JP3170139B2 - Effervescent tablet - Google Patents

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 An effervescent tablet containing an effervescent component comprising an active ingredient, a carbonate and an acidic substance foams and rapidly dissolves when poured into water, so that it can be used for pharmaceuticals, gargles, denture cleaners, It is used in a wide range of fields such as bath additives. In particular, in the case of internal medicines, in addition to the above-mentioned rapid solubility in water, the carbon dioxide gas generated has the effect of promoting absorption of medicinal components, masking bitter components, protecting the stomach wall, etc. It has become.

Conventionally, effervescent tablets containing a carbonate and an acidic substance have been produced by a dry method (direct tableting method) or a wet method (wet granulation tableting method) in the same manner as a general tablet production method. However, both methods are problematic in terms of the compressibility at the time of tablet compression and the stability over time. The former problem is that the composition containing an active ingredient, a carbonate and an acidic substance is very poor in compression moldability as compared with a general tablet composition, and the latter problem is that an effervescent tablet reacts with water. Because it has the property of generating carbon dioxide gas, it generates carbon dioxide gas 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 inferior. .

[0004] For this reason, the compression moldability is determined by adding dextrin or pregelatinized starch (Japanese Patent Laid-Open No.
264518), a method of directly compressing sodium bicarbonate by spray drying (Int. J. Pharm.
45 (1988) 1-26) and the like. However, in these methods, sticking (adhesion of powder to the punch surface) and binding (adhesion of powder to the die) occur at the time of tableting, and it is necessary to frequently clean the die and punch. It was not something. Regarding the stability over time, a method of adding dimethylpolysiloxane (JP-A-57-56434), a method of adding a natural protein (JP-A-49-39582),
A method using anhydrous carbonate (JP-A-55-7246) and a method using potassium carbonate (JP-A-3-120).
No. 212), a method of separately coating an acidic substance and a basic substance with a specific polymer (JP-A-61-2073).
No. 22) has been proposed. However, these methods also have problems in that, when used, dissolution is delayed, foaming power is reduced, insoluble substances are generated, and deformation or breakage of the container occurs due to generation of carbon dioxide gas during storage,
To prevent this, measures such as the use of a desiccant were indispensable.

[0005]

SUMMARY OF THE INVENTION Accordingly, an object of the present invention is to provide an effervescent tablet containing a carbonate and an acidic substance, which has good compression moldability without sticking or binding at the time of tableting, and has an advantage in manufacturing. Another object of the present invention is to provide an effervescent tablet which is stable over time and does not generate carbon dioxide gas during storage after production.

[0006]

In view of such circumstances,
The present inventors have conducted intensive studies and found that in the production of effervescent tablets containing carbonates and acidic substances, if a specific amount of sodium metaphosphate is used as a lubricant and compression-molded, sticking, binding, etc. The present invention has been found to be able to obtain an effervescent tablet having no compression, good compression moldability and good stability over time.

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

In the effervescent tablet of the present invention, the carbonates include sodium hydrogen carbonate, sodium carbonate, potassium hydrogen carbonate, potassium carbonate and the like, and the acidic substances include:
Citric, tartaric, fumaric, succinic, maleic,
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 is preferably adjusted so that the pH when the effervescent tablet is dissolved in water is 7 (neutral). Generally, the carbonate is 10 to 50% by weight.
(Hereinafter simply referred to as "%"), particularly preferably 20 to 40%, and the acidic substance is preferably 10 to 50%, particularly preferably 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 has excellent sequestering action, dispersing action, washing action, buffering action and the like. It has properties and is highly safe and widely used in foods and the like.

The amount of sodium metaphosphate incorporated into the effervescent tablet of the present invention is at least 6%, preferably at least 8%, particularly preferably 8 to 24%, based on the total composition. If the amount of sodium metaphosphate is less than 6%, compression moldability and stability over time are inferior. If it exceeds 24%, no effect commensurate with the addition is observed, and the tablet shape becomes large. It is not preferable because it becomes.

The sodium metaphosphate may be added as a powder or as an aqueous solution of sodium metaphosphate, but it is preferable to spray 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, gastrointestinals,
Examples thereof include antispasmodics and bactericides, but the application target is not particularly limited.

The effervescent tablet of the present invention may further contain a binder such as polyvinylpyrrolidone which is usually used; an excipient such as purified sucrose; a disintegrant such as sodium carboxymethylcellulose; a thickener such as methylcellulose;
A surfactant such as 00; an electrolyte such as sodium chloride; a sweetener such as sodium saccharin; a flavor such as orange;

In order to produce the effervescent tablet of the present invention, for example, a pre-dried active ingredient, carbonate, acidic substance and other additives are mixed by a mixer such as a vertical granulator, and then mixed with a fluid bed such as Glatt. It is preferable to charge the mixture in a granulator, spray an aqueous solution of sodium metaphosphate on the granulated granules, dry the granulated granules, dry the granules, and compress the granules with a tableting machine. The carbonate and the acidic substance may be separately granulated with an aqueous solution of sodium metaphosphate, and then mixed at the time of tableting for tableting.

[0016]

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

[0017]

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

Example 1 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium bicarbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 1 were used in a perfect oven PH.
After drying using -200 (manufactured by Tabai Espec Co., Ltd.), crystal citric acid pulverized with a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added, and the vertical granulator FM was added.
-VG-25 (manufactured by Powrex Corporation). Next, after making it react at 40 degreeC, it dried at 50 degreeC. This was charged into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of a 20% aqueous solution of polyvinylpyrrolidone was sprayed thereon, followed by spraying 1212 g of a 33% aqueous sodium metaphosphate solution. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). There were obtained effervescent tablets weighing 20 mm and 1.6646 g per tablet.

[0019]

TABLE 1 Formulation Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Tartaric acid 872 Citric acid 592 Saccharin sodium 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 400 Sodium benzoate 193.8 Fragrance 5 Total 4993.8

Example 2 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 2 were used in a perfect oven PH.
After drying using -200 (manufactured by Tabai Espec Co., Ltd.), crystal citric acid pulverized with a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added, and the vertical granulator FM was added.
-VG-25 (manufactured by Powrex Corporation). Next, after making it react at 40 degreeC, it dried at 50 degreeC. This was charged into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of a 20% aqueous solution of polyvinylpyrrolidone was sprayed thereon, followed by spraying 2667 g of a 33% aqueous sodium metaphosphate solution. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). An effervescent tablet of 20 mm and 1.8312 g of one tablet was obtained.

[0021]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Tartaric acid 872 Citric acid 592 Saccharin sodium 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Fragrance 5.5 Total 5493.7

Example 3 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 3 were used in a perfect oven PH.
After drying using -200 (manufactured by Tabai Espec Co., Ltd.), crystal citric acid pulverized with a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added, and the vertical granulator FM was added.
-VG-25 (manufactured by Powrex Corporation). Next, after making it react at 40 degreeC, it dried at 50 degreeC. This was charged into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of a 20% aqueous solution of polyvinylpyrrolidone was sprayed thereon, followed by spraying 4430 g of a 33% aqueous sodium metaphosphate solution. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). 2.0333 g of effervescent tablets (20 mm, 1 tablet) were obtained.

[0023]

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

Example 4 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, caffeine anhydride, sodium hydrogen carbonate, tartaric acid, citric anhydride,
Saccharin sodium and D-mannitol in Perfect Oven PH-200 (manufactured by Tabai Espec Corp.)
, And then poured into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), sprayed with 431 g of a 20% aqueous solution of polyvinylpyrrolidone, and then sprayed with 2667 g of a 33% aqueous solution of sodium metaphosphate. . next,
V-type blender V-10 with addition of sodium benzoate and fragrance
(Made by Tokuju Seisakusho Co., Ltd.), and then the single-shot tablet press FK-
Type 2 (manufactured by Okada Manufacturing Co., Ltd.) with a diameter of 20 mm and a tablet of 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 bicarbonate 1650 Tartaric acid 872 Anhydrous citric acid 592 Saccharin sodium 37.5 D-mannitol 39. 8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Fragrance 5.5 Total 5493.7

Example 5 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 5 were used in a perfect oven PH.
-200 (manufactured by Tabaispec Co., Ltd.), and then charged into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho), and sprayed with 431 g of an aqueous solution of 20% polyvinylpyrrolidone. 2667 g of a 33% sodium metaphosphate aqueous solution was sprayed. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). An effervescent tablet of 20 mm and 1.8312 g of one tablet was obtained.

[0027]

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

Example 6 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium bicarbonate, fumaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 6 were used in a perfect oven P.
After drying using H-200 (manufactured by Tabai Espec Co., Ltd.), the mixture was charged into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho), and sprayed with 431 g of an aqueous solution of 20% polyvinylpyrrolidone. And 2667 g of a 33% aqueous sodium metaphosphate solution were sprayed. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). An effervescent tablet of 20 mm and 1.8312 g of one tablet was obtained.

[0029]

(Formulation) Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Fumaric acid 1464 Sodium saccharin 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium metaphosphate 880 Sodium benzoate 213.2 Fragrance 5.5 Total 5493.7

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

[0031]

[Table 7]

Example 8 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, D-mannitol, sodium metaphosphate (hammer) Mill crushed product) Perfect Oven PH-20
0 (manufactured by Tabai Espec Corp.), mixed with a vertical granulator FM-VG-25 (manufactured by Powrex), and granulated by adding 431 g of an aqueous solution of 20% polyvinylpyrrolidone. Dry at ℃.
Next, sodium benzoate and fragrance were added, and a V-type mixer V was added.
After mixing with -10 (manufactured by Tokuju Seisakusho), effervescent tablets having a diameter of 20 mm and one tablet of 1.8312 g were obtained with a single-shot tableting machine FK-2 (manufactured by Okada Seisakusho).

[0033]

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

Comparative Example 1 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 9 were used in a perfect oven PH.
After drying using -200 (manufactured by Tabai Espec Co., Ltd.), crystal citric acid pulverized with a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added, and the vertical granulator FM was added.
-VG-25 (manufactured by Powrex Corporation). Next, after making it react at 40 degreeC, it dried at 50 degreeC. This was put into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho), and 431 g of an aqueous solution of 20% polyvinylpyrrolidone was sprayed. Next, sodium benzoate and a fragrance were added and mixed with a V-type mixer V-10 (manufactured by Tokuju Seisakusho). An effervescent tablet of 20 mm and 1.5258 g of one tablet was obtained.

[0035]

Table 9 Formulation Weight (g) Acetaminophen 900 Chlorpheniramine maleate 7.5 Tipepidine citrate 60 Anhydrous caffeine 150 Sodium bicarbonate 1650 Tartaric acid 872 Citric acid 592 Saccharin sodium 37.5 D-mannitol 39.8 Polyvinylpyrrolidone 86.2 Sodium benzoate 177.7 Fragrance 4.6 Total 4577.3

Comparative Example 2 (Preparation method) Acetaminophen, chlorpheniramine maleate, tipepidine citrate, anhydrous caffeine, sodium hydrogen carbonate, tartaric acid, sodium saccharin, and D-mannitol in the formulation shown in Table 10 were used in a perfect oven P.
After drying using H-200 (manufactured by Tabai Espec Corp.), crystal citric acid pulverized with a hammer mill (manufactured by Fuji Paudal Co., Ltd.) was added, and the vertical granulator FM was added.
-VG-25 (manufactured by Powrex Corporation). Next, after making it react at 40 degreeC, it dried at 50 degreeC. This was put into a fluidized bed granulation dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.), and 431 g of a 20% aqueous solution of polyvinylpyrrolidone was sprayed thereon, followed by spraying 653 g of a 33% aqueous sodium metaphosphate solution. Next, sodium benzoate,
After adding a fragrance and mixing with a V-type mixer V-10 (manufactured by Tokuju Seisakusho), a single-shot type tableting machine FK-2 (manufactured by Okada Seisakusho), diameter 20 mm, 1.6 g per tablet. Was obtained.

[0037]

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

Test Example 1 (Compression Moldability) With respect to Examples 1 to 8 and Comparative Examples 1 and 2, the presence or absence of tableting trouble during compression molding was visually evaluated. From the results in Table 11, while tableting was performed without any problem in Examples 1 to 8,
In Comparative Examples 1 and 2, occurrence of binding and sticking was observed.

[0039]

[Table 11]

Test Example 2 (Stability Over Time) The tablets of Examples 1 to 8 and Comparative Examples 1 and 2 were heat-sealed with aluminum and stored in a constant temperature room at 40 ° C. to change the properties and generate carbon dioxide. Was tested. Evaluation criteria are shown in Table 12.
Followed. From the results in Table 13, in Examples 1 to 8, there was no property change and no generation of carbon dioxide gas, but in Comparative Examples 1 and 2, property change and generation of carbon dioxide gas were recognized.

[0041]

[Table 12]-: No change in properties, no generation of carbon dioxide +: No change in properties, slight generation of carbon dioxide ++: Change in properties (yellowing), generation of carbon dioxide

[0042]

[Table 13]

Continuation of front page (56) References JP-A-2-180814 (JP, A) JP-A-47-11596 (JP, A) JP-B-40-24792 (JP, B1) (58) Fields investigated (Int) .Cl. ⁷ , DB name) A61K 9/20-9/46 A61K 47/02 A61K 7/00-7/50

Claims (1)

(57) [Claims] 1. An effervescent tablet comprising a carbonate and an acidic substance, wherein sodium metaphosphate is incorporated in an amount of 6% by weight or more.