JP3048881B2 - Whisker generation suppression method - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for suppressing the occurrence of whiskers in caffeine-containing drugs, quasi-drugs, foods and the like.

[0002]

2. Description of the Related Art Caffeine is a drug showing excitement of the respiratory center and vasomotor center, increase in contractility of the heart muscle, diuretic action, relieving headache and the like, and is used in many preparations such as analgesics and cold remedies. I have. However, in a preparation containing caffeine, caffeine is formed as needle-like crystals on the surface of the preparation during storage and grows over time. In particular, granules have problems that fluidity is deteriorated due to needle-like crystals formed on the surface, the appearance is deteriorated, and the quality of tablets is remarkably impaired, such as the appearance is deteriorated.

[0003] Conventionally, as a method for suppressing caffeine whiskers, a method comprising coexisting a preparation containing caffeine, a preparation containing a mustard crystal-forming drug and charcoal, silicic anhydride or (and) montmorillonite (Japanese Patent Publication No. 56-37970). JP-B-56-53525), a method of coating a sublimable drug with a coating agent containing cyclodextrins (Japanese Patent Application Laid-Open (JP-A) No. Sho 61).
No. 129138), a method of including a β-1,4-glucan powder having a specific size and a specific surface area in a formulation that easily generates whiskers (JP-A-63-267733).
No.), a method of blending an antacid with caffeine (Japanese Unexamined Patent Publication No.
-85214) and the like. Also, a method of adding activated carbon or bentonite to caffeine (hydrate) [Yamada et al., Pharmaceutical Magazine, 96 (10) 1223-122.
8 (1976)], anhydrous caffeine and white alundum or light silicic anhydride (Aerosil 200)
[Yasa et al., Pharmaceutical Sciences, 41 (3) 161-
171 (1981)].

[0004] However, these methods have problems such as a complicated manufacturing method and a reduced effect, and the generation of whiskers cannot be sufficiently suppressed, which is not satisfactory.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide a method for easily suppressing the occurrence of whiskers in a caffeine-containing preparation.

[0006]

Under such circumstances, the present inventors have conducted intensive studies. As a result, if a preparation containing caffeine is mixed with anhydrous caffeine, an antacid, or hydrated silicon dioxide, it is convenient. It has been found that the generation of whiskers can be sufficiently suppressed by a simple method, and the present invention has been completed.

That is, the present invention provides a whisker of a caffeine-containing preparation, characterized by mixing caffeine-containing granules or tablets with at least one selected from anhydrous caffeine, antacids and hydrous silicon dioxide. It is intended to provide a method for suppressing occurrence.

The antacid used in the present invention is not particularly limited as long as it is usually used as a medicament. Examples thereof include dried aluminum hydroxide gel, magnesium silicate aluminate, magnesium silicate, synthetic aluminum silicate, Aldioxa, synthetic hydrotalcite, magnesium oxide, alumina magnesium hydroxide (magnesium hydroxide / aluminum potassium sulfate co-precipitated product), aluminum hydroxide gel, aluminum hydroxide / sodium hydrogen carbonate co-precipitated product, aluminum hydroxide / carbonic acid Magnesium mixed dry gel, aluminum hydroxide / magnesium carbonate / calcium carbonate co-precipitated product, magnesium hydroxide, sodium hydrogen carbonate, magnesium carbonate, precipitated calcium carbonate, magnesium metasilicate aluminate, anhydrous calcium hydrogen phosphate Calcium hydrogen phosphate, Torizokukotsu, stone Ke'Akira, Borei, amino acid, dihydroxy aluminum aminoacetate (aluminum glycinate)
And the like. Of these, synthetic hydrotalcite, aluminum hydroxide / sodium hydrogen carbonate coprecipitated product, and synthetic aluminum silicate are particularly preferred.

The anhydrous caffeine may be a caffeine-containing component such as caffeine or sodium benzoate in addition to anhydrous caffeine.

The particle size of the anhydrous caffeine, antacid and hydrous silicon dioxide is not particularly limited, but is preferably 300 μm or less in view of the appearance of granules or tablets. Among them, it is particularly preferable to use anhydrous caffeine.

In the present invention, caffeine-containing granules or tablets are mixed with one or more selected from the above-mentioned anhydrous caffeine, antacids and hydrous silicon dioxide. Here, the caffeine-containing granules or tablets may be any of caffeine-containing drugs, quasi-drugs, foods, and the like. When two or more of anhydrous caffeine, an antacid and hydrous silicon dioxide are used in combination, whisker generation can be further suppressed, which is preferable. Preferred combinations include anhydrous caffeine and synthetic hydrotalcite, anhydrous caffeine and aluminum hydroxide / sodium bicarbonate coprecipitated product, anhydrous caffeine and synthetic aluminum silicate, and anhydrous caffeine and hydrous silicon dioxide. No. The mixing ratio of anhydrous caffeine or the like to the caffeine-containing granules or tablets is not particularly limited as long as the effects of the present invention can be obtained, but 0.001 to 20% by weight of the caffeine-containing granules or tablets. It is particularly preferable that the content is 0.01 to 5% by weight, whereby a sufficient whisker suppressing force can be obtained and the appearance is also preferable. These mixing methods are not particularly limited, for example, a V-type mixer,
What is necessary is just to mix using a coating pan, a stirring mixer, etc. Furthermore, when mixing caffeine-containing granules or tablets with anhydrous caffeine or the like, other components used in ordinary pharmaceuticals and the like, such as acetaminophen and magnesium stearate, may impair the effects of the present invention. Mixing can be appropriately performed within a range not known.

[0012]

EXAMPLES Next, the present invention will be further described with reference to examples, but the present invention is not limited to these examples.

REFERENCE EXAMPLE 1 400 ml of a 30% aqueous ethanol solution was added to 1300 g of a component having the composition shown in Table 2, and the mixture was granulated using a New Gram Machine (manufactured by Daiwa Kakoki Co., Ltd.). Dried. Then, the mixture was sieved with a sieve to obtain granules having a mesh size of 42 mesh to 16 mesh.

Each of the obtained granules was packaged with an aluminum foil laminated film. After this was stored at 70 ° C. for 10 days or 30 days, the surface of the granules was observed with a stereoscopic microscope,
The occurrence of whiskers was evaluated according to the following criteria. Table 2 shows the results.

[0015]

[Table 1] Score 0: No whisker occurred. 1: Whiskers slightly occurred. 2: Whiskers are generated slightly densely, and aggregation is observed. 3: Whiskers are generated densely and many agglomerations are observed. 4: Whiskers are extremely generated, and the whole becomes lumps.

[0016]

[Table 2]

Example 1 The granule No. obtained in Reference Example 1 To 5 was added the powder shown in Table 3 and mixed with a V-type mixer. This was packaged with an aluminum foil laminated film, and generation of whiskers was evaluated in the same manner as in Reference Example 1. Table 3 shows the results.

[0018]

[Table 3]

Example 2 The granule No. obtained in Reference Example 1 5 was added with the powder shown in Table 4 and mixed with a V-type mixer. This was packaged with an aluminum foil laminated film, and generation of whiskers was evaluated in the same manner as in Reference Example 1. Table 4 shows the results.

[0020]

[Table 4]

REFERENCE EXAMPLE 2 400 ml of a 30% aqueous ethanol solution was added to 1300 g of a component having the composition shown in Table 5, and the mixture was granulated using a New Gla Machine (manufactured by Daiwa Kakoki Co., Ltd.). Dried. Next, the mixture was sieved with a sieve to obtain granules for tableting having passed 42 mesh. To the granules for tableting, magnesium stearate was added at 2% based on the weight of the granules,
After mixing with a V-type mixer, tableting was performed, and the surface deposits were removed with a blower to obtain tablets.

[0022]

(Ingredients) (parts by weight) Acetaminophen 180 Dextromethorphan hydrobromide 9.6 dl-Methylephedrine hydrochloride 30 d-Chlorpheniramine maleate 1.75 Anhydrous caphen 37.5 Kikyo powder 200 Licorice Powder 300 glycinal 150 carmellose calcium 200 polyvinylpyrrolidone 10 corn starch 51.15 crystalline cellulose 130

The obtained tablets were packaged with an aluminum foil laminated film. After this was stored at 70 ° C. for 10 days or 30 days, the tablet surface was observed with a stereoscopic microscope, and the occurrence of whiskers was evaluated according to the following criteria.

[0024]

[Table 6] Score 0: No whisker occurred. 1: Whiskers slightly occurred. 2: Whiskers are generated slightly densely, and aggregation is observed. 3: Whiskers are generated densely and can be visually confirmed. 4: The whiskers are extremely generated, and the tablets are in a bonded state.

As a result, the score after storage for 10 days was 3, and the score after storage for 30 days was 4.

Reference Example 3 Reference Example 2 was conducted using 1262.5 g of a component having the composition shown in Table 7.
In the same manner as in the above, granules for tableting were obtained. 2% by weight of magnesium stearate and the powders shown in Table 8 were added to the granules for tableting, mixed with a V-type mixer, tableted, and the surface deposits were removed with a blower to give tablets. Obtained.

The obtained tablets were packaged with an aluminum foil laminated film, and the occurrence of whiskers was evaluated in the same manner as in Reference Example 2. Table 8 shows the results.

[0028]

[Table 7] (Components) (parts by weight) Acetaminophen 180 Dextromethorphan hydrobromide 9.6 dl-Methylephedrine hydrochloride 30 d-Chlorpheniramine maleate 1.75 Kikyo powder 200 Licorice powder 300 Glycinal 150 Carme Loose calcium 200 Polyvinylpyrrolidone 10 Corn starch 51.15 Microcrystalline cellulose 130

[0029]

[Table 8]

Example 3 Magnesium stearate was added to the granules for tableting obtained in Reference Example 2 in an amount of 5% by weight based on the weight of the granules, mixed with a V-type mixer, and then tableted. To give tablets. The powders shown in Table 9 were added to the obtained tablets, mixed by stirring in a coating pan, packaged with an aluminum foil laminated film, and evaluated for generation of whiskers in the same manner as in Reference Example 2. Table 9 shows the results.

[0031]

[Table 9]

[0032]

According to the present invention, the generation of whiskers in caffeine-containing drugs, quasi-drugs, foods, and the like can be suppressed by a simple method, and the quality is not significantly impaired such as deterioration in appearance. Thus, a preparation having a high commercial value can be obtained.

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Claims (3)

(57) [Claims] 1. A method for suppressing whisker formation of a caffeine-containing preparation, comprising mixing caffeine-containing granules or tablets with at least one selected from anhydrous caffeine, antacids and hydrous silicon dioxide. 2. The method for suppressing whisker generation according to claim 1, wherein the antacid is synthetic hydrotalcite, aluminum hydroxide / sodium bicarbonate coprecipitate, or synthetic aluminum silicate. 3. A method for suppressing whisker generation of a caffeine-containing preparation, comprising mixing caffeine-containing granules or tablets with anhydrous caffeine.