JP2019172644A - Agent for improving hardness and wear of tablet containing lanthanum carbonate - Google Patents

Abstract

To provide an agent for improving hardness and wear of a tablet containing lanthanum carbonate hydrate, and a method or the like using the same.SOLUTION: At least one of crospovidone and low-substitution-degree hydroxypropyl cellulose is mixed with lanthanum carbonate hydrate, and the mixture is tableted, so that the hardness and wear of a tablet containing lanthanum carbonate hydrate are improved.SELECTED DRAWING: None

Description

  The present invention relates to a tablet hardness and friability improver comprising lanthanum carbonate and uses thereof.

The number of end-stage kidney disease (ESKD) patients requiring dialysis and transplantation is increasing worldwide. The number of dialysis patients at the end of 2014 is 320,000.
Recognized as a reserve for this ESKD is chronic kidney disease (CKD). CKD is a concept encompassing chronic kidney disease regardless of the underlying disease, and there is a decrease in renal function expressed by glomerular filtration rate (GFR), or findings suggestive of kidney damage. It is a concept that includes all chronic (3 months or more) pathological conditions.
When CKD deteriorates, renal function decreases and phosphorus is not excreted outside the body, resulting in hyperphosphatemia. Hyperphosphatemia not only causes secondary hyperparathyroidism, but is also greatly involved in an increased risk of death through vascular calcification. Therefore, prevention and treatment of hyperphosphatemia is important.
Currently, hyperphosphatemia is prevented and treated by diet and drug therapy. As a drug therapy, a phosphorus adsorbent that suppresses absorption of phosphorus from the digestive tract is used, and lanthanum carbonate hydrate is used as one of the phosphorus adsorbents.
As preparations containing lanthanum carbonate hydrate, orally disintegrating tablets, chewable tablets and granules are known (Patent Document 1 and Patent Document 2).
However, in these known documents, crospovidone and low-substituted hydroxypropylcellulose are described as disintegrants, and crospovidone or low-substituted hydroxypropylcellulose is described as improving tablet hardness and friability. Absent.

Japanese Patent No. 6093929 Japanese Patent No. 4896719

  An object of the present invention is to provide a drug for improving the hardness and / or friability of a tablet containing lanthanum carbonate.

As a result of intensive studies to solve the above-mentioned problems, the present inventors have found that crospovidone and low-substituted hydroxypropylcellulose used as disintegrants have enhanced the hardness of a preparation containing lanthanum carbonate hydrate, resulting in wear and tear. As a result, the present invention was completed.

  In one aspect, the present invention provides a tablet hardness-increasing agent and / or friability-reducing agent comprising lanthanum carbonate hydrate, the agent comprising at least one of crospovidone and low-substituted hydroxypropylcellulose. To do.

  In one aspect, the present invention provides a tablet hardness enhancer and / or friability reducing agent comprising lanthanum carbonate hydrate, wherein the drug is selected from crospovidone and low substituted hydroxypropylcellulose.

  In one aspect, the present invention is a method for increasing the hardness and / or reducing the friability of a tablet containing lanthanum carbonate hydrate, comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate. A method comprising tableting a mixture comprising

  In one aspect, the present invention is a method for increasing the hardness and / or reducing the friability of a tablet containing lanthanum carbonate hydrate, comprising using at least one of crospovidone and low-substituted hydroxypropylcellulose. A method of including is provided.

  In one aspect, the present invention is a use for increasing the hardness and / or reducing the friability of a tablet comprising lanthanum carbonate hydrate, comprising the use of crospovidone and / or low-substituted hydroxypropylcellulose. provide.

  In one aspect, the present invention provides a method for producing a tablet comprising lanthanum carbonate hydrate, comprising the step of tableting a mixture comprising at least one of crospovidone and low-substituted hydroxypropyl cellulose and lanthanum carbonate hydrate. provide.

  The drug or method provided by the present invention enhances the hardness of tablets containing lanthanum carbonate hydrate. The medicament or method provided by the present invention reduces the friability of tablets containing lanthanum carbonate hydrate.

The average value of the hardness of an orally disintegrating tablet produced by tableting at 781 kgf containing 5.6% by mass of crospovidone and 2.8% by mass of crospovidone produced by tableting at 1174 kgf was taken as 100. FIG. 5 is a graph showing the relationship between the tableting pressure and the hardness relative to the average value when the crospovidone content is 5.6% by mass and 2.8% by mass. Tablets with a crospovidone content of 5.6% by weight show higher hardness than tablets with 2.8% by weight. The average value of the friability of an orally disintegrating tablet produced by tableting at 781 kgf containing 5.6% by mass of crospovidone and that of an orally disintegrating tablet produced by tableting at 1174 kgf containing 2.8% by mass of crospovidone. FIG. 5 is a graph showing the relationship between the tableting pressure and the relative value with respect to the average value of the friability when the crospovidone content is 5.6% by mass and 2.8% by mass. Tablets with a crospovidone content of 5.6% by weight show lower friability than tablets with 2.8% by weight.

  The hardness enhancers, friability reducing agents, methods or uses provided by the present invention are useful for improving the hardness and / or friability of tablets containing lanthanum carbonate hydrate.

In one embodiment, by using at least one of crospovidone and low substituted hydroxypropylcellulose to produce tablets containing lanthanum carbonate hydrate in a manner known in the pharmaceutical arts, / Or a reduction in friability is achieved. For example, crospovidone is used to produce tablets containing lanthanum carbonate hydrate in a manner known in the pharmaceutical arts to achieve increased tablet hardness and / or reduced friability.
In one embodiment, at least one of crospovidone and low substituted hydroxypropyl cellulose is mixed with lanthanum carbonate hydrate and tableting of the mixture achieves increased tablet hardness and / or reduced friability. Is done. For example, crospovidone is mixed with lanthanum carbonate hydrate and the mixture is tableted to achieve increased tablet hardness and / or reduced friability.
In one embodiment, by using a composition comprising at least one of crospovidone and low substituted hydroxypropylcellulose to produce a tablet comprising lanthanum carbonate hydrate in a manner known in the pharmaceutical arts, Increased hardness and / or reduced friability. A composition containing at least one of crospovidone and low-substituted hydroxypropylcellulose has additives commonly used in the pharmaceutical field (for example, excipients, disintegrants, lubricants, binders, surfactants, A sweetening agent, a corrigent, a flavoring agent / fragrance, a fluidizing agent and a stabilizing agent). In this embodiment, the composition comprising crospovidone and at least one of low substituted hydroxypropylcellulose may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate. For example, when a tablet containing lanthanum carbonate hydrate is produced using a composition containing crospovidone by a method known in the pharmaceutical field, an increase in tablet hardness and / or a reduction in friability may be achieved. The composition comprising crospovidone may be a tablet hardness enhancer and / or friability reducing agent comprising lanthanum carbonate hydrate.
In one embodiment, an additive comprising at least one of crospovidone and low-substituted hydroxypropylcellulose, optionally used conventionally in the pharmaceutical field (eg, excipients, disintegrants, lubricants, binders, A composition containing at least one agent selected from the group consisting of a surfactant, a sweetener, a corrigent, a flavoring agent / flavoring agent, a fluidizing agent and a stabilizer) and lanthanum carbonate hydrate, By tableting the mixture, increased hardness and / or reduced friability of the tablet is achieved. In this embodiment, the composition comprising crospovidone and at least one of low substituted hydroxypropylcellulose may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate. For example, crospovidone and optionally additives commonly used in the pharmaceutical field (for example, excipients, disintegrants, lubricants, binders, surfactants, sweeteners, flavoring agents, flavoring agents / flavoring agents) A composition containing at least one agent selected from the group consisting of a fluidizing agent and a stabilizing agent) is mixed with lanthanum carbonate hydrate, and the mixture is compressed to increase tablet hardness and / or Where friability is achieved, the composition comprising crospovidone can be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate.
In one embodiment, using a drug selected from crospovidone and low-substituted hydroxypropyl cellulose to increase tablet hardness by producing tablets containing lanthanum carbonate hydrate in a manner known in the pharmaceutical arts. And / or a reduction in friability is achieved. In this embodiment, the agent selected from crospovidone and low substituted hydroxypropylcellulose may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate. For example, when a tablet comprising lanthanum carbonate hydrate is produced using a drug composed of crospovidone by a method known in the pharmaceutical field, an increase in tablet hardness and / or a decrease in friability can be achieved. The drug consisting of crospovidone may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate.
In one embodiment, mixing a drug selected from crospovidone and low substituted hydroxypropylcellulose with lanthanum carbonate hydrate and compressing the mixture results in increased tablet hardness and / or reduced friability. Achieved. In this embodiment, the agent selected from crospovidone and low substituted hydroxypropylcellulose may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate. For example, when an increase in tablet hardness and / or reduction in friability is achieved by mixing a drug composed of crospovidone with lanthanum carbonate hydrate and tableting the mixture, the drug composed of crospovidone It may be a tablet hardness enhancer and / or friability reducer comprising lanthanum carbonate hydrate.

In the preparation of the preparation, mixing can be performed using a V-type mixer, a W-type mixer, a container mixer, a tumbler mixer, a stirring mixer, or the like. The mixture may be granulated before tableting, and the mixture may be produced by a direct compression method. The granulation method is not particularly limited, and granulation methods usually used in the pharmaceutical field such as dry granulation and wet granulation can be used, but dry granulation is preferable. The tableting method is not particularly limited. For example, a tablet or tablet can be tableted using a tableting machine known in the pharmaceutical field such as a single-shot tableting machine or a rotary tableting machine. Can do. When using a single-punch tableting machine, a rotary tableting machine, etc. 100kgf-3400kgf, 100kgf-3200kgf, 100kgf-2800kgf, 100kgf-2000kgf, 300kgf-3400kgf, 300kgf-3200kgf, 300kgf-2800kgf, 300kgf-2000kgf, 600kgf-3400kgf, 600kgf-3200kgf, 600kgf600-2800kgf Tableting pressures of up to 3400 kgf, 1200 kgf to 3200 kgf, 1200 kgf to 2800 kgf, 1200 kgf to 2000 kgf can be employed.

As used herein, lanthanum carbonate hydrate can be any hydrated form of lanthanum carbonate hydrate. For example, the lanthanum carbonate hydrate that can be used in the present invention is a lanthanum carbonate hydrate represented by the general formula: La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 3 to 8). obtain. From the viewpoint of availability, preferable examples of lanthanum carbonate hydrate include lanthanum carbonate tetrahydrate and lanthanum carbonate octahydrate.
The lanthanum carbonate hydrate that can be used in the present invention may be only one kind of lanthanum carbonate hydrate (for example, lanthanum carbonate octahydrate), or a mixture of two or more lanthanum carbonate hydrates ( For example, it may be a mixture of lanthanum carbonate tetrahydrate and lanthanum carbonate octahydrate.

Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the lanthanum carbonate hydrate in the tablet containing the lanthanum carbonate hydrate in which the reduction in the degree is achieved can be appropriately set by those skilled in the art, for example, 1% by mass to 99% by mass, 10% by mass to 99% by mass. %, 20% to 99%, 30% to 99%, 50% to 99%, 60% to 99%, 70% to 99%, 1% to 90%, 10% to 90%, 20% to 90%, 30% to 90%, 40% to 90%, 50% to 90%, 60% to 90%, 70% % To 90% by mass, 1% to 80% by mass 10% to 80%, 20% to 80%, 30% to 80%, 40% to 80%, 50% to 80%, 60% to 80%, 1% % -85 mass%, 10 mass% -85 mass%, 20 mass% -85 mass%, 30 mass% -85 mass%, 40 mass% -85 mass%, 50 mass% -85 mass%, 60 mass%- 85% by mass, 70% by mass to 85% by mass, 80% by mass to 90% by mass, 80% by mass to 95% by mass, 85% by mass to 95% by mass, 90% by mass to 99% by mass or 90% by mass It can be -99 mass%.
From the viewpoint of size reduction of the tablet, the content of lanthanum carbonate hydrate is preferably higher, and may be, for example, 70% by mass or more.

  Crospovidone that can be used in the present invention is a cross-linked polymer of 1-vinyl-2-pyrrolidone, and may be crospovidone that can be easily obtained from the market. For example, Kollidon CL (BASF Japan), Polyplusdon XL (ISP Japan) and the like may be used in the present invention.

  Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of crospovidone in the tablet containing lanthanum carbonate hydrate in which a decrease in the degree is achieved can be appropriately set by those skilled in the art, for example, 0.1% by mass to 30% by mass, 0.1% by mass to 20% Mass%, 0.1 mass% to 12 mass%, 0.1 mass% to 10 mass%, 0.1 mass% to 6 mass%, 0.1 mass% to 3 mass%, 0.5 mass% to 30 mass% Mass%, 0.5 mass% to 20 mass%, 0.5 mass% to 12 mass%, 0.5 mass% to 10 mass%, 0.5 mass% to 6 mass%, 0.5 mass% to 3 mass% % By mass, 1% by mass to 30% by mass, 1% by mass to 20% by mass, 1% by mass to 12% by mass, 1% by mass to 0% by mass, 1% by mass to 6% by mass, 1% by mass to 3% by mass, 2% by mass to 30% by mass, 2% by mass to 20% by mass, 2% by mass to 12% by mass, 2% by mass to 10% by mass %, 2% to 6%, 3% to 30%, 3% to 20%, 3% to 12%, 3% to 10%, 3% to 6%, Or it may be 3 mass%-5 mass%.

In one embodiment, the crospovidone used in the present invention is usually crospovidone used as a super disintegrant, and functions as a disintegrant and a hardness enhancer and / or friability reducer in the present invention. To do.

  The low-substituted hydroxypropyl cellulose that can be used in the present invention may be a low-substituted hydroxypropyl cellulose that can be easily obtained from the market. For example, LH-11, LH-21, LH-22, LH-B1, LH-31, LH-32, NBD-022, NBD-021, and NBD-020 manufactured by Shin-Etsu Chemical Co., Ltd. are used in the present invention. May be.

  Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the low-substituted hydroxypropyl cellulose in the tablet containing lanthanum carbonate hydrate in which a reduction in the degree has been achieved can be appropriately set by those skilled in the art, for example, 0.1 mass% to 30 mass%, 0.1 % By mass to 20% by mass, 0.1% by mass to 12% by mass, 0.1% by mass to 10% by mass, 0.1% by mass to 6% by mass, 0.1% by mass to 3% by mass, 0.5% by mass % To 30%, 0.5% to 20%, 0.5% to 12%, 0.5% to 10%, 0.5% to 6%, 0.5% % By mass to 3% by mass, 1% by mass to 30% by mass, 1% by mass to 20% by mass, 1% by mass to 2% by mass, 1% by mass to 10% by mass, 1% by mass to 6% by mass, 1% by mass to 3% by mass, 2% by mass to 30% by mass, 2% by mass to 20% by mass, 2% by mass to 12% by mass %, 2% to 10%, 2% to 6%, 3% to 30%, 3% to 20%, 3% to 12%, 3% to 10%, It may be 3% to 6% by mass, or 3% to 5% by mass.

In one embodiment, the low-substituted hydroxypropyl cellulose used in the present invention is a low-substituted hydroxypropyl cellulose usually used as a super disintegrant, and in the present invention, as a disintegrant and a hardness enhancer and Functions as a friability reducing agent.

In the present specification, the “tablet” is not particularly limited as long as it is a solid preparation that can be administered as a medicine. Examples of “tablets” include orally disintegrating tablets, chewable tablets, and plain tablets. Examples of preferred “tablets” include film-coated tablets with the tablet surface coated, tablets excluding sugar-coated tablets, and tablets without tablet coating. More preferable examples of the “tablet” include an orally disintegrating tablet that is not coated and an orally disintegrating tablet that is an uncoated tablet.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The weight of the tablet containing lanthanum carbonate hydrate in which a decrease in the degree is achieved is not particularly limited, and may be, for example, 400 mg to 1500 mg, 500 mg to 1300 mg.

In the present specification, the “orally disintegrating tablet” is a tablet that easily disintegrates in the oral cavity with only a small amount of water or saliva.
The oral disintegration time of the orally disintegrating tablet (the time until the orally disintegrating tablet completely disintegrates with the saliva in the oral cavity of healthy adult boys and girls) is, for example, within 70 seconds, within 60 seconds, preferably 50 Within seconds, more preferably within 45 seconds.
In one embodiment, an orally disintegrating tablet comprising lanthanum carbonate hydrate that has been increased in hardness and / or reduced in friability according to the present invention is purified using purified water according to the disintegration test method of the Japanese Pharmacopoeia. When a test is performed, for example, it collapses within 600 seconds, within 300 seconds, within 120 seconds or within 60 seconds without an auxiliary plate, and with an auxiliary plate within 120 seconds, within 60 seconds or within 30 seconds To do.
In one preferred embodiment, an orally disintegrating tablet comprising lanthanum carbonate hydrate, which has been increased in hardness and / or reduced in friability according to the present invention, is purified using purified water according to the disintegration test method of the Japanese Pharmacopoeia. When the test is performed, for example, it collapses within 60 seconds without an auxiliary plate, and within 30 seconds with an auxiliary plate.

In one embodiment, an orally disintegrating tablet comprising a lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, the present invention The hardness of the orally disintegrating tablet containing lanthanum carbonate hydrate, which has been increased in hardness and / or reduced in friability by the invention, is 20 to 380N, 20 to 300N, 20 to 200N, 30 to 380N, 30 to 30 300N, 30-200N, 50-380N, 50-300N, 50-200N, 80-380N, 80-300N, 80-200N, 100-200N, or 100N or more.
In one embodiment, an orally disintegrating tablet comprising a lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, the present invention The degree of friability of the orally disintegrating tablet containing lanthanum carbonate hydrate, which has achieved increased hardness and / or reduced friability by the invention, is 0-1%, 0-0.5%, 0.01-1%, 0.01- 0.5%, 0.1-1% or 0.1-0.5%.

  Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The tablet containing lanthanum carbonate hydrate in which a reduction in the degree has been achieved may contain additives commonly used in the pharmaceutical field. The additive used may be any pharmaceutically acceptable, for example, excipients, disintegrants, lubricants, binders, surfactants, sweeteners, flavoring agents, flavoring agents / fragrances. , Fluidizers, colorants, stabilizers, coating agents, plasticizers, brighteners and the like.

The excipient is not particularly limited, and examples thereof include celluloses (crystalline cellulose, ethyl cellulose, hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropylmethylcellulose (hypromellose), etc.) and derivatives thereof, starch (Corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, hydroxypropyl starch, etc.) and derivatives thereof, sugar (glucose, lactose, sucrose, purified sucrose, powdered sugar, trehalose, dextran, dextrin, etc.), sugar Alcohol (D-mannitol, xylitol, sorbitol, erythritol, etc.), glycerin fatty acid ester, inorganic powder (magnesium aluminate metasilicate, synthetic hydrotalcite), anhydrous Calcium phosphate, precipitated calcium carbonate, calcium silicate, calcium hydrogen hydrate phosphoric acid, inorganic salts such as sodium hydrogen carbonate. An excipient | filler may be used independently and may be used in mixture of 2 or more types.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the excipient in the lanthanum carbonate hydrate tablet in which a reduction in the degree is achieved depends on the type of excipient used, and is not particularly limited. 90% by mass, 0.1% by mass to 80% by mass, 0.1% by mass to 30% by mass, 0.1% by mass to 20% by mass, 0.1% by mass to 10% by mass, 0.1% by mass to 5% by mass, 0.1% by mass to 3% by mass %, 0.1% to 1%, 0.5% to 90%, 0.5% to 80%, 0.5% to 30%, 0.5% to 20%, 0.5% to 10%, 0.5% to 5%, 0.5% to 3%, 0.5% to 1%, 1% to 90%, 1% to 80%, 1% to 30% The amount%, 1% to 20 wt%, 1 wt% to 10 wt%, at 1% to 5%, or 1 wt% to 3 wt%.
In one embodiment, two or more excipients may be used, in which case the total amount of excipient is the same as described above.
In one embodiment, a tablet comprising lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, hardness according to the present invention In the case where the tablet containing lanthanum carbonate hydrate in which the enhancement and / or reduction of the friability is achieved) is an orally disintegrating tablet, a sugar alcohol such as D-mannitol is used as an excipient.
In one embodiment, an orally disintegrating tablet comprising a lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, the present invention The orally disintegrating tablet comprising lanthanum carbonate hydrate, which has achieved increased hardness and / or reduced friability according to the invention, does not contain excipients.
In one embodiment, an orally disintegrating tablet comprising a lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, the present invention An orally disintegrating tablet comprising lanthanum carbonate hydrate, which has achieved increased hardness and / or reduced friability according to the invention, is a sugar (eg, glucose, lactose, sucrose, trehalose, dextran, dextrin, dextranate), And / or free of sugar alcohols (eg D-mannitol, xylitol, sorbitol, erythritol).

The disintegrant is not particularly limited, and examples thereof include crospovidone, low-substituted hydroxypropyl cellulose, croscarmellose sodium, carmellose, carmellose calcium, carmellose sodium, carboxymethyl starch sodium, hydroxypropyl starch. And partially pregelatinized starch.
In the present invention, crospovidone and low-substituted hydroxypropylcellulose are disintegrating agents and may be hardness enhancing agents and / or friability reducing agents.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the disintegrant in the tablet containing lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of disintegrant used, and is not particularly limited. 30% by mass, 0.1% by mass to 20% by mass, 0.1% by mass to 12% by mass, 0.1% by mass to 10% by mass, 0.1% by mass to 6% by mass, 0.1% by mass to 0.1% by mass 3% by mass, 0.5% by mass to 30% by mass, 0.5% by mass to 20% by mass, 0.5% by mass to 12% by mass, 0.5% by mass to 10% by mass, 0.5% by mass to 0.5% by mass 6% by mass, 0.5% by mass to 3% by mass, 1% by mass to 30% by mass, 1% by mass to 20% by mass, 1 quality % -12 mass%, 1 mass% -10 mass%, 1 mass% -6 mass%, 1 mass% -3 mass%, 2 mass% -30 mass%, 2 mass% -20 mass%, 2 mass%- 12% by mass, 2% by mass to 10% by mass, 2% by mass to 6% by mass, 3% by mass to 30% by mass, 3% by mass to 20% by mass, 3% by mass to 12% by mass, 3% by mass to 10% by mass %, 3% to 6% by weight, or 3% to 5% by weight.
In one embodiment, two or more disintegrants may be used, in which case the content of the total amount of disintegrant is the same as described above.

The lubricant is not particularly limited, and examples thereof include calcium stearate,
Examples include glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, sodium stearyl fumarate, sucrose fatty acid ester, zinc stearate, stearic acid, talc, carnauba wax, L-leucine, and macrogol.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the lubricant in the tablet containing the lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of lubricant used and is not particularly limited. % To 10%, 0.01% to 5%, 0.01% to 3%, 0.01% to 1%, 0.01% to 0.1%, 0. 1% to 10%, 0.1% to 5%, 0.1% to 3%, 0.1% to 1%, 0.3% to 10%, It may be 3% to 5%, 0.3% to 3%, or 0.3% to 1% by weight.
In one embodiment, two or more lubricants may be used, in which case the content of the total amount of disintegrant is the same as described above.

The binder is not particularly limited, and examples thereof include hydroxypropylcellulose, polyvinyl alcohol, pregelatinized starch, povidone (polyvinylpyrrolidone), hydroxypropylmethylcellulose (hypromellose), agar, and gelatin.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the binder in the tablet containing the lanthanum carbonate hydrate in which the reduction in the degree is achieved varies depending on the type of the binder used, and is not particularly limited. %, 1% to 20% by weight, 1% to 10% by weight, and 1% to 5% by weight.
In one embodiment, two or more binders may be used, in which case the content of the total amount of disintegrant is the same as described above.

The surfactant is not particularly limited, and examples thereof include sodium lauryl sulfate, polysorbate, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyl stearate, macrogol and poloxamer.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the surfactant in the tablet containing the lanthanum carbonate hydrate in which the reduction in the degree is achieved varies depending on the type of the surfactant used, and is not particularly limited. % To 3% by mass, 0.03% to 1% by mass, 0.03% to 0.5% by mass.
In one embodiment, two or more surfactants may be used, and in this case, the total amount of the surfactant is the same as described above.

The sweetener is not particularly limited, and examples thereof include lactose (lactose hydrate, anhydrous lactose), sucrose, sucrose, fructose, fructooligosaccharide, glucose, maltose, reduced maltose, powdered sugar, and powdered koji. Sugars such as reduced lactose, sugar alcohols such as erythritol, sorbitol, maltitol, xylitol, D-mannitol, aspartame, saccharin, sodium saccharin, dipotassium glycyrrhizinate, stevia, thaumatin, sucralose, acesulfame potassium, neotame, etc. Sweeteners.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the sweetener in the tablet containing the lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of sweetener used, and is not particularly limited. 3% by mass, 0.01% by mass to 1% by mass, 0.01% by mass to 0.1% by mass, 0.1% by mass to 3% by mass, 0.1% by mass to 1% by mass, 0.1% by mass % To 0.3% by weight.
In one embodiment, the sweetening agent may be powdery or granular, for example, powdered aspartame or granular aspartame may be used. Also good.
In one embodiment, two or more sweeteners may be used, in which case the total amount of sweetener is the same as described above.

The flavoring agent is not particularly limited, and examples thereof include citric acid, malic acid, fumaric acid, tartaric acid, ascorbic acid and other organic acids and salts thereof, orange oil, lemon oil, plum meat extract. .
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the corrigent in the tablet containing lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of the corrigent used, and is not particularly limited. 3% by mass, 0.01% by mass to 1% by mass, 0.01% by mass to 0.1% by mass, 0.1% by mass to 3% by mass, 0.1% by mass to 1% by mass, 0.1% by mass % To 0.3% by weight.
In one embodiment, two or more kinds of corrigents may be used, in which case the content of the corrigent is the same as described above.

  Flavorings and fragrances are not particularly limited, and examples include fragrances such as maltol, ethyl maltol and vanillin, citrus fragrances such as lemon, orange and grapefruit, peppermint, spearmint, menthol, pineapple, Examples include cherry, peach, strawberry, grape, yogurt, and coffee. Flavoring agents and fragrances can be appropriately added in an appropriate amount by combining one or more kinds.

The fluidizing agent is not particularly limited, and examples thereof include light anhydrous silicic acid and magnesium aluminate metasilicate.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the fluidizing agent in the tablet containing the lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of the fluidizing agent to be used, and is not particularly limited. % To 10%, 0.1% to 5%, 0.1% to 3%, 0.1% to 2%, 0.1% to 1%, 0.3% % To 3%, 0.3% to 2%, or 0.3% to 1% by weight.
In one embodiment, two or more fluidizing agents may be used, in which case the total amount of fluidizing agent is the same as described above.

The stabilizer is not particularly limited, and examples thereof include citric acid (eg, anhydrous citric acid), malic acid, acetic acid, tartaric acid, maleic acid, ascorbic acid, sodium edetate, and tocopherol.
Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The content of the stabilizer in the tablet containing lanthanum carbonate hydrate in which the degree of reduction has been achieved varies depending on the type of stabilizer used, and is not particularly limited. % To 30%, 0.1% to 10%, 0.1% to 3%, 0.3% to 3%, or 0.3% to 1% by weight.
In one embodiment, two or more kinds of stabilizers may be used, and in this case, the total amount of the stabilizer is the same as described above.

Tablets comprising lanthanum carbonate hydrate with improved hardness and / or friability by the hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, increased hardness and / or friability according to the present invention) The tablet containing lanthanum carbonate hydrate that has been reduced in degree can be an uncoated tablet without a coating layer, or a film-coated tablet with a coating layer. The content of the coating layer can be appropriately set by those skilled in the art, and may be, for example, 0.1 to 10% by mass with respect to the uncoated tablet. In the coating layer, in addition to the coating base, a plasticizer, a coloring agent, a brightening agent, and the like can be appropriately included.
Examples of coating bases include hydroxypropylcellulose, hydroxypropylmethylcellulose, ethylcellulose, cellulose acetate phthalate, methacrylic acid copolymer and polyvinylpyrrolidone, with hydroxypropylmethylcellulose being particularly preferred. The content of the coating base may be 0.01 to 10% by mass, preferably 0.3 to 3% by mass with respect to the tablet.
Examples of plasticizers include triethyl citrate, medium chain fatty acid triglycerides, triacetin, glycerin, propylene glycol and polyethylene glycol (eg, macrogol 6000), with macrogol 6000 being particularly preferred. The content of the plasticizer in the tablet may be 0.01 to 1% by mass, preferably 0.03 to 3% by mass with respect to the tablet.
Examples of colorants include titanium oxide, yellow iron sesquioxide, iron sesquioxide, black iron oxide, edible blue No. 2 and edible blue No. 2 aluminum lake. The content of the colorant in the tablet may be 0.01 to 1% by mass, preferably 0.03 to 3% by mass with respect to the tablet.
An example of a brightening agent is carnauba wax. The content of the brightening agent in the tablet may be 0.0001 to 0.1% by mass, preferably 0.001 to 0.01% by mass, based on the tablet.

The hardness and friability of the tablet can be appropriately measured by those skilled in the art according to the common general technical knowledge in this field. For example, the hardness of the tablet may be measured by a commercially available hardness meter (for example, a Schleuniger hardness meter). The friability of the tablet may be measured, for example, by a friability test method for tablets (Japanese Pharmacopoeia reference information).
In one embodiment, by utilizing the hardness enhancer, friability reducing agent, method or use provided by the present invention, tablet hardness enhancement and / or friability compared to when the present invention is not utilized. Degradation is shown. For example, by including crospovidone and / or low-substituted hydroxypropyl cellulose in the tablet, the tablet hardness can be increased and / or compared to when the tablet does not include crospovidone and / or low-substituted hydroxypropyl cellulose. A decrease in friability is indicated.
In one embodiment, increased hardness and / or reduced friability compared to the pre-enhanced tablet by increasing the degree of utilization of the hardness enhancer, friability reducing agent, method or use provided by the present invention. Is shown. For example, increasing the content of crospovidone and / or low substituted hydroxypropylcellulose in the tablet indicates an increase in tablet hardness and / or a decrease in friability compared to before the increase.

In one embodiment, a tablet comprising lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, hardness according to the present invention The hardness of the tablet containing lanthanum carbonate hydrate in which the increase in the strength and / or the reduction in the friability is achieved is 30 to 380N, 30 to 300N, 30 to 200N, 50 to 380N, 50 to 300N, 50 to 200N, 80 to 380N, 80 to 300N, 80 to 200N, 100 to 200N, or 100N or more.
In one embodiment, a tablet comprising lanthanum carbonate hydrate with improved hardness and / or friability by a hardness enhancer, friability reducing agent, method or use provided by the present invention (ie, hardness according to the present invention The friability of tablets containing lanthanum carbonate hydrate in which an increase in the strength and / or a reduction in the friability is achieved is 0-1%, 0-0.5%, 0.01-1%, 0.01-0.5%, 0.1-1 % Or 0.1 to 0.5%.

Examples of embodiments provided by the present invention include the following (1) to (59), (1-1) to (1-55), and (2-1) to (2-55).
(1)
A tablet hardness enhancer comprising lanthanum carbonate hydrate comprising at least one of crospovidone and low substituted hydroxypropylcellulose;
(2)
A friability reducing agent for tablets comprising lanthanum carbonate hydrate, comprising at least one of crospovidone and low substituted hydroxypropylcellulose;
(3)
A tablet hardness enhancer comprising lanthanum carbonate hydrate, selected from crospovidone and low substituted hydroxypropylcellulose;
(4)
A friability reducing agent for tablets comprising lanthanum carbonate hydrate, selected from crospovidone and low substituted hydroxypropylcellulose;
(5)
The hardness enhancing agent or friability reducing agent according to any one of (1) to (4), wherein the tablet is an orally disintegrating tablet;
(6)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The hardness enhancer or friability reducing agent according to any one of (1) to (5), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(7)
The hardness enhancer or friability reducing agent according to any one of (1) to (6), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(8)
The hardness enhancer or friability reducer according to any one of (1) to (7), wherein at least one of crospovidone and low-substituted hydroxypropylcellulose also functions as a disintegrant;
(9)
The hardness enhancer or friability reducer according to any one of (1) to (8), which is a hardness enhancer and is a friability reducer;
(10)
As a result of the hardness enhancer or friability reducing agent according to any one of (1) to (9) being contained in a tablet together with lanthanum carbonate hydrate, the content of lanthanum carbonate hydrate in the tablet is 70 masses. % To 99% by mass, the hardness enhancer or friability reducer according to any one of (1) to (9);
(11)
As a result of the hardness enhancer or friability reducing agent according to any one of (1) to (10) being contained in a tablet together with lanthanum carbonate hydrate, the content of lanthanum carbonate hydrate in the tablet is 70 masses. % To 90% by mass, the hardness enhancer or friability reducing agent according to any one of (1) to (10);
(12)
As a result of the hardness enhancer or friability reducing agent according to any one of (1) to (11) being contained in the tablet together with the lanthanum carbonate hydrate, the content of crospovidone in the tablet is 0.5% by mass. The hardness enhancer or friability reducing agent according to any one of (1) to (11), which is -30% by mass;
(13)
As a result of the hardness enhancer or friability reducing agent according to any one of (1) to (12) being contained in the tablet together with the lanthanum carbonate hydrate, the content of low substituted hydroxypropylcellulose in the tablet is 0. The hardness enhancer or friability reducing agent according to any one of (1) to (12), which is 5% by mass to 30% by mass;
(14)
The hardness enhancing agent or friability reducing agent according to any one of (1) to (13), wherein the tablet does not contain an excipient;
(15)
The hardness enhancing agent or friability reducing agent according to any one of (1) to (14), wherein the tablet does not contain sugar;
(16)
A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising tableting a mixture comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(17)
A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising using at least one of crospovidone and low-substituted hydroxypropylcellulose as a disintegrant;
(18)
A method for reducing the friability of a tablet comprising lanthanum carbonate hydrate comprising the step of tableting a mixture comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(19)
A method for reducing the friability of tablets comprising lanthanum carbonate hydrate comprising using at least one of crospovidone and low-substituted hydroxypropylcellulose as a disintegrant;
(20)
The method according to any one of (16) to (19), wherein the tablet is an orally disintegrating tablet;
(21)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (16) to (20), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(22)
The method according to any one of (16) to (21), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(23)
The method according to any one of (16) to (22), which is a method of increasing the hardness of a tablet and reducing the friability.
(24)
The method according to any one of (16) to (23), wherein the tablet in which hardness enhancement and / or friability reduction is achieved, has a lanthanum carbonate hydrate content of 70% by mass to 99% by mass;
(25)
The method according to any one of (16) to (24), wherein the tablet in which hardness enhancement and / or friability reduction is achieved has a content of lanthanum carbonate hydrate of 70% by mass to 90% by mass;
(26)
The method according to any one of (16) to (25), wherein the content of crospovidone in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5% by mass to 30% by mass;
(27)
The method according to any one of (16) to (26), wherein the content of the low-substituted hydroxypropylcellulose in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5% by mass to 30% by mass. ;
(28)
The method according to any one of (16) to (27), wherein the tablet is produced by a direct compression method;
(29)
Before the tablet is compressed, a granulated product that is a mixture comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method. And the method according to any one of (16) to (27);
(30)
The method according to any one of (16) to (29), wherein the tablet does not contain an excipient;
(31)
The method according to any one of (16) to (30), wherein the tablet does not contain sugar;
(32)
The use of at least one of crospovidone and low substituted hydroxypropylcellulose to increase the hardness of tablets containing lanthanum carbonate hydrate;
(33)
Use of at least one of crospovidone and low substituted hydroxypropylcellulose for reducing the friability of tablets containing lanthanum carbonate hydrate;
(34)
The use according to (32) or (33), wherein the tablet is an orally disintegrating tablet;
(35)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The use according to any one of (32) to (34), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(36)
The use according to any one of (32) to (35), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(37)
The use according to any of (32) to (36), which is a use for increasing the hardness of a tablet and reducing the friability.
(38)
The use according to any one of (32) to (37), wherein the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved;
(39)
The use according to any one of (32) to (38), wherein the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved;
(40)
The use according to any one of (32) to (39), wherein the content of crospovidone is 0.5% by mass to 30% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved;
(41)
The use according to any one of (32) to (40), wherein the content of low-substituted hydroxypropylcellulose is 0.5% by mass to 30% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. ;
(42)
The use according to any one of (32) to (41), wherein the tablet is produced by a direct compression method;
(43)
Before the tablet is compressed, a granulated product that is a mixture comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method. , (32) to (41)
(44)
Use according to any of (32) to (43), wherein the tablet does not contain excipients;
(45)
Use according to any of (32) to (44), wherein the tablet does not contain sugar;
(46)
A method for producing a tablet comprising lanthanum carbonate hydrate, comprising tableting a mixture comprising at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(47)
The method according to (46), which is a method for producing a tablet that achieves increased hardness or reduced friability;
(48)
The method according to (46) or (47), wherein the tablet is an orally disintegrating tablet;
(49)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (46) to (48), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(50)
The method according to any one of (46) to (49), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(51)
The method according to any one of (46) to (50), which is a method for producing a tablet that achieves increased hardness and reduced friability;
(52)
In the tablet obtained by the method according to any one of (46) to (51), the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass, and any one of (46) to (51) Described method;
(53)
In the tablet obtained by the method according to any one of (46) to (52), the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass, and any one of (46) to (52) Described method;
(54)
In the tablet obtained by the method according to any one of (46) to (53), the content of crospovidone is 0.5% by mass to 30% by mass, and any one of (46) to (53) the method of;
(55)
(46) to (54), wherein the content of the low-substituted hydroxypropylcellulose in the tablet obtained by the method according to any one of (46) to (54) is 0.5% by mass to 30% by mass. The method according to any one.
(56)
The method according to any one of (46) to (55), wherein the tablet is produced by a direct compression method;
(57)
Before the tablet is compressed, a granulated product that is a mixture containing at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method. , (46) to (55)
(58)
The method according to any one of (46) to (57), wherein the tablet does not contain an excipient;
(59)
The method according to any one of (46) to (58), wherein the tablet does not contain sugar;
(1-1)
A tablet hardness enhancer comprising lanthanum carbonate hydrate, comprising crospovidone;
(1-2)
A friability reducing agent for tablets comprising lanthanum carbonate hydrate, comprising crospovidone;
(1-3)
A tablet hardness enhancer comprising lanthanum carbonate hydrate, comprising crospovidone;
(1-4)
A friability reducing agent for tablets comprising lanthanum carbonate hydrate, comprising crospovidone;
(1-5)
The hardness enhancer or friability reducing agent according to any one of (1-1) to (1-4), wherein the tablet is an orally disintegrating tablet;
(1-6)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The hardness enhancer or friability reducing agent according to any one of (1-1) to (1-5), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8) ;
(1-7)
The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-6), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(1-8)
The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-7), wherein crospovidone also functions as a disintegrant;
(1-9)
The hardness enhancer or friability reducer according to any one of (1-1) to (1-8), which is a hardness enhancer and is a friability reducer;
(1-10)
When the hardness enhancer or friability reducing agent according to any one of (1-1) to (1-9) is contained in the tablet together with the lanthanum carbonate hydrate, the lanthanum carbonate hydrate in the tablet The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-9), wherein the content is 70% by mass to 99% by mass;
(1-11)
As a result of the hardness enhancer or friability reducing agent according to any one of (1-1) to (1-10) being contained in the tablet together with the lanthanum carbonate hydrate, the lanthanum carbonate hydrate in the tablet The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-10), wherein the content is 70% by mass to 90% by mass;
(1-12)
When the hardness enhancer or friability reducing agent according to any one of (1-1) to (1-11) is contained in the tablet together with the lanthanum carbonate hydrate, the content of crospovidone in the tablet is 0. The hardness enhancer or friability reducing agent according to any one of (1-1) to (1-11), which is 5% by mass to 30% by mass;
(1-13)
The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-12), wherein the tablet does not contain an excipient;
(1-14)
The hardness enhancing agent or friability reducing agent according to any one of (1-1) to (1-13), wherein the tablet does not contain sugar;
(1-15)
A method for increasing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising the step of tableting a mixture comprising crospovidone and lanthanum carbonate hydrate;
(1-16)
A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate comprising using crospovidone as a disintegrant;
(1-17)
A method for reducing the friability of tablets containing lanthanum carbonate hydrate, comprising tableting a mixture comprising crospovidone and lanthanum carbonate hydrate;
(1-18)
A method for reducing the friability of tablets comprising lanthanum carbonate hydrate comprising using crospovidone as a disintegrant;
(1-19)
The method according to any one of (1-15) to (1-18), wherein the tablet is an orally disintegrating tablet;
(1-20)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (1-15) to (1-19), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(1-21)
The method according to any one of (1-15) to (1-20), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(1-22)
The method according to any one of (1-15) to (1-21), which is a method for increasing the hardness of a tablet and reducing the friability.
(1-23)
The tablet according to any one of (1-15) to (1-22), wherein the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. Method;
(1-24)
The tablet according to any one of (1-15) to (1-23), wherein the content of the lanthanum carbonate hydrate in the tablet in which the hardness enhancement and / or the friability reduction is achieved is 70% by mass to 90% by mass. Method;
(1-25)
The method according to any one of (1-15) to (1-24), wherein the content of crospovidone is 0.5% by mass to 30% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. ;
(1-26)
The method according to any one of (1-15) to (1-25), wherein the tablet is produced by a direct compression method;
(1-27)
Before the tablet is compressed, a granulated product which is a mixture containing crospovidone and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method, (1-15) to (1- 25) The method according to any one of
(1-28)
The method according to any one of (1-15) to (1-27), wherein the tablet does not contain an excipient;
(1-29)
The method according to any one of (1-15) to (1-28), wherein the tablet does not contain sugar;
(1-30)
Use of crospovidone to increase the hardness of tablets containing lanthanum carbonate hydrate;
(1-31)
The use of crospovidone for reducing the friability of tablets containing lanthanum carbonate hydrate;
(1-32)
The use according to (30) or (31), wherein the tablet is an orally disintegrating tablet;
(1-33)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The use according to any one of (1-30) to (1-32), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(1-34)
The use according to any one of (1-30) to (1-32), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(1-35)
The use according to any one of (1-30) to (1-34), which is a use for increasing the hardness of a tablet and reducing the friability.
(1-36)
The tablet according to any one of (1-30) to (1-35), wherein the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. use;
(1-37)
The tablet according to any one of (1-30) to (1-36), wherein the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. use;
(1-38)
The use according to any one of (1-30) to (1-37), wherein the content of crospovidone is 0.5% by mass to 30% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. ;
(1-39)
The use according to any one of (1-30) to (1-38), wherein the tablet is produced by a direct compression method;
(1-40)
Before the tablet is compressed, a granulated product which is a mixture containing crospovidone and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method, (1-30) to (1- 39) The use according to any one of
(1-41)
The use according to any one of (1-30) to (1-40), wherein the tablet does not contain an excipient;
(1-42)
The use according to any one of (1-30) to (1-41), wherein the tablet does not contain sugar;
(1-43)
A process for producing a tablet comprising lanthanum carbonate hydrate, comprising the step of tableting a mixture comprising crospovidone and lanthanum carbonate hydrate;
(1-44)
The method according to (1-43), which is a method for producing a tablet that achieves increased hardness or reduced friability;
(1-45)
The method according to (1-43) or (1-44), wherein the tablet is an orally disintegrating tablet;
(1-46)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (1-43) to (1-45), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(1-47)
The method according to any one of (1-43) to (1-46), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(1-48)
The method according to any one of (1-43) to (1-47), which is a method for producing a tablet in which increased hardness and reduced friability are achieved;
(1-49)
In the tablet obtained by the method according to any one of (1-43) to (1-48), the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass (1-43) to ( 1-48)
(1-50)
In the tablet obtained by the method according to any one of (1-43) to (1-49), the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass (1-43) to ( 1-49)
(1-51)
(1-43) to (1), wherein the content of crospovidone in the tablet obtained by the method according to any one of (1-43) to (1-50) is 0.5% by mass to 30% by mass. -50);
(1-52)
The method according to any one of (1-43) to (1-51), wherein the tablet is produced by a direct compression method;
(1-53)
Before the tablet is compressed, a granulated product which is a mixture containing crospovidone and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method, (1-43) to (1- 52)
(1-54)
The method according to any one of (1-43) to (1-53), wherein the tablet does not contain an excipient;
(1-55)
The method according to any one of (1-43) to (1-54), wherein the tablet does not contain sugar;
(2-1)
A hardness enhancer for tablets comprising lanthanum carbonate hydrate, comprising low substituted hydroxypropylcellulose;
(2-2)
A friability reducing agent for tablets comprising lanthanum carbonate hydrate, comprising low substituted hydroxypropylcellulose;
(2-3)
A tablet hardness enhancer comprising lanthanum carbonate hydrate, comprising a low-substituted hydroxypropylcellulose;
(2-4)
A friability reducing agent for tablets containing lanthanum carbonate hydrate, comprising low-substituted hydroxypropylcellulose;
(2-5)
The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-4), wherein the tablet is an orally disintegrating tablet;
(2-6)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The hardness enhancer or friability reducer according to any one of (2-1) to (2-5), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8). ;
(2-7)
The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-6), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(2-8)
The hardness enhancer or friability reducer according to any one of (2-1) to (2-7), wherein the low-substituted hydroxypropylcellulose also functions as a disintegrant;
(2-9)
The hardness enhancer or friability reducer according to any one of (2-1) to (2-8), which is a hardness enhancer and is a friability reducer;
(2-10)
When the hardness enhancer or friability reducing agent according to any one of (2-1) to (2-9) is contained in the tablet together with the lanthanum carbonate hydrate, the lanthanum carbonate hydrate in the tablet The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-9), wherein the content is 70% by mass to 99% by mass;
(2-11)
As a result of the hardness enhancer or friability reducing agent according to any one of (2-1) to (2-10) being contained in the tablet together with the lanthanum carbonate hydrate, the lanthanum carbonate hydrate in the tablet The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-10), wherein the content is 70% by mass to 90% by mass;
(2-12)
As a result of the hardness enhancer or friability reducing agent according to any one of (2-1) to (2-11) being contained in a tablet together with lanthanum carbonate hydrate, low substituted hydroxypropylcellulose in the tablet The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-11), wherein the content of is from 0.5% by mass to 30% by mass;
(2-13)
The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-12), wherein the tablet does not contain an excipient;
(2-14)
The hardness enhancing agent or friability reducing agent according to any one of (2-1) to (2-13), wherein the tablet does not contain sugar;
(2-15)
A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising the step of tableting a mixture comprising low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(2-16)
A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising using low-substituted hydroxypropylcellulose as a disintegrant;
(2-17)
A method for reducing the friability of tablets containing lanthanum carbonate hydrate, comprising tableting a mixture comprising low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(2-18)
A method for reducing the friability of tablets containing lanthanum carbonate hydrate comprising using low substituted hydroxypropylcellulose as a disintegrant;
(2-19)
The method according to any one of (2-15) to (2-18), wherein the tablet is an orally disintegrating tablet;
(2-20)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (2-15) to (2-19), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(2-21)
The method according to any one of (2-15) to (2-20), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(2-22)
The method according to any one of (2-15) to (2-21), which is a method for increasing the hardness of a tablet and decreasing the friability.
(2-23)
The tablet according to any one of (2-15) to (2-22), wherein the content of the lanthanum carbonate hydrate is 70% by mass to 99% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. Method;
(2-24)
The tablet according to any one of (2-15) to (2-23), wherein the content of the lanthanum carbonate hydrate is 70% by mass to 90% by mass in the tablet in which the hardness enhancement and / or the friability reduction is achieved. Method;
(2-25)
Any of (2-15) to (2-24), wherein the content of the low-substituted hydroxypropylcellulose in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5% by mass to 30% by mass The method described in;
(2-26)
The method according to any one of (2-15) to (2-25), wherein the tablet is produced by a direct compression method;
(2-27)
Before the tablet is compressed, a granulated product that is a mixture containing low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method, (2-15) -The method in any one of (2-25);
(2-28)
The method according to any one of (2-15) to (2-27), wherein the tablet does not contain an excipient;
(2-29)
The method according to any one of (2-15) to (2-28), wherein the tablet does not contain sugar;
(2-30)
At least one use of low substituted hydroxypropylcellulose to increase the hardness of tablets containing lanthanum carbonate hydrate;
(2-31)
At least one use of low substituted hydroxypropylcellulose to reduce the friability of tablets containing lanthanum carbonate hydrate;
(2-32)
The use according to (2-30) or (2-31), wherein the tablet is an orally disintegrating tablet;
(2-33)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The use according to any one of (2-30) to (2-32), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(2-34)
The use according to any one of (2-30) to (2-33), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(2-35)
The use according to any one of (2-30) to (2-34), which is a use for increasing the hardness of the tablet and reducing the friability.
(2-36)
The tablet according to any one of (2-30) to (2-35), wherein the content of the lanthanum carbonate hydrate is 70% by mass to 99% by mass in the tablet in which the hardness enhancement and / or the friability reduction is achieved. use;
(2-37)
The tablet according to any one of (2-30) to (2-36), wherein the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. use;
(2-38)
Any of (2-30) to (2-37), wherein the content of low-substituted hydroxypropylcellulose is 0.5% by mass to 30% by mass in the tablet in which hardness enhancement and / or friability reduction is achieved. Use as described in;
(2-39)
The use according to any one of (2-30) to (2-38), wherein the tablet is produced by a direct compression method;
(2-40)
Before the tablet is compressed, a granulated product which is a mixture containing low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method, (2-30) -Use according to any of (2-39);
(2-41)
The use according to any one of (2-30) to (2-40), wherein the tablet does not contain an excipient;
(2-42)
The use according to any one of (2-30) to (2-41), wherein the tablet does not contain sugar;
(2-43)
A method for producing a tablet comprising lanthanum carbonate hydrate, comprising the step of tableting a mixture comprising low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate;
(2-44)
The method according to (2-43), which is a method for producing a tablet in which hardness enhancement or friability reduction is achieved;
(2-45)
The method according to (2-43) or (2-44), wherein the tablet is an orally disintegrating tablet;
(2-46)
Lanthanum carbonate hydrate has the general formula La ₂ (CO ₃ ) ₃ XH ₂ The method according to any one of (2-43) to (2-45), which is a lanthanum carbonate hydrate represented by O (wherein x is 3 to 8);
(2-47)
The method according to any one of (2-43) to (2-46), wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate;
(2-48)
The method according to any one of (2-43) to (2-47), which is a method for producing a tablet in which hardness enhancement and friability reduction are achieved;
(2-49)
In the tablet obtained by the method according to any one of (2-43) to (2-48), the content of lanthanum carbonate hydrate is 70% by mass to 99% by mass (2-43) to ( 2-48) the method according to any one of the above;
(2-50)
In the tablet obtained by the method according to any one of (2-43) to (2-49), the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass (2-43) to ( 2-49) the method according to any one of the above;
(2-51)
The content of the low-substituted hydroxypropylcellulose in the tablet obtained by the method according to any one of (2-43) to (2-50) is 0.5% by mass to 30% by mass (2-43 ) To (2-50).
(2-52)
The method according to any one of (2-43) to (2-51), wherein the tablet is produced by a direct compression method;
(2-53)
Before the tablet is compressed, a granulated product, which is a mixture containing low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate, is produced by a dry granulation method or a wet granulation method, (2-43) -The method in any one of (2-51);
(2-54)
The method according to any one of (2-43) to (2-53), wherein the tablet does not contain an excipient;
(2-55)
The method according to any one of (2-43) to (2-54), wherein the tablet does not contain sugar;

  EXAMPLES Hereinafter, although an Example demonstrates this invention further, this invention is not limited to these.

Formula A
Lanthanum carbonate tetrahydrate 477mg, Crospovidone 30mg, Aspartame 10mg, Light anhydrous silicic acid 7mg and Magnesium stearate 7mg were mixed, and the mixture was put into a rotary tableting machine. 11 tablets were pressed for each tableting pressure to obtain tablets. The content of crospovidone in the tablet was 5.6%.
Tableting pressure: 781, 1180, 1941, 2484 kgf

Formula B
Lanthanum carbonate tetrahydrate 477mg, crospovidone 15mg, D-mannitol 15mg, aspartame 10mg, light anhydrous silicic acid 7mg and magnesium stearate 7mg were mixed, and the mixture was put into a rotary tableting machine. Eleven tablets were tableted for each tableting pressure with the following tableting pressure to obtain tablets. The content of crospovidone in the tablet was 2.8%.
Tableting pressure: 1174, 1779, 1811, 2017, 2372, 2941 kgf

Test 1
The hardness of the obtained tablets was measured using a Schleuniger hardness tester. The average value of the hardness of the preparation obtained by tableting with a tableting pressure of 781 kgf of the formulation A and the hardness of the preparation obtained by tableting with a tableting pressure of 1174 kgf of the formulation B was determined. The hardness of the preparation obtained at each tableting pressure of Formula A and Formula B was expressed as a relative value and plotted (FIG. 1).
For formulation A containing 5.6% crospovidone in the formulation, the hardness increased in proportion to the tableting pressure, whereas for formulation B containing 2.8% crospovidone in the formulation, up to about 2000 kgf was proportional to the tableting pressure. The hardness increased, but the hardness did not increase at higher tableting pressures. In all tableting pressure ranges tested, Formulation A had a higher hardness than Formulation B, and increased hardness was observed with increasing crospovidone content (FIG. 1).

Test 2
The friability of the obtained tablets was measured according to the friability test method (Japanese Pharmacopoeia reference information). The average value of the friability of the preparation obtained by tableting with a tableting pressure of 781 kgf for the formulation A and the tableting pressure of 1174 kgf for the formulation B was determined. As a result, the friability of the preparations obtained with the tableting pressures of Formulation A and Formulation B were expressed as relative values and plotted (FIG. 2).
For Formula A containing 5.6% crospovidone in the formulation and Formula B containing 2.8% crospovidone in the formulation, the friability decreased in proportion to the tableting pressure. In all tableting pressure ranges tested, Formulation A was less friable than Formulation B (improved friability), and increased crospovidone content resulted in lower friability (improved friability). It was recognized (FIG. 2).

  By comparing the hardness and friability of Formulation B, it is shown that the relationship that the friability is lowered (the friability is improved) simply by increasing the hardness is not recognized, and the friability is not completely dependent on the hardness. It was done.

Use of the present invention provides tablets containing lanthanum carbonate hydrate useful for the treatment of hyperphosphatemia.

Claims (45)

A tablet hardness enhancer comprising lanthanum carbonate hydrate, comprising at least one of crospovidone and low-substituted hydroxypropylcellulose. A tablet friability reducing agent comprising lanthanum carbonate hydrate, comprising at least one of crospovidone and low-substituted hydroxypropylcellulose. Hardness enhancer for tablets comprising lanthanum carbonate hydrate, selected from crospovidone and low substituted hydroxypropylcellulose. A friability reducing agent for tablets comprising lanthanum carbonate hydrate, selected from crospovidone and low substituted hydroxypropylcellulose. The hardness enhancer or friability reducing agent according to any one of claims 1 to 4, wherein the tablet is an orally disintegrating tablet. Lanthanum carbonate hydrate has the general formula _{La 2 (CO 3) 3 ·} xH ( where, x is a 3 to 8) 2 O is a lanthanum carbonate hydrate represented by the claims 1 to 5 The hardness enhancer or friability reducing agent according to any one of the above. The hardness enhancer or friability reducing agent according to any one of claims 1 to 6, wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate. The hardness enhancer or friability reducer according to any one of claims 1 to 7, wherein at least one of crospovidone and low-substituted hydroxypropylcellulose also functions as a disintegrant. The hardness enhancer or friability reducer according to any one of claims 1 to 8, which is a hardness enhancer and a friability reducer. The hardness enhancer or friability reducing agent according to any one of claims 1 to 9 is contained in the tablet together with the lanthanum carbonate hydrate, so that the content of the lanthanum carbonate hydrate in the tablet is 70% by mass or more. The hardness enhancer or friability reducing agent according to any one of claims 1 to 9, which is 99% by mass. As a result of the hardness enhancer or friability reducing agent according to any one of claims 1 to 10 being contained in a tablet together with lanthanum carbonate hydrate, the content of lanthanum carbonate hydrate in the tablet is 70% by mass to The hardness enhancer or friability reducing agent according to any one of claims 1 to 10, which is 90% by mass. As a result of the hardness enhancer or friability reducing agent according to any one of claims 1 to 11 being contained in a tablet together with lanthanum carbonate hydrate, the content of crospovidone in the tablet is 0.5 mass% to 30 mass%. The hardness enhancer or friability reducing agent according to any one of claims 1 to 11, which is in mass%. When the hardness enhancer or friability reducing agent according to any one of claims 1 to 12 is contained in a tablet together with lanthanum carbonate hydrate, the content of low-substituted hydroxypropylcellulose in the tablet is 0.5. The hardness enhancer or friability reducing agent according to any one of claims 1 to 12, wherein the hardness enhancer or the friability lowering agent is 1% by mass to 30% by mass. The hardness enhancer or friability reducing agent according to any one of claims 1 to 13, wherein the tablet does not contain an excipient. The hardness enhancer or friability reducing agent according to any one of claims 1 to 14, wherein the tablet does not contain sugar.   A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising tableting a mixture comprising crospovidone and at least one of low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate.   A method for enhancing the hardness of a tablet comprising lanthanum carbonate hydrate, comprising using at least one of crospovidone and low-substituted hydroxypropylcellulose as a disintegrant.   A method for reducing the friability of a tablet comprising lanthanum carbonate hydrate, comprising tableting a mixture comprising crospovidone and at least one of low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate.   A method for reducing the friability of a tablet comprising lanthanum carbonate hydrate, comprising using at least one of crospovidone and low-substituted hydroxypropylcellulose as a disintegrant. The method according to any one of claims 16 to 19, wherein the tablet is an orally disintegrating tablet. The lanthanum carbonate hydrate is a lanthanum carbonate hydrate represented by the general formula La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 3 to 8). The method according to any one. The method according to any one of claims 16 to 21, wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate. The method according to any one of claims 16 to 22, which is a method of increasing the hardness of a tablet and decreasing the friability. The method according to any one of claims 16 to 23, wherein the content of the lanthanum carbonate hydrate in the tablet in which the hardness enhancement and / or the friability reduction is achieved is 70% by mass to 99% by mass. The method according to any one of claims 16 to 24, wherein the content of the lanthanum carbonate hydrate in the tablet in which the hardness enhancement and / or the friability reduction is achieved is 70% by mass to 90% by mass. The method according to any one of claims 16 to 25, wherein the content of crospovidone in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5 mass% to 30 mass%. The method according to any one of claims 16 to 26, wherein the content of the low-substituted hydroxypropylcellulose in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5 mass% to 30 mass%. The method according to any one of claims 16 to 27, wherein the tablet is produced by a direct compression method. Before the tablet is compressed, a granulated product that is a mixture containing at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method. The method according to any one of claims 16 to 27. 30. A method according to any of claims 16 to 29, wherein the tablet is free of excipients. 31. A method according to any of claims 16-30, wherein the tablet does not contain sugar. Use of at least one of crospovidone and low substituted hydroxypropylcellulose for enhancing the hardness of tablets containing lanthanum carbonate hydrate. Use of at least one of crospovidone and low substituted hydroxypropylcellulose for reducing the friability of tablets containing lanthanum carbonate hydrate. 34. Use according to claim 32 or claim 33, wherein the tablet is an orally disintegrating tablet. The lanthanum carbonate hydrate is a lanthanum carbonate hydrate represented by the general formula La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 3 to 8). Use as described in any one. 36. Use according to any of claims 32 to 35, wherein the lanthanum carbonate hydrate is lanthanum carbonate tetrahydrate or lanthanum carbonate octahydrate. 37. Use according to any of claims 32-36, wherein the use is for increasing the hardness of a tablet and reducing the friability. The use according to any one of claims 32 to 37, wherein the content of lanthanum carbonate hydrate in the tablet in which hardness enhancement and / or friability reduction is achieved is 70% by mass to 99% by mass. The use according to any one of claims 32 to 38, wherein the content of lanthanum carbonate hydrate is 70% by mass to 90% by mass in a tablet in which hardness enhancement and / or friability reduction is achieved. 40. Use according to any of claims 32-39, wherein the content of crospovidone in the tablet in which hardness enhancement and / or friability reduction has been achieved is 0.5% to 30% by weight. The use according to any one of claims 32 to 40, wherein the content of low-substituted hydroxypropylcellulose in the tablet in which hardness enhancement and / or friability reduction is achieved is 0.5 mass% to 30 mass%. 42. Use according to any of claims 32-41, wherein the tablet is produced by a direct compression method. Before the tablet is compressed, a granulated product that is a mixture containing at least one of crospovidone and low-substituted hydroxypropylcellulose and lanthanum carbonate hydrate is produced by a dry granulation method or a wet granulation method. 42. Use according to any of claims 32-41. 44. Use according to any of claims 32-43, wherein the tablet is free of excipients. 45. Use according to any of claims 32-44, wherein the tablet does not contain sugar.

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