JPH10120554A - Quickly dispersible particle containing inorganic antiacid, and its production and internal medicine to be suspended on use - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject particles capable of being suspended in an aqueous medium in a short time by dispersing an inorganic antiacid, a sugar alcohol and a disintegrating agent and subsequently spray-drying the suspension. SOLUTION: The particles are obtained by homogeneously dispersing an inorganic antiacid (e.g. aluminum hydroxide gel), a sugar alcohol (e.g. mannitol) and a disintegrating agent (e.g. dextrin) in an aqueous medium, and subsequently spray-drying the dispersion. The inorganic antiacid, the sugar alcohol and the disintegrating agent and compounded in amounts of 50-95wt.%, 1-35wt.% and 1-15wt.%, respectively, based on the whole weight of the particles. The particles have large hardness, are hardly pulverized, are easy in storage, can rapidly be dispersed in water, and give mild and non-rough mount touch, since the particles are fine. The particles are convenient for carriage, can rapidly and homogeneously be dispersed and suspended in an aqueous medium, and can orally be administered without giving any uncomfortable touch. The particles are useful for improving the syndromes of digestion acceleration, indigestion, anorexia, gluttony, dull feelings in stomachs, pyrosis, feelings of fullness in stomach and abdomen parts due to indigestion, stomach ache, gastric hyperacidity, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an inorganic antacid, sugar alcohol and disintegrant obtained by uniformly dispersing and spray-drying an inorganic antacid, a sugar alcohol and a disintegrant, which can be suspended and dispersed in an aqueous medium in a very short time. The present invention relates to an acid agent-containing rapidly dispersible granulated product and a method for producing the granulated product.

[0002]

2. Description of the Related Art Medical antacids are used for improving symptoms such as acceleration of digestion, indigestion, loss of appetite, overeating, leaning of the stomach, chest stomach, stomach / abdominal distension due to indigestion, stomach pain, and gastric hyperacidity. Can be These are usually used as solid preparations such as fine granules, granules and tablets or as liquid preparations. These fine granules, granules and tablets are lightweight and non-bulky, so they are convenient to carry, but they take time to disintegrate and disperse in the stomach after taking them, and quickly show antacid action. There was a problem in that respect. In addition, tablets and the like become large in shape when administered in an effective amount, and often adhere to the pharynx and esophagus and take a stagnation during administration even in healthy individuals. In particular, there has been a demand for the development of an antacid that is easy to drink and improved for children and the elderly, who have poor chewing and swallowing power. Suspensions are a method of solving the above problems. Suspensions are superior in that they exhibit an antacid action earlier than solids such as fine granules, granules, and tablets. Because of this, the packaging form of the container is large,
Due to its weight, it is inconvenient to carry, and it requires uniform suspension and dispersion when taking it.There are many problems with the enrichment of microorganisms over time during storage and the stability of contained components. was there.

[0003]

DISCLOSURE OF THE INVENTION The present invention relates to an inorganic antacid, a sugar alcohol and a disintegrant which are uniformly dispersed and spray-dried, and can be suspended and dispersed in an aqueous medium in a very short time. An object of the present invention is to provide a fast-dispersing granule containing an inorganic antacid and a method for producing the same. More specifically, the present invention provides a fine-granular inorganic antacid-containing fast-dispersing granule that is convenient to carry, can be rapidly and uniformly suspended and dispersed in an aqueous medium when taken, and can be taken without giving a sense of incongruity. The purpose is to:

[0004]

Means for Solving the Problems The present inventors have conducted intensive studies to solve the above problems, and as a result, uniformly disperse the inorganic antacid, sugar alcohol and disintegrant in an aqueous medium,
The present inventors have found that a rapidly dispersible granule containing an inorganic antacid obtained by spray-drying can solve the above-mentioned problems, and have reached the present invention. Although the inorganic antacid-containing fast-dispersing granules of the present invention are hard fine particles having a high particle strength, when these particles are dispersed in water, they can be uniformly dispersed in an extremely short time of 1 to 3 minutes. It becomes a dispersed suspension.

As the inorganic antacid used in the present invention, water-insoluble metal oxides, metal hydroxides, metal salts or composite metal compounds are used. More specifically, metal oxides such as magnesium oxide, dried aluminum hydroxide gel, aluminum hydroxide gel, metal hydroxides such as magnesium hydroxide, precipitated calcium carbonate, metal carbonates such as magnesium carbonate, or metasilicic acid At least one selected from the group consisting of composite metal compounds such as magnesium aluminate, magnesium silicate aluminate, magnesia hydroxide alumina, and synthetic hydrotalcite can be given. Preferably, the inorganic antacid is selected from the group consisting of aluminum hydroxide gel, magnesium carbonate, magnesium metasilicate aluminate, magnesium aluminate silicate, synthetic hydroxytalcite, dry aluminum hydroxide gel, magnesium hydroxide, precipitated calcium carbonate. One or more combinations.

The amount of the inorganic antacid is usually 50 to 95% by weight, preferably 70 to 95% by weight, more preferably 70 to 95% by weight, based on the total amount of the inorganic antacid-containing fast-dispersing granules.
~ 85% by weight. In addition, these inorganic antacids may be natural products or those obtained by synthesis, and when using those already in powder form, it is better to pulverize as much as possible and use them as fine powder. The particle size is 15
Those having a size of μm or less are preferred.

[0007] The sugar alcohol is obtained by hydrogenating or hydrolyzing a reducing terminal group in the molecule of the saccharide, and there are various sugar alcohols depending on the difference of the raw sugar. In the present invention, any of these may be used or they may be used in combination. Specific examples include sorbitol, mannitol, xylitol, reduced maltose syrup, erythritol, maltitol, lactitol or palatinit, and the like, and preferably sorbitol, mannitol, xylitol, reduced maltose syrup, erythritol and the like. The mixing amount of these sugar alcohols is 1 to 3 with respect to the total amount of the inorganic antacid-containing fast-dispersing granules of the present invention.
It is 5% by weight, preferably 1 to 25% by weight, more preferably 5 to 20% by weight.

As the disintegrant, disintegrants of starch type, cellulose type, vinyl type and the like are used. More specifically, corn starch, potato starch, dextrin, hydroxypropyl starch, partially pregelatinized starch, starch disintegrants such as sodium carboxymethyl starch, carmellose calcium, carmellose, cross-linked sodium carboxymethyl cellulose, low-substituted hydroxypropyl One or more selected from the group consisting of cellulose-based disintegrants such as cellulose and vinyl-based disintegrants such as cross-linked polyvinyl pyrrolidone can be used in appropriate combination. Preferably, it is at least one combination selected from the group consisting of corn starch, dextrin, carmellose calcium, and partially pregelatinized starch. The amount of these components is 1 to 15% by weight, preferably 5 to 10% by weight, based on the total amount of the inorganic antacid-containing rapidly dispersible granules.

[0009] In addition to the above components, the inorganic antacid-containing fast-dispersing granules of the present invention may further contain crude drugs such as cinnamon, clove, red bud, licorice, etc .; Preservatives such as methyl benzoate and sodium benzoate, flavors such as peppermint oil, menthol and lemon oil, and sweeteners such as saccharin sodium and glycyrrhizic acid can be added as required. As these components, those commonly used in the production of pharmaceuticals, foods and the like can be used alone or in combination as appropriate.

The preparation of the rapidly dispersible granules containing an inorganic antacid according to the present invention is a wet granulation method, which is characterized in that the granulation is carried out by a spray drying granulator. On the other hand, when prepared by a conventional wet granulation method using a water kneading machine, an extrusion granulator, a stirring granulator or a tumbling granulator, water is added to the raw material powder to knead or granulate. Since the consolidation due to kneading is added at the time of mixing, the granulated material has high density and strong cohesive properties, and as a result, the obtained granulated material has poor dispersibility in water. There is also a means of replacing a part of water with an organic solvent such as ethanol in order to improve the physical properties of the high-density granulated material.However, when the amount of the organic solvent is large, the dried granulated material tends to lose its shape. It is inconvenient to handle such as severe powdering and poor fluidity.
Setting the optimum mixing ratio of water and the organic solvent, it is extremely difficult to obtain a granulated product having the desired physical properties, and there is a problem that the organic solvent remains in the granulated product, which is not a preferable method. .

The rapidly dispersible granules containing an inorganic antacid according to the present invention can be prepared in an aqueous system by using a spray drying granulation method, and have the following characteristic properties. That is, the obtained granules were obtained using a microscope (Keyence VH-610).
Observation at 0) shows that the product is a fine-grained sphere, has extremely good fluidity (angle of repose is 31 to 34 °), and has almost no particle collapse during transportation, mixing, and packaging in a later step. Since the granulated material is a porous aggregate, it has a characteristic of being easily dispersed uniformly in an aqueous medium, and becomes a uniformly dispersed suspension in an extremely short time of 1 to 3 minutes or less. The inorganic antacid-containing fast-dispersing granules containing the inorganic antacid of the present invention having excellent physical properties can be used as an antacid for internal use in suspension when used, which is characterized by containing as an active ingredient.

The mechanism by which the granulated product of the present invention provides physical properties that are fine-grained, have a high particle strength, and have good dispersibility in water can be estimated as follows. That is, at the same time that the sugar alcohol acts between the aggregated particles of the inorganic antacid during spray-drying granulation and acts to suppress shrinkage, and at the same time, a portion thereof precipitates on the particle surface to form a film, so that the water wetting is improved, As a result, by facilitating the incorporation of water into the disintegrant in the fine-grained particles, it is considered that the dispersibility is high and uniform dispersion is achieved. The formation of a film on the surface of the particles also functions to increase the particle strength.

The following examples and comparative examples show the method for producing the inorganic antacid-containing fast-dispersing granules of the present invention and the physicochemical properties of the products. Table 1 shows the amounts of the components of the formulations of Examples and Comparative Examples, Table 2 shows the physicochemical properties thereof, and Table 3 shows the results of the sensory test in the mouth when dispersed in water.

[0014]

【Example】

Example 1 25 kg of purified water was placed in a 50 L container, and while stirring, mannitol 0.50 kg, dextrin 0.48 kg,
Methyl paraoxybenzoate 0.01 kg, aspartame 0.01 kg, dried aluminum hydroxide gel 4.50 k
g and 4.00 kg of magnesium hydroxide are sequentially added, and the mixture is uniformly dispersed with a homogenizer. Then, using a spray-drying granulator (N-50, S-50N / R type)
Nozzle diameter 1.4mm, heat input temperature 230-240 ° C, exhaust heat temperature 130-140 ° C, feed pressure 10-12kg
/ Cm ² to obtain 9.5 kg of granules. The apparent density of the obtained granules is 0.43 and the angle of repose is 3
2 °.

Examples 2 to 5 Spherical granules of Examples 2 to 5 were obtained according to the formulations shown in the columns of Examples 2 to 5 in Table 1 in accordance with the method of Example 1. The yield was as shown in Example 2 (9.2 kg), Example 3
(9.3 kg), Example 4 (9.4 kg) and Example 5
(9.4 kg).

Comparative Examples 1 and 2 Spherical granules of Comparative Examples 1 and 2 were obtained according to the formulations shown in Comparative Examples 1 and 2 in Table 1 based on the method of Example 1. The yield was as follows: Comparative Example 1 (9.3 kg) and Comparative Example 2 (9.4
kg).

Comparative Examples 3 and 4 Prescription raw materials shown in the columns of Comparative Examples 3 and 4 in Table 1 were mixed with a stirring granulator (manufactured by Powrex, Vertical Granulator, VG).
-25), the blade rotation speed is 300 r. p.
m. , Cross screw rotation speed 3000r. p. m. And mix for 5 minutes, then add 3.70 kg of water in 5 minutes,
The granulated product obtained by further stirring for 5 minutes is subjected to 85
After drying at 7 ° C. for 7 hours, an amorphous granule was obtained.

Comparative Example 5 In accordance with the method of Comparative Examples 3 and 4, the mixture was stirred and granulated using 4.00 kg of 70% ethanol according to the formulation shown in the column of Comparative Example 5 in Table 1. Prepared in a similar manner as in 4,
An amorphous granulate was obtained.

The formulations of Examples 1 to 5 and Comparative Examples 1 to 5 are shown in Table 1 below. Each component in the table is weight (k
g), the total amount of each component is 10.0 kg in Examples 1 to 5 and Comparative Examples 1 and 2, and Comparative Examples 3 to 5
Each weighs 5.0 kg.

Table 2 below shows the particle strength test [74 μpass (%)], the disintegration test (minute), the particle size distribution in water dispersion [50% average particle diameter (μm) of the products obtained in each of Examples and Comparative Examples. ), Maximum particle diameter (μm)] and the angle of repose are shown.

Table 3 below shows the results of a sensory test in the mouth when the granules obtained in the above Examples and Comparative Examples were dispersed in water. In the table, the symbols have the following meanings (◎ indicates no roughness, ○ indicates almost no roughness, Δ indicates slight roughness, and × indicates strong roughness).

[0022]

[Table 1]

[0023]

[Table 2]

[0024]

[Table 3]

Test Method (1) Particle Strength Test A sample of 10 g was weighed, and a tablet friability tester (4 manufactured by Kayagaki Medical Science Co., Ltd.)
G-18 type) together with 10 g of glass beads of φ10 mm, 6R, φ2 mm, and rotated for 10 minutes.
m, sieve the sample through a sieve, weigh the amount of pass,
Divide by 10 g of sample and show the amount of 74 μm passage as a percentage. The higher the value, the weaker the particle strength and the easier it is to powder.

(2) Disintegration Test A disintegration test was conducted by the following method using a disintegration test apparatus of the Japanese Pharmacopoeia. The sample is sieved with a 150 μm mesh sieve, and 0.1 g of the residue on the sieve is placed in an auxiliary cylinder equipped with a 150 μm mesh net, and vertically moved in water at 37 ° C. The time until no residue of the sample was observed in the auxiliary cylinder was measured. The faster the disintegration, the shorter the residue disappears.

(3) Particle Size Distribution Measurement Test in Water Dispersion The particle size distribution of the sample dispersed in water was measured using a laser diffraction type particle size distribution analyzer (Nikkiso and Microtrac MKIISPA type). Tables 4 and 5 show the 50% average particle size and the maximum particle size.

(4) Measurement of angle of repose Using a repose angle measuring device (powder tester, manufactured by Hosokawa Micron), while gently shaking a predetermined amount of sample,
Drop the sample on the measuring table. When the sample starts to spill from around the table, stop shaking and measure the angle of repose with a protractor. The lower the angle of repose, the better the fluidity.

(5) Sensory Test in Mouth at the Time of Dispersion in Water 5 panelists (3 boys, 2 girls)
) Was evaluated by a sensory test. That is, water 1
1 g of the sample was added to 0 mL, and the mixture was slightly shaken and dispersed by hand to prepare a suspension. After 3 minutes, the whole mouth was contained and the roughness was evaluated.

From the results shown in Table 2, it can be seen that the granules of the present invention obtained from the formulations of Examples 1 to 5 have a high particle strength, are hard to be powdered, are rapidly dispersed in water, and have fine dispersed particles. It turns out that it is in a state close to the raw material particles, and even if it is contained in the mouth, it is not round and rough. On the other hand, the granulated products according to the formulations of Comparative Examples 1 and 5 have a low particle strength, and even when dispersed in water a little later, they have a rough feeling. Comparative Example 2, Comparative Example 3
The granulated product according to the formulation of Comparative Example 4 has a high particle strength and is hardly powdered. However, when dispersed in water, it disintegrates slowly and many agglomerates remain.

[0031]

Industrial Applicability According to the present invention, an inorganic antacid which can be suspended and dispersed in an aqueous medium in a very short time, obtained by uniformly dispersing an inorganic antacid, a sugar alcohol and a disintegrant and spray-drying it. It was possible to provide a rapidly dispersible granulated material and a method for producing the same. The granulated product of the present invention has a hard particle strength, is hard to be powdered, is easy to store, is quick to be dispersed in water, and is in a state where the dispersed particles are fine and close to the raw material particles and are round and rough even when included in the mouth. It has no sensation and is most suitable as an antacid in suspension when used. Further, the granulated material is a fast-dispersing granule containing a fine inorganic antacid, which is convenient to carry, can be suspended and dispersed very quickly and uniformly in an aqueous medium when taken, and can be taken without feeling uncomfortable. It is used to improve digestion, indigestion, anorexia, eating too much, leaning the stomach, holding on to the chest, stomach and abdominal distension due to indigestion, stomach pain, and gastric acidity. Very useful as an acid agent.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Kiyoshi Takami 55 Kamiichi-cho, Kamiichi-cho, Toyama Prefecture Inside Fuji Chemical Industry Co., Ltd. Address Fuji Chemical Co., Ltd. (72) Inventor Tatsuo Murakami 55 Yokohoonji Temple, Kamiichi-cho, Nakashinagawa-gun, Toyama Prefecture Fuji Chemical Co., Ltd.

Claims (7)

[Claims] 1. An inorganic antacid-containing rapidly dispersible granule obtained by uniformly dispersing an inorganic antacid, a sugar alcohol and a disintegrant in an aqueous medium and spray-drying. 2. The inorganic antacid is aluminum hydroxide gel,
The inorganic compound according to claim 1, comprising at least one selected from the group consisting of magnesium hydroxide, magnesium metasilicate aluminate, magnesium aluminate silicate, synthetic hydrotalcite, dried aluminum hydroxide gel, magnesium carbonate, and precipitated calcium carbonate. Acid agent-containing rapidly dispersible granules. 3. The amount of the antacid is 50 to 50% of the total amount of the granulated product.
The inorganic antacid-containing fast-dispersing granule according to claim 1, which is 95% by weight. 4. The inorganic antacid-containing fast-dispersing granule according to claim 1, wherein the sugar alcohol is at least one selected from the group consisting of sorbitol, mannitol, xylitol, reduced maltose syrup, and erythritol. 5. The disintegrant is at least one selected from the group consisting of corn starch, dextrin, carmellose calcium, and partially pregelatinized starch.
5. The rapidly dispersible granulated product containing an inorganic antacid according to any one of items 4 to 4. 6. The inorganic antacid-containing fast-dispersing composition according to claim 1, wherein the inorganic antacid, sugar alcohol and disintegrant are uniformly dispersed in an aqueous medium and spray-dried. A method for producing granules. 7. An antacid preparation for oral use in suspension containing the inorganic antacid-containing fast-dispersing granules according to claim 1 as an active ingredient.