JPS62283919A - Tablet - Google Patents

Abstract

PURPOSE:To provide a tablet composed of a main drug layer and a foaming layer exposed to the outer environment and foamable in contact with gastric juice, retained in the stomach in foamed state, capable of continuously releasing the main drug over a long period and prolonging the active period of the drug. CONSTITUTION:The objective tablet is composed of a main drug layer 1 consisting of a drug which is absorbed in the digestive tracts by oral administration and an additive and a foaming layer 2 containing a foaming salt foamable in contact with gastric juice (e.g. sodium bicarbonate) as a main component in a state exposed to the outer environment. The amount of the foamable salt in the foaming layer is 4-70%, especially 20-50% and is preferably 2-35%, especially 10-25% in the whole tablet. The exposed area of the foaming layer is 5-60%, especially 10-40% of the total surface area of the tablet and the volume of the foaming layer is preferably 10-80%, especially 30-50% of the volume of the tablet. A slow-releasing agent can be produced by adding a slow- releasing substrate to the foaming layer.

Description

Detailed Description of the Invention 3. Detailed Description of the Invention 1 Kagami Mento 191 The present invention relates to a tablet floating in the stomach, and more specifically, a tablet that foams upon contact with gastric juice to create buoyancy in the tablet. This invention relates to a tablet that foams and floats in the stomach by forming a foam layer.

In order to maintain the effectiveness of pharmaceutical drugs, it is important to maintain the effective blood concentration of the drug. The administered drug reaches its maximum blood concentration after a certain period of time after being absorbed, and after excretion, the blood concentration decreases within a short period of time and the drug's efficacy disappears. Therefore, in order to maintain the effective blood concentration of the drug, the drug is administered several times per day.However, as the number of times the drug is administered increases, the amount of drug administered also increases, which can lead to the hassle of taking one dose, administration errors, and side effects. The problem also arises. In addition, there are individual differences in the absorption of drugs, and even if the same amount of drug is administered, the drug may not be effective or may have an excessive effect, so the effective blood concentration that is suitable for each individual may be determined. It is difficult to set a drug dosage and administration frequency that can be maintained.

For this reason, research has been carried out on preparations that can maintain drug efficacy for a long period of time after only one drug administration, and these preparations have been put into practical use.

Incidentally, tablets administered orally are usually absorbed within the gastrointestinal tract, and the duration of their medicinal efficacy is influenced by the solubility of the tablet within the gastrointestinal tract and the residence time within the gastrointestinal tract.

Taking these points into consideration, various methods have been developed to maintain drug efficacy for a long time by adjusting the solubility and degree of disintegration of tablets.
Particularly effective methods include mixing various sustained-release bases into tablet additives or coating tablets to release herbal medicines in the gastrointestinal tract for a sustained period of time.

However, the durability of these methods varies from person to person,
It has the disadvantage that it is affected by the state of the stomach and the contents of the stomach. In addition, although the drug's efficacy lasts for a longer time than that of regular tablets, even with these methods, the residence time of the tablet in the gastrointestinal tract is limited to about 8 hours, and it has not been possible to extend the duration of the drug's efficacy any further.

Therefore, research is being conducted to extend the residence time of tablets in the gastrointestinal tract to maintain their medicinal efficacy for a longer period of time.

This is a method of prolonging the residence time of the tablet in the stomach, as drugs are normally absorbed in the gastrointestinal tract, particularly in the small intestine. For example, tablets may be made larger to take advantage of the selective action of the gastric pylorus, or preparations with lower specific gravity may be used, such as auxiliary drugs, fatty substances,
Method using hydrocolloid etc. (JP-A-51-1159)
Attempts have been proposed to extend the residence time in the stomach by suspending solid preparations in the stomach, such as by methods using hard capsules, styrofoam, foamed rice, etc. (Japanese Patent Publication No. 12411/1982). ing.

However, these methods have problems such as insufficient buoyancy in the stomach and troublesome formulation.

Therefore, there has been a demand for the development of a formulation that can reliably float in the stomach and is easy to manufacture.

The present invention was made in view of the above circumstances, and an object of the present invention is to provide a gastric floating tablet that foams in the stomach and floats quickly, and is easy to formulate.

As a result of extensive research into gastric suspension type preparations, the present inventors have developed a tablet foaming agent mainly containing effervescent salts that effervesce with gastric juices such as sodium bicarbonate. By forming the layer in an externally exposed state and preparing the tablet into a multi-layer tablet or a dry-coated tablet consisting of the main drug layer and this foaming layer, the foaming layer foams with gastric juice to ensure that the tablet floats in the stomach. The present inventors discovered that when a sustained-release base is added to the main drug layer, the herbal medicine can be released continuously for a long period of time, and a tablet can be formed as a sustained-release drug.This discovery led to the present invention. .

Therefore, the present invention is characterized in that it comprises an active drug layer and a foam layer that foams upon contact with gastric juice to create buoyancy in the tablet, and that the foam layer is formed in a state where it is exposed to the outside. It provides tablets.

The present invention will be explained in more detail below.

As described above, the tablet of the present invention comprises a main drug layer and a foam layer.

Here, the main drug layer consists of a drug and various additives. There are no particular restrictions on the drug, but drugs that are orally administered and absorbed in the gastrointestinal tract are preferably used6. For example, antacids such as magnesium silicate, magnesium oxide, synthetic aluminum silicate, sodium bicarbonate, Intestinal agents such as berberine, antispasmodics such as butylscopolamine bromide and budropium bromide, antitussive and sputum agents such as eprazinone chloride, dextromethorphan hydrobromide, and ketotifen fumarate;
Antipyretic, analgesic, and antiinflammatory agents such as pranoprofen, peptic ulcer agents such as cimetidine, antihypertensive agents such as cabtril and labetalol hydrochloride, cardiovascular agents such as nicardipine hydrochloride, calcium channel blockers such as diltiazem hydrochloride, and β-stimulants such as carteolol hydrochloride. -Blocker agents, antiarrhythmic agents such as pindolol, psychiatric agents such as sulpiride, hemostatic agents such as tranexamic acid, and the like are preferably used. In particular, since the tablet according to the present invention remains in the stomach for a long time, it is effective for drugs whose absorption site is limited to the stomach, such as antacids, and is more preferably used.

Here, the compounded amount of the drug can be varied in various ways, taking into consideration the usual dose of the compounded drug, administration conditions, and tablet formulation conditions.

In addition, additives that form the main drug layer may include additives that are commonly used in one tablet, such as excipients, preservatives, stabilizers, buffers, etc. In such cases, it is preferable to incorporate a sustained release base.

In this case, the sustained release base may include commonly used substances such as carnauba wax, beeswax, paraffin wax,
Wax matrices such as microcrystalline wax, fatty acids, fatty alcohols, etc. and their esters, gum arabic, gum tragacanth, locust bean gum, guar gum, gum karaya, agar, pectin, carrageenan,
Hydrocolloids and synthetic polymers such as soluble and insoluble alginates, methylcellulose, hydroxypropylmethylcellulose, and hydroxypropylcellulose can be used, and sustained release bases suitable for drugs and various conditions can be used alone or in combination. It can be selected and blended.

Moreover, the blending amount thereof is 0 to 80%.

The tablet according to the present invention includes a foam layer as described above, and the foam layer is formed so that the foam layer is foamed by gastric fluid and its buoyancy causes the tablet to float in the stomach. Specifically, it is mainly composed of effervescent salts that foam with gastric juice, and is formed by adding additives as necessary.

In this case, effervescent salts are not particularly limited, but include salts that effervesce quickly under acidic conditions in the stomach, are harmless at the dose of the tablet, and do not impede the therapeutic effect, such as sodium bicarbonate. Suitably used. In addition, as for the additives, it is preferable to incorporate commonly used tablet additives, as in the case of the main drug layer, and it is particularly preferable to incorporate a sustained release base. This improves the retention of salt bubbles and provides good flotation. In addition, the type of sustained release base to be blended is as follows:
Similar to the main drug layer, one or more commonly used substances can be used in combination, and the blending amount is 0 to 80.
%.

Here, the amount of foaming salts used is 4 to 70% in the foam layer.
%, particularly preferably 20 to 50%, and preferably 2 to 35%, especially 10 to 25% of the total tablet. In addition, the external exposed area of the foam layer containing foaming salts is 5
It is preferably 5 to 60%, particularly 10 to 40%, of the total surface area of the tablet, and the volume is preferably 10 to 80%, particularly 30 to 50%, of the tablet volume.

Forming the tablet in this way ensures that the tablet floats.6 In other words, tablets containing sodium bicarbonate have been known, but conventional tablets of this type simply contain sodium bicarbonate in the tablet. The tablets are evenly dispersed, and although sodium bicarbonate is foamed by gastric juices in such tablets, the gastric juices do not float. However, by configuring one foam layer as described above, the foaming of the effervescent salts exerts a buoyant force that makes the tablets float, thereby making the tablets float.

The tablet of the present invention can be formed as a multilayer tablet or a dry-coated tablet comprising the above-mentioned active ingredient layer and foam layer. For example, as shown in FIG.
A three-layer tablet consisting of a main drug layer 1 and a foam layer 2 as shown in Fig. 2, a three-layer tablet consisting of a main drug layer 1 and a foam layer 2 as shown in Fig. 3, and a foam layer 2 formed between two main drug layers 1 as shown in Fig. 3. Examples include three-layer tablets, and dry-coated tablets having the main drug layer 1 within the foam layer 2 as shown in FIG. It can be shaped according to the following. For example, the planar shape of the tablet is usually circular as shown in FIGS. 1 to 4, but it may be formed into a polygonal shape. Further, in the embodiment shown in FIG. 1, a recess is formed in the center of one surface of the active ingredient layer 1, and the foam layer 2 is provided within this recess, but the recess does not necessarily need to be formed in the center of the active ingredient M1. Further, in the embodiments shown in FIGS. 1 to 4, the side surface of the tablet is formed into a substantially elliptical shape, but it may be formed into any other suitable shape, for example, a rectangular shape as shown in FIG. 5.

Further, the tablets are compressed using a conventional tableting method, but it is preferable to compress the tablets by a method suitable for the shapes of the main drug layer and the foamed layer.

As described above, the tablet according to the invention foams and floats in the stomach and remains in the stomach, and is easy to formulate because the main drug layer and foam layer are simply compressed into a tablet using a conventional method. It is something.

EXAMPLES Hereinafter, the present invention will be specifically explained with reference to Examples and Comparative Examples, but the present invention is not limited to the Examples below.

In addition, in the following examples, all parts indicate parts by weight.

[Example 1, Comparative Examples 1 and 2] As the main drug layer, 18 parts of diltiazem hydrochloride, hydroxypropyl methylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd., Metrose 9)
0 SH30,000) 18.75 parts, milk M1'1.
75 parts of hydroxypropyl cellulose, 0.5 parts of hydroxypropyl cellulose, and 1 part of magnesium stearate to give a total amount of 250 mg, and Lovely Wax 15 as a foam layer forming component.
Department.

15 parts of sodium bicarbonate, Avicel PH3017.2
7 parts, 0.5 parts of hydroxypropyl cellulose, 1 part of magnesium stearate, 2.03 parts of hydroxymethyl cellulose (Metrose 90 5H30,000), total amount 140 mg, and a key press (wood type single-shot tablet press). A three-layer tablet as shown in FIG. 1 was formed by tabletting using a KS-type (type ■).

Next, a dissolution test of one tablet was conducted using the paddle method according to the Japanese Pharmacopoeia.

That is, the first liquid used in the Japanese Pharmacopoeia disintegration test method (add 24.0 mQ of diluted hydrochloric acid and water to 2.0 g of sodium chloride to make 100 mQ; pH approximately 1.2) was maintained at a liquid temperature of 37 ± 2 ° C. The tablets were added to the solution and stirred at a rotational speed of 1100 rpm using a dissolution tester (manufactured by Toyama Sangyo Co., Ltd.). At this time, the foaming and floating state of the tablets was observed with the naked eye. Furthermore, the elution results were determined by measuring the UV absorbance of the eluate at a wavelength of 236 nm, and determining the elution rate (%).

The results of the dissolution test are shown in Figure 6.

For comparison, commercially available diltiazem hydrochloride (Comparative Example 1
), and tablets prepared by blending and compressing only the main drug layer components of Example 1 (Comparative Example 2), a similar experiment was conducted.

As a result, the product of the present invention was observed to float 3 to 4 minutes after the start of the dissolution test, and the dissolution rate after 10 hours was about 85%, indicating excellent sustainability. In contrast, the tablets of Comparative Examples 1 and 2 did not float and did not last long enough.

[Examples 2 and 3] The main drug layer and the foam layer were mixed in the same formulation as in Example 1.
The tablets were each compressed into the shapes shown in Figure 3.4.

Next, an elution test and foaming and floating state were observed in the same manner as in Example 1. As in Example 1, foaming and floating were observed, and excellent sustainability was observed.

[Brief explanation of drawings]

FIG. 1 shows an embodiment of the present invention, in which (A) is a sectional view, (B) is a top view, (C) is a bottom view, and FIGS.
The figures are cross-sectional views showing other examples of the present invention, and FIG. 6 is a graph showing the persistence of tablets according to the present invention and comparative tablets. 1... Main drug layer 2... Foaming layer Figure 1 Figure 2 Figure 3

Claims (1)

[Claims] 1. It is characterized by comprising a main drug layer and a foam layer that foams upon contact with gastric juice to create buoyancy in the tablet, and is formed in a state where the foam layer is exposed to the outside. tablets. 2. The tablet according to claim 1, wherein the foam layer mainly contains effervescent salts. 3. The tablet according to claim 2, wherein the effervescent salt comprises sodium hydrogen carbonate. 4. Claim 1 in which the foam layer contains a sustained release base
Tablets listed in section.