JPS585695B2 - Manufacturing method of effervescent tablets - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a process for producing effervescent tablets that are stable over long periods of time.

"Effervescent tablets" are generally made into tablets by mixing an acid such as a crystalline organic acid with an alkali such as an alkali carbonate, and when the mixture is poured into water, the two are neutralized and gases such as carbon dioxide are released. This refers to a tablet that dissolves as it develops.

Effervescent tablets can be advantageously used not only for oral purposes such as medical oral drugs and raw materials for preparing soft drinks, but also for various parenteral purposes such as solvents, detergents, agricultural chemicals, and rust preventives.

However, if acid and alkali carbonate are mixed and tableted,
For example, it is well known that the presence of even a small amount of water (humidity) immediately causes a neutralization reaction, and within a few hours or days, the tablet disintegrates without retaining its original shape, rendering it completely unusable. Technically, this is expressed in the term contraindication of drug combination.

In order to prevent such significant changes, the following preventive measures are usually taken.

(1) Coat with one or both of acid and alkali, granulate, and tablet without direct contact.

(2) Water (humidity) that cannot be completely removed is attempted to be removed by enclosing a desiccant in the product container.

(3) Use a completely moisture-proof container.

(4) The tablet manufacturing operation is performed in a humidity-controlled room.

If water is completely absent, the neutralization reaction will not occur, but in reality this is virtually impossible.

Thus, the production of water-soluble effervescent tablets has hitherto required advanced technology and complete production equipment.

Naturally, it is inevitable that the product will cost more.

Therefore, there are only a few products such as vitamin C preparations used as pharmaceuticals and products for soft drinks, and only a few examples have been commercialized in the past. Currently, there are almost no such products on the market.

The present invention provides a new method for easily and inexpensively manufacturing effervescent tablets that can be used for a variety of purposes, such as oral medicines, raw materials for the preparation of soft drinks, bath additives, facial cleansers, etc. For human use or industrial use,
Small amounts of active ingredients can be dissolved or dispersed in large amounts of water without stirring.

The method for manufacturing effervescent tablets according to the present invention is characterized in that a hygroscopic but substantially non-deliquescent water-soluble substance (for example, anhydrous sodium sulfate) is used as a tablet stabilizer or a part thereof. It is.

The material used as the effervescent tablet stabilizer or part thereof in the present invention must meet the following conditions: (1) be hygroscopic; (2) be substantially non-deliquescent; 3) Be water-soluble.

There are many substances that meet this condition, some of which are as follows: inorganic anhydrous salts such as anhydrous sodium sulfate, anhydrous magnesium sulfate; in the form of porous crystals with a large specific surface area...alkali halides. , especially sodium chloride (Japanese Patent Publication No. 51-28685), non-deliquescent and water-soluble anhydrous saccharides, organic acid salts (for example, alkali citrate), etc.

Note that in addition to substantially anhydrous substances, lower hydrates can also generally be used.

For example, not only fully dehydrated products of higher hydrates but also partially dehydrated products can be used.

The present invention is based on the idea that the tablet itself is stable unless it contains free water, and has the following features.

The first feature is the ability to incorporate relatively large amounts of a substantially non-deliquescent, hygroscopic, and preferably substantially anhydrous material into the tablet, such as anhydrous sodium sulfate, which is used as a desiccant.

The second feature is that the effervescent component drug can be appropriately selected from a wide range; for example, in the case of parenteral tablets, even malic acid and sodium carbonate can be used.

Next, substantially anhydrous sodium sulfate, which can be very advantageously used as an effervescent tablet stabilizer in accordance with the present invention, particularly in the parenteral field, will be explained in detail.

Although the substance sodium sulfate is highly hygroscopic, it does not dissolve and flow out like calcium chloride when it absorbs moisture.On the other hand, unlike silica gel, it is not insoluble but water-soluble.

Because it is an abundant and inexpensive raw material in Japan, it is widely used as a desiccant and for other purposes.

Sodium sulfate (Na2SO4・10
H20) is already used as a solvent.

However, it has now been discovered that if an anhydride (i.e., substantially anhydrous sodium sulfate) is added and compressed into tablet form in accordance with the present invention, the following remarkable effects can be obtained. .

In other words, if a large amount of anhydrous sodium sulfate is blended into the tablet itself, the moisture contained in other mixed raw materials and the moisture contained in the air will be immediately absorbed into the anhydrous sodium sulfate itself as crystal water. As a result, it was confirmed that as long as the tablets were kept in a dry state without free water, the neutralization reaction described above did not occur at all and they were stable for a long period of time.

Even if one drop of water is intentionally added to the surface of the tablet, the neutralization reaction stops only around that area, and the tablet remains completely stable even when left naked indoors for a long period of time.

If such a tablet continues to absorb moisture from the air, one might expect that it would eventually reach a saturation point and stop absorbing water, eventually being unable to maintain its shape and disintegrating within about seven days or less. However, in reality, it is completely stable for a long period of time as described in the Examples below.

The reason for this is thought to be that a kind of moisture-resistant "wall" is formed once a certain amount of moisture has been absorbed.

Various substances, including anhydrous sodium carbonate, can be considered as substitutes for anhydrous sodium sulfate, etc., but the results of tests conducted on substances that do not meet the three conditions mentioned above are poor in terms of stability, hygroscopicity, and solubility. It was confirmed that they are inferior in terms of quality, price, etc.

Another advantage of anhydrous sodium sulfate is that it also has a buffering effect that reduces mutual contact between acid and alkali when added in large amounts.

Next, the second feature of the present invention, that is, the feature that acid and alkaline chemicals can be selected from a wide range will be explained in detail.

Malic acid as an acidic substance and sodium carbonate and sodium sesquicarbonate as alkaline substances are generally not used for oral purposes due to their poor taste.

Alternative drugs include tartaric acid, citric acid, and acidic sodium carbonate (baking soda), but these are expensive and
Furthermore, experiments have revealed that malic acid, sodium carbonate, and sodium sesquicarbonate are more effective than these substances in terms of stability when incorporated into tablets.

A method for manufacturing effervescent tablets according to the present invention will be explained.

The desired tablet can be obtained by the direct method, which consists of mixing raw materials one after another according to a predetermined formulation and then compressing the tablets, but it is also possible to obtain the desired tablet by the indirect method, which involves granulating each component individually and then mixing and tableting. Similar results are obtained.

For this purpose, anhydrous sodium sulfate may be added to both the acid and the alkali, or granulated anhydrous sodium sulfate 4 may be mixed with all other raw materials.

When the amount of anhydrous sodium sulfate is relatively small (
(approximately 10%), the amount of foaming is large, and the dissolution is quick, but the moisture resistance is somewhat inferior.

On the other hand, when the amount of anhydrous sodium sulfate is quite large (approximately 80%), the amount of foaming is not large, it takes time to dissolve, and insoluble residue may remain, but the moisture resistance is of course greatly increased. do.

Therefore, it is advantageous to appropriately increase or decrease the amount of anhydrous sodium sulfate, for example, between about 10 and 90%, depending on the intended use of the tablet.

The features of the effervescent tablet according to the present invention are as follows.

(1) Be stable.

Stability over time is significantly increased by incorporating a suitable tablet stabilizer such as anhydrous sodium sulfate, preferably in excess.

In particular, when the tablet absorbs moisture to a certain degree, it becomes more stable and at the same time the hardness of the tablet increases.

(2) It should be easy to manufacture.

Raw materials can be mixed one after another and tableted directly.

Of course, the same results can also be obtained by indirect methods involving granulation.

Further, it is unnecessary to take the trouble to provide a dehumidifying device in the manufacturing room.

(3) It should be inexpensive.

As raw materials, it is abundant and inexpensive domestically and can be supplied stably.

Manufacturing equipment investment is also saved, and the product does not require expensive moisture-resistant containers.

(4) Convenience and ease of use.

When this tablet is immersed in K water, it foams and dissolves transparently in a few minutes.

For example, in the tablet described in Example 1 below, one tablet (13f
) generates carbon dioxide gas of 450eC and is pleasant to use.

Still, according to the present invention, effervescent tablet-shaped confectioneries, medicines, etc., which are administered directly into the mouth, can also be produced.

When this type of effervescent tablet is put into the mouth, it dissolves in saliva during the day and effervesces, giving a refreshing feeling.

In the case of pesticides, etc., if they are powdered, they may scatter during handling, causing poisoning to humans and animals by inhaling them, or contaminating the surrounding area. However, when processed into effervescent tablets according to the present invention, There is no danger like the above.

This effervescent tablet form of pesticides is stable in the air and easy to handle, and does not absorb moisture and disintegrate during storage. Moreover, when placed in water, it quickly expands and disintegrates, dissolving uniformly. However, it is still dispersed and fully exerts its effect as an agrochemical.

Therefore, this effervescent tablet-shaped pesticide can be directly administered into water, etc. of paddy fields in the form of a tablet, and the pesticide can be sprayed safely and easily.

Furthermore, since the pesticide content per tablet is constant,
It is very easy to apply a fixed amount of pesticides.

Furthermore, effervescent tablets are very convenient when making liquid pesticides on site, for example for spraying, i.e.
When a predetermined number of tablets are put into a predetermined volume of water, they immediately foam and dissolve, and a sprayable liquid preparation of a predetermined concentration can be easily obtained.

Example 1 Bath additive anhydrous sodium sulfate 42 (%) malic acid
30 Anhydrous sodium carbonate
25 Tableting aids such as lubricants and release agents Appropriate amounts of coloring agents and flavoring agents Add appropriate amounts of starting ingredients to a mixing tank, mix, and tablet by conventional methods.

Pack the finished tablets in resin film or aluminum foil, or place them in a large container.

There is no need to install air control equipment in the manufacturing room or double pack the tablets with a desiccant agent.

These tablets may seem to consist of only common ingredients for bath additives, but by processing them into tablets, a very unique and superior product is obtained.

Regarding this point, please refer to the description of the test examples below.

Example 2 Facial cleanser anhydrous sodium sulfate 20(%) malic acid
50 Sodium sesquicarbonate 25 L-ascorbic acid 3 Tableting aids such as lubricants 2 The starting components of the above composition were tableted in the same manner as in Example 1.

When this tablet is placed in water in a basin, it dissolves quickly in about 30 seconds, and its acidity is approximately 5th in pH.

Example 3 Bath Salts Effervescent tablets were manufactured according to the following recipe according to the same manufacturing method as in Example 1.

Anhydrous sodium sulfate 40 (%) tartaric acid (
Substantially free of water of crystallization (25) Anhydrous sodium carbonate (30) Tableting aids, coloring agents, flavoring agents (appropriate amounts) This effervescent tablet was as good as the tablet described in Example 1.

Test results of stability over time (humidity resistance) Test 1 (standing test under high temperature and humidity conditions) The tablet (bath agent) described in Example 1 was loosely contained, and the temperature was 4.
It was kept at 5°C and 90-100% humidity for 14 days.

This tablet did not change at all, and its size etc. were the same as before the test.

When this was dissolved in hot water at a temperature of 40°C, 450 cc of carbon dioxide gas, the same amount as the standard product, was generated and the product was dissolved transparently.

On the other hand, when the control sample (tablet with the same composition as the effervescent tablet described in Example 1 except that anhydrous sodium sulfate was not added) was examined after this test, the volume had increased by about 1.5 times. This was only used as a standard (after putting it into the water).

Test 2 The tablets described in Example 1 were stripped and tested on June 10, during the rainy season.
I have left it indoors since then.

No change was observed even after 180 days had passed.

On the other hand, the control sample that did not contain anhydrous sodium sulfate absorbed moisture in the room, expanded to about twice its original volume, and collapsed even after only 7 days.

Example 4 Cold Medicine Tablets Effervescent cold medicine tablets were obtained by compressing the following ingredients into tablets.

Acetylsalicylic acid 0.3 (g) Anhydrous sodium citrate 0.7 Anhydrous citric acid
1.0 anhydrous sodium carbonate
0.6 Glucose 0.
5 Artificial Sweeteners, Flavorings, etc. Appropriate Amount Tableting Auxiliary Appropriate Amount Test 3 The effervescent cold medicine tablets obtained in Example 4 were tested by the method of Test 1 described above.

This was stable when left standing, and when placed in water, it foamed and dissolved well.

On the other hand, when testing commercially available effervescent cold medicine tablets (approximately 3 g per tablet) as a control sample, it was found that the moisture resistance of the sealed product did not change at all, but the one that was left uncovered indoors absorbed indoor moisture. It generates carbon dioxide gas, and each tablet contains about 0.
The weight was reduced by 1 g, and on the 5th day, the shape started to collapse, and even when it was placed in water, it hardly foamed.

Example 5 Soft drink tablets After thoroughly mixing the following ingredients, the mixture was made into tablets using a tablet machine.

Anhydrous sodium citrate 30(%) glucose
20 Anhydrous citric acid
31 Anhydrous sodium carbonate 19 Flavoring, artificial sweeteners, etc. When an appropriate amount of this tablet was poured into water, it foamed violently and immediately dissolved, yielding a soft drink.

This tablet did not show any deformation even if the storage container was left open for a long period of time.

Example 6 Orange Beverage Tablet The following well-dried ingredients were mixed and compressed to form a tablet.

Anhydrous sodium citrate 30 (parts) Sodium bicarbonate 6 Sucrose 55 Malic acid 9 Citrus flavor and color Appropriate amount When this tablet is poured into water, it immediately dissolves while foaming.
An orange drink was obtained.

Also, when this tablet was taken during the day and sucked, the foam collapsed with saliva, giving a very refreshing feeling.

Example 7 Pesticide tablets for use in water The following ingredients were mixed well and compressed to obtain tablets.

Pesticide 40 (%) Anhydrous sodium sulfate 20 Anhydrous citric acid 4 Sodium bicarbonate 5 Surfactant 5 Carrier powder 26 Separately, control tablet samples with the same composition except for the anhydrous sodium sulfate were prepared.

The conditions after leaving these without packaging for 90 days were as follows.

In other words, the tablets of the present invention show a change in foaming and dissolving quickly when placed in water, whereas the tablets of the control product swell and burst, and do not foam and disintegrate even when placed in water. It was very inferior.

Claims (1)

[Claims] 1. A method for producing effervescent tablets, characterized in that a hygroscopic but substantially non-deliquescent water-soluble substance is used as a tablet stabilizer or as a part thereof.