JPH061717A - New process for producing foamable tablet - Google Patents

Abstract

PURPOSE:To obtain a foamable tablet having quick disintegrating and foaming property and excellent aging stability by using an alkali metal halide as a forming, lubricating and binding agent, mixing the alkali metal halide with a (bi)carbonate and an organic acid exhibiting solid state at normal temperature and tableting the obtained powdery mixture. CONSTITUTION:An alkali metal halide such as sodium chloride, potassium chloride, sodium bromide and potassium bromide is used as a forming, lubricating and binding agent and compounded with a carbonate and/or bicarbonate (e.g. sodium carbonate) used as a main agent and an organic acid exhibiting solid state at normal temperature (especially preferably citric acid, tartaric acid, succinic acid, maleic acid or ascorbic acid). The obtained powdery mixture is tableted to obtain the objective foamable tablet. The compression moldability can be improved by the use of the alkali metal halide in the production process.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing an effervescent tablet used as a drug, a drug for in-vitro diagnosis, a soft drink tablet, a bath salt and the like.

[0002]

BACKGROUND OF THE INVENTION Effervescent tablets are tablets that have the property of reacting with water to generate carbon dioxide gas, and are characterized in that they are carbonates or carbonates in addition to the main drug or drug (usually called the main drug). This is because it contains hydrogen salt and an organic acid such as citric acid or tartaric acid as main components. Further, the effervescent tablet is manufactured by tableting after adding and mixing a excipient, a lubricant, a binder and the like to these main components as appropriate.

The manufacturing method of the effervescent tablet is roughly divided into the dry method and the wet method, like the general tablet, and the outline of each manufacturing method is as follows. -Dry method A method for producing an effervescent tablet by mixing and crushing a main ingredient, a carbonate or hydrogen carbonate, an organic acid, if necessary, a excipient, a lubricant, etc. and crushing the resulting powder.・ Wet method Main ingredients, carbonates or hydrogen carbonates, organic acids, if necessary, excipients, lubricants, etc. are mixed and pulverized, and the obtained powder is ethanol solution containing a binder such as polyethylene glycol. After wetting with, granulate. A method for producing an effervescent tablet by drying, sizing, and compressing the obtained granules.

However, whichever method is used, there are many problems in producing effervescent tablets. That is, the main agent,
Since a composition containing only a carbonate or hydrogen carbonate and an organic acid has a property of poor compression moldability,
If the production is carried out under a strong compression condition, there is a problem that sticking (damage of the tablet surface due to sticking to the punch) is likely to occur. Moreover, this problem cannot be solved even by using a method of adding a molding aid such as a lubricant, which is a general method for solving such a problem. That is, in the case of the dry method, when an effervescent tablet is prepared by using a lubricant such as magnesium stearate or talc which is commonly used to solve such a problem, the obtained tablet is dissolved in water. There is a problem that an insoluble matter remains when dissolved, and in the case of a wet method, when an effervescent tablet is prepared by using, for example, polyethylene glycol generally used to solve such a problem, Disintegration and effervescence of the effervescent tablets obtained (tablet components dissolve in water while carbon dioxide is generated when the tablets are added to water)
However, there are problems such as poor quality and destabilization of the base compound over time.

In order to avoid sticking,
The tablet may be produced by reducing the degree of compression, but in this case, only a tablet having low strength and high friability can be obtained, so this method cannot be said to be a preferable solution.

Further, of the above-mentioned two methods, the dry method has a problem that the fluidity of the powder is deteriorated depending on, for example, the components of the powder to be used for tablet molding, resulting in a large variation in the weight of the obtained tablet. On the other hand, in the wet method, the components in the tablet are likely to be denatured due to moisture contained in the organic solvent used during granule production or to absorb moisture during the granule production process, and the stability over time tends to be poor. There is a problem to say. Therefore, there is a demand for development of a method for producing an effervescent tablet that does not cause such a problem.

[0007]

SUMMARY OF THE INVENTION The present invention has been made in view of the above situation, and has good compression moldability during production of effervescent tablets,
It is an object of the present invention to provide a method for producing an effervescent tablet having both rapid disintegrating effervescence and good stability over time.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention is characterized in that a mixed powder containing a main ingredient, a carbonate or / and a hydrogen carbonate, an organic acid which is solid at room temperature, and an alkali halide is compressed into tablets. Is an invention of a method for producing an effervescent tablet.

That is, the inventors of the present invention have made earnest researches to solve the above-mentioned problems in effervescent tablets, and as a result, for example, alkali halides such as sodium chloride and potassium bromide were found to be generated during effervescent tablet production. It has been found that it has excellent properties as a excipient, a lubricant and a binder, and when it is used as an excipient, a lubricant or a binder to produce an effervescent tablet, The inventors have found that it is possible to produce an effervescent tablet having good compression moldability at that time, and having both rapid disintegrating effervescence and good stability over time, and completed the present invention.

The alkali halide according to the present invention is a salt composed of a halogen atom such as a chlorine atom, a bromine atom, an iodine atom and a fluorine atom and an alkali metal such as a lithium atom, a sodium atom and a potassium atom. Although not particularly limited, sodium chloride, potassium chloride, sodium bromide, potassium bromide and the like are preferable from the viewpoint of easy availability and easy handling. In addition, these salts may be used alone or in any combination of two or more kinds.

The carbonate or hydrogen carbonate according to the present invention is not particularly limited as long as it is usually used in the preparation of effervescent tablets. More specifically, ammonium salts, for example, alkali metal salts such as lithium salt, sodium salt, potassium salt and the like, alkaline earth metal salts such as calcium salt, magnesium salt, barium salt and the like are preferably mentioned. Incidentally, these salts may be used alone or in any combination of two or more kinds.

The organic acid which is solid at room temperature according to the present invention is not particularly limited as long as it is one that is usually used when preparing effervescent tablets. More specifically, for example, citric acid, tartaric acid, succinic acid, maleic acid,
Preferable examples include ascorbic acid. In addition, these organic acids may be used alone or in any combination of two or more kinds.

The main ingredient that can be retained in the effervescent tablet according to the present invention is not particularly limited as long as it does not have the property that its stability is deteriorated by other coexisting components. More specifically, for example, dyes used in the field of clinical tests such as o-phenylenediamine · 2HCl, 3,3′-diaminobenzidine · 4HCl, for example, p-nitrophenylphosphate 2Na · 6H ₂ O, Preferable examples include substrates for measuring enzyme activity such as phenylphosphate 2Na · 2H ₂ O, drugs and the like.

The effervescent tablet can be produced by the production method of the present invention, for example, as follows. That is, using a ball mill mixer or the like, for example, a carbonate or / and a hydrogen carbonate, an organic acid, a drug or a drug (base compound) to be contained in the effervescent tablet, and an alkali halide are mixed, Effervescent tablets can be easily obtained by crushing and mixing the obtained mixed powder into tablets using a tableting machine which is usually used for producing tablets.

In the effervescent tablet obtained by the production method of the present invention, for example, the content of carbonate, hydrogen carbonate, organic acid or main agent in the tablet and the content ratio thereof are the same as those in ordinary effervescent tablets. Is not particularly limited as long as it is contained in
It may be appropriately determined in consideration of pH and the like at the time of dissolution. Further, in the production method of the present invention, as the content of the alkali halide used as a excipient, a lubricant, a binder, etc., the excipient, lubricant, binder, etc. in a usual effervescent tablet It is not particularly limited as long as it is within the range of the content used, but the content in the tablet is usually 5 to 30 W / W%, preferably 5 to 20 W / W.
Used to be in the range of%.

It is desirable that each raw material used in the production method of the present invention is sufficiently dried in advance by heat treatment, reduced pressure drying treatment or the like. That is, since the effervescent tablet originally has a property of reacting with water to generate carbon dioxide gas, when water is contained in the raw material used for the production thereof, the gas during the production of the tablet is reduced. This is because the production reaction may proceed and the effervescent tablet obtained as a result may have poor temporal stability. It should be noted that the alkali halide may be deliquescent depending on the type of impurities contained therein, so that special attention is required.

Further, the effervescent tablet of the present invention has a flavoring / flavoring agent and a stabilizer which are used in the preparation of general tablets, as long as they do not affect the disintegrating effervescence and stability over time. Needless to say, a shaping agent, a lubricant and the like may be appropriately contained. Hereinafter, the present invention will be described more specifically with reference to Examples, Experimental Examples, etc., but the present invention is not limited to these Examples.

[0018]

【Example】

Example 1. o-Phenylenediamine ・ 2HCl (OPD) 13
g, sodium carbonate 15 g, succinic acid 29 g and sodium chloride 6 g were put into a ball mill mixer, mixed and pulverized. The obtained powder was made into tablets (63 mg / 1 tablet, diameter 5 mm) with a tableting machine (Kikusui Seisakusho) to obtain effervescent tablets.
The results of statistically processing the weight measurement results of 50 tablets obtained by the above method and the results of statistically processing the OPD content of the 50 tablets are shown below. The OPD content in tablets was determined according to the method described in the literature (Analytical Chemistry Handbook, Revised 3rd Edition, edited by The Analytical Chemistry Society of Japan, Maruzen Co., Ltd., p. 546, published September 20, 1981). It was -Weight measurement result-Average value 62.19 mg. -Standard deviation (SD) 0.75 mg. -Coefficient of variation (CV) 1.21%. -OPD content quantitative result-Average value 10.05 mg. -Standard deviation (SD) 0.228 mg. -Coefficient of variation (CV) 2.27%. As is clear from this result, in the effervescent tablet obtained by the method of the present invention, the weight variation between tablets and the main ingredient (O
It can be seen that there is almost no change in the PD) content.

Example 2. OPD 13g, sodium carbonate
15 g, 29 g of succinic acid and 6 g of sodium bromide were put into a ball mill mixer, mixed and pulverized. The obtained powder was tableted (63 mg / 1 tablet, diameter 5) with a tableting machine (Kikusui Seisakusho).
mm) to give effervescent tablets. The results of statistically processing the weight measurement results of 50 tablets obtained by the above method and the results of statistically processing the OPD content of the 50 tablets are shown below. The OPD content in tablets was determined by the method described in the literature (Analytical Chemistry Handbook, Revised Third Edition, edited by The Japan Society for Analytical Chemistry, Maruzen).
Co., Ltd., page 546, issued September 20, 1981). -Weight measurement result-Average value 62.71 mg. -Standard deviation (SD) 0.67 mg.・ Coefficient of variation (CV) 1.06%.・ Results of quantitative OPD content ・ Average value 10.06mg. -Standard deviation (SD) 0.28 mg. -Coefficient of variation (CV) 2.80%. As is clear from this result, in the effervescent tablet obtained by the production method of the present invention, it is found that there is almost no variation in weight between tablets and variation in the main ingredient (OPD) content.

Reference Example Preparation of Effervescent Tablet by Wet Method OPD (13 g), sodium carbonate (15 g), succinic acid (29 g) and lactose (5 g) were put into a ball mill mixer and mixed and pulverized. The obtained powder is polyethylene glycol 6000
After kneading with a 10% ethanol solution (manufactured by Wako Pure Chemical Industries, Ltd.), this was granulated by an extrusion granulation method using a 32 mesh screen and dried in vacuum. The obtained granules were sieved to obtain fine granules that remained on an 80 mesh sieve. The granules were made into tablets (63 mg / 1 tablet, diameter 5 mm) with a tableting machine (Kikusui Seisakusho) to obtain effervescent tablets. The results of statistically processing the weight measurement results of 50 tablets obtained by the above method and the results of statistically processing the OPD content of the 50 tablets are shown below. The OPD content in tablets was determined by the method described in the literature (Analytical Chemistry Handbook, Revised Third Edition, edited by The Japan Society for Analytical Chemistry, Maruzen).
Co., Ltd., page 546, issued September 20, 1981). -Weight measurement result-Average value 62.50 mg. -Standard deviation (SD) 1.56 mg. -Coefficient of variation (CV) 2.50%. -OPD content quantitative result-Average value 9.90 mg. -Standard deviation (SD) 0.30 mg. -Coefficient of variation (CV) 3.02%. As is clear from this result, the weight variation between tablets and the variation of the main ingredient (OPD) content in the effervescent tablet prepared by the wet method are more comparable to those in the effervescent tablet produced by the present invention. It turns out that it is obviously large.

Experimental Example 1. Raw material prescription (A
~ E), an effervescent tablet was prepared by the same operation method as in Example 1. Table 1 also shows the number of occurrences of sticking when 100 tablets were produced with each raw material formulation, and the results of the disintegrating foaming test and stability test of the obtained tablets. In addition, Table 1 shows the number of occurrences of sticking when 100 effervescent tablets were prepared by the same raw material formulation as in Reference Example (wet method) and by the same operation method as in Reference Example, and the collapsed effervescence of the obtained tablets. The results of the sex test and the stability test are also shown. The operation method of the tablet disintegration foaming test and stability test is as follows. -Disintegration and effervescence test One prescribed tablet was placed at room temperature (25 ° C) in a test tube containing 10 ml of water, and the time (minutes) required immediately after the introduction until the end of foaming was measured. -Stability test After preparation, the presence or absence of a change in OPD content in tablets before and after storage for 1 year in a refrigerator (4 ° C) was examined. The OPD content was measured in the same manner as in Example 1.

[Table 1] *: Colored yellow-orange, and the OPD content also decreased. As is clear from the results in Table 1, it is understood that the sticking during the tablet production can be suppressed by using sodium chloride as the excipient. It is also found that the basic properties of the effervescent tablet obtained do not change even when sodium chloride is contained. On the other hand, in the effervescent tablet prepared by the wet method, although the number of occurrences of sticking during tablet production is small, it takes time for disintegration and effervescence (2 minutes ↑) and the stability during storage is poor.

[0022]

As is clear from the above description, the production method of the present invention has been observed when effervescent tablets were produced by a conventional method. It has the effect of producing an effervescent tablet without causing problems such as poor disintegration and effervescence of the tablet and destabilization of the main ingredient over time, which greatly contributes to the industry. It is another invention.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Office reference number FI technical display location A61K 47/12 Z 7433-4C

Claims (3)

[Claims] 1. A main agent, a carbonate or / and a hydrogen carbonate,
A method for producing an effervescent tablet, which comprises tableting a mixed powder comprising an organic acid that is solid at room temperature and an alkali halide into tablets. 2. The alkali halide is sodium chloride,
The production method according to claim 1, which is potassium chloride, sodium bromide or potassium bromide. 3. The organic acid, which is solid at room temperature, is at least one selected from the group consisting of citric acid, tartaric acid, succinic acid, maleic acid and ascorbic acid.
The manufacturing method described in.