JP2818892B2 - Foam formulation - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to a method for stabilizing an effervescent preparation, a stabilizer for the effervescent preparation, and an effervescent preparation having a high storage stability.

2. Description of the Related Art An effervescent preparation is a preparation containing sodium carbonate, sodium bicarbonate, or the like as an effervescent component, and an organic acid as a neutralizing agent. When this is brought into contact with water, the foaming component and the organic acid undergo a neutralization reaction to generate carbon dioxide gas, thereby promoting the disintegration, dispersion or dissolution of the preparation. Since this type of preparation has high hygroscopicity and the neutralization reaction occurs with a small amount of water, it has to be kept as dry as possible during storage. Even when stored in a closed container, there is a risk that a reaction may occur due to residual moisture or water of crystallization during formulation. If carbon dioxide is generated during storage,
The internal pressure of the sealed storage container increases, which may cause deformation or breakage of the container, and cause the product not to foam during use. Foaming during storage is accelerated particularly at high temperatures, and the generated carbon dioxide and reaction water accelerate the reaction. Therefore, in order to prevent this and maintain the commercial value, it is essential to take measures such as use of a desiccant.

An object of the present invention is to provide a foam formulation having excellent stability during storage.

The present inventors have surprisingly found that when potassium carbonate is added to an effervescent formulation, the formulation is stabilized, and a high degree of storage stability can be obtained without the need for measures such as the use of a desiccant. Completed the invention.

Means for Solving the Problems That is, the present invention relates to an effervescent preparation containing sodium carbonate and / or sodium bicarbonate as an effervescent component, wherein sodium carbonate and / or sodium bicarbonate is contained in the preparation in an amount of 10 to 35% ( (% By weight, hereinafter the same) and potassium carbonate in an amount of 0.3 to 1.0%.

The present invention also provides a method and a stabilizer for stabilizing the effervescent preparation.

The foam formulation of the present invention has a high storage stability, prevents foaming during storage, and is maintained for a long period without impairing the commercial value such as color and taste. In addition, the foamed preparation of the present invention can maintain the reactivity at the time of use for a long period of time while being the same as before storage. Moreover, the stabilization by the potassium carbonate of the present invention does not impair the effervescence, taste, etc. of the effervescent preparation, even if a stabilizer is added.

Potassium carbonate as a stabilizer contained in the effervescent preparation of the present invention exhibits a stabilizing effect in 0.2% or more of the preparation. In order not to impair the taste, solubility, etc., the content is preferably 1.0% or less, and more preferably 0.3 to 1.0%. The potassium carbonate to be used is not particularly limited, but preferably does not contain water such as crystallization water, and for example, anhydrous potassium carbonate is more preferable.

The effervescent preparation of the present invention contains sodium bicarbonate and / or sodium carbonate as effervescent components. The mixing ratio of the foaming component to the preparation of the present invention can be appropriately selected depending on the shape, use, purpose of use and the like of the preparation. In order to obtain foaming properties, it is preferably selected from the range of 10 to 35%.

The effervescent preparation of the present invention contains an organic acid usually used for effervescent preparations as a neutralizing agent. The neutralizing agent may be selected singly or plurally from, for example, citric acid, tartaric acid, fumaric acid, ascorbic acid, lactic acid, and malic acid depending on the shape, use, purpose of use, etc. of the preparation. The mixing ratio of the above neutralizing agent to the preparation of the present invention is appropriately selected depending on the content of the foaming component, and it is preferable that the total amount of the neutralizing agent is 10 to 70% of the preparation.

Due to the combination of the foaming component and the neutralizing agent, the preparation of the present invention has an acidic pH in a solution obtained by dissolving the same in water, obtains good solubility, sufficiently generates carbon dioxide gas, and has a taste of the aqueous solution. It will be delicious.

The effervescent preparation of the present invention can contain various drugs selected according to the purpose of use, such as vitamins and iron salts. For example, when this is used as a nutrient, vitamins, iron salts, other inorganic salts, saccharides and the like can be blended. Also, this
When used as an NMR contrast agent, metal salts for various contrast agents,
For example, an iron salt or the like can be blended.

In addition, the foaming preparation of the present invention may contain various additives as required in addition to the above-mentioned agents, such as a binder, an excipient, a disintegrant, a lubricant, a thickener, a surfactant, and an osmotic pressure regulator. Agents, electrolytes, sweeteners, flavors, dyes, pH adjusters, and the like can be appropriately added and blended.

The preparation of the preparation of the present invention can be prepared by blending potassium carbonate in the same manner as in the production method of an ordinary effervescent preparation, and can be prepared by a direct powder compression method or a dry or wet granulation compression method.

The form of the preparation of the present invention may be any suitable form used by dissolving and dispersing in water, such as granules, powders and capsules, in addition to tablets.

Although the dosage form of the preparation of the present invention varies depending on the purpose of use, when the preparation is orally administered, the preparation is put into water to obtain a beverage form suitable for oral administration.

The dose is appropriately determined according to the purpose of use and the age, sex, weight, degree of disease, etc. of the living body to which it is applied, and is not particularly limited. About 1.5 to 6.0 g of the preparation of the present invention at a time with 100 to 30 water
You only need to dissolve it in 0ml and take it.

Preferred embodiments of the present invention include a foam formulation for supplementing L-ascorbic acid, a foam formulation for iron supplementation, and an iron-containing foam formulation for NMR imaging.

The effervescent formulation for L-ascorbic acid supplementation is characterized by containing 5 to 30% of L-ascorbic acid as a neutralizing agent and 10 to 35% of sodium carbonate and / or sodium bicarbonate as essential components. This preparation can contain the above-mentioned various neutralizing agents in addition to the above-mentioned L-ascorbic acid as a neutralizing agent. The compounding ratio is 10 to 70
%.

Foam preparations for iron supplementation, iron-containing compounds as iron 0.01 ~
It is characterized by containing 3.5%, and 10-35% of sodium carbonate and / or sodium bicarbonate as essential components.

Examples of the iron-containing compound constituting the present preparation include iron ammonium citrate, sodium ferrous citrate, iron citrate, ferrous gluconate, ferrous pyrophosphate, ferric pyrophosphate, iron lactate, and sulfuric acid. Examples include ferrous, ferric chloride, ferric sesquioxide, sodium iron chlorofin, ferrous fumarate, iron threonine, ferrous orotate, ferrous oxidized sugar, and ferric gluconate. Of these, ammonium iron citrate, sodium ferrous citrate and iron citrate are particularly preferred. These iron-containing compounds can be advantageously used in the present invention in the form obtained respectively, usually in the form of powder having a particle size of 200 μm or less. These may be used alone in the present preparation, or two or more of them may be used in combination. The compounding amount is preferably selected from the range of 0.01 to 3.5%, preferably 0.6 to 0.06%, as iron, and the addition within this range provides the present preparation with the desired excellent iron supplementation effect. Particularly preferred amounts of the iron-containing compound are 0.6 to 1.8% for ammonium iron citrate, 0.6 to 3.0% for sodium ferrous citrate, and 0.4 to 1.8% for iron citrate.

The blending ratio of the foaming component and the neutralizing agent contained in the preparation is as follows:
The foaming component is preferably selected from the range of sodium carbonate and / or sodium bicarbonate 10-35% and neutralizing agent 20-70%. In particular, sodium carbonate is selected from the range of 11 to 31%, preferably 22 to 26%, and sodium bicarbonate is preferably selected from the range of 10 to 35%, preferably 20 to 30%. Most preferably, it is used in the range of 2525%. The neutralizing agent is 20-70%, preferably
L-tartaric acid is selected from the range of 30 to 40%.
% And ascorbic acid are most preferably used in the range of 8 to 15%. By combining the above components, the desired effects of the present formulation are achieved.

Iron-containing effervescent preparations for NMR imaging are characterized by containing 0.1 to 10% of iron-containing compound as iron and 8-35% by weight of sodium carbonate and / or sodium bicarbonate as essential components.

The iron-containing compound constituting the present preparation is selected from the same compounds as the above-mentioned foam preparation for supplementing iron. Among these, the taste is good, it is easy to drink, and the point that the contrast effect is excellent,
Particularly, ammonium iron citrate, sodium ferrous citrate, iron citrate and the like are preferable, and a trivalent iron salt is preferable from the viewpoint of a nuclear magnetic moment. These are widely used in the pharmaceutical field, the food field, and the like, and are highly safe. These iron-containing compounds can be advantageously used in the present formulation in the form obtained, usually in the form of powder having a particle size of 200 μm or less, alone or in combination of two or more. Its compounding amount is 0.1 to 10% as iron, preferably 0.5 to 10%.
It is preferable to select from the range of ５5%. This blending amount is about 10 to 300 m / tablet in the case of this preparation in the form of an effervescent tablet.
g, preferably about 25 to 100 mg, and in powder form, the same weight range per packet as described above. Formulation within the above range provides the present formulation with the desired excellent NMR imaging effect.

The mixing ratio of the foaming component and the neutralizing agent in the present preparation is selected from the range of 8 to 35% of sodium carbonate and / or sodium hydrogencarbonate as the foaming component and 10 to 70% of the neutralizing agent. In particular, sodium carbonate is 9 to 35%, preferably 22 to 26%.
%, Sodium bicarbonate is 8-35%, preferably 20-35%
%. Neutralizer is preferably 20
To 50%, more preferably 30 to 40%, and it is particularly preferable to use at least an equivalent amount to sodium bicarbonate or the like. By the addition of this foaming component, the desired effects of the present formulation are exhibited.

The NMR contrast agent of the present invention thus obtained is orally administered after being put into water, and the dose is appropriately determined depending on the organ or tissue of the living body to be imaged. For example, in the case of contrast imaging of the pancreas, the present preparation (tablet prepared to 1.5 to 6.0 g per tablet or powder prepared to 1.5 to 6.0 g per packet)
1 to 2 tablets or 1 to 2 tablets may be dissolved in 100 to 300 ml of water and taken.

Effect of the Invention The foam formulation of the present invention has high storage stability, prevents foaming during storage, and is maintained for a long period without impairing the commercial value such as color and taste. In addition, the foamed preparation of the present invention can maintain the reactivity at the time of use for a long period of time while being the same as before storage. Moreover, the stabilization by the potassium carbonate of the present invention does not impair the effervescence, taste, etc. of the effervescent preparation, even if a stabilizer is added.

EXAMPLES Hereinafter, formulation examples and stability tests will be given as examples to explain the present invention in more detail. All the following percentages are by weight.

<Formulation Example> L-ascorbic acid supplementation foam formulations of Formulation Example Formulation Example 1 Granulated sugar 34% L-ascorbic acid 21% L-tartaric acid 20% sweetener qs Sodium bicarbonate 21% sodium chloride proper amount of potassium carbonate 0.5% fragrance Coloring agent trace 100% (total amount 5g) Mix the above ingredients and prepare by direct compression (tablet),
Alternatively, each component was weighed and mixed and divided (powder), or each component was weighed and mixed, granulated and dried, and then divided (granules) to produce a preparation.

 Hereinafter, Formulation Examples 2 to 10 were prepared in the same manner as Formulation Example 1.

Formulation Example 2 Granulated sugar 40% L-Ascorbic acid 10% L-Tartaric acid 23% Sweetener Suitable amount Sodium hydrogen carbonate 22% Sodium citrate Suitable amount Potassium carbonate 0.4% Flavoring / coloring agent Trace 100% (Total amount 5g) Foaming formulation for iron supplementation Formulation example Formulation example 3 Granulated sugar 40% L-ascorbic acid 11% L-tartaric acid 23% Sweetener Appropriate amount Ferric ammonium citrate 0.8% Sodium bicarbonate 22% Cyanocobalamin trace sodium citrate trace potassium carbonate 0.4% Flavor / colorant trace 100% (total amount: 4.6 g) In the same manner as in Formulation Example 3, the foaming preparations for iron supplementation shown in Table 1
9 was produced.

Formulation example of foaming formulation for NMR imaging Formulation example 10 Granulated sugar 40% L-tartaric acid 29% Sweetener Suitable amount Ammonium iron citrate 3.6% Sodium hydrogen carbonate 24% Cyanocobalamin Trace amount of potassium carbonate 0.5% Flavoring / coloring agent Suitable amount 100% (Total 4g) <Stability Test> The stability of each tablet of the following Formulation A and Formulation B was subjected to a comparative test using a tablet to which potassium carbonate was not added (a tablet without potassium carbonate) as a control. Each tablet was prepared by direct compression, individually packaged with aluminum-laminated glassine paper, stored in a thermostatic chamber, and evaluated for stability effect. The test items are as follows.

1) Swelling of packaging material The amount of gas generated in the packaging material was extracted with a graduated syringe, and the volume was measured.

2) Discoloration of tablets Color difference meter (Color Ace MODEL TC-I Tokyo Denshoku Co., Ltd.)
The time-dependent change in the color of the tablet surface was expressed in NBS units (ΔE = color difference) and Lab, using the tablet before the start of transformation (stored at 4 ° C. after tableting) as a standard.

* Indication of the relationship between NBS unit and sensation Difference in sensation NBS unit Slightly 0 to 0.5 Slightly 0.5 to 1.5 1.5 to 3.0 so that it can be perceived 3.0 to 6.0 so that it is noticeable 6.0 to 12.0 Very much 12.0 or more (Reference: "Color matters" Nippon Denshoku Industries) * Lab L: The larger the value, the higher the brightness.

a: The degree of red is shown on the (+) side, and the degree of green is shown on the (-) side.

b: The degree of yellow is shown on the (+) side, and the degree of blue is shown on the (-) side.

3) Dissolution time The tablet was put into about 140 ml of cold water at 8 to 9 ° C, and the time required for complete dissolution was measured.

4) Change in taste A comparison with the tablet before the start of change over time (a product stored at 4 ° C. in a cold place after tableting) was performed by a sensory test by two persons, and expressed by a five-point score evaluation.

1 point: no change 2 points: slight change but no problem 3 points: change 4 points: clear change 5 points: significant change Formulation Example A Purified sucrose 34% L-ascorbic acid 21% L-tartaric acid 19% sweetener appropriate amount sodium hydrogen carbonate 21% sodium chloride appropriate amount potassium carbonate 0.5% flavor appropriate amount 100% (total amount 4.7g) The results of the stability test of Formulation Example A are shown below.

Formulation Example B Purified sucrose 40% L-ascorbic acid 11% L-tartaric acid 23% Sweetener suitable amount Sodium hydrogen carbonate 22% iron ammonium citrate 0.8% cyanocobalamin trace amount sodium citrate suitable amount Potassium carbonate 0.4% flavor and pigment proper amount 100% (total amount) 4.6g) The results of the stability test of Formulation Example B are shown below.

──────────────────────────────────────────────────の Continuing on the front page (51) Int.Cl. ⁶ Identification code FI A61K 47/02 A23L 2/40 49/00 (72) Inventor Toshio Nakamura Tokishima-cho, Kitajima-cho, Itano-gun, Tokushima Pref. 72) Inventor Toshiaki Matsumoto 463-10 Kagasuno, Kawauchi-machi, Tokushima City, Tokushima Prefecture Inside Otsuka Pharmaceutical Co., Ltd. Imagiri Dormitory (56) References JP-A-47-35116 (JP, A)

Claims (5)

(57) [Claims] An effervescent preparation containing sodium carbonate and / or sodium bicarbonate as an effervescent component, wherein the preparation contains 10 to 35% by weight of sodium carbonate and / or sodium bicarbonate and 0.3 to 1.0% by weight of potassium carbonate. % Stabilized foam formulation. 2. Stabilization of an effervescent preparation characterized in that 0.3 to 1.0% by weight of potassium carbonate is contained in an effervescent preparation containing 10 to 35% by weight of sodium carbonate and / or sodium bicarbonate as an effervescent component. Method. 3 to 5% by weight of L-ascorbic acid and 10 to 35% of sodium carbonate and / or sodium bicarbonate.
An L-ascorbic acid supplement foam formulation stabilized by containing 0.3% to 1.0% by weight of potassium carbonate in the formulation, which contains 0.1% by weight as an essential component. 4. An iron-containing compound containing 0.01 to 3.5% by weight of iron, 10 to 35% by weight of sodium carbonate and / or sodium hydrogencarbonate as essential components, and 0.3 to 1.0% by weight of potassium carbonate in the preparation. % Iron-supplemented foaming formulation stabilized by containing 5. An iron-containing compound in an amount of 0.1 to 10% by weight as iron,
And an iron-containing foaming agent for NMR imaging stabilized by containing sodium carbonate and / or sodium hydrogencarbonate as an essential component in an amount of 8 to 35% by weight, and containing 0.3 to 1.0% by weight of potassium carbonate in the formulation.