JP2016147827A - Pharmaceutical formulations containing lanthanum carbonate hydrate - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide pharmaceutical formulations in which the hydration level of Lanthanum carbonate hydrate represented by formula La(CO)×xHO (where, x is 8-9) is maintained.SOLUTION: Disclosed is a pharmaceutical formulation containing Lanthanum carbonate hydrate represented by formula La(CO)×xHO (where, x is 8-9) and a pharmaceutically acceptable additive, wherein the water content of the formulation after manufacturing is 9 mass% or more to 20 mass% or less. Also disclosed is a method for stabilizing the hydration level of the Lanthanum carbonate hydrate in the formulation by adding a pharmaceutically acceptable additive to the Lanthanum carbonate hydrate of the formula, and setting the water content of the formulation to 9 mass% or more to 20 mass% or less.SELECTED DRAWING: None

Description

  The present invention relates to a pharmaceutical preparation containing lanthanum carbonate hydrate.

  Lanthanum carbonate hydrate preparations are used as therapeutic agents for hyperphosphatemia. Orally administered lanthanum carbonate strongly binds to phosphate ingested in the intestine to form extremely insoluble lanthanum phosphate, and is excreted in the feces without separation. Phosphorus absorption is suppressed and serum phosphorus concentration is thought to decrease.

  Hyperphosphatemia occurs in many patients with chronic kidney disease (CKD) during dialysis as well as in conservative phase, and is caused by a decrease in phosphorus excretion from the kidney. It tends to cause lime deposits. In particular, it has been pointed out that calcification on the blood vessel wall causes arteriosclerosis and increases the risk of developing myocardial infarction and angina. In patients with CKD, it is important to appropriately control the serum phosphorus concentration . Therefore, the dose of the therapeutic agent for hyperphosphatemia is appropriately increased or decreased based on the serum phosphorus concentration. Therefore, a pharmaceutical preparation that stably contains a desired amount of active ingredient is desired.

  Patent Document 1 discloses a lanthanum carbonate-containing pharmaceutical preparation produced without wet granulation or drying, since granulation and drying can affect the hydration level of the drug.

  Patent Document 2 discloses that decarboxylation of lanthanum carbonate into lanthanum hydroxide is promoted by humidity and heat, and that monosaccharides or disaccharides suppress decarboxylation of lanthanum carbonate.

Japanese Patent No. 4896719 Special table 2009-514940 specification

Lanthanum carbonate hydrate represented by the formula La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 8 to 9) (hereinafter referred to as lanthanum carbonate hydrate of the above formula) is an unstable drug. For this reason, there has been a problem that the number of water of crystallization decreases due to factors such as heating. When the number of water of crystallization decreases and the hydration level is not maintained, the mass of the pharmaceutical preparation is affected. Then, this invention makes it a subject to provide the pharmaceutical formulation with which the hydration level of the lanthanum carbonate hydrate of the said formula was maintained.

  In view of the above problems, the present inventors have intensively studied, and by setting the water content of a pharmaceutical preparation containing lanthanum carbonate hydrate of the above formula and a pharmaceutically acceptable additive to a certain value or more, It was found that the hydration level of lanthanum carbonate hydrate can be maintained, and the present invention has been completed. The main configuration of the present invention is as follows.

(1) A pharmaceutical preparation comprising lanthanum carbonate hydrate of the above formula and a pharmaceutically acceptable additive, wherein the water content of the preparation after preparation is 9% by mass or more and 20% by mass or less.
(2) The pharmaceutical preparation according to (1), wherein the additive contains a saccharide.
(3) The saccharide is at least one selected from the group consisting of lactose, glucose, fructose, isomalt, erythritol, xylitol, sorbitol, maltitol, mannitol, dextrate, dextrose, crystalline cellulose, and dextrin. The pharmaceutical preparation according to 2).
(4) The pharmaceutical preparation according to (2) or (3), wherein the additive further contains a water-soluble polymer.
(5) The pharmaceutical preparation according to (4), wherein the water-soluble polymer is at least one selected from the group consisting of hydroxypropylcellulose, hypromellose, methylcellulose, and povidone.
(6) The pharmaceutical preparation according to any one of (1) to (5), wherein at least the lanthanum carbonate hydrate is wet granulated.
(7) The pharmaceutical preparation according to (6), wherein the lanthanum carbonate hydrate is wet granulated together with a part or all of the additive.
(8) A pharmaceutically acceptable additive is added to the lanthanum carbonate hydrate of the above formula, and the water content of the formulation is 9% by mass or more and 20% by mass or less, whereby lanthanum carbonate hydration in the formulation A method of stabilizing the level of hydration of an object.
(9) The method according to (8), wherein a saccharide is used as the additive.
(10) The saccharide is at least one selected from the group consisting of lactose, glucose, fructose, isomalt, erythritol, xylitol, sorbitol, maltitol, mannitol, dextrate, dextrose, crystalline cellulose, and dextrin. The method according to 9).
(11) The method according to (9) or (10), wherein a water-soluble polymer is further used as the additive.
(12) The method according to (11), wherein the water-soluble polymer is at least one selected from the group consisting of hydroxypropylcellulose, hypromellose, methylcellulose, and povidone.
(13) The method according to any one of (8) to (12), comprising a step of wet granulating at least the lanthanum carbonate hydrate.
(14) The method according to (13), wherein the lanthanum carbonate hydrate is wet granulated together with a part or all of the additive.

  ADVANTAGE OF THE INVENTION According to this invention, the pharmaceutical formulation by which the hydration level of the lanthanum carbonate hydrate of the said formula was maintained and stabilized can be provided.

  Hereinafter, embodiments of the present invention will be described in more detail. However, the present invention is not limited to the following embodiments.

  The pharmaceutical preparation of the present invention is a pharmaceutical preparation comprising lanthanum carbonate hydrate of the above formula and a pharmaceutically acceptable additive, wherein the water content of the preparation is 9% by mass or more and 20% by mass or less. In addition, the present invention adds a pharmaceutically acceptable additive to the lanthanum carbonate hydrate of the above formula, and the water content of the preparation is 9% by mass or more and 20% by mass or less. It is also a method of stabilizing the hydration level of lanthanum hydrate.

  The lanthanum carbonate hydrate of the above formula contained in the pharmaceutical preparation of the present invention can be produced by a method known to those skilled in the art according to the production method described in Japanese Patent No. 3224544.

  The hydration level of the lanthanum carbonate hydrate of the above formula is a method known to those skilled in the art such as powder X-ray diffraction (XRPD) according to the method described in Japanese Patent No. 3224544 or Japanese Translation of PCT International Publication No. 2009-536356. Can be measured. Specifically, lanthanum carbonate octahydrate has a characteristic peak at a diffraction angle (2θ) near 10.4 °, and a characteristic peak at a diffraction angle (2θ) near 13.5 °. (FIG. 2 of JP-T-2009-536356). Lanthanum carbonate 8.8 hydrate also has a characteristic peak at a diffraction angle (2θ) around 10.4 ° (FIG. 4 of Japanese Patent No. 3224544). Lanthanum carbonate tetrahydrate has a characteristic peak at a diffraction angle (2θ) near 13.5 °, and does not have a characteristic peak at a diffraction angle (2θ) near 10.4 ° (special table) 2009-536356 gazette 1). The value of the diffraction angle (2θ) is preferably within ± 0.3 °, more preferably within ± 0.2 °, and still more preferably within ± 0.1 °.

  Lanthanum carbonate hydrate is a compound in which the hydration level is likely to change under specific conditions such as high temperature, high humidity (hydrolysis), and drying, due to hydration transition (the number of water of crystallization changes). Specifically, when lanthanum carbonate octahydrate is dried at a predetermined temperature, the peak characteristic of lanthanum carbonate octahydrate (2θ around 10.4 °) gradually decreases, and lanthanum carbonate tetrahydrate The peak (2θ near 13.5 °) characteristic of the Japanese product gradually increases. From the presence or absence of these characteristic peaks, the hydration transition of lanthanum carbonate octahydrate to lanthanum carbonate tetrahydrate can be confirmed. The maintenance or stabilization of the hydration level is to suppress the reduction of water of crystallization, specifically to suppress the hydration transition of lanthanum carbonate hydrate of the above formula to lanthanum carbonate tetrahydrate. In other words. The hydration level may be maintained at 95%, preferably 97%, more preferably 99%, and even more preferably 99.5% of the lanthanum carbonate hydrate of the above formula contained in the pharmaceutical preparation.

  In the present invention, the amount of water in the pharmaceutical preparation refers to the amount of water contained in the pharmaceutical preparation such as crystal water and adhering water. Crystallized water and adhering water of lanthanum carbonate hydrate, and water of crystallizing and adhering water of pharmaceutically acceptable additives are included. The amount of moisture refers to a value measured using a thermogravimetric method (halogen moisture meter). The water content of the pharmaceutical preparation of the present invention is 9% by mass to 20% by mass, preferably 9.5% by mass to 19% by mass, and more preferably 10% by mass to 18% by mass. If the water content of the pharmaceutical preparation is within the above range, the hydration level of the lanthanum carbonate hydrate of the above formula can be maintained or stabilized, and the hydration transfer to lanthanum carbonate tetrahydrate can be suppressed.

  In the present invention, the water content of the pharmaceutical preparation can be appropriately adjusted by those skilled in the art by adding water (humidification), drying, or a combination of additives. Examples of the adjustment of hydration (humidification) include granulation using a water-containing solvent, increasing / decreasing the granulation time, and the like. Examples of the adjustment of drying include increasing / decreasing the drying time using a drying apparatus, adjusting the drying temperature, and the like. Examples of the adjustment of the combination of additives include increasing and decreasing the amount of water-absorbing (hygroscopic) additive. When sugars and water-soluble polymers described later are added, moisture adjustment can be facilitated. In addition, it can also be adjusted by increasing or decreasing the amount of desiccant used at the time of storage of the preparation.

  The content of the lanthanum carbonate hydrate of the above formula per pharmaceutical preparation can be determined according to the sex, age, symptoms, etc. of the user, but it is 65% by weight or more, preferably 70% by weight of the whole pharmaceutical preparation. As mentioned above, More preferably, it is 75 mass% or more. An upper limit is 98.5 mass% or less of the whole pharmaceutical formulation, Preferably it is 95 mass% or less, More preferably, it is 90 mass% or less.

  Pharmaceutically acceptable additives refer to additives such as excipients, binders, disintegrants, lubricants, fluidizers, sweeteners and the like that are commonly used in pharmaceutical preparations. The excipient preferably contains a saccharide, and more preferably contains a saccharide and a water-soluble polymer.

  Sugars include monosaccharides, disaccharides, oligosaccharides, polysaccharides, and sugar alcohols, and those commonly used as pharmaceutical preparations can be used. Examples include lactose, glucose, fructose, isomalt, erythritol, xylitol, sorbitol, maltitol, mannitol, dextrate, dextrose, crystalline cellulose, and dextrin, but are not limited thereto. Among these, lactose, isomalt, erythritol, maltitol, mannitol, and dextrate are preferable, and lactose, mannitol, and dextrate are more preferable.

  The content of the saccharide is preferably 1% by mass or more and 35% by mass or less, more preferably 5% by mass or more and 30% by mass or less, based on the whole pharmaceutical preparation. When the saccharide content is 1% by mass or more, the hydrated state of the lanthanum carbonate hydrate of the above formula tends to be maintained. The upper limit of the saccharide content can be appropriately set according to the contents of the active ingredient and other additives.

  Water-soluble saccharides tend to dissolve when contacted with water and suppress the transpiration of water by retaining the free water contained in the pharmaceutical preparation. Water-insoluble saccharides tend to maintain the hydrated state of the lanthanum carbonate hydrate of the above formula when used in combination with a water-soluble polymer described below.

  A water-soluble polymer refers to a polymer that dissolves in water. Examples include, but are not limited to, water-soluble cellulose polymers such as hydroxypropylcellulose, hypromellose, and methylcellulose, and povidone. Among these, methyl cellulose is preferable.

  The content of the water-soluble polymer is preferably 0.5% by mass or more and 6% by mass or less, more preferably 0.8% by mass and 3.5% by mass, based on the whole pharmaceutical preparation. The pharmaceutical preparation containing 0.5% by mass or more of the whole water-soluble polymer tends to maintain the hydration state of the lanthanum carbonate hydrate of the above formula. The upper limit of the content of the water-soluble polymer can be appropriately set according to the contents of the active ingredient and other additives.

  The water-soluble polymer has a certain amount of free water, and when dissolved in water, it dissolves into a highly viscous gel. Due to this property, free water contained in the pharmaceutical preparation is retained, and a microscopic gel is formed, thereby tending to suppress moisture transpiration. This is because most of the heat stress applied to the pharmaceutical preparation is consumed by the transpiration of water retained by the water-soluble polymer in the pharmaceutical preparation, so that the water crystallized in the lanthanum carbonate hydrate of the above formula is used. This is thought to contribute to reducing the heat stress load.

  Examples of the additive that may be further contained in the pharmaceutical preparation of the present invention include a binder, a disintegrant, a lubricant, a fluidizing agent, and a sweetener.

  Examples of the binder include pregelatinized starch, starch paste, carmellose sodium, polyvinyl alcohol, carboxyvinyl polymer, gelatin, pullulan and the like.

  Examples of the disintegrant include crospovidone, croscarmellose sodium, carmellose, carmellose calcium, low-substituted hydroxypropyl cellulose, partially pregelatinized starch, and carboxymethyl starch sodium.

  Examples of the lubricant include stearic acid, calcium stearate, magnesium stearate, talc, sodium stearyl fumarate, hydrogenated oil, castor oil, carnauba wax, and sucrose fatty acid ester.

  Examples of the fluidizing agent include silica, colloidal anhydrous silica, magnesium aluminate metasilicate, and the like.

  Examples of the sweetener include sucralose, saccharin sodium, aspartame, trehalose, acesulfame potassium and the like.

  The pharmaceutical preparation of the present invention may be in dosage forms such as tablets, chewable agents, granules, fine granules, capsules, and dry syrups.

  The pharmaceutical preparation of the present invention can be produced by, for example, a dry granulation method. Examples of the dry granulation method include a method in which the mixed powder is compressed into a slug material, or the mixed powder is roller-compressed into a strand material and pulverized. Moreover, the pharmaceutical formulation of this invention can also be manufactured by the wet granulation method etc., for example. Examples of the wet granulation method include a fluidized bed granulation method, a stirring granulation method, and an extrusion granulation method. Furthermore, the granule obtained by the dry granulation method or the wet granulation method can be compression-molded. Regardless of the production method, the stable pharmaceutical preparation of the present invention is obtained by controlling the water content of the pharmaceutical preparation within a predetermined range and using a combination of saccharide and / or water-soluble polymer as necessary. Can be obtained.

  The pharmaceutical preparation according to an embodiment of the present invention is prepared by adding an additive to the lanthanum carbonate hydrate of the above formula, saccharide, and water-soluble polymer and mixing them as necessary. And it can obtain by adjusting the moisture content of a formulation to a desired range. In the mixing step, the lanthanum carbonate hydrate of the above formula may be subjected to wet granulation together with the saccharide and the water-soluble polymer, if necessary. Here, pharmaceutical preparations produced by dry granulation and the like tend to have roughness in the oral cavity and lingering mouth, but pharmaceutical preparations produced by wet granulation and the like are pharmaceutical preparations with good dosing properties. This is particularly preferable for dialysis patients who have water intake restrictions.

Hereinafter, the present invention will be described in detail with reference to examples, but the present invention is not limited to these examples.

  The moisture content and XRPD were measured by the following methods.

(1) Water content The water content of each pharmaceutical preparation was measured using a halogen moisture meter (HG63, manufactured by METTLER TOLEDO). The measurement conditions were 15 minutes at 105 ° C. per 3 g of the pharmaceutical preparation.

(2) XRPD
XRPD uses an X-ray powder crystal diffractometer (Miniflex, manufactured by Rigaku Corporation) to scan each pharmaceutical preparation under the conditions of a scan speed of 2 ° / min, a sampling width of 0.01 °, and a scan range of 5 to 35 °. It was measured. Maintenance of the hydration level of lanthanum carbonate octahydrate was evaluated at the characteristic peak of XRPD. Specifically, a characteristic peak (2θ near 10.4 °) is observed in lanthanum carbonate octahydrate, and a characteristic peak (2θ near 13.5 °) is found in lanthanum carbonate tetrahydrate. "○" indicates that is not observed, and "X" indicates that a peak characteristic of lanthanum carbonate tetrahydrate (2θ around 13.5 °) is observed.

<Test 1>
About the pharmaceutical formulation of the following Examples 1-4 and Comparative Examples 1-3, the moisture content and XRPD of a formulation were measured.

[Example 1]
Lanthanum carbonate octahydrate and sorbitol (sorbitol SP, manufactured by Food Science Co., Ltd.) were mixed at the mixing ratio shown in Table 1. An appropriate amount of purified water was added to the mixture and granulated in a mortar. The granulated product is wet-sized using a 24-mesh sieve, divided into three parts, and each is dried for 30 minutes, 60 minutes, and 120 minutes on a shelf dryer (DO-600FA, manufactured by ASONE) set at 60 ° C. did. After drying, a pharmaceutical preparation (granulated granule) was obtained.

[Example 2]
The sorbitol of Example 1 was replaced with anhydrous lactose (DuraLacH, manufactured by MEGLE), and a pharmaceutical preparation (granulated granule) was obtained in the same manner as in Example 1.

[Example 3]
The sorbitol of Example 1 was replaced with crystalline cellulose (Ceolus PH-101, manufactured by Asahi Kasei Chemicals Corporation), and a pharmaceutical preparation (granulated granule) was obtained in the same manner as in Example 1. The drying time was 30 minutes and 60 minutes.

[Example 4]
Example 1 Sorbitol was replaced with D-mannitol (Mannit-P, manufactured by Mitsubishi Corporation Foodtech Co., Ltd.) to obtain a pharmaceutical preparation (granulated granules) in the same manner as in Example 1. The drying time was 30 minutes and 60 minutes.

[Comparative Example 1]
The drying time was changed to 120 minutes, and a pharmaceutical preparation (granulated granules) was obtained in the same manner as in Example 3.

[Comparative Example 2]
The drying time was changed to 120 minutes, and a pharmaceutical preparation (granulated granules) was obtained in the same manner as in Example 4.

[Comparative Example 3]
Only lanthanum carbonate octahydrate was dried for 120 minutes with a shelf dryer (DO-600FA, manufactured by ASONE).

Results The results of Test 1 are shown in Table 2. In Examples 1 to 4, the water content of the pharmaceutical preparation was 9% by mass or more, and hydration transfer to lanthanum carbonate tetrahydrate characterized by XRPD was not observed. In Comparative Examples 1 to 3, the water content of the pharmaceutical preparation was less than 9% by mass, and a peak showing hydration transition to lanthanum carbonate tetrahydrate was observed by XRPD. In addition, the moisture content measured before the drying process with only the lanthanum carbonate octahydrate of Comparative Example 3 was 15.0%.

<Test 2>
About the pharmaceutical formulation of the following Examples 5-9, the moisture content and XRPD of the formulation were measured.

[Example 5]
Lanthanum carbonate octahydrate, glucose (Nippon Glucose, manufactured by Nippon Shokuhin Kako Co., Ltd.), and hydroxypropyl cellulose (HPC-SL, manufactured by Nippon Soda Co., Ltd.) were mixed at the mixing ratio shown in Table 3. An appropriate amount of purified water was added to the mixture and granulated in a mortar. The granulated product was wet-sized using a 24-mesh sieve, divided into two, and dried for 60 minutes and 120 minutes using a shelf dryer (DO-600FA, manufactured by ASONE) set to 60 ° C, respectively. After completion of drying, the powder was dry-sized using a 24-mesh sieve to obtain a pharmaceutical preparation (granulated granules).

[Example 6]
The saccharide of Example 5 was replaced with lactose hydrate (Pharmacatose 200M, manufactured by DMV) and blended according to the blending ratios in Table 3, and a pharmaceutical preparation (granulated granules) was obtained in the same manner as in Example 5.

[Example 7]
The saccharide of Example 5 was replaced with D-mannitol (Mannit-P, manufactured by Mitsubishi Shoji Foodtech Co., Ltd.) and blended according to the blending ratios in Table 3, and the pharmaceutical preparation (granulated granules in the same manner as in Example 5) )

[Example 8]
The saccharide of Example 5 was replaced with erythritol (erythritol 100M, manufactured by Food Science Co., Ltd.) and blended according to the blending ratio in Table 3, and a pharmaceutical preparation (granulated granule) was obtained in the same manner as in Example 5.

[Example 9]
The saccharide of Example 5 was replaced with maltitol (Mabit 100M, manufactured by Hayashibara Co., Ltd.), and blended according to the blending ratio in Table 3. A pharmaceutical preparation (granulated granules) was obtained in the same manner as in Example 5.

Results The results of Test 2 are shown in Table 4. In Examples 5 to 9 containing saccharides and water-soluble polymers as additives, the water content of the preparations was 9% by mass or more regardless of the drying time, and to lanthanum carbonate tetrahydrate characterized by XRPD No hydration transition was observed. Comparison between Example 7 and Comparative Example 2 with a drying time of 120 minutes shows that hydroxypropylcellulose, which is a water-soluble polymer, is effective in retaining the moisture content.

<Test 3>
About the pharmaceutical formulation of the following Examples 10-12, the moisture content and XRPD of the formulation were measured.

[Example 10]
Lanthanum carbonate octahydrate, D-mannitol (Mannit-P, manufactured by Mitsubishi Corporation Foodtech Co., Ltd.) and hypromellose (TC-5R, manufactured by Shin-Etsu Chemical Co., Ltd.) as a water-soluble polymer, according to the blending ratios in Table 5 Mixed. An appropriate amount of purified water was added to the mixture and granulated in a mortar. The granulated product was wet-sized using a 24-mesh sieve, divided into two, and dried for 60 minutes and 120 minutes using a shelf dryer (DO-600FA, manufactured by ASONE) set to 60 ° C, respectively. After completion of drying, the powder was dry-sized using a 24-mesh sieve to obtain a pharmaceutical preparation (granulated granules).

[Example 11]
The water-soluble polymer of Example 10 was replaced with methylcellulose (Metroses SM-15, manufactured by Shin-Etsu Chemical Co., Ltd.) and blended according to the blending ratios in Table 5, and the pharmaceutical preparation (granulated granules in the same manner as in Example 10) )

[Example 12]
The water-soluble polymer of Example 10 was replaced with povidone (Kollidon K30, manufactured by BASF) and blended according to the blending ratios in Table 5, and a pharmaceutical preparation (granulated granules) was obtained in the same manner as in Example 10.

Results of Test 3 are shown in Table 6. In Examples 10 to 12 containing saccharides and water-soluble polymers as additives, the water content of the preparation was 9% by mass or more regardless of the drying time. To the lanthanum carbonate tetrahydrate characterized by XRPD No hydration transition was observed. Comparison with Comparative Example 2 at a drying time of 120 minutes shows that various water-soluble polymers are effective in retaining the moisture content.

<Test 4>
About the pharmaceutical formulation of the following Examples 13-15, the moisture content and XRPD of the formulation were measured.

[Example 13]
Lanthanum carbonate octahydrate, D-mannitol (Mannit-P, manufactured by Mitsubishi Corporation Foodtech Co., Ltd.) and methylcellulose (Metroses SM-15, manufactured by Shin-Etsu Chemical Co., Ltd.) were mixed according to the blending ratios in Table 7. An appropriate amount of purified water was added to the mixture and granulated in a mortar. The granulated product was wet-sized using a 24 mesh sieve and dried for 60 minutes with a shelf dryer (DO-600FA, manufactured by ASONE) set at 60 ° C. After completion of drying, the powder was dry-sized using a 24-mesh sieve to obtain a pharmaceutical preparation (granulated granules).

[Example 14]
The blending ratio of methyl cellulose of Example 13 (Metroses SM-15, manufactured by Shin-Etsu Chemical Co., Ltd.) was 0.8 mass%, blended according to the blending ratio of Table 7, and a pharmaceutical preparation ( Granulated granules) were obtained.

[Example 15]
The blending ratio of methyl cellulose of Example 13 (Metroses SM-15, manufactured by Shin-Etsu Chemical Co., Ltd.) was 0.5% by mass, blended according to the blending ratio of Table 7, and the pharmaceutical preparation ( Granulated granules) were obtained.

The results of Test 4 are shown in Table 8. In Examples 13 to 15 containing 0.5% by mass or more of a water-soluble polymer together with sugars, the water content of the preparation is 9% by mass or more, and hydration transfer to lanthanum carbonate tetrahydrate characterized by XRPD Was not recognized.

Claims (14)

A pharmaceutical preparation comprising a lanthanum carbonate hydrate represented by the following formula and a pharmaceutically acceptable additive, wherein the water content of the preparation after preparation is 9% by mass or more and 20% by mass or less.
La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 8 to 9)   The pharmaceutical formulation according to claim 1, wherein the additive comprises a saccharide.   The saccharide is at least one selected from the group consisting of lactose, glucose, fructose, isomalt, erythritol, xylitol, sorbitol, maltitol, mannitol, dextrate, dextrose, crystalline cellulose, and dextrin. The pharmaceutical preparation described.   The pharmaceutical preparation according to claim 2 or 3, wherein the additive further contains a water-soluble polymer.   The pharmaceutical preparation according to claim 4, wherein the water-soluble polymer is at least one selected from the group consisting of hydroxypropylcellulose, hypromellose, methylcellulose, and povidone.   The pharmaceutical preparation according to any one of claims 1 to 5, wherein at least the lanthanum carbonate hydrate is wet granulated.   The pharmaceutical preparation according to claim 6, wherein the lanthanum carbonate hydrate is wet granulated together with a part or all of the additive. A pharmaceutically acceptable additive is added to the lanthanum carbonate hydrate represented by the following formula, and the water content of the formulation is 9% by mass or more and 20% by mass or less, whereby lanthanum carbonate hydration in the formulation is obtained. A method of stabilizing the level of hydration of an object.
La ₂ (CO ₃ ) ₃ · xH ₂ O (wherein x is 8 to 9)   The method according to claim 8, wherein a saccharide is used as the additive.   The saccharide is at least one selected from the group consisting of lactose, glucose, fructose, isomalt, erythritol, xylitol, sorbitol, maltitol, mannitol, dextrate, dextrose, crystalline cellulose, and dextrin. The method described.   The method according to claim 9 or 10, wherein a water-soluble polymer is further used as the additive.   The method according to claim 11, wherein the water-soluble polymer is at least one selected from the group consisting of hydroxypropylcellulose, hypromellose, methylcellulose, and povidone.   The method according to any one of claims 8 to 12, comprising a step of wet granulating at least the lanthanum carbonate hydrate.   14. The method of claim 13, wherein the lanthanum carbonate hydrate is wet granulated with some or all of the additives.