JPH07277959A - Foaming tablet - Google Patents

Abstract

PURPOSE:To obtain a foaming tablet excellent in compression molding properties in formation of tablet and stability with time. CONSTITUTION:This is a foaming tablet contains a carbonate and an acid substance. In this foaming tablet, >=6wt.% sodium metaphosphate is blended.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an effervescent tablet having good compression moldability during tableting and excellent stability over time.

[0002]

2. Description of the Related Art Effervescent tablets containing an active ingredient and an effervescent ingredient composed of a carbonate and an acidic substance effervesce when dissolved in water and dissolves rapidly. Therefore, pharmaceuticals, gargles, denture cleaners, It is used in a wide range of fields such as bath salts. In particular, in the case of oral medicines, in addition to the rapid solubility in water described above, it has been increasingly attracting attention in recent years because it has the effects of promoting absorption of medicinal components by generated carbon dioxide, masking bitterness components, and protecting the stomach wall. It's starting to happen.

Conventionally, effervescent tablets containing a carbonate and an acidic substance are manufactured by a dry method (direct tableting method) or a wet method (wet granulation tableting method), similar to the method for manufacturing a general tablet. However, a problem with either method is the compression moldability during tableting and the stability with time. The former problem is that the composition containing the active ingredient, the carbonate and the acidic substance is very poor in compression moldability as compared with the composition of general tablets, and the latter problem is that the effervescent tablet reacts with water. Since it has a property of generating carbon dioxide gas, carbon dioxide gas is generated over time due to the moisture of the raw materials used in the production and the moisture remaining in the production process, and the stability is deteriorated. .

Therefore, regarding compression moldability, a method of adding dextrin or pregelatinized starch (JP-A-63-63)
264518), a method of directly tableting sodium hydrogen carbonate by spray drying (Int. J. Pharm.
45 (1988) 1-26) and the like have been proposed. However, in these methods, sticking (powder adhesion to the punch surface) and binding (powder adhesion to the die) occur during tableting, and it is necessary to clean the die frequently, which is not always satisfactory. It wasn't something. Regarding stability over time, a method of adding dimethylpolysiloxane (JP-A-57-56434), a method of adding natural protein (JP-A-49-39582),
A method of using anhydrous carbonate (JP-A-55-7246) and a method of adding potassium carbonate (JP-A-3-120).
212), a method of separately coating an acidic substance and a basic substance with a specific polymer (Japanese Patent Laid-Open No. 61-2073).
No. 22) is proposed. However, these methods also have problems such as delayed dissolution, reduced foaming power, generation of insoluble substances, and deformation and damage of the container due to generation of carbon dioxide gas during storage during use,
In order to prevent this, measures such as the use of desiccant were indispensable.

[0005]

Therefore, an object of the present invention is to provide an effervescent tablet containing a carbonate and an acidic substance with good compression moldability without sticking or binding at the time of tableting and during production. Another object of the present invention is to provide an effervescent tablet that is stable over time without generating carbon dioxide during storage after manufacture or after production.

[0006]

[Means for Solving the Problems] In view of such a situation,
As a result of intensive studies by the present inventors, in the production of effervescent tablets containing a carbonate and an acidic substance, if a specific amount of sodium metaphosphate was used as a lubricant and compression molding was performed, sticking, binding, etc. Thus, the inventors have found that an effervescent tablet having no compression-molding property, good compression moldability, and good stability over time can be obtained, and completed the present invention.

That is, the present invention provides an effervescent tablet containing a carbonate and an acidic substance, and 6% by weight or more of sodium metaphosphate is blended therein.

In the effervescent tablet of the present invention, as the carbonate, sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate, etc., and as the acidic substance,
Citric acid, tartaric acid, fumaric acid, succinic acid, maleic acid,
Examples include adipic acid, malic acid, ascorbic acid, monosodium citrate, disodium citrate, potassium hydrogen tartrate, sodium dihydrogen phosphate and the like.

The amount of the carbonate and the acidic substance blended is preferably such that the pH of the effervescent tablet when dissolved in water is 7 (neutral). Generally, the carbonate is 10 to 50% by weight.
(Hereinafter, simply referred to as%), particularly 20 to 40%, and the acidic substance is preferably 10 to 50%, particularly 20 to 40%.

The sodium metaphosphate used in the present invention is a colorless to white glassy lump, piece or fibrous crystal or powder, and is excellent in sequestering action, dispersing action, washing action, buffering action and the like. It is a highly safe product that has properties and is widely used in foods and the like.

The content of sodium metaphosphate in the effervescent tablet of the present invention is preferably 6% or more, preferably 8% or more, and particularly preferably 8 to 24% based on the total composition. If the content of sodium metaphosphate is less than 6%, the compression moldability and stability over time will be poor, and if it exceeds 24%, no effect commensurate with the addition will be observed and the tablet shape will be large. It is not preferable because

Although sodium metaphosphate may be added as a powder or as an aqueous solution of sodium metaphosphate, it is preferably sprayed as an aqueous solution as described later.

Further, the active ingredients of the effervescent tablet of the present invention include antipyretic analgesics, antitussive expectorants, vitamins, gastrointestinal agents,
Antispasmodics, bactericides and the like can be mentioned, but the application target is not particularly limited.

Further, in the effervescent tablet of the present invention, a binder such as polyvinylpyrrolidone which is usually used; an excipient such as purified sucrose; a disintegrating agent such as sodium carboxymethylcellulose; a thickener such as methylcellulose; Macrogol 60
A surfactant such as 00; an electrolyte such as sodium chloride; a sweetener such as saccharin sodium; a flavoring agent such as orange; a dye such as a tar dye.

To produce the effervescent tablet of the present invention, for example, the previously dried active ingredient, carbonate, acidic substance and other additives are mixed in a mixer such as a vertical granulator, and then a fluidized bed such as Glatt. It is preferable that the mixture is charged into a granulator, sprayed with an aqueous solution of sodium metaphosphate, granulated, dried, and tableted with a tableting machine. The carbonate and the acidic substance may be granulated separately with an aqueous solution of sodium metaphosphate, and then the two may be mixed and compressed into tablets.

[0016]

The effervescent tablet of the present invention has good compression moldability during tableting and has excellent stability over time.

[0017]

EXAMPLES The present invention is described in detail below with reference to examples and test examples, but the present invention is not limited to these.

Example 1 (Preparation) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 1 were used as a perfect oven PH.
-200 (manufactured by Tabai Espec Co., Ltd.) and then dried with a hammer mill (manufactured by Fuji Paudal Co., Ltd.)
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. Next, after reacting at 40 ° C., it was dried at 50 ° C. This was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and after spraying 431 g of a 20% polyvinylpyrrolidone aqueous solution, 1212 g of a 33% sodium metaphosphate aqueous solution was sprayed. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. 20 mm, one effervescent tablet of 1.6646 g was obtained.

[0019]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogen carbonate 1650 Tartaric acid 872 Citrate 592 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 400 Sodium benzoate 193.8 Perfume 5 Total 4993.8

Example 2 (Production Method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 2 were used as a perfect oven PH.
-200 (manufactured by Tabai Espec Co., Ltd.) and then dried with a hammer mill (manufactured by Fuji Paudal Co., Ltd.)
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. Next, after reacting at 40 ° C., it was dried at 50 ° C. This was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and after spraying 431 g of an aqueous solution of 20% polyvinylpyrrolidone, 2667 g of a 33% sodium metaphosphate aqueous solution was sprayed. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. Effervescent tablets weighing 20 mm and 1.8312 g were obtained.

[0021]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogen carbonate 1650 Tartaric acid 872 Citrate 592 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Perfume 5.5 Total 5493.7

Example 3 (Production Method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogencarbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulations shown in Table 3 were used as a perfect oven PH.
-200 (manufactured by Tabai Espec Co., Ltd.) and then dried with a hammer mill (manufactured by Fuji Paudal Co., Ltd.)
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. Next, after reacting at 40 ° C., it was dried at 50 ° C. This was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho), and 431 g of an aqueous solution of 20% polyvinylpyrrolidone was sprayed, and then 4430 g of an aqueous solution of 33% sodium metaphosphate was sprayed. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. Effervescent tablets weighing 20 mm and 2.0333 g each were obtained.

[0023]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Tartaric acid 872 Citrate 592 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 1462 Sodium benzoate 236.8 Fragrance 6.1 Total 6099.9

Example 4 (Production method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, anhydrous citric acid in the formulations shown in Table 4
Perfect saccharin sodium and D-mannitol PH-200 (Tabay Espec Co., Ltd.)
After being dried by using, was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.) and sprayed with 431 g of an aqueous solution of 20% polyvinylpyrrolidone, and then 2667 g of a 33% sodium metaphosphate aqueous solution. . next,
V-type mixer V-10 with sodium benzoate and flavor added
(Made by Tokuju Seisakusho Co., Ltd.), then single-shot tablet press FK-
Type 2 (manufactured by Okada Manufacturing Co., Ltd.), diameter 20 mm, 1 tablet 1.8
312 g of effervescent tablets were obtained.

[0025]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogencarbonate 1650 Tartaric acid 872 Anhydrous citrate 592 Sodium saccharin 37.5 D-mannitol 39. 8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Perfume 5.5 Total 5493.7

Example 5 (Production method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogencarbonate, tartaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 5 were used as a perfect oven PH.
After drying with -200 (manufactured by Tabai Espec Co., Ltd.), the mixture was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of an aqueous solution of 20% polyvinylpyrrolidone was sprayed, 2667 g of 33% sodium metaphosphate aqueous solution was sprayed. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. Effervescent tablets weighing 20 mm and 1.8312 g were obtained.

[0027]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogencarbonate 1650 Tartaric acid 1464 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86 .2 Sodium metaphosphate 880 Sodium benzoate 213.2 Perfume 5.5 Total 5493.7

Example 6 (Production method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogencarbonate, fumaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 6 were used in Perfect Oven P.
After drying using H-200 (manufactured by Tabay Espec Co., Ltd.), it was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho) and sprayed with 431 g of an aqueous solution of 20% polyvinylpyrrolidone. , 2% of a 33% sodium metaphosphate aqueous solution was sprayed. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. Effervescent tablets weighing 20 mm and 1.8312 g were obtained.

[0029]

Table 6 (Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogencarbonate 1650 Fumarate 1464 Saccharin sodium 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Perfume 5.5 Total 5493.7

Example 7 (Production Method) Acetaminophen, tartaric acid, sodium saccharin, and D-mannitol in the formulation (A) in Table 7 were dried using Perfect Oven PH-200 (manufactured by Tabay Espec Co., Ltd.) and then flowed. Layer granulation dryer WSG-
Type 5 (manufactured by Okawara Seisakusho Co., Ltd.) and sprayed with 215.5 g of a 20% aqueous solution of polyvinylpyrrolidone, and then 3
1333 g of 3% sodium metaphosphate aqueous solution was sprayed. Similarly, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogencarbonate, sodium saccharin, and D-mannitol in the formulation (B) were used using Perfect Oven PH-200 (manufactured by Tabay Espec Co., Ltd.). After drying, fluidized bed granulation dryer W
20% by throwing into SG-5 type (manufactured by Okawara Manufacturing Co., Ltd.)
After spraying 215.5 g of an aqueous solution of polyvinylpyrrolidone, 1333 g of a 33% sodium metaphosphate aqueous solution was sprayed. Sodium benzoate and a fragrance were added to these two types of granulated powder and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), and then a single-shot tableting machine FK-2 type (Okada Co., Ltd.) (Manufactured by Seisakusho) to obtain an effervescent tablet having a diameter of 20 mm and a tablet of 1.8313 g.

[0031]

[Table 7]

Example 8 (Production Method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, D-mannitol, sodium metaphosphate in the formulations shown in Table 8 (hammer) Mill crushed product) Perfect Oven PH-20
After drying using 0 (manufactured by Tabai Espec Co., Ltd.) and mixing with a vertical granulator FM-VG-25 (manufactured by Paulec Co., Ltd.), 431 g of an aqueous solution of 20% polyvinylpyrrolidone was added to granulate 50. It was dried at ° C.
Next, add sodium benzoate and a fragrance and add V-type mixer V
After mixing with -10 (manufactured by Tokuju Seisakusho), a single shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to obtain an effervescent tablet having a diameter of 20 mm and a tablet of 1.8312 g.

[0033]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogencarbonate 1650 Tartaric acid 1464 Saccharin sodium 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86 .2 Sodium metaphosphate 880 Sodium benzoate 213.2 Perfume 5.5 Total 5493.7

Comparative Example 1 (Production Method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 9 were used as a perfect oven PH.
-200 (manufactured by Tabai Espec Co., Ltd.) and then dried with a hammer mill (manufactured by Fuji Paudal Co., Ltd.)
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. Next, after reacting at 40 ° C., it was dried at 50 ° C. This was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho) and sprayed with 431 g of an aqueous 20% polyvinylpyrrolidone solution. Next, after adding sodium benzoate and a fragrance and mixing them with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot tableting machine FK-2 type (manufactured by Okada Seisakusho) was used to measure the diameter. Effervescent tablets weighing 20 mm and 1.5258 g were obtained.

[0035]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Tartaric acid 872 Citrate 592 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium benzoate 177.7 Perfume 4.6 Total 4577.3

Comparative Example 2 (Production Method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin and D-mannitol in the formulations shown in Table 10 were used in Perfect Oven P.
After drying using H-200 (manufactured by Tabai Espec Co., Ltd.), crystalline citric acid crushed by a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added to the vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. Next, after reacting at 40 ° C., it was dried at 50 ° C. This was put into a fluidized bed granulation dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of an aqueous solution of 20% polyvinylpyrrolidone was sprayed, and then 653 g of an aqueous solution of 33% sodium metaphosphate was sprayed. Next, sodium benzoate,
After adding fragrance and mixing with V-type mixer V-10 (manufactured by Tokuju Seisakusho), single-shot tablet press FK-2 type (manufactured by Okada Seisakusho), diameter 20 mm, 1.6 g per tablet To obtain effervescent tablets.

[0037]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium hydrogen carbonate 1650 Tartaric acid 872 Citrate 592 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 215.4 Sodium benzoate 186.4 Perfume 4.8 Total 4801.6

Test Example 1 (Compression Moldability) The above Examples 1 to 8 and Comparative Examples 1 and 2 were visually evaluated for the presence or absence of tableting failure during compression molding. From the results of Table 11, the tablets were pressed without problems in Examples 1 to 8,
In Comparative Examples 1 and 2, occurrence of binding and sticking was recognized.

[0039]

[Table 11]

Test Example 2 (Stability over Time) The tablets of Examples 1 to 8 and Comparative Examples 1 and 2 above were heat-sealed with aluminum and stored in a thermostatic chamber at 40 ° C. to change the properties and generate carbon dioxide gas. Was tested. Table 12 shows the evaluation criteria.
Obeyed. From the results in Table 13, in Examples 1 to 8, no change in properties and generation of carbon dioxide gas were observed, but in Comparative Examples 1 and 2, changes in properties and generation of carbon dioxide gas were observed.

[0041]

[Table 12] −: No property change, no carbon dioxide gas generated ＋: No property change, slight carbon dioxide gas generation ++: Property change (yellowing), carbon dioxide gas generation

[0042]

[Table 13]

Claims (1)

[Claims] 1. An effervescent tablet containing a carbonate and an acidic substance, containing 6% by weight or more of sodium metaphosphate.