JP2901812B2 - Formulation with reduced whisker generation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a caffeine-containing preparation in which whisker formation is suppressed.

[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, and relief of headache, and is incorporated in many preparations such as analgesics and cold medicine. Caffeine-containing formulations produce needle-like crystals on the surface of the formulation during storage and grow over time. Powders and granules have poor fluidity due to needle-like crystals formed on the surface. And the quality is significantly impaired, such as deterioration of the appearance.

Heretofore, as a method for suppressing caffeine whiskers, a preparation containing caffeine, a preparation containing a mustard crystal-forming agent, and charcoal, silicic acid anhydride and / or montmorillonite are coexistent (Japanese Patent Publication No. 56-37970; No. 56-53525), a sublimable drug is coated with a coating agent containing cyclodextrins (JP-A-61-129).
138), a β-1.4 glucan powder having a specific size and a specific surface area is contained in a pharmaceutical formulation that easily generates whiskers (JP-A-63-267733), and an antacid is added to caffeine. Compounding method (JP-A-2-8521)
4) has been proposed. In addition, caffeine (hydrate)
Activated carbon or bentonite [Yamada et al., Pharmaceutical Magazine, 96 (10) 1223-1228 (197)
6)] and a method of mixing white alundum or light silicic anhydride (Aerosil 200) with anhydrous caffeine [Yuasa et al., Pharmaceutical Sciences, 41 (3) 161-17].
1 (1981)].

[0004]

However, the method of coating a caffeine-containing preparation with a coating agent or the use of activated carbon requires a complicated production method and takes time.
The latter has the drawback that the appearance becomes black and the effectiveness may be reduced due to the adsorption of the drug. Therefore,
An object of the present invention is to provide a preparation having a high commercial value that does not cover the caffeine-containing preparation with a coating agent, suppresses the generation of caffeine whiskers, and does not have the above-mentioned disadvantages.

[0005]

Means for Solving the Problems The present inventors have intensively studied to solve the above-mentioned problems. As a result, when hydrous silicon dioxide is added to a preparation containing caffeine,
We found that whisker generation was suppressed.

The hydrous silicon dioxide used in the present invention is:
In order to enhance the effect of suppressing the generation of whiskers, it is preferable to form a fine powder. Average powder particle size 4-6μ, surface area 6
It is preferably from 70 to 730 m2 / g. Specifically, for example, Adsolider 102 manufactured by Freund Corporation
(Trade name), Carplex manufactured by Shionogi & Co., Ltd. (trade name)
And the like, but are not limited to these. In the present invention, the use amount of hydrous silicon dioxide is suitably 5 to 30% of the total weight of the preparation, considering the minimum necessary amount for suppressing the generation of whiskers and the attrition of granules.

[0007] The present invention is applied to a wide range of drugs, quasi-drugs, and foods containing caffeine. Pharmaceuticals include, for example, antipyretics / analgesics, cold remedies, antitussive expectorants and the like. For example, when applied to a cold remedy, examples of the main drug include aspirin, acetaminophen, etensamide, chlorpheniramine maleate, tipepidine hibenzate, carbetapentane citrate, noscapine, potassium guaiacol sulfonate, and crude drugs. Examples of the extract include respective extracts such as ephedra, liquorice, cinnamon, gohi, ground dragon, carrot, and the like, and Kampo extract includes respective extracts such as kakkonto, shosaikoto, shosairyuto, and saikokeishito.

[0008] Further, in the preparation of the preparation of the present invention, commonly used additives such as excipients such as lactose, starch, crystalline cellulose and the like, disintegrant hydroxypropyl starch,
Partially pregelatinized starch, such as carboxymethylcellulose, binder hydroxypropylcellulose, polyvinylpyrrolidone, hydroxypropylmethylcellulose, etc., lubricants magnesium stearate, talc, etc.
In addition, a coloring agent, a sweetening agent, a flavor, and the like can be added as needed.

In the present invention, caffeine and hydrated silicon dioxide need only be allowed to coexist, and they need not necessarily be mixed. For example, in the case of granules, hydrous silicon dioxide is added to caffeine, and if necessary, other active ingredients and excipients, disintegrants and binders are added and mixed, and then water or alcohol is added and granulated. To make granules.

[0010]

EXAMPLES The present invention will be described below in more detail with reference to examples, but the present invention is not limited to these examples. Example 1 45 g of acetaminophen, 3 g of anhydrous caffeine, 3.75 g of tipepidine hibenzate, 0.175 g of chlorpheniramine d-maleate, powder of Saiko-Keishito extract 36
g, hydroxypropyl starch 18 g, lactose 53.6
75 g, 1.8 g of hydroxypropylcellulose, and 0.6 g of sodium saccharin in 1 g of hydrous silicon dioxide 1
After adding 8 g and uniformly mixing in a mortar, 85% ethanol was added as a binding solution and kneaded, and the mixture was granulated with a uniaxial pelletizer (0.7 mm screen). The granulated product was dried at 60 ° C. in a shelf-type through-air dryer. Further, the dried granules were sieved through 16 mesh and 60 mesh to obtain granules that passed through 16 mesh and did not pass through 60 mesh.

As control granules, 18 g of the hydrous silicon dioxide of Example 1 were replaced with 18 g of light anhydrous silicic acid (control granule A), 18 g of montmorillonite (control granule B) and 18 g of bentonite (control granule C). Obtained in a similar manner to Example 1. Example 2 45 g of acetaminophen, 3 g of anhydrous caffeine, 3.75 g of tipepidine hibenzate, 0.175 g of chlorpheniramine d-maleate, Saikokeishito extract powder 36
g, hydroxypropyl starch 18 g, lactose 42.5
75 g, hydroxypropylcellulose 0.9 g and saccharin sodium 0.6 g in hydrated silicon dioxide 30
g, and uniformly mixed in a mortar.
5% ethanol was added and kneaded, and the mixture was granulated with a uniaxial pelletizer (screen 0.7 mm). The granulated product was dried at 60 ° C. in a shelf-type through-air dryer. In addition, dry granulated
The mixture was sieved with 6 mesh and 60 mesh to obtain granules that passed through 16 mesh and did not pass through 60 mesh.

As control granules, 30 g of the hydrous silicon dioxide of Example 2 was synthesized with 30 g of synthetic aluminum silicate (control granule D), 30 g of magnesium oxide (control granule E), 30 g of magnesium silicate (control granule F), and aluminum hydroxide. 30 g of gel (control granule G), 30 g of synthetic hydrotalcite (control granule H), 30 g of aluminum hydroxide / sodium hydrogen carbonate coprecipitate (control granule I), 30 g of magnesium metasilicate aluminate (control granule J) and crystalline cellulose Each granule having a weight of 30 g (control granule K) was obtained in the same manner as in Example 2.

The granules obtained in Examples 1 and 2 were each wrapped in an aluminum foil laminated film (1.2 g each) and stored at 60 ° C. for 24 hours, and then opened. The degree of whisker formation on the granule surface was observed with a loupe (magnification). (50 times) and the fluidity was also observed.

[0014]

EFFECTS OF THE INVENTION The caffeine-containing preparation according to the present invention suppresses the formation of whiskers, produces caffeine as needle-like crystals on the surface of the preparation during storage, and does not grow over time. With the agent, needle-like crystals formed on the surface deteriorate fluidity and the quality is not significantly impaired, such as deterioration of appearance, and a preparation having high commercial value can be provided.

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Junichi Takano 1-27-7 Wada, Suginami-ku, Tokyo Inside Shinshin Pharmaceutical Co., Ltd. (58) Field surveyed (Int.Cl. ⁶ , DB name) A61K 31/52 A61K 47/04 CA (STN)

Claims (1)

(57) [Claims] 1. A caffeine-containing preparation which suppresses the formation of whiskers, characterized by containing hydrous silicon dioxide.