JPS6033406B2 - Acetylsalicylic acid tablets - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an acetylsalicylic acid tablet containing acetylsalicylic acid or a derivative thereof, methylephedrine or a salt thereof.

Derivatives such as acetylsalicylic acid (aspirin) or aluminum acetylsalicylate have excellent antipyretic effects,
Because it has anti-inflammatory effects, it has been widely used as an antipyretic analgesic. In this case, acetylsalicylic acid is
It is usually used in combination with antacids to increase the initial absorption rate and reduce gastric irritation, but when acetylsalicylic acid and antacids are used together, acetylsalicylic acid reacts with the antacid. However, since there is a problem of decomposition, the decomposition of acetylsalicylic acid has been reduced by forming the tablet into a two-layer tablet in which acetylsalicylic acid and an antacid are separate layers. On the other hand, aluminum acetylsalicylate is made in a form that can be absorbed through the intestinal tract in order to alleviate gastric disorders, which is a disadvantage of acetylsalicylic acid.For this reason, when aluminum acetylsalicylate is used, it is not necessary to use it together with an antacid. Therefore, it was usually formed into a single-layer tablet form. In addition, acetylsalicylic acid and its derivatives have shown strong efficacy as an antipyretic agent, and are excellent when used alone as antipyretic and analgesic drugs.However, acetylsalicylic acid and its derivatives have been shown to be effective as an antipyretic and analgesic agent. It has been desired to mix methylephedrine or its salts with different effects and effects, and conventionally when blending methylephedrine or its salts, it was mixed with acetylsalicylic acid or its derivatives.

However, as a result of various studies conducted by the present inventors, it has been found that when a mixture of acetylsalicylic acid or its derivatives and methylephedrine or its salt is stored for a long period of time, especially under high temperature and humidity, the airtightness Using aluminum and thermoplastic resin with good water vapor permeability, P.
T. P. Even if packaged, methylephedrine acetate will be produced in significant amounts, and acetylsalicylic acid or its derivatives will decompose into salicylic acid in significant amounts, and acetylsalicylic acid or its derivatives and methylephedrine or its salts will be separated. It was found that they cannot be used together effectively.

Therefore, even when methylephedrine or its salt is used in combination with acetylsalicylic acid or its derivatives, the production of methylephedrine acetate is suppressed, and the decomposition of acetylsalicylic acid and its derivatives is reduced.We further investigated the dosage form. As a result, methylephedrine or its salt is mixed with a swelling polymer compound such as carboxymethyl cellulose sodium, and the mixture is granulated by means such as dawn mist drying, or methylephedrine crystals are used. This is subjected to fluid granulation using an ethanol solution containing a swelling polymer compound such as ethyl cellulose to obtain a granulated product in which methylephedrine or its salt is co-isolated. When mixed with its conductor and made into tablets in the same layer, the formation of methylephedrine acetate is small even when stored under high temperature and humidity, and the decomposition of acetylsalicylic acid and its derivatives is suppressed. The present inventors have discovered that it is possible to effectively use methylephedrine or a salt thereof in combination, and have accomplished the present invention.

Hereinafter, the present invention will be described with reference to embodiments shown in the drawings.

When acetylsalicylic acid is used, the tablet according to the present invention is a two-layer tablet in which an antacid-containing layer 2 is laterally layered on an acetylsalicylic acid-containing layer 1, as shown in FIG.
As shown in the figure, the antacid-containing layer 2 has an internal core A (
Or conversely, it is preferable to form the acetylsalicylic acid-containing layer 1 with the internal core A), and if aluminum acetylsalicylate is used,
As shown in FIG. 3, it can be formed into a single-layer tablet comprising a layer 3 containing aluminum acetylsalicylate.

In the present invention, in the acetylsalicylic acid-containing layer 1 or aluminum acetylsalicylic acid-containing layer 3, granules 4 of a non-toxic salt such as methylephedrine or its hydrochloride or saccharin salt and a swelling polymer compound are provided. Disperse and contain.

In this case, the bulk polymer compounds include sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, polyvinyl acetate, gelatin, cellulose, ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polypynypyrrolidone, polyvinylpyrrolidone-vinylacetate, etc. One or more types of polymers, bluraso, etc. can be used. When forming granules 4 of these swelling polymer compounds and methylephedrine or its salt, for example, the swelling polymer compound is dissolved or dispersed in water, and methylephedrine or its salt is added thereto. At the same time, if necessary, add an antihistamine such as d1- or d-chlorpheniramine maleate, an antitussive such as codine phosphate, an expectorant such as calcium benzoate, caffeine, etc., and then dry the mixture with a mist. A solution containing a swellable polymer compound that is granulated or dissolved in an organic solvent such as ethanol or water with crystalline methylephedrine as a core, blended with the above-mentioned active ingredients as necessary, and then stirred at a low temperature. , can be granulated by fluidized granulation at relatively high temperatures. The average particle size of the granulated material 4 is preferably between about 5 mesh and 100 mesh. As a method for dispersing and incorporating the granules 4 into the acetylsalicylic acid-containing layer 1 or the aluminum acetylsalicylic acid-containing layer 3, the granules 4 are mixed with acetylsalicylic acid or a derivative thereof such as an aluminum salt, and if necessary, starch, carboxylic acid, etc. Methylcellulose, crystalline cellulose, borivinylpylene.

Contains various ingredients such as excipients such as lydone, polyvinylflucol, talc, and lactose, disintegrants, binders, and lubricants.
A method of compressing the tablet into a double-layer tablet with the antacid-containing layer 2, a form having an inner core A, or a single-layer tablet can be adopted using a conventional tabletting apparatus and tabletting conditions according to a conventional method. in this case,
The blending amount of the granules 4 is from 1/1000 to 1/1/1 of the acetylsalicylic acid or its derivative to be blended, in order to enhance the effect of methylephedrine or its salt.
It is preferable to blend them in a weight ratio of 20. In addition,
The antacid-containing layer 2 includes amide/acetic acid, a coprecipitation product of aluminum hydroxide and carbonate such as a coprecipitation product of basic magnesium carbonate/calcium carbonate/aluminum hydroxide, magnesium silicate, magnesium oxide, etc. In addition to containing antacids such as , aluminum silicate, aluminum hydroxide gel, and aluminum glycinate, starches such as gelatin and Q starch, other excipients, binders,
Ingredients such as lubricants may be included.

Therefore, the acetylsalicylic acid tablet according to the present invention is obtained by mixing granules of methylephedrine or its salt and a swelling polymer compound with acetylsalicylic acid or a derivative thereof, and then mixing the granules with acetylsalicylic acid or a derivative thereof. Since the derivatives and its derivatives are formed in the same layer, the formation of methylephedrine acetate is suppressed even if left for a long period of time under high temperature and humidity conditions, for example, in an atmosphere of 40°C and 80% RH. Decomposition of the conductor is suppressed.

Therefore, acetylsalicylic acid or its derivatives and methylphephedrine or its salt can be used effectively in combination, and their medicinal effects are well exhibited even after long-term storage. below,
The present invention will be explained in more detail by showing Examples and Comparative Examples. Example 1 A two-layer tablet as shown in FIG. 1, consisting of an acetylsalicylic acid-containing layer 1 containing methylephedrine hydrochloride granules 4 dispersed therein and an antacid-containing layer 2 laminated thereon, was made by a conventional method. Locked.

The ingredients of each layer 1 and 2 are as follows.

0 Acetylsalicylic acid-containing layer Acetylsalicylic acid 250 9 Starch 28 Crystalline cellulose 40 Talc
2. Methylphedrine hydrochloride granules 10. Saw P Methylphedrine granules are hydroxyf made by dissolving crystalline methylephedrine in ethanol.

It was obtained by atomizing a lopyl cellulose solution at about 30°C and fluidizing it at 5,000°C. o Antacid-containing layer magnesium carbonate 100% aluminum glycinate 50% starch
10 Gelatin
10 Next, this double-layered tablet is coated with a single-sided aluminum plate. T. P. After packaging and storing indoors at a temperature of 3yo
, humidity (relative humidity) 80% and temperature 40°C, humidity 80%
The samples were left in an atmosphere of 1 month, 2 months, and 3 months, and the amount of free salicylic acid produced and the amount of methylephedrine acetate hydrochloride produced were examined.

Tables 1 and 2 show the results. For comparison, a two-layer tablet with the following composition of an acetylsalicylic acid-methylepedrine-containing layer and an antacid-containing layer was formed by directly mixing acetylsalicylic acid and methylephedrine hydrochloride, and the amount of free salicylic acid produced and methylephedrine were similarly determined. The amount of acetate hydrochloride produced was investigated. o Acetylsalicylic acid-methylephedrine-containing layer Acetylsalicylic acid 250m
g starch 28
〃Crystalline cellulose 40〃talc
2. Methylphedrine hydrochloride 5. Hydroxypropyl cellulose 5. Antacid-containing layered magnesium carbonate
100 9 Aluminum Glycinate
50″ starch
10 Gelatin 1
0 The amount of methylephedrine acetate hydrochloride produced was examined by the following method.

That is, the tablets were powdered and methylephedrine hydrochloride 75
Accurately measure the amount corresponding to 9 of 0.1N-HC130
Add M accurately and stir for 20 minutes with a magnetic stirrer.

After washing, the contents were transferred to a 50 centrifuge tube and heated to 300 centimeters. p.
m. Centrifuge for 5 minutes. Additionally, accurately measure 20' of the lighting solution and transfer it to a separating funnel. Add about 30 pieces of ether and a specified amount of internal standard solution (n-nonyl alcohol/chloroform solution), add 5% NaHC03 aqueous solution until pH 9, and shake. The aqueous layer is further extracted twice with about 30M ether, the ether layers are combined, and the ether layer is washed with saturated saline until neutral, then dehydrated and filtered with E-nitrogen (using dry filter paper). Approximately 0.5 ether in an evaporator
Concentrate the mixture to 0.6 mm and apply it to gas chromatography (using a Hitachi 06 matrix device equipped with a hydrogen flame ionization detector) to determine the peak height ratio and calculate the amount of methylephedrine acetate hydrochloride. do. Gas chromatograph conditions Separation tube: Glass column 3 rails x 2 carbon wax 20M, 5% core ink Chromosolve W, AW-DMCS (60-80 mesh) Separation tube temperature: 150°C Inlet temperature: 220℃ Detection Chamber temperature: 220°C Carrier gas and flow rate: N2, 20'/min Sensitivity: 10 (Range) x 4 (A ratio enj tion) Table 1 Amount of free salicylic acid produced Table 2 Amount of methyl efeto 1-phosphoacetate hydrochloride produced ( As is clear from the results in Tables 1 and 2 for methylephedrine hydrochloride, the tablets of the present invention show less decomposition of acetylsalicylic acid and less production of methylephedrine acetate even after long-term storage under hot and humid conditions. In particular, it has been found that the production of methylephedrine acetate can be effectively suppressed, and therefore acetylsalicylic acid or its derivatives and methylephedrine or its salt can be used effectively together.

Example 2 A single-layer tablet containing aluminum acetylsalicylate in a downward formulation was compressed by a conventional method.

Aluminum acetylsalicylate 300 Female gelatin 10 Crystalline cellulose 40 Starch
28 Talc
2. Methylphedrine hydrochloride granules 20. Chlorpheniramine maleate 1. For the forehead granules, methylephedrine hydrochloride and codine phosphate were added to cold water containing pullulan, uniformly dispersed, and freeze-dried. was adjusted to a 75 mesh pass.

This tablet is P. T. P. We did the packaging and sold it for 4yo.
80%R. Even when stored under sunlight for 45 days, the amount of salicylic acid decomposed was approximately less than 1%.

[Brief explanation of the drawing]

1 to 3 are sectional views each showing an embodiment of the present invention. 1...acetylsalicylic acid-containing layer, 3...
...Aluminum acetylsalicylate-containing layer, 4...
...Granulated material. Figure 1 Figure 2 Figure 3

Claims (1)

[Scope of Claims] 1. An acetylsalicylic acid tablet characterized in that it is formed by mixing granules of methylephedrin or its salt and a swelling polymer compound with acetylsalicylic acid or a derivative thereof to form the same layer. . 2. The swelling polymer compound is selected from shellac, ethylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, and polyvinylpyrrolidone-vinyl acetate copolymer1.
The tablet according to claim 1, which is a species or a combination of two or more species.