JPH0747534B2 - Tablets - Google Patents

Description

TECHNICAL FIELD The present invention relates to a gastric floating tablet, and more particularly, to a gastric foam by forming a foaming layer that foams upon contact with gastric juice to cause buoyancy in the tablet. Relates to tablets that are effervescent in.

Problems to be Solved by Conventional Techniques and Inventions In order to maintain the effects of pharmaceuticals, it is important to maintain an effective blood concentration of the drug. The administered drug exhibits a maximum blood concentration after a certain period of time after being absorbed, and after excretion, the blood concentration decreases in a short time and the drug effect disappears. Therefore, in order to maintain the effective blood concentration of the drug, the drug is administered several times a day.However, if the number of times of administration of the drug is increased, the dose is naturally increased, resulting in troublesome administration and misadministration and side effects. The problem of occurs. In addition, there are individual differences in the absorption of drugs, and even if the same amount of drug is administered, the drug effect may not appear, or conversely, an excessive drug effect may appear. It is difficult to set the dose and frequency of administration of a drug that can be maintained.

Therefore, conventionally, studies have been made and put into practical use for formulations capable of sustaining the drug effect for a long time by single drug administration.

By the way, since orally administered tablets are usually absorbed in the digestive tract, the duration of the drug effect is affected by the solubility of the tablets in the digestive tract and the residence time in the digestive tract.

In consideration of these points, various methods have been developed to adjust the solubility and disintegration degree of tablets to maintain the drug effect for a long time.
In particular, a method in which various sustained-release bases are mixed with an additive for tablets or coated on tablets to continuously release the active ingredient in the digestive tract for a long time has been adopted as an effective method.

However, in these methods, the persistence of the medicinal effect varies among individuals,
It has the drawback of being affected by the condition of the stomach and the contents of the stomach. Further, the drug effect lasts longer than that of ordinary tablets, but even in these methods, the retention time of the tablet in the digestive tract is limited to about 8 hours, and the drug effect cannot be extended any longer.

Therefore, studies have been conducted to extend the residence time of tablets in the digestive tract to maintain the drug effect for a long time. This is a method of prolonging the retention time of the tablet in the stomach because the drug is usually absorbed in the digestive tract, particularly in the small intestine. For example, a tablet is made larger to utilize the selective action of the gastric pylorus, or a preparation having a small specific gravity, specifically, an auxiliary drug, a fatty substance, a method using a hydrocolloid (JP-A-51-115910), An attempt has been proposed to extend the retention time in the stomach by suspending the solid agent in the stomach by a method using a hard capsule, styrofoam, foam rice or the like (Japanese Patent Publication No. 55-12411).

However, these methods have problems that the floating property in the stomach is not always sufficient and that formulation is troublesome.

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

The present invention has been 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 quickly floats, and that can be easily formulated.

Means and Actions for Solving Problems That is, the present inventors have conducted extensive studies on a gastric suspension type formulation, and as a result, have mainly made effervescent salts, which are effervescent in tablets, by gastric juice such as sodium hydrogen carbonate. By forming the effervescent layer in an externally exposed state and preparing a tablet into a multi-layered tablet or a dry-coated tablet comprising a main drug layer and this effervescent layer, the effervescent layer is foamed by gastric juice to reliably float the tablet in the stomach. Further, it was found that when a sustained-release base is blended in the main drug layer, the main drug can be continuously released for a long time to form a tablet as a sustained-release drug, and the present invention has been completed. It was

Therefore, the present invention is characterized by comprising a main drug layer and a foam layer that foams upon contact with gastric juice to generate buoyancy in the tablet, and is formed in a state where the foam layer is exposed to the outside. It provides tablets.

Hereinafter, the present invention will be described in more detail.

As described above, the tablet of the present invention comprises the active ingredient layer and the foam layer.

Here, the main drug layer is composed of tablets and various additives. The drug is not particularly limited, but a drug that is orally administered and is absorbed in the digestive tract is preferably used. For example, magnesium silicate, magnesium oxide, impregnated aluminum silicate, antacid such as sodium hydrogencarbonate, intestinal agent such as berberine oxide, butyl scopolamine bromide, antispasmodic such as budropium bromide, prazinone chloride, dextrate hydrobromide. Antitussive and sputum agents such as lometorphan, ketotifen fumarate, antipyretic and analgesic antiinflammatory agents such as pranoprofen, peptic ulcer agents such as cimetidine, blood pressure lowering agents such as captoril and labetalol hydrochloride, cardiovascular agents such as nicardipine hydrochloride, diltiazem hydrochloride Calcium antagonists, such as carteolol hydrochloride β
-A blocker agent, an arrhythmic agent such as pindolol, a psychotropic agent such as sulpiride, and a hemostatic agent such as tranexamic acid are preferably used. In particular, since the tablet according to the present invention stays in the stomach for a long time, it is effective for a drug whose absorption site is limited to the stomach, such as an antacid, and is more preferably used.

Here, the compounding amount of the drug can be variously changed in consideration of the usual dose of the compounded drug, administration conditions and tablet formulation conditions.

Further, as the additive forming the main drug layer, additives usually used for tablets, such as excipients, preservatives, stabilizers, buffers, etc. may be blended, but in the case of releasing the drug slowly It is preferable to blend a sustained-release base.

In this case, as the sustained-release base, commonly used substances, for example, wax matrixes such as carnauba wax, beeswax, paraffin wax, microcrystalline wax, fatty acids, fatty acid alcohols and their esters, gum arabic, tragacanth gum, etc. , Carob gum, guar gum, karaya gum, agar, pectin, carrageenan, hydrocolloids such as soluble and insoluble alginates, methylcellulose, hydroxypropylmethylcellulose, hydroxypropylcellulose and synthetic polymers can be used. A suitable sustained-release base may be used alone or in combination of two or more. Moreover, the compounding quantity is 0 to 80%.

The tablet according to the present invention is provided with the foam layer as described above, and the foam layer is formed so as to be foamed by gastric juice and float due to the buoyancy of the tablet in the stomach. Specifically, it is formed mainly by effervescent salts that are foamed by gastric juice, and if necessary, additives are mixed.

In this case, the effervescent salts are not particularly limited, but salts that quickly foam under acidic conditions in the stomach, are harmless in the dosage of the tablet, and do not impair the therapeutic effect,
For example, sodium hydrogen carbonate is preferably used. Further, as the additive, as in the case of the main drug layer, it is preferable to add a commonly used tablet additive, and it is particularly preferable to add a sustained release base. By blending this sustained-release base, the foam of the foamable salt is better stored, and good floating properties can be obtained. Also, the types of sustained-release bases to be blended are
Like the main drug layer, one or more substances commonly used can be used in combination, and the compounding amount is 0 to 80%.
It is possible to

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

Forming the tablet in this manner ensures that the tablet floats. That is, although a tablet containing sodium hydrogen carbonate has been conventionally known, a conventional tablet of this type is simply one in which sodium hydrogen carbonate is evenly dispersed in the tablet. Causes sodium hydrogen carbonate to foam, but does not suspend gastric juice. However, by constructing the foam layer as described above, the buoyancy that floats the tablet acts due to the foaming of the foaming salt, and the tablet can be floated.

The tablet of the present invention can be formed as a multilayer tablet or a dry-coated tablet comprising the above-mentioned main drug layer and foam layer. For example, as shown in FIG. 1, a base material layer 1 having a concave shape is provided with a foam layer 2 in a concave portion at the center of one surface.
, A two-layer tablet comprising the active drug layer 1 and the foam layer 2 as shown in FIG. 2, and the foam layer 2 formed between the active drug layer 1 and the foam 1 as shown in FIG. Examples thereof include a three-layer tablet, and a dry-coated tablet having the active ingredient layer 1 in the foam layer 2 as shown in FIG. 4, but the shape is not limited to these, and the type of drug and the administration method The shape can be set according to the above. For example, the tablet has a plane shape that is usually circular as shown in FIGS. 1 to 4, but may have a polygonal shape. Further, in the embodiment shown in FIG. 1, the recess is formed in the center of one surface of the main drug layer 1 and the foam layer 2 is provided in the recess, but the recess does not necessarily have to be formed in the center of the main drug layer 1. . Further, in the embodiment of FIGS. 1 to 4, the side surface shape of the tablet is formed into a substantially elliptical shape, but other suitable shapes,
For example, it may be formed in a rectangular shape as shown in FIG.

Further, tablets are tableted using a conventional tableting method, but it is preferable to tablet them by a method suitable for the shapes of the active ingredient layer and the foam layer.

EFFECTS OF THE INVENTION As described above, the tablet according to the invention is easy to formulate because it foams and floats in the stomach and stays in the stomach, and only the active ingredient layer and the foamed layer are compressed by a conventional method. is there.

Hereinafter, the present invention will be specifically described with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, all parts are parts by weight.

[Example 1, Comparative Examples 1 and 2] As a main drug layer, 18 parts of diltiazem hydrochloride, hydroxypropyl methylcellulose (manufactured by Shin-Etsu Chemical Co., Ltd., Metroze 90SH)
30,000) 18.75 parts, lactose 11.75 parts, hydroxypropyl cellulose 0.5 part, magnesium stearate 1 part to make the total amount 250 mg, and as a foam layer forming component 15 parts lovely wax, sodium hydrogencarbonate 15 parts, Avicel PH3017.27 Part, hydroxypropyl cellulose 0.5 part,
Magnesium stearate 1 part, hydroxymethyl cellulose (Metroses 90SH30,000) 2.03 parts, total 14
0 mg tablet machine (Kimura single-shot tablet machine KS-II
It was tableted using a mold to form a bilayer tablet as shown in FIG.

Next, according to the Japanese Pharmacopoeia, the tablet dissolution test was performed by the paddle method.

That is, the first liquid used in the Japanese Pharmacopoeia disintegration test method (sodium chloride 2.0 g, dilute hydrochloric acid 24.0 ml and water to make 100 ml, pH about 1.2) was kept at a liquid temperature of 37 ± 2 ° C., and tablets were added to this liquid. Then, the mixture was stirred with a dissolution tester (manufactured by Toyama Sangyo Co., Ltd.) at a rotation speed of 100 rpm. At this time, the foaming and floating state of the tablet was visually observed. The elution result was obtained by measuring the UV absorbance of the eluate at a wavelength of 236 nm to determine the elution rate (%).

The results of the dissolution test are shown in FIG.

For comparison, the same experiment was performed using a commercially available diltiazem hydrochloride (Comparative Example 1) and a tablet (Comparative Example 2) in which only the main drug layer components of Example 1 were blended and compressed.

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%, showing excellent sustainability. On the other hand, the tablets of Comparative Examples 1 and 2 did not float and the sustainability was not sufficient.

[Examples 2 and 3] A main ingredient layer and a foam layer were prepared in the same formulation as in Example 1,
The tablets were compressed into the shapes shown in Fig. 4.

Next, when the elution test and the foaming and floating states were observed by the same method as in Example 1, the excellent sustainability of foaming and floating was observed as in Example 1.

[Brief description of drawings]

FIG. 1 shows an embodiment of the present invention. (A) is a sectional view, (B) is a plan view, (C) is a bottom view, and FIGS.
FIG. 6 is a cross-sectional view showing another embodiment of the present invention, and FIG. 6 is a graph showing the sustainability of the tablet according to the present invention and the tablet of the comparative example. 1 ... Main drug layer, 2 ... Foam layer

Claims (4)

[Claims] 1. A tablet comprising a main drug layer and a foam layer that foams upon contact with gastric juice to generate buoyancy in the tablet, and the foam layer is formed in a state of being exposed to the outside. . 2. The tablet according to claim 1, wherein the effervescent layer mainly contains effervescent salts. 3. The tablet according to claim 2, wherein the effervescent salt comprises sodium hydrogen carbonate. 4. The tablet according to claim 1, wherein the foam layer contains a sustained-release base.