JPS6033408B2 - acetylsalicylic acid tablets - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an acetylsalicylic acid tablet formed into a three-layer tablet comprising acetylsalicylic acid, methylephedrine or its salt, and an antacid in separate layers.

Acetylsalicylic acid (aspirin) has excellent antipyretic and antiinflammatory effects, and has thus far been widely used as an antipyretic analgesic.

In this case, acetylsalicylic acid is usually used in combination with an antacid to increase its initial absorption rate and reduce gastric irritation; Since there is a problem that salicylic acid reacts with antacids and decomposes, the dosage form is a two-layer tablet with acetylsalicylic acid and antacid as separate layers to reduce the decomposition of acetylsalicylic acid. Something was being done. In addition, acetylsalicylic acid has shown strong effectiveness as an antipyretic agent, and is excellent when used alone as an antipyretic analgesic.However, it is necessary to treat the initial symptoms of a cold in a way that is different from the effects of acetylsalicylic acid. It is desirable to blend methylephedrine or its salt, and when blending methylephedrine or its salt, it should be mixed with acetylsalicylic acid in the same layer, and the antacid should be added separately. The decomposition of acetylsalicylic acid was suppressed by forming it into a two-layer tablet dosage form with two layers.

However, as a result of various studies conducted by the present inventors, we found that when a mixture of acetylsalicylic acid and methylephedrine or its salt is stored for a long period of time, especially under high temperature and humidity, the airtightness is good. , using aluminum and thermoplastic resin with low water vapor permeation, P. T. P. Even if packaged, a considerable amount of methylephedrine acetate is produced, and a considerable amount of acetylsalicylic acid is decomposed into salicylic acid, forming acetylsalicylic acid and methylephedrine or its salt in the same layer, resulting in an antacid. Double-layer tablets with separate layers of the drug are extremely unstable because these ingredients react with each other, and the decomposition of acetylsalicylic acid is more rapid than in tablets that do not contain methylephedrine or its salts. I put it out.

In other words, methylephedrine acetate is relatively toxic (its LD5o is approximately 1.0 mm) than that of methylephedrine.
In addition, the effective dose of these active ingredients is not expected to be sufficient due to the decomposition of acetylsalicylic acid and the change of methylephedrin to methylephedrine acetate, so the effects of these active ingredients cannot be expected to be sufficient. This was the first time I realized that mixing it with salt poses a serious problem, so I put it out there.

Therefore, even if methylephedryso or its salt is used in combination with acetylsalicylic acid, the production of methylephedrine acetate is suppressed, and the decomposition of acetylsalicylic acid is reduced.As a result of further investigation into the dosage form, we found that acetylsalicylic acid and methyl A three-layer tablet is formed in which ephedrine or its salt and an antacid are made into separate layers, and a layer of methylephedrine or its salt is used as an intermediate layer, and acetylsalicylic acid is sandwiched between this intermediate layer. When a three-layer tablet is formed with the antacid layer and the antacid layer spaced apart from each other, less methylphephedrine acetate is produced and the decomposition of acetylsalicylic acid is suppressed even when stored under high temperature and humidity. Having discovered this, we have come up with the present invention.

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

The tablet according to the present invention includes a layer containing acetylsalicylic acid;
It is formed into a three-layer tablet with a layer containing methylephedrine or its salt and a layer containing an antacid as separate layers. In this case, as shown in Figure 1, acetylsalicylic acid The tablet is a three-layer tablet in which a methylephedrine-containing layer 2 is laminated on a methylephedrine-containing layer 1, and a lytic acid agent-containing layer 3 is further laminated on this layer 2.

In this way, the methylepedrine-containing layer 2 is used as an intermediate layer,
By stacking the acetylsalicylic acid-containing layer 1 and the antacid-containing layer 3 in a state where they are sandwiched between them, the decomposition of acetylsalicylic acid can be suppressed even better. The acetylsalicylic acid-containing layer 1 contains acetylsalicylic acid, as well as excipients such as starch, carboxymethyl cellulose, crystalline cellulose, polyvinylpyrrolidone, polyvinyl alcohol, talc, and lactose, disintegrants, binders, and lubricants. Various ingredients can be blended.

In addition, the methylephedrine-containing layer 2 contains methylephedrine or a non-toxic salt of methylephedrine such as methylephedrine hydrochloride, saccharin salt, etc. Antihistamines such as niramine, key cough medicines such as codiso phosphate, expectorants such as calcium benzoate, active ingredients such as caffeine, excipients such as lactose, starch, crystalline cellulose, hydroxypropylcellulose, talc, etc. Agents, binders, thickeners, etc. may be included.

The antacid-containing layer 2 contains aminoacetic acid, a co-product of aluminum hydroxide and carbonate such as a co-pillar product of basic magnesium carbonate, calcium carbonate, and aluminum hydroxide, magnesium silicate, and magnesium oxide. In addition to antacids such as , aluminum silicate, aluminum hydroxide gel, and aluminum glycinate, ingredients such as gelatin, starches such as Q starch, other excipients, binders, and lubricants may be contained. .

The three-layer tablet of the present invention can be manufactured according to a conventional method, and the tableting equipment, tableting conditions, etc. can be the same as in the conventional case.

Since the acetylsalicylic acid tablet according to the present invention is formed into a three-layer tablet having an acetylsalicylic acid-containing layer, a methylephedrine-containing layer, and an antacid-containing layer as separate layers, it can withstand high temperatures and high humidity. Even if it is left for a long period of time under conditions such as 4 psi and 80% RH, the production of methylephedrine acetate and the decomposition of acetylsalicylic acid are suppressed.

Therefore, acetylsalicylic acid and methylepedrine or its salt can be used effectively together, and their medicinal efficacy is well exhibited even after long-term storage. In particular, in the present invention,
It has a three-layer tablet form with a methylephedrine-containing layer as an intermediate layer, and above and below it are an acetylsalicylic acid-containing layer and an antacid-containing layer, so there is no effect of acetylsalicylic acid antacids, and acetylsalicylic acid It is stored very stably for a long period of time. Examples and comparative examples are shown below.
The present invention will be explained more specifically.

EXAMPLES AND COMPARATIVE EXAMPLES A three-layer tablet as shown in FIG. 1, consisting of an acetylsalicylic acid-containing layer 1, a methylephedrine-containing layer 2, and an antacid-containing layer 3, was compressed in a conventional manner.

The ingredients of each layer 1, 2, and 3 are as follows.

0 acetylsalicylic acid-containing layer acetylsalicylic acid
250 female starch
30〃o Methylphedrine-containing layer Methylphedrine hydrochloride 5-9 Chlorpheniramine maleate 1〃Crystalline cellulose
45〃Starch
10 Talc 2o Antacid-containing layer magnesium carbonate 100/9 Aluminum glycinate 50 Starch
11 Gelatin
10〃Next, this three-layered tablet is coated with a single-sided aluminum plate. T. P. Packaging is done indoors and at a temperature of 35o.
o, humidity (relative humidity) 80% and temperature 400, humidity 8
The samples were left in a 0% atmosphere for 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 of an acetylsalicylic acid-methylephedrine-containing layer and an antacid-containing layer having the following composition was formed, and the amount of free salicylic acid produced and the amount of methylephedrine acetate hydrochloride produced were similarly examined. o Acetylsalicylic acid-methylephedrine-containing layer Acetylsalicylic acid 250 9 Starch 40 Methylepedrine hydrochloride 5 Chlorpheniramine maleate 1 Crystalline cellulose
45 Talc 2
〃oAntacid-containing layer Magnesium carbonate 100:9 Aluminum glycinate 50〃Starch
11 Gelatin
10. The amount of methylephedrine acetate hydrochloride produced was measured by the following method.

That is, the tablets were powdered and methylephedrine hydrochloride 75
Accurately calculate the amount corresponding to 9, 0.1N daily CI30
Add the correct amount of heat and stir with a magnetic stirrer for 20 minutes. After clearing, transfer the contents to a centrifuge tube containing 300 ml of
ratio. p. m. Centrifuge for 5 minutes. Additionally, accurately measure 20' of the lighting solution and transfer it to a separating funnel. ether about 30',
Add 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 30 g of ether, the ether layers are combined, the ether layer is washed with saturated saline until neutral, and then dehydrated and filtered (using dry filter paper) with ramie. Concentrate the ether to about 0.5' in an evaporator, apply the 0.6 filtrate to gas chromatography (using a Hitachi 06 box-type device equipped with a hydrogen flame ionization detector), and determine the peak height ratio. Calculate the amount of hydrochloride. Gas chromatograph conditions Separation tube: Glass column 3 sails x 2 Carbowax 2M, 5% coating - Chromosolve W, AW-DMCS (60-80 mesh) Separation tube temperature: 150℃ Inlet temperature: 22020 Detector temperature :220oC Carrier gas and flow rate: N2, 2'/min Sensitivity:
10 (Range) x 4 (Attenuation) Table 1 Amount of free salicylic acid produced Table 2 Amount of methylephedrine acetate hydrochloride produced (% of methylephedrine hydrochloride) As is clear from the results in Tables 1 and 2, the tablets of the present invention Even after long-term storage under high temperature and humidity conditions, the decomposition of acetylsalicylic acid and the production of methylephedrine acetate are small, and the production of methylephedrine acetate is particularly well suppressed. It has been found that these can be used together effectively.

[Brief explanation of drawings]

FIG. 1 is a sectional view showing one embodiment of the present invention. 1...acetylsalicylic acid-containing layer, 2...
... Methylphedrine-containing layer, 3... Antacid-containing layer.

Claims (1)

[Claims] 1. In an acetylsalicylic acid tablet containing acetylsalicylic acid and methylefedrin or its salt as active ingredients, and also containing an antacid, a layer containing acetylsalicylic acid and an antacid are formed above and below the layer containing methylefedrin or its salt, respectively. 1. An acetylsalicylic acid tablet having a three-layer tablet form, each layer comprising an acid agent.