WO2016088816A1

WO2016088816A1 - Tablet comprising zinc acetate hydrate and method for manufacturing same

Info

Publication number: WO2016088816A1
Application number: PCT/JP2015/083941
Authority: WO
Inventors: 恒雄藤居; 宏晃板東
Original assignee: ノーベルファーマ株式会社
Priority date: 2014-12-03
Filing date: 2015-12-02
Publication date: 2016-06-09
Also published as: JP6716464B2; JPWO2016088816A1; JP2020128442A; JP2019214625A; JP6768984B2

Abstract

Provided are: a compact-sized granulate of zinc acetate hydrate, in which the loss of crystallization water is suppressed during a manufacturing process by controlling the material temperature of the granulate to lower than 40^°C during the manufacturing process and which has a small occupied volume; and a method for manufacturing the same. The granulate is in the form of a tablet comprising zinc acetate hydrate, said tablet containing 5-200 mg of zinc acetate hydrate (C₄H₆O₄Zn^·2H₂O), having a diameter of 5-12 mm and a thickness of 1-6 mm, and showing an elution ratio of zinc of 85% or more after 15 minutes when measured in accordance with the Japanese pharmacopeia elution method (paddle method: 50 rpm, test liquid: water 900 ml).

Description

Zinc acetate hydrate tablets and process for producing the same

The present invention relates to a zinc acetate hydrate tablet containing zinc acetate hydrate as an active ingredient and a method for producing the same.

Wilson's disease is a disease that causes severe damage to the liver, nerves, etc., because copper ingested by diet is not normally excreted from the liver into the bile and intestinal tract, and a large amount of copper accumulates in the liver, brain, kidney, etc. It is.
As a therapeutic agent for Wilson's disease, capsules containing zinc acetate hydrate (C ₄ H ₆ O ₄ Zn.2H ₂ O) as an active ingredient in 1997 in the United States, 2004 in Europe, and 2008 in Japan The agent has been approved and is currently in use.

However, the zinc acetate hydrate capsules currently used have a very large total amount of ingredients packed in the capsule and are a physical mixture. Therefore, when the ingredients are filled into the capsule in the manufacturing process, The fluidity is poor, causing problems such as uneven filling, which is a major obstacle to continuous production of the preparation.
In addition, since the capsule has a large drug diameter (for example, the No. 1 capsule has an outer diameter of 7 mm and a length of 19 to 20 mm), there is a problem that it is difficult to swallow (does not swallow) when taken. Therefore, an agent having zinc acetate hydrate as an active ingredient is required to have a smaller agent diameter (diameter).

In view of the present situation, the present invention controls the drying temperature in the production process of the granulated product to a product temperature of less than 40 ° C., thereby suppressing the disappearance of crystal water in the zinc acetate hydrate in the production process. An object of the present invention is to provide a compacted granulated product of zinc acetate hydrate with a small volume and a method for producing the same.

As a method for obtaining an agent of zinc acetate hydrate that is more efficient than capsules and easy to swallow, a method of filling capsules with smaller diameters or changing to other dosage forms such as tablets can be considered.
On the other hand, zinc acetate hydrate is known as dihydrate and has been recognized to be relatively stable (for example, stable to about 100 ° C. even when heated in sulfuric acid). However, when the present inventors have conducted research on zinc acetate hydrate, when zinc acetate hydrate is heated at a relatively low temperature (for example, about 40 ° C.), Disappeared and metastasized to an anhydride, resulting in an anhydride that was not approved as an active ingredient for Wilson's disease treatment.
Therefore, the present inventors have to avoid the anhydrous formation of zinc acetate hydrate in the manufacture of tablets containing zinc acetate hydrate as an active ingredient. Considering that the disappearance of water is inevitable, an attempt was made to produce zinc acetate hydrate tablets with a small drug size by dry granulation. However, the dry granulation method could not obtain a zinc acetate hydrate tablet with a small dosage size.

As a result of further earnest studies to solve the above-mentioned problems, the inventors of the present invention contain 5-200 mg of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), and the size is a diameter. Zinc acetate water that is 5 to 12 mm, thickness 1 to 6 mm, and zinc elution amount after 15 minutes is measured by 50 rotations of paddle method 50 days (test solution: water 900 mL). Surprisingly, it has been found that Japanese tablets can be produced by a specific production method (for example, wet granulation method, fluidized bed granulation method).
In addition to the above, the present inventors have obtained various unexpected new findings as described below, and have further conducted intensive studies to complete the present invention.

That is, the present invention relates to the following zinc acetate hydrate tablets and the like.
[1] containing 5 to 200 mg of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), having a diameter of 5 to 12 mm and a thickness of 1 to 6 mm, A zinc acetate hydrate tablet, wherein the zinc elution amount after 15 minutes measured by the paddle method 50 rotations (test solution: water 900 mL) is 85% or more.
[2] The zinc acetate hydrate tablet according to [1], wherein the size is 5 to 10 mm in diameter and 2 to 5 mm in thickness.
[3] The zinc acetate hydrate tablet according to [1] or [2], wherein the total mass is twice or less the zinc acetate hydrate content.
[4] (1) A step of granulating a mixture of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), an excipient, a disintegrant, and a solvent and then drying to obtain a granulated product, (2) comprising a step of tableting the granulated product to obtain an uncoated tablet, and (3) a step of film-coating the uncoated tablet and then drying, wherein the product temperature in the step (1) does not exceed 40 ° C. And containing 5 to 200 mg of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), characterized in that the product temperature in the step (3) is 50 ° C. or less, and the size is the diameter Zinc acetate water that is 5 to 12 mm, thickness 1 to 6 mm, and zinc elution amount after 15 minutes is measured by 50 rotations of paddle method 50 days (test solution: water 900 mL). Manufacturing method of Japanese tablets.

ADVANTAGE OF THE INVENTION According to this invention, the zinc acetate hydrate by which the loss | disappearance of the crystal water in the zinc acetate hydrate in a manufacturing process was suppressed by performing the drying in the manufacturing process of a granulated material at the temperature below 40 degreeC. You can get a lock.
In addition, since the zinc acetate hydrate tablet of the present invention is small in size, it is easier to swallow at the time of taking than the conventional zinc acetate hydrate capsule.
In addition, the powder for tableting of the zinc acetate hydrate tablet of the present invention can be used as a granule as it is or filled into a capsule.

Hereinafter, the present invention will be described in detail.
<Zinc acetate hydrate tablets>
The zinc acetate hydrate tablet of the present invention contains 5-200 mg of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn.2H ₂ O), has a size of 5 to 12 mm in diameter and 1 to 6 mm in thickness. Then, the elution amount of zinc after 15 minutes as measured by 50 revolutions of the paddle method of JP (equivalent to 900 mL of water) is 85% or more. In addition, the zinc acetate hydrate tablet may be an uncoated tablet of zinc acetate hydrate, or a film-coated tablet of the uncoated tablet.

In the zinc acetate hydrate tablet of the present invention, the content of zinc acetate hydrate is usually about 5 to 200 mg, preferably about 50 to 180 mg, more preferably about 80 to 170 mg. If it is such a range, the drying after granulation in the manufacturing process of a zinc acetate hydrate tablet can be performed at a temperature of less than 40 ° C., and the crystal water in the zinc acetate hydrate in the manufacturing process can be performed. Since disappearance can be suppressed, it is preferable.

The diameter of the zinc acetate hydrate tablet of the present invention is usually about 5 to 12 mm, preferably about 5 to 10 mm, more preferably about 6 to 9 mm.
The thickness of the zinc acetate hydrate tablet of the present invention is usually about 1 to 6 mm, preferably about 2 to 5 mm, more preferably about 3 to 4 mm.
In this invention, the measuring method of the diameter and thickness of a zinc acetate hydrate tablet is not specifically limited, You may follow the measuring method of the conventionally well-known tablet size.

The zinc acetate hydrate tablet of the present invention has an elution amount of zinc of 15% or more after 15 minutes measured by the JP dissolution method paddle method 50 rotations (test solution: water 900 mL). The zinc acetate hydrate tablet of the present invention can be dried in the granulated product production process at a temperature of less than 40 ° C., and can suppress the disappearance of crystal water in the zinc acetate hydrate in the production process. Therefore, the zinc elution amount falls within such a range.

The total mass of the zinc acetate hydrate tablet of the present invention is usually about 2 times or less, preferably about 1.6 times or less the zinc acetate hydrate content.

The zinc acetate hydrate tablet of the present invention can contain appropriate amounts of additives and pharmaceutically active ingredients generally used in pharmaceuticals. These can be used alone or in combination of two or more.
Examples of the additive include an excipient, a disintegrant, a lubricant, a binder, a coating agent, a brightener, a coloring agent, a corrigent, a sweetener, and a fragrance, and preferably an excipient. Disintegrants, binders, lubricants and the like.

Examples of excipients include, but are not limited to, sugar alcohols such as mannitol, sorbitol, xylitol, erythritol, maltitol, isomalt; sugars such as lactose hydrate, fructose, sucrose, glucose, trehalose; corn starch , Starches such as potato starch, wheat starch and rice starch; amino acids such as glycine and alanine; silicic acids such as light anhydrous silicic acid, synthetic aluminum silicate, magnesium aluminate metasilicate and calcium silicate; crystalline cellulose, powder Celluloses such as cellulose; talc; titanium oxide and the like. The excipient is preferably crystalline cellulose, corn starch, lactose hydrate or the like. These excipients can be used alone or in combination of two or more.

The content of the excipient contained in the zinc acetate hydrate tablet of the present invention is not particularly limited, but is preferably about 5 to 80% by mass with respect to the total mass of the zinc acetate hydrate tablet of the present invention. More preferably, it is about 10 to 50% by mass.

The disintegrant is not particularly limited, for example, crospovidone, carmellose calcium, carmellose, croscarmellose, croscarmellose sodium, low-substituted hydroxypropylcellulose, corn starch, potato starch, wheat starch, rice starch, partial Alpha-ized starch, pregelatinized starch, carboxymethyl starch sodium and the like can be mentioned. The disintegrant is preferably crospovidone, carmellose, croscarmellose, low-substituted hydroxypropylcellulose, or the like. These disintegrants can be used alone or in combination of two or more.

The content of the disintegrant contained in the zinc acetate hydrate tablet of the present invention is not particularly limited, but is preferably about 1 to 50% by mass with respect to the total mass of the zinc acetate hydrate tablet of the present invention. More preferably, it is about 5 to 20% by mass.

The lubricant is not particularly limited, and examples thereof include magnesium stearate, calcium stearate, talc, sucrose fatty acid ester, and sodium stearyl fumarate. The lubricant is preferably talc, magnesium stearate or the like. These lubricants can be used alone or in combination of two or more.

The content of the lubricant contained in the zinc acetate hydrate tablet of the present invention is not particularly limited, but is preferably about 0.1 to 20 relative to the total mass of the zinc acetate hydrate tablet of the present invention. % By weight, more preferably about 0.5 to 10% by weight.

The binder is not particularly limited. For example, povidone, hydroxypropylcellulose, hypromellose phthalate, hydroxypropylmethylcellulose acetate succinate, magnesium magnesium aluminosilicate, synthetic aluminum silicate, light anhydrous silicic acid, silicic acid Calcium, sodium carmellose, ethylcellulose, methylcellulose, hypromellose, gum arabic, sodium alginate, dextrin, corn starch, potato starch, wheat starch, rice starch, partially pregelatinized starch, pregelatinized starch, crystalline cellulose, powdered cellulose, low substitution degree Examples thereof include hydroxypropylcellulose, gelatin, pullulan, carboxyvinyl polymer, and the like. These binders can use 1 type (s) or 2 or more types.

Although it does not specifically limit as a coating agent, For example, water-soluble polymer, water-insoluble polymer, gastric polymer, enteric polymer, etc. are mentioned.
Examples of water-soluble polymers include natural polymers such as gum arabic powder, gelatin pullulan, dextrin, sodium carboxymethyl starch, sodium alginate; polysaccharides; carmellose, carmellose sodium, carmellose calcium, hydroxypropylcellulose, hypromellose , Cellulose derivatives such as hydroxyethyl cellulose, hydroxymethyl cellulose, methyl cellulose, carboxymethyl cellulose; and water-soluble vinyl derivatives such as polyvinyl pyrrolidone and polyvinyl alcohol.
Examples of the water-insoluble polymer include ethyl cellulose, vinyl acetate polymer, aminoalkyl methacrylate copolymer, ethyl acrylate / methyl methacrylate copolymer dispersion, and the like.

Examples of the gastric soluble polymer include aminoacetal compounds such as polyvinyl acetal and diethylaminoacetate.
Examples of the enteric polymer include enteric cellulose esters such as cellulose acetate propionate, hydroxypropylmethylcellulose acetate succinate, hypromellose phthalate, hydroxymethylethylcellulose phthalate, carboxymethylethylcellulose, and cellulose acetate phthalate. Can be mentioned.
In addition to the above, titanium oxide, polyethylene glycol, talc, etc. can also be used as the coating agent.
These coating agents can use 1 type (s) or 2 or more types.

The brightening agent is not particularly limited. For example, carnauba wax, hydrogenated oil, vinyl acetate resin, white beeswax, titanium oxide, stearic acid, calcium stearate, polyoxyl 40 stearate, magnesium stearate, purified shellac, purified paraffin and carnauba wax. Examples thereof include mixed wax, cetanol, talc, white shellac, paraffin, povidone (polyvinylpyrrolidone), polyethylene glycol 1500, polyethylene glycol 4000, polyethylene glycol 6000, beeswax, glyceryl monostearate, and rosin.

Examples of the colorant include food dyes, food lake dyes, iron sesquioxide, yellow iron sesquioxide, and the like.
Examples of the corrigent include citric acid, tartaric acid, malic acid, ascorbic acid and the like.
Examples of the sweetening agent include aspartame, acesulfame potassium, saccharin, saccharin sodium, dipotassium glycyrrhizinate, stevia, thaumatin, and sucralose.
Examples of the fragrance include fennel oil, orange oil, chamomile oil, spearmint oil, cinnamon oil, clove oil, mint oil, bergamot oil, eucalyptus oil, lavender oil, lemon oil, rose oil, roman chamomile oil, menthol and the like. It is done.

The zinc acetate hydrate tablet of the present invention can contain an appropriate amount of a pharmaceutically active ingredient. The active pharmaceutical ingredient is a kind and amount that does not impair the disappearance of crystallization water in the zinc acetate hydrate in the production process of the zinc acetate hydrate tablet of the present invention and the disintegration and moldability of the tablet. Good, not particularly limited.

<Method for producing zinc acetate hydrate tablet>
The method for producing a zinc acetate hydrate tablet of the present invention usually comprises (1) a mixture of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), an excipient, a disintegrant and a solvent. A step of granulating and drying to obtain a granulated product, (2) tableting the granulated product to obtain an uncoated tablet, and (3) a step of film-coating the uncoated tablet and then drying. The product temperature in the step (1) usually does not exceed 40 ° C. In the drying after film coating in the step (3), the product temperature is usually 50 ° C. or lower. In the present invention, these steps are usually performed in the order of steps (1) to (3). In addition, the method for producing a zinc acetate hydrate tablet of the present invention may include steps other than the steps (1) to (3).

<Granulation>
In the present invention, a method for granulating a mixture of zinc acetate hydrate (C ₄ H ₆ O ₄ Zn · 2H ₂ O), an excipient, a disintegrant and a solvent is not particularly limited. A granulation method, a wet granulation method and the like are preferable. These granulation methods have been well established in the past, and the present invention may also follow conventionally known methods.

The fluidized bed granulation method is a process of granulating raw material granules while spraying a solvent or a mixed solution of a solvent and a binder, and, if necessary, a method or an apparatus used for general tablet production. (A fluidized bed granulator or the like) can be used. In the present invention, the fluidized bed granulation process may be a rolling fluidized bed granulation process.
In the present invention, the fluidized bed granulation method includes, for example, mixing zinc acetate hydrate, excipient and disintegrant in a fluidized bed granulator and spraying a solution of a binder and a solvent, It can be carried out.

The wet granulation method is a process of mixing a raw material granule with a solvent and then granulating it, and a method and an apparatus used for general tablet production can be used as necessary. In the present invention, the stirring granulation method is preferable among the wet granulation methods.
In the present invention, the stirring granulation method can be performed, for example, by putting a mixture of zinc acetate hydrate, excipient, disintegrant, binder and solvent into an agitation granulator and stirring.

In addition, the solvent used in the fluidized bed granulation method and the wet granulation method is not particularly limited. For example, alcohols such as ethanol and isopropanol used for the production of general tablets, water, and the like are used. Can do.

Subsequent to the granulation, a processed product obtained by the granulation is dried to obtain a granulated product.
The drying method is not particularly limited. If the drying temperature is less than 40 ° C., a conventionally known drying method in tablet production using a fluidized bed dryer, a shelf dryer or the like may be used.

Generally, the drying temperature after granulation in the production process of the granulated product is around 60 ° C. When zinc acetate hydrate is heated at a temperature of 40 ° C. or higher, water of crystallization in zinc acetate hydrate disappears and transitions to an anhydride. In the production of zinc acetate hydrate tablets of the present invention, Can suppress the loss of crystal water in the zinc acetate hydrate in the granulated product production process by performing drying after granulation at a product temperature of less than 40 ° C.

Further, after the drying, it may be further subjected to operations necessary for producing tablets such as sizing using a comb mill, screen mill, jet mill, hammer mill, pin mill, etc .; sieving using a vibrating sieve.

The granulated product is preferably mixed to obtain a tableting powder before the tableting process in order to make it uniform. The mixing method is not particularly limited, and a conventionally known method can be used. For example, the granulated product and the lubricant can be put into a container rotary mixer and mixed. . The obtained powder for tableting can be directly used as a granule, or can be filled into a capsule by a conventional method to form a capsule. The capsule filled with the tableting powder of the zinc acetate hydrate tablet of the present invention can be smaller in size than the conventional zinc acetate hydrate capsule.

<Tablet>
In the production of the zinc acetate hydrate tablet of the present invention, subsequent to the granulated product production step, the granulated product is compressed and molded to give a plain tablet. At the time of compression molding, if necessary, the additives and pharmaceutical active ingredients may be mixed and compression molded.
The compression molding method is not particularly limited, and for example, a method or an apparatus generally used for tablet formation such as a rotary tableting machine and a single-shot tableting machine can be used. Moreover, the compression pressure in this compression molding is not specifically limited.
The mass of the uncoated tablet obtained by tableting is, for example, about 120 to 130 mg when the finally obtained zinc acetate hydrate tablet of the present invention contains 25 mg of zinc. When the obtained zinc acetate hydrate tablet of the present invention contains 50 mg of zinc, it is about 245 to 255 mg.

<Film coating>
Subsequent to the tableting step of obtaining the uncoated tablet, the uncoated tablet is coated with a film and then dried to obtain the zinc acetate hydrate tablet of the present invention.
The film coating method is not particularly limited, and may be a method generally used in tablet production. Film coating can be performed, for example, by wet spray coating the uncoated tablet with a suspension of a coating agent and a solvent using a coating machine. As the solvent, for example, alcohols such as ethanol and isopropanol; water can be used.

The weight of the tablet after film coating is, for example, about 124 to 134 mg when the finally obtained zinc acetate hydrate tablet of the present invention contains 25 mg of zinc. When the zinc acetate hydrate tablet contains 50 mg of zinc, it is about 251 to 261 mg.

After the film coating, the obtained tablet is dried to obtain the zinc acetate hydrate tablet of the present invention.
The drying method is not particularly limited, and the drying method of the coating agent in the production of a conventionally known tablet may be used as long as the drying temperature is 50 ° C. or less.
In the present invention, the drying can be performed at a product temperature of 50 ° C. or lower, and the disappearance of crystal water in the zinc acetate hydrate can be suppressed. In the step (1) for obtaining a granulated product, the product temperature is less than 40 ° C. If the drying temperature after film coating after obtaining the uncoated tablet is 50 ° C or less, the zinc acetate water is used. Disappearance of crystal water in the Japanese product can be suppressed.
The zinc acetate hydrate tablet of the present invention obtained by drying may be sprayed with a brightening agent using a conventional method.

The zinc acetate hydrate tablet of the present invention obtained as described above can be usually stored in a container or a bag by a conventional method. The container or bag is not particularly limited as long as it can be used as a tablet container or bag, and conventionally known ones can be used.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples, A various change and correction are possible in the range which does not deviate from the technical scope of this invention.
In Examples 1 to 3 below, the zinc elution amount after 15 minutes is the zinc elution amount after 15 minutes as measured by the JP dissolution method paddle method 50 rotations (test solution: water 900 mL). .

<Manufacture of zinc acetate hydrate tablets>
(Example 1)
83.9 g of zinc acetate hydrate, 30.1 g of corn starch (excipient) and 10 g of partially pregelatinized starch (binder) were mixed in a stirring granulator (manufactured by Fukae Kogyo Co., Ltd., high speed mixer) for purification. Granulated by adding water. This was dried at a product temperature of 35 ° C. until the loss on drying (water content) reached 13.8% using a stationary dryer (Advantech, a ventilation dryer). Sized using a sieve (710 μm). To this sized product, magnesium stearate (lubricant) was mixed so that the mixing ratio (mass ratio) was sized product / magnesium stearate = 124/1 to produce a powder for tableting. . This powder was tableted with a diameter of 6 mm and a tablet mass of 125 mg to give zinc acetate hydrate tablets. The obtained zinc acetate hydrate tablet had a thickness of 3.4 mm, a disintegration time of 7 to 15 minutes, and a zinc elution amount of 88% after 15 minutes.

(Example 2)
83.9 g of zinc acetate hydrate, 20.1 g of corn starch (excipient) and 12 g of carmellose (disintegrant) were mixed in a fluid bed granulator (manufactured by POWREC, multiplex), and hydroxypropylcellulose (bonded) Agent) 3 g was dissolved in purified water, and this liquid was sprayed and granulated. This was dried at an air supply temperature of 60 ° C. until the product temperature reached 32 ° C., and then sized using a granulator (Pauleck Co., Comil). For this sized product, magnesium stearate (lubricant) is mixed so that the mixing ratio (mass ratio) is sized product / magnesium stearate = 119/1 to produce a powder for tableting. did. This powder was tableted with a diameter of 6 mm and a tablet mass of 120 mg to give zinc acetate hydrate tablets. The obtained zinc acetate hydrate tablet had a thickness of 3.4 mm, a disintegration time of 4 to 7 minutes, and a zinc elution amount of 98% after 15 minutes.

(Example 3)
839 g of zinc acetate hydrate, 101 g of corn starch (excipient) and 116 g of crystalline cellulose (excipient) were mixed with a stirring granulator (manufactured by Fukae Kogyo Co., Ltd., high speed mixer), and hydroxypropylcellulose (binder) ) 14 g was dissolved in purified water, and this liquid was added to granulate. This was dried using a fluidized bed dryer (manufactured by POWREC Co., Ltd., multiplex) until the product temperature reached 32 ° C at a supply air temperature of 60 ° C, and the resulting dried product was granulated (Powrec Co., Ltd. ). To this sized product, croscarmellose sodium (disintegrant) was added so that the mixture ratio (mass ratio) was sized product / croscarmellose sodium / magnesium stearate = 107/12/1. After mixing well, magnesium stearate (lubricant) was mixed to produce tableting powder. This powder was tableted with a diameter of 6 mm and a tablet mass of 120 mg to give zinc acetate hydrate tablets. The obtained zinc acetate hydrate tablet had a thickness of 3.3 mm, a disintegration time of 8 to 9 minutes, and a zinc elution amount of 95% after 15 minutes. A film coating machine (Freund Sangyo Co., Ltd., High Coater) was used in a solution in which 21 g of hypromellose and 3 g of macrogol 6000 were dissolved in 420 mL of purified water, and 3.6 g of titanium oxide and 2.4 g of talc were further dispersed. Then, the film was coated, and dried at an air supply temperature of 60 ° C. until the drying end temperature (article temperature) reached 50 ° C. to obtain a film-coated tablet. The obtained tablet had a tablet weight of 123 mg, a diameter of 6 mm, a thickness of 3.4 mm, a disintegration time of 9 to 11 minutes, and an elution amount of zinc after 15 minutes: 93%.

From the results of Examples 1 to 3, the zinc acetate hydrate tablet of the present invention has a zinc dissolution amount of 85 after 15 minutes as measured by the JP dissolution paddle method 50 revolutions (test solution: water 900 mL). % Or more, it was confirmed that the tablets were sufficiently compacted and sufficiently containing zinc acetate hydrate.

Since the zinc acetate hydrate tablet of the present invention is small in size and easy to swallow when taken, it can be suitably used as a therapeutic agent for Wilson's disease.

Claims

Containing 5-200 mg of zinc acetate hydrate (C 4 H 6 O 4 Zn.2H 2 O),
The size is 5 to 12 mm in diameter and 1 to 6 mm in thickness.
A zinc acetate hydrate tablet characterized by having an elution amount of zinc of 15% or more after 15 minutes as measured by the JP Dissolution Test Method Paddle Method 50 rotations (test solution: water 900 mL).
The zinc acetate hydrate tablet according to claim 1, wherein the size is 5 to 10 mm in diameter and 2 to 5 mm in thickness.
The zinc acetate hydrate tablet according to claim 1 or 2, wherein the total mass is not more than twice the content of zinc acetate hydrate.
(1) A step of granulating a mixture of zinc acetate hydrate (C 4 H 6 O 4 Zn · 2H 2 O), an excipient, a disintegrant and a solvent and then drying to obtain a granulated product, (2) A step of tableting the granulated product to obtain an uncoated tablet, and (3) a step of film-coating the uncoated tablet and then drying, wherein the product temperature in the step (1) does not exceed 40 ° C. The product temperature in (3) is 50 ° C. or less,
Containing 5-200 mg of zinc acetate hydrate (C 4 H 6 O 4 Zn.2H 2 O),
The size is 5 to 12 mm in diameter and 1 to 6 mm in thickness.
A method for producing a zinc acetate hydrate tablet, wherein the zinc elution amount after 15 minutes measured by the JP dissolution method paddle method 50 rotations (test solution: water 900 mL) is 85% or more.