablets may be packaged in PTP packaging, bottle filling, aluminum packaging, or the like, if necessary.
Examples of the material of the PTP packaging include resins such as polyvinyl chloride, polypropylene, polyvinylidene chloride, polychlorotrifluoroethylene, polyethylene, polystyrene or polycarbonate, and metals such as aluminum. These materials may be used alone or in combination of two or more. Examples of the combination include, for example, laminating polyvinyl chloride and polyvinylidene chloride, laminating polyvinyl chloride and polychlorotrifluoroethylene, and the like. It can be packaged by putting a tablet in a molded pocket of a resin sheet obtained by molding the above resin by a known method and covering it with aluminum foil.
The PTP package containing the tablets may be further packaged with an aluminum pillow. The aluminum pillow may further contain a desiccant. Examples of the desiccant include calcium chloride, calcium oxide, magnesium oxide, silica gel, zeolite and the like.

One embodiment of the present invention is a method for producing a tablet containing oseltamivir as an active ingredient in an amount of 60% by mass or more and 90% by mass or less of the total mass of the tablet. This manufacturing method will be described below.

First, oseltamivir and a tablet additive excluding lubricant are mixed to obtain a granulation mixture. Mixing of oseltamivir with a tablet additive other than a lubricant can be performed by a method known in the art. When the mixing is carried out by the method, for example, oseltamivir and the excipient may be put in an appropriate bag and stirred in a bag. When mixing is performed by a machine, a mixer known in the art may be used. The mixer may be either a rotary mixer or a fixed mixer. The rotary mixer is a machine that mixes powder contained in the container by rotating the container itself. The fixed type mixer is a machine that mixes powder contained in the container by rotating a stirring blade, a screw, or the like provided in the container. Examples of the mixer include a V-type mixer, a double conical type mixer, a ribbon type mixer, a conical screw type mixer, and the like. Alternatively, it may be introduced into a device such as a stirring granulator that can also perform the granulation step described later and mixed. The amount of oseltamivir and tablet additives to be mixed can be appropriately set according to the mixer used.

The additive for tablets can be appropriately selected from the above-mentioned ones. Among the additives for tablets, it is preferable to use an excipient and / or a binder, and it is preferable to use D-mannitol as an excipient and hydroxypropyl cellulose as a binder.
The oseltamivir and / or the additive for tablets may be subjected to an impact crusher or the like and pulverized in advance before mixing. The impact type crusher is not particularly limited, and an apparatus known in the art can be used. Examples of such a device include a pin mill and a hammer mill.

Next, the mixture for granulation is placed in a granulator and granulated to obtain a granulated product containing oseltamivir as an active ingredient. The granulator is not particularly limited as long as it does not affect the physical properties of oseltamivir. As the granulator, for example, a stirring granulator, a fluidized bed granulator, a dry granulator, or the like can be used. Further, the device may have a drying function. The granulating mixture or granulated product may be classified by subjecting it to a sieve having a specific mesh. By passing through a sieve, the particle size of the granulation mixture or the granulated product can be adjusted to an appropriate size.
The water content of the obtained granulated product is not particularly limited, but is preferably 3% by mass or less, more preferably 2.5% by mass or less, still more preferably 2% by mass or less, and 1.5% by mass. It is more preferably less than or equal to, and more preferably 1.0% by mass or less. The water content in the present specification is a value measured based on the dry weight loss test method. The water content in the present invention is a value measured based on the dry weight loss test method.

The obtained granulated product is mixed with stearyl fumarate as a lubricant to obtain a tableting mixture. The above-mentioned mixer can be used for mixing the granulated product with stearyl fumarate. The amount of the granulated product to be mixed and the amount of stearyl fumarate can be appropriately set depending on the mixer to be used.

Tablets (uncoated tablets) can be obtained by compression-molding the obtained mixture for tableting with a tableting machine. "Uncoated tablet" refers to a tablet that has not been coated. A known tableting machine can be used for compression molding. As a known locking machine, for example, a rotary type locking machine can be used.

The resulting tablets may be further coated, if desired. As a coating method, a known coating method can be used. For example, a pan coating method, a fluidized bed coating method, or the like can be used. The coating agent to be used can be appropriately selected from the above. The coating agent can be appropriately prepared and used as a film coating liquid. As the film coating liquid, for example, hypmerose, hydroxypropyl cellulose, talc and titanium oxide can be dispersed in purified water to obtain a film coating liquid.

The mass of the tablet produced is not particularly limited, but a mass in which the tablet can contain at least 75 mg as the compound represented by the formula (I) is preferable. The mass of the tablet is, for example, 50 mg or more and 500 mg or less, preferably 100 mg or more and 400 mg or less, more preferably 100 mg or more and 300 mg or less, and 100 mg or more and 200 mg or less per tablet. More preferred.

By producing a tablet using stearyl fumarate as a lubricant, a tablet having excellent hardness can be obtained. The higher the hardness of the tablet, the more preferable it is because it can prevent chipping during manufacturing. The hardness of the tablet is preferably 75 N or more, more preferably 80 N or more, more preferably 85 N or more, and even more preferably 90 N or more.

The tableting pressure at the time of producing a tablet is not particularly limited and may be appropriately set according to the composition and weight of the tablet. The locking pressure can be set to be, for example, 3 kN or more and 12 kN or less, and is preferably 4 kN or more and 10 kN or less.

The water content of the obtained tablet is not particularly limited and varies depending on the control conditions of the tablet, but it is preferably 3% by mass or less, more preferably 2.5% by mass or less, and 2% by mass or less. It is more preferably 1.5% by mass or less, more preferably 1.0% by mass or less, and even more preferably 0.8% by mass or less.

One embodiment of the present invention is a method of suppressing the occurrence of binding in compression molding. By using stearyl sodium fumarate as a lubricant and producing a tablet containing oseltamivir as an active ingredient in an amount of 60% by mass or more and 90% by mass or less of the total mass of the tablet, it is possible to suppress the occurrence of binding in compression molding. can. The details of tablet production in this method are the same as those described for the tablet production method of the present embodiment described above.

Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but the present invention is not limited thereto.

(Examination of physical characteristics of tablets with lubricant)
Here, in the case of producing tablets using oseltamivir and stearyl sodium fumarate as a lubricant (Examples 1 and 2), tablets using magnesium stearate instead of sodium stearyl fumarate as a lubricant. (Comparative Examples 1 to 4) and when tablets were produced using calcium stearate instead of stearyl sodium fumarate as a lubricant (Comparative Examples 5 and 6), binding and physical properties of the produced tablets. Was examined.

-Preparation of granulated product containing oseltamivir as an active ingredient Oseltamivir phosphate was put into an impact crusher to crush oseltamivir phosphate. When the particle size (D ₅₀ ) of this oseltamivir phosphate pulverized product was measured by the Mastersizer 3000, D ₅₀ was 22 μm. The crushed oseltamivir phosphate and D-mannitol were put into a stirring granulator and mixed. After mixing, purified water was sprayed to granulate. The granulated powder was dried and sized to obtain a granulated product containing oseltamivir as an active ingredient. The water content of this granulated product was 0.06% by mass.

-Manufacturing of Tablets of Example 1 and Example 2 Table 1 below shows the formulations of the tablets of Example 1 and Example 2 (ingredient amount per tablet). This tablet was produced as follows.
The granulated product prepared in the above-mentioned preparation of the granulated product and stearyl sodium fumarate were mixed in a bag to obtain a tableting mixture. The obtained tableting mixture was tableted at a tableting pressure of 7 kN using a rotary tableting machine to obtain tablets of Example 1 and Example 2. The obtained tablets were observed to confirm that binding had occurred.

The tablet thickness, hardness and disintegration time of the obtained tablets were measured. The tablet thickness refers to the length from the apex of the ridge on the upper surface to the apex of the ridge on the lower surface of the manufactured tablet, and was measured using a dial thickness gauge (TECLOCK). The hardness was measured using a tablet hardness tester (ERWAKA). The disintegration time was measured according to the disintegration test method of the Japanese Pharmacopoeia.

-Manufacturing of Tablets of Comparative Examples Table 1 below shows the formulations (ingredient amounts per tablet) of the tablets of Comparative Examples 1 to 6. Each tablet contains 75 mg of oseltamivir represented by formula (I). Comparative Example 1 and Comparative Example 2 used magnesium stearate (general: Taihei Kagaku Sangyo Co., Ltd.) instead of stearyl sodium fumarate as a lubricant, and Comparative Examples 3 and 4 used fumarate as a lubricant. Examples of Comparative Example 5 and Comparative Example 6 used magnesium stearate (light: Taihei Kagaku Sangyo Co., Ltd.) instead of stearyl sodium, except that calcium stearate was used as a lubricant instead of stearyl sodium fumarate. Tablets were produced in the same manner as in 1 and 2. The two types of magnesium stearate used in the comparative example have different particle sizes, and the light magnesium stearate has a smaller particle size than general magnesium stearate. The tablet thickness, hardness and disintegration time of each of the obtained tablets were measured in the same manner as in Examples 1 and 2.

The measurement results of each tablet of Examples and Comparative Examples are shown in Table 2 below. In addition, examples of observing each tablet are shown in FIGS. 1A to 4B. 1A is Example 1, FIG. 1B is Example 2, FIG. 2A is Comparative Example 1, FIG. 2B is Comparative Example 2, FIG. 3A is Comparative Example 3, FIG. 3B is Comparative Example 4, and FIG. 4A is Comparative Example 5, FIG. 4B shows the tablet of Comparative Example 6. 〇 in the binding column in Table 2 indicates that almost no binding occurred in the measured tablet, and × indicates that binding frequently occurred in the measured tablet. The tablet thickness of each tablet was 3.3 mm.

The results in Table 2 show that tablets made with stearyl fumarate as a lubricant have almost no binding, and the use of sodium stearyl fumarate as a lubricant reduces the occurrence of binding. Was shown. It was also shown that tablets produced using stearyl sodium fumarate as a lubricant have a high hardness, whereas magnesium stearate as a lubricant reduces the hardness. It was shown that the tablets produced using stearyl sodium fumarate had excellent physical properties as tablets.

(Prescription example)
Tables 3 and 4 below show tablet formulation examples and the physical characteristics of the manufactured tablets. Granulation and tableting can be carried out in the same manner as, for example, the preparation of the granulated product and the production of tablets, or can be produced as follows.

1) The osertamivir phosphate is put into an impact crusher and crushed to obtain a pulverized product of oseltamivir phosphate (D ₅₀ of the pulverized product of oseltamivir phosphate in the following formulation example 1 is 22 μm. The oseltamivir phosphate may be used without pulverization. In the following formulation examples 2 to 4, uncrushed oseltamivir phosphate is used, and D ₅₀ is 90 μm).
2) The pulverized product (or uncrushed oseltamivir phosphate), D-mannitol and hydroxypropyl cellulose of 1) were put into a stirring granulator and mixed. After mixing, purified water is sprayed to obtain granulated powder containing oseltamivir phosphate as an active ingredient.
3) The granulated powder of 2) is dried and sized to obtain a granulated product containing oseltamivir phosphate as an active ingredient.
4) Mix the granulated product of 3) and sodium stearyl fumarate using a diffusion mixer (before mixing the granulated product and sodium stearyl fumarate, add hydroxypropyl cellulose to the granulated product and mix. To obtain a tableting mixture containing oseltamivir phosphate as an active ingredient.
5) The tableting mixture of 4) is tableted using a rotary tableting machine to obtain a tablet (uncoated tablet) containing oseltamivir phosphate as an active ingredient.

The lock diameter was measured using a dial thickness gauge in the same manner as the lock thickness. The film coating can be performed, for example, by the following procedure.

1) Dissolve hypromellose and hydroxypropyl cellulose in purified water. Talc is added to this solution and dispersed to obtain dispersion I.
2) Disperse titanium oxide in purified water to obtain dispersion II.
3) Mix the dispersion I and the dispersion II to obtain a film coating solution.
4) Place tablets containing oseltamivir as an active ingredient (tablets may be placed in a constant temperature and humidity chamber before coating and humidity control) in a coating pan, coat with a film coating solution, and then dry to obtain a film-coated tablet. obtain.

Claims (8)

It contains stearyl sodium fumarate as a lubricant and oseltamivir or a pharmaceutically acceptable salt thereof or a solvent mixture thereof as an active ingredient, and the content of the active ingredient is 60% by mass or more of the total weight of the tablet. Tablets that are 90% by weight or less. The tablet according to claim 1, wherein the active ingredient is oseltamivir phosphate. The tablet according to claim 1 or 2, wherein the mass ratio of the sodium stearyl fumarate to the active ingredient is 0.010 or more and 0.030 or less. The tablet according to any one of claims 1 to 3, wherein the content of the sodium stearyl fumarate is 0.9% by mass or more and 2.0% by mass or less based on the total mass of the tablet. The tablet according to any one of claims 1 to 4, which is coated with a coating agent. A method for producing a tablet containing oseltamivir, a pharmaceutically acceptable salt thereof, or a solvate thereof as an active ingredient in an amount of 60% by mass or more and 90% by mass or less of the total mass of the tablet.
The step of obtaining the granulated product containing the active ingredient and
A step of mixing the granulated product with stearyl fumarate as a lubricant to obtain a tableting mixture.
The step of compression-molding the tableting mixture to obtain a tablet, and
A method for manufacturing a tablet containing. The production method according to claim 6, further comprising a step of coating the tablet. Sodium stearyl fumarate is used as a lubricant in the production of tablets containing oseltamivir or a pharmaceutically acceptable salt thereof or a solvate thereof as an active ingredient in an amount of 60% by mass or more and 90% by mass or less of the total mass of the tablets. By doing so, a method of suppressing the occurrence of binding in compression molding.

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