JP2021120357A - tablet - Google Patents

Abstract

To provide a tablet that can be evenly colored and is less likely to cause defects.SOLUTION: The present invention provides a tablet that can be evenly colored and is less likely to cause defects by containing an active ingredient, iron oxide, and silicon dioxide.SELECTED DRAWING: None

Description

The present invention relates to tablets.

There is an increasing need for a drug having excellent disintegration in the oral cavity for people who have difficulty swallowing to take the drug, such as the elderly and children. As such a tablet, for example, a tablet produced by a wet tableting method in which a wet material is filled in a mold, compressed, molded, and dried to form a tablet (hereinafter, also referred to as a wet tablet) is known. (Patent Documents 1 and 2). Since this wet tablet is molded at a low pressure, it becomes a porous tablet having appropriate voids when dried, and has excellent disintegration property in the oral cavity.

On the other hand, tablets may contain iron oxide (iron sesquioxide Fe ₂ O ₃ ) as a colorant (Patent Documents 3 and 4). This iron oxide is water-insoluble and is difficult to be uniformly mixed with other chemical raw materials in the powder state. In particular, it is difficult to mix sufficiently uniformly in wet tablets, which causes red spots or iron oxides solidified on the surface during the tableting process to be rubbed and cause streaks.

Japanese Unexamined Patent Publication No. 8-19589 JP-A-2007-314448 WO2012 / 147873 Japanese Patent No. 5690925

The present invention has been made in view of the above-mentioned problems of the prior art, and an object of the present invention is to provide a tablet that can be uniformly colored and is less likely to cause defects.

The present invention includes an active ingredient, iron oxide, and silicon dioxide.

In the present invention, the silicon dioxide may be at least one selected from fumed silica, light anhydrous silicic acid, and hydrous silicon dioxide.

In the present invention, the iron oxide may be at least one selected from iron sesquioxide, yellow iron sesquioxide and black iron dioxide.

In the present invention, a sugar compound may be further contained.

In the present invention, the content of the silicon dioxide may be 0.001% by mass or more and 2.0% by mass or less.

In the present invention, the iron oxide content may be 0.001% by mass or more and 0.2% by mass or less.

In the present invention, the silicon dioxide may be contained in a mass ratio of 0.2 to 10 with respect to the iron oxide.

According to the present invention, it is possible to provide a tablet that can be uniformly colored and is less likely to cause defects.

FIG. 1 is an SEM photograph (30 times) of the double powder of the comparative example. FIG. 2 is an SEM photograph (30 times) showing the elemental analysis mapping result of the double powder of the comparative example. FIG. 3 is an SEM photograph (100 times) of the double powder of the comparative example. FIG. 4 is an SEM photograph (100 times) showing the elemental analysis mapping result of the double powder of the comparative example. FIG. 5 is an SEM photograph (30 times) of the double powder of the example. FIG. 6 is an SEM photograph (30 times) showing the elemental analysis mapping result of the double powder of the example. FIG. 7 is an SEM photograph (100 times) of the double powder of the example. FIG. 8 is an SEM photograph (100 times) showing the elemental analysis mapping result of the double powder of the example.

Hereinafter, embodiments of the tablet according to the present invention will be described.
The tablet of this embodiment is a tablet containing an active ingredient, iron oxide, and silicon dioxide.

(Active ingredient)
The tablets of the present invention contain an active ingredient. The active ingredient can be appropriately selected according to the purpose, and examples thereof include medicinal ingredients and food ingredients.
Examples of the medicinal ingredient include antitumor agents, antibiotics, antiinflammatory agents, analgesics, osteoporosis agents, antihyperlipidemic agents, antibacterial agents, sedatives, tranquilizers, antiepileptic agents, and antidepressants. Drugs, digestive disorders, allergic disorders, hypertension, arteriosclerosis, diabetes, hormones, fat-soluble vitamins and other drugs, vitamins; minerals such as calcium, zinc and iron Kind: Non-pharmaceutical products other than drugs such as amino acids such as aspartic acid and arginine, foods for specified health use, foods with nutritional function, etc.

The content of the active ingredient is not particularly limited, and can be appropriately selected within a range that produces the desired effect.

(iron oxide)
The tablets of the present invention contain iron oxide. Iron oxide is contained in tablets as a coloring component.
The iron oxide is not particularly limited as long as the tablet can be colored, and examples thereof include iron sesquioxide, yellow iron sesquioxide, and black iron dioxide. These iron oxides may be used alone or in combination of two or more.
Of these, iron sesquioxide (Fe ₂ O ₃ ) is often added to tablets as pharmaceuticals as a red colorant.
Since iron sesquioxide has a small particle size and high cohesiveness, uneven dispersion is likely to occur when mixed with other powder components. If the tablet is tableted in a state where uneven dispersion occurs as a powder, pigment spots may occur on the tablet, which may cause product complaints and the like.
In the tablet of the present embodiment, by using silicon dioxide described later in combination with iron oxide, the dispersibility of iron oxide can be improved and the color unevenness of the tablet can be suppressed.

In the tablet of the present embodiment, the content of the iron oxide is not particularly limited and can be arbitrarily selected from the range in which the desired coloring effect can be obtained. For example, 0.001% by mass or more is 0. It may be 2% by mass or less, preferably 0.005% by mass or more and 0.15% by mass or less.

(Silicon dioxide)
The tablet of this embodiment contains silicon dioxide.
The silicon dioxide is not particularly limited, and may be appropriately selected from the fine powder _{having the composition formula SiO 2.} In this embodiment, artificially produced synthetic silica is suitable as silicon dioxide contained in tablets.
These silicas are classified into wet silica and dry silica (thermal decomposition method or high heat method or fumed silica) depending on the manufacturing method, or are classified into hydrophilic silica, hydrophobic silica and the like based on their properties, or are light. It is also classified as silica anhydride and hydrous silicon dioxide. Among these silicon dioxides (silica), dry silica such as fumed silica, hydrous silicon dioxide, or light anhydrous silicic acid is preferable.

By using silicon dioxide in combination with the iron oxide, the dispersibility of iron oxide can be improved, and color unevenness of tablets can be suppressed.

In the tablet of the present embodiment, the content of the silicon dioxide is not particularly limited and can be arbitrarily selected from the range in which the effect of dispersing iron oxide as the colorant can be obtained. For example, 0.001. It may be mass% or more and 2.0 mass%, preferably 0.0015 mass% or more and 1.0 mass% or the like.

In the tablet of the present embodiment, the dispersibility of iron oxide can be improved and the color unevenness of the tablet can be improved by combining silicon dioxide and iron oxide.
The amount of silicon dioxide suitable for improving the dispersibility of iron oxide can be appropriately set in consideration of the type and content of other components, and is not particularly limited, but for example. , Silicon dioxide is contained in a mass ratio of 0.2 to 10 and further in a ratio of 1 to 5 with respect to the iron oxide.

(Sugar compound)
The tablet of the present embodiment may further contain a sugar compound.
The sugar compound can be appropriately selected without limitation as long as it does not inhibit the effects of the active ingredient and the like. For example, lactose, sucrose, mannitol and the like can be mentioned. The sugar compound may be used alone or in combination of two or more.

In the tablet of the present embodiment, the content of the pre-sugar compound is not particularly limited and can be arbitrarily selected.

(Other ingredients)
The tablet of the present embodiment may contain any other ingredient. The optional component is not particularly limited, but for example, water, a water-soluble organic solvent, an excipient, a flavoring agent, a disintegrant, a fluidizing agent, an adsorbent, a lubricant, a odorant, and a surfactant. Examples include agents, fragrances, antioxidants, adsorbents, antistatic agents, wetting agents and the like. These components may be used alone or in combination of two or more.

(Dosage form, manufacturing method)
The tablet of the present embodiment is not particularly limited, but may be a wet tablet tableted by a wet tableting method or a tablet produced by a general dry tableting method.
First, a method for producing the tablet of the present embodiment as a wet tablet will be described. The following manufacturing method is an embodiment of the tablet manufacturing method of the present embodiment.

As a method for producing a tablet of the present embodiment, first, a mixed powder (double powder) is obtained by mixing powder components mixed in a required ratio with a sieve, a mixer or the like.
Next, this double powder and an amount of powder obtained from an arbitrary component so as to have a desired composition in a tablet are taken and mixed with a liquid component such as a solvent.
At this time, the amount of the liquid component with respect to the double powder is adjusted so that the double powder is mixed with the liquid component to be in a wet state (wet powder).
Further, the wet powder is molded by a molding machine and dried to obtain tablets.

When molding a wet powder in the above molding machine, a tablet having a constant weight is formed by filling the molding die with the wet powder and then rubbing the upper part.

When the above-mentioned double powder is obtained, when the wet powder, which is the next step, is obtained while the iron oxide is not sufficiently dispersed in the powder, the iron oxide is present in a non-uniform state even in the wet powder. As a result, it may cause color unevenness in the tablets.

Further, if iron oxide is present in the wet powder in a non-uniform state, the solidified portion of iron oxide may be rubbed and streaks may be generated when the iron oxide is scraped off by the molding machine.

Next, as another embodiment, a method for producing a tablet by a dry tableting method will be described.
First, a mixed powder (double powder) is obtained by mixing the powder components mixed in the required ratio in the same manner as described above with a sieve, a mixer or the like. Next, an arbitrary component such as a disintegrant, a binder, an excipient, and a liquid component such as water are added to the double powder to granulate, and after drying and sizing, a lubricant is added as necessary. Etc. are added and molded with a tableting machine to obtain tablets.

As described above, the tablet of the present embodiment has good dispersibility in the iron oxide powder, so that color unevenness of the tablet can be suppressed.

The tablets according to this embodiment are as described above, but it should be considered that the embodiments disclosed this time are exemplary in all respects and are not restrictive. The scope of the present invention is shown not by the above description but by the scope of claims, and it is intended that all modifications within the meaning and scope equivalent to the scope of claims are included.

Next, examples of the present invention will be described together with comparative examples. The present invention is not construed as being limited to the following examples.

(Test 1)
A powder mixture (double powder) was prepared with the formulations shown in Table 1. The following components were used as each component.
Lactose 200M: DEF phama, trade name Phamatose 200M, lactose hydrate Iron sesquioxide: Iron Mi Kasei Co., Ltd., trade name Iron sesquioxide Aerosil: Light anhydrous silicic acid, Japan Aerosil Co., Ltd., trade name AEROSIL 200
Titanium oxide: Made by Junsei Chemical Co., Ltd., trade name Japanese Pharmacopoeia Titanium oxide

Using the above-mentioned double powder, a wet powder was prepared according to the formulation (preparation formulation) shown in Table 2, and further molded by a molding machine to obtain a tablet. As each component, the same component as in Test 1 above and the following components were used.
Gosenol EG-03P: Polyvinyl alcohol (partially saponified product), manufactured by Nippon Synthetic Chemical Industry Co., Ltd. Ethanol 99.5%
purified water

The specific manufacturing conditions for tablets are as follows.
(1) Mixing of double powder powder Each component in Table 1 is mixed and sieved through a sieve to obtain a double powder powder.
(2) Granulation Add powder and lactose 200M to a stirring and mixing granulator (FM-VG-10, manufactured by Paulec Co., Ltd.), mix for 3 minutes, and mix with Gosenol EG-03P, purified water, and ethanol (99). A binder solution consisting of .5%) is added and kneaded for 1 minute to obtain a wet powder. A tablet having a mass of 110 mg was formed by a molding machine (device name: EMT60, manufactured by Sankyo Seisakusho Co., Ltd.) and dried to obtain tablets of each Example and Comparative Example.

The presence or absence of color unevenness was confirmed by visually observing the number of inspections shown in Table 3 of the tablets of each Example and Comparative Example. Tablets with even one color unevenness were regarded as defective tablets, and the number of defective tablets out of the total number inspected was shown in%. The results are shown in Table 3.

As shown in Table 3, each Example had a lower rate of color unevenness than each Comparative Example.

(Test 2)
A powder mixture (double powder) was prepared with the formulations shown in Table 4. As each component, the same component as in Test 1 above, and Adsolider 101: Light Siliconic Anhydrous, manufactured by Freund Sangyo Co., Ltd. was used.

Using the above-mentioned double powder, a wet powder was prepared according to the formulation (preparation formulation) shown in Table 5, dried, mixed with magnesium stearate, and molded with a tableting machine to obtain tablets. The following components were used as each component.
Cornstarch: Corn starch, manufactured by Nippon Shokuhin Kako Co., Ltd. Solar eclipse bureau cornstarch PH-102: Crystalline cellulose: manufactured by Asahi Kasei Co., Ltd. Theoras PH-102
HPC-SSL: Hydroxypropyl cellulose: Made by Nippon Soda Co., Ltd. Purified water Magnesium stearate: Made by Taihei Kagaku Sangyo Co., Ltd. Japanese Pharmacopoeia Magnesium stearate Vegetable

The manufacturing conditions for tablets are as follows.
(1) Double powder mixing Each component in Table 4 is mixed and doubled with a sieve.
(2) Granulation Agitated and mixed granulators (FM-VG-10, manufactured by Paulec Co., Ltd.) were charged with purified water and components other than magnesium stearate according to the preparation formulas shown in Table 5, and mixed for 3 minutes. Further, the purified water shown in Table 5 is added and kneaded to obtain a granulated powder. After drying, the granules are sized, magnesium stearate is added, mixed for 1 minute, and molded into a tablet having a mass of 150 mg with a tableting machine (PICCOLA NOVA B-10, manufactured by RIVA). An example tablet was obtained.

The presence or absence of color unevenness was confirmed by visually checking the number of inspections shown in Table 6 of the tablets of each Example and Comparative Example. Tablets with even one color unevenness were regarded as defective tablets, and the number of defective tablets out of the total number inspected was shown in%. The results are shown in Table 6. As shown in Table 6, each Example had a lower rate of color unevenness than the Comparative Example.

Next, the dispersibility of iron sesquioxide in the state of double powder is SEM (scanning electron microscope:
It was observed by Scanning Electron Microscope) and elemental analysis mapping.
First, the powders having the formulations shown in Table 7 were mixed in a plastic bag for 1 minute and sieved through a 180 μm sieve to obtain 100-fold powder. The lactose 200M, iron sesquioxide and Aerosil were the same as in Test 1 above.

The results of elemental analysis mapping of the doubled powders of the above Examples and Comparative Examples using the device name: scanning electron microscope S-3400N and Hitachi High-Technologies Corporation are shown. In addition, scanning electron micrographs (30 times, 100 times) of powder are also shown.
As shown in FIG. 1-8, from the SEM and elemental analysis mapping results, agglomerates of iron sesquioxide were observed in the comparative example, but not in the examples. Therefore, it is considered that silicon oxide uniformly disperses iron sesquioxide.

Claims (7)

A tablet containing the active ingredient, iron oxide, and silicon dioxide. The tablet according to claim 1, wherein the silicon dioxide is at least one selected from fumed silica, light anhydrous silicic acid, and hydrous silicon dioxide. The tablet according to claim 1 or 2, wherein the iron oxide is at least one selected from iron sesquioxide, yellow iron sesquioxide and black iron dioxide. The tablet according to any one of claims 1 to 3, further comprising a sugar compound. The tablet according to any one of claims 1 to 4, wherein the content of silicon dioxide is 0.001% by mass or more and 2.0% by mass or less. The tablet according to any one of claims 1 to 5, wherein the iron oxide content is 0.001% by mass or more and 0.2% by mass or less. The tablet according to any one of claims 1 to 6, wherein the silicon dioxide is contained in a mass ratio of 0.2 to 10 with respect to the iron oxide.

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