METHOD FOR PRODUCING FOAMING COMPOSITION

Abstract: Rapidlydisintegratable active-component-containing foamable compositions can be obtained by the present method: an active component (Component-C) is mixed into a solid alkali metal or alkali earth metal salt of carbonic acid (Component-A) and/or a solid aliphatic carboxylic acid (Component-B), and then mixed together after being moistu­ rized separately with approx. 0.5-5% (w/w) water.

Description: The present invention relates to foaming or foamable compositions with excellent quality in that they disintegrate to foam in a short time. A wide variety of methods for producing foamable compositions are known, French Patent No. 69.15360 (Laid Open No. 2,044,216) and US Patent No. 3,773,922 being especially notable. In these patented methods, foamable components, i.e. a carbonic acid compound and an acid compound, are moisturized with a small amount of water to obtain tablets as final products. In the said French-patented method, a powdered base component such as sodium cyclamate or sodium saccharinate and a powdered acid component are separately moisturized with water, mixed together and dried. The resulting dry mixture, after a medicinal content is added, is tableted into foamable tablets. This method, however, has some drawbacks, e.g. the moisturized granules are extremely fine. The method can not be utilized in the case of a sensitive active component which tends to discolor when heating, e.g. due to heat of neutralization. In addition, the powder ratio is too high due to the medicinal content which is added after the moisturization/drying processes. These factors cause various disadvantages such as adhesion and die friction in the tableting process. When the powder ratio is too high (40% or more), tableting is sometimes impossible because powder mixture fluidity is so degraded that the powder mixture does not flow out of the tableting machine hopper. In the method specified in US Patent No. 3,773,922; a carbonic acid compound, an acid compound and a medicinal content are mixed, granulated and moisturized, and then the resulting granules after being dried, are tableted to produce foamable tablets. However, this method, in which water is added in a ratio of 1 wt.% or less to the amount of an alkali bicarbonate, also has some problems. When the total amount of a medicinal content and citric acid added exceeds the amount of the alkali bicarbonate added, the ratio of water added to the whole weight equals that obtained in the said French-patented method (0.5% or less). This means that nothing but extremely fine particles are produced as shown above; adhesion or die friction is caused in the tableting process because the effect of the lubricant is weakened. To obtain granules, water is vaporized in different ratios to the acid-alkali mixture; however, specially-designed equipment is required so this method is not recommended. In addition, moisturization with water vapor requires more time than that by water addition and it is difficult to control the moisture of the granules. As a working example shown in the said US Patent, dry citric anhydride is added after sodium bicarbonate is moisturized. In this case, it is difficult to obtain a uniform mixture; until the citric anhydride is completely moisturized by the moisturized sodium bicarbonate, the acid-alkali reaction does not proceed uniformly because there is an uneven water distribution in the citric anhydride. The inventors, after studying how to produce a quickly-decomposable, fast-foamable and easiliy-producible foamable composition, found that a foamable composition satisfying the said requirements can be produced via a process in which an active component (vitamine C) is mixed into a carbonic acid compound or an acid compound or to both and then mixed with each other after being separately moisturized with approx. 0.5 ∼ 5% water, and completed this invention after further studies. The present invention is a method for producing an active -component-containing a foamable composition, characterized in that vitamine C as an active component (Component-C), and a binder, if necessary, is mixed into a solid alkali metal or alkali earth metal salt of carbonic acid (Component-A, hereinafter called "alkali component" in some cases) and a solid aliphatic carboxylic acid (Component-B, hereinafter called "acid component" in some cases) and that they are mixed with each other after being separately moisturized with approx. 0.5 ∼ 5% (w/w) water relative to the mixture. Alkali metal carbonates, alkali metal bicarbonates, alkaline earth metal carbonates, etc. can be used as the alkali component. Sodium, potassium, etc. and calcium, magnesium, barium, etc. can be listed as alkali metals and alkaline earth metals, respectively. As alkali metal carbonates, sodium carbonate, potassium carbonate, etc. can be used, sodium carbonate being especially preferable. As alkali metal bicarbonates, sodium bicarbonate, potassium bicarbonate, etc. can be used, sodium bicarbonate being especially preferable. As alkaline earth metal salts, calcium carbonate, magnesium carbonate, barium carbonate, etc. can be used, calcium carbonate being especially preferable. A mixture of the said compounds can be used as the alkali component. The alkali component must be solid, e.g. powdered salts and granulated salts; granulated ones being especially preferable. As the aliphatic carboxylic acids used in this invention, monobasic, dibasic, tribasic, etc. are listed below. These aliphatic carboxylic acids are those having 2-10 carbon atoms, preferably 2-6 carbon atoms. As monobasic aliphatic carboxylic acids, glycolic acid, etc. can be used. As dibasic aliphatic carboxylic acids, tartaric acid, fumaric acid, maleic acid, malonic acid, malic acid, succinic acid, etc. can be used. As tribasic aliphatic carboxylic acids, citric anhydride, citric acid, isocitric acid, etc. can be used. A mixture of the said compounds can be used as an aliphatic carboxylic acid. Among the aliphatic carboxylic acids shown above, citric anhydride is especially preferable. As solid aliphatic carboxylic acids, powdered ones, granulated ones, etc. can be used; granulated ones being especially preferable. The desirable ratio of Component-A to Component-B is approx. 1 : 1 ∼ 1 : 2 (w/w). As active components; medicines, foods, agricultural chemicals, drugs for animals, etc. can be used. As medicine vitamine C (L-ascorbic acid, sodium L-ascorbate, calcium L-ascorbate) is used. In addition to vitamine C, para-acetamol (acetaminophen), Aspirin (acetylsalicylic acid), their combinations, multi-vitamin compounds [e.g. vitamins A, B₁, B₂, B₃, B₅, B₆, B₁₂, C, D and E, folic acid, and minerals (e.g. iron, calcium, copper, potassium, magnesium, manganese, zinc, and iodine)], etc. can be added. When vitamine C is used as an active component, the desirable ratio to the foamable components (Component-A and Component-B) is approx. 40% or less (by weight). As foods vitamine C is used. In addition to vitamine C powdered liquor, aspartame (α-L-aspartyl-L-phenylalanine methyl ester), acesulfam [6-methyl-1,2,3-oxathiazine-4-(3H)-one-2,2-dioxan] or its alkali metal salts (potassium salt, etc.), sweetenings such as saccharin and sugar, vitamine/mineral mixtures such as sports drinks, teas containing crude-drug extracts, etc. can be used. Active components to be used in this invention can be powdered or granulated, granulated ones being especially preferable. As for the addition of an active component, it is recommended that a basic active component is mixed with the alkali component (Component-A). It is recommended that an acid active component is mixed with an aliphatic carboxylic acid (Component-B). A neutral active component can be mixed with Component-A or Component-B or with both. The compositions obtained in this invention can assume such forms as tablets and granules. The method for producing the foamable composition is hereinafter described. An active component and a binder, if necessary, are added to the alkali component (Component-A). The resulting mixture is moisturized with approx. 0.5 ∼ 5% (w/w) water. As binders to be added, polyvinyl pyrrolidone, dextrin, dextrose, lactose, acacia powder, methyl cellulose, hydroxypropyl methyl cellulose, etc. can be used. A desirable amount of water used for moisturization is approx. 1 ∼ 3% (w/w), preferably approx. 1 ∼ 2% (w/w). An organic solvent can be added to the water, if required. As organic solvents, ethanol, acetone, etc. can be used. In such cases, the recommended ratio of water to the organic solvent is approx. 1 : 1 ∼ 1 : 4 (v/v). Coloring agents, sweetenings, etc. can be added to the water to make a solution. As coloring agents, riboflavin, synthetic coloring agents such as tartrazine and sunset yellow, etc. can be used. As sweetening, saccharin, aspartame, sugar, etc. can be used. As for moisturization methods, water is sprayed or little by little dropped, with the component mixture being stirred in a stirrer. An active component, if required, and a binder, if further required, are added to a solid aliphatic carboxylic acid (Component-B), the resulting mixture being moisturized with approx. 0.5 ∼ 5% (w/w) water. As binders to be added, those used in the process of moisturizing Component-A can be used as well. A desirable amount of water used for moisturization is approx. 1 ∼ 3% (w/w), preferably approx. 1 ∼ 2% (w/w). An organic solvent, if required, can be added to the water. As organic solvents, those used in the process of moisturizing Component-A can be used as well. The desirable amount of the organic solvent is equal to that used in the moisturization process. Component-A and Component-B, either or both of which now contain Component-C, after being separately moisturized, are mixed with each other. For example, they are stirred and mixed in a stirrer such as a Vertical Granulator for approx. 3 ∼ 5 minutes. Usually, the resulting granules are immediately subjected to the next process; however, it is preferable that they be sieved so that they can pass through a ca. 2.5mm (8-mesh) sieve (JIS) but cannot pass through a ca. 0.15mm (100-mesh) sieve (JIS). The resulting granules are next subjected to the drying process. For example: they are dried in a vacuum oven at approx. 40 ∼ 60°C and approx. 0 to 660 Pa (0 ∼ 5mmHg), for approx. 8 ∼ 16 hours; or dried in a forced-convention oven at approx. 40 ∼ 60°C for about 1 ∼ 3 hours. When granules for tableting are prepared, a lubricant diluted may be added to foamable granules containing the acid component and the alkali component. The lubricant may be diluted with, for example, the acid component, the alkali component, a perfume or a binder shown below. In this case, the lubricant should be uniformly dispersed. This is because a lubricant, when directly mixed with foamable granules, is liable to become large spherical granules in the presence of static electricity. That is, by preventing the granulization of the lubricant itself in the said procedure, the effect of the lubricant is improved so that the mixture can be easily tableted. In addition, the foamable power of tablets to be produced can be improved by adding an alkali metal carbonate that has been granulated separately. The dry granules prepared via the said processes are then tableted. To the granules, if desired, coloring agents, perfumes, sweetenings, seasonings, binders, compression lubricants, etc., can be added prior to the tableting process. As coloring agents; riboflavin, tartrazine, sunset yellow, etc., can be used. As perfumes; orange oil, lemon oil, orange powder, lemon powder, etc., can be used. As sweetenings; saccharin, Aspartame, sugar, etc., can be used. As seasonings; sodium glutamate, nucleic acid seasonings, succinic acid, powdered bonito broth, etc., can be used. As binders used in the tableting process; polyvinyl pyrrolidone, dextrin, acacia powder, methyl cellulose, hydroxypropyl methyl cellulose, sugar, etc., can be used. As compression lubricants used in the tableting process; sodium stearate, sodium benzoate, polyethylene glycol 4000, polyethylene glycol 6000, etc., can be listed. A conventional method is used in the tableting process. When vitamine C is the active component of the foamable composition, the composition containing an effective dose of the medicine is administered in the following manners: The composition is put into mouth, foamed, dissolved or suspended, and then swallowed (oral administration). The composition is put into water, foamed, and dissolved or suspended; the resulting liquid (solution or suspension) being orally administered. The composition is put into water, foamed, and dissolved or suspended, the resulting liquid (solution or suspension) being applied to skin (percutaneous administration). The composition is put into hot water in a bathtub, foamed, and dissolved or suspended; the medicinal component being percutaneously absorbed. The composition (tablet) is inserted into the vagina, foamed, and dissolved or suspended; the medicinal component being absorbed there. As a concrete example: 1 ∼ 2 foamable tablets containing approx. 500 ∼ 1,000mg of ascorbic acid per tablet are put into approx. 60 ∼ 200mℓ water to foam and dissolve, the resulting solution being orally administered. When vitamine C as a foodstuff is the active component of the foamable composition, a composition wherein it contains an effective amount of the foodstuff is used in the following manners: The composition is put into mouth, where it foams and dissolves or suspends, and is then swallowed. The composition is put into water, foamed, and dissolved or suspended; the resulting liquid (solution or suspension) being swallowed. The composition is added to or sprinkled over cooking materials during cooking. The composition (granules) is sprinkled over washed vegetables. As a concrete example: 1 ∼ 2 foamable tablets containing approx. 500 ∼ 1,000mg/tablet of a tea containing crude-drug extracts are put into approx. 60 ∼ 100mℓ hot water at 40 ∼ 80°C, foamed and dissolved, the resulting solution being swallowed. When the foamable composition is used in the form of granules, the granules are not only easily strip-wrapped but also unsatisfactory adhesion due to the sticking of fine particles to the wrapping-film connections is never caused. Therefore, the granules can be easily handled. This is because the granules are uniform in size with few fine particles. In addition, their size is sufficiently large so that they sink and then foam well when put into water. Because the amount of water required in granulating the composition is so little the granules can be easily dried. Because uniform granules are obtainable by mixing a moisturized acid component and a moisturized alkali component; the uniformization process, which is required prior to the drying process in ordinary granulation processes can be omitted. In addition, the granules, after being dried, can be easily uniformized by sieving because they do not adhere to each other. For these reasons the foamable composition can be easily granulated on an industrial scale. In conventional methods, an acid component and an alkali component should be separately kneaded, granulated, dried, and uniformized, to produce foamable tablets. In the present method, however, the two components can be mixed with each other prior to the kneading, granulating, drying and uniformization processes, i.e. the number of processes can be reduced. The granules obtained by the present method contain few fine particles. Therefore, since a smaller amount of a lubricant is required; the granules are favorably tabletable. In addition, adhesion and die friction can be prevented. The granules obtained by the present method satisfy the requirements of foamable tablets; they are easily decomposed in water and remain settled at the bottom for long periods of time. In the present method, the hardness of a tablet can be properly changed between approx. 2kg and 15kg. The decomposition time, which increases in proportion to the hardness, can be also controlled according to the intended purpose. In the present method, the foaming state of a tablet can also be controlled: when its hardness is 2 ∼ 4kg, the tablet forms a great amount of fine foam which decomposes within a minute; when the hardness is 5kg or more, the tablet forms a coarser foam and its disintegration time exceeds 1 minute. When 10 foamable tablets containing vitamin C obtained by the present method are stored with silica gel in a screw-capped bottle at 60°C for 1 month, no considerable change is caused in their color, taste, foaming state, foaming time and vitamin C content. Therefore, it is thought that vitamine C-containing foamable tablets obtained by the present method can be kept stable at room temperature for at least 2 ∼ 3 years in the above packing form. Vitamin C is particularly likely to discolor and is sensitive against heat and moisture, but can be kept stable in the said tablet. The compositions obtainable by the present invention can be effectively used as rapidly-disintegrating/foamable compositions of medicines, foods, agricultural chemicals or drugs for animals. The present invention is hereinafter more concretely described with examples. The percentages shown are indicated by weight (w/w%) unless specified. Example 1 Foamable tablets with the following composition (Composition-A) were produced. Production Method (1) 5g of sunset yellow was dissolved in water to make 100mℓ of colored water. 1.8kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 18mℓ of the said colored water was added little by little. Separately, 2.062kg of C-97 and 1.2kg of powdered citric anhydride were stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 33mℓ of the said colored water was added little by little. The two resulting mixtures were mixed together for 3 minutes. The resulting mixture was dried in a vacuum oven at 40°C 660 Pa (5mmHg) for 16 hours to produce foamable granules. (2) 1kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 10mℓ of the said colored water was added little by little. The resulting moisturized colored sodium bicarbonate was dried in a vacuum oven at 40°C and 660 Pa (5mmHg) for 16 hours to produce colored sodium bicarbonate. (3) 400g of the colored sodium bicarbonate, 40g of saccharin sodium powder and 200g of sodium benzoate, were mixed and sieved 3 times by a 0.5mm (32-mesh) sieve (JIS). 586g of the resulting mixture and 5,000g of the foamable granules obtained in (1) were stirred and mixed with each other in a Vertical Granulator at 600rpm for 3 minutes in a room at 50% relative humidity. (4) A Stokes-B2 (F.J. Stokes Corp., USA) was used as a tableting machine. Dry compressed air (22°C, 10% relative humidity) was blown around the tableting table of the tableting machine to keep the relative humidity near the pounder at 10%. The mixture obtained in (3) was tableted at 14rpm using a corner-rounded pounder. The diameter, thickness, weight and hardness of the resulting foamable tablets, and the foaming time, foaming state, pH and taste of them when they are dissolved in 100mℓ of water at 24°C under normal pressure, are shown in the following. Diameter (mm) Thickness (mm) Weight (g) Hardness (kg) Foaming time Foaming state pH Taste 15.10 6.01 1.457 5 1'20" Good 5.62 Sweet Example 2 Foamable tablets with the following composition (Composition-B) were produced. Composition-B C-97 515.5mg (500mg as vitamine C) Citric anhydride 450 mg Sodium bicarbonate 525 mg Saccharin sodium 7.5mg Cidercorton (perfume) 22.5mg Sodium benzoate 50 mg Total 1,570.5mg (per tablet) Production Method (1) 5g of sunset yellow was dissolved in water to make 100mℓ of colored water. 1.5kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 15mℓ of the said colored water was added little by little. Separately, 2.062kg of C-97 and 1.8kg of citric anhydride were stirred in a Vertical Granulator at 600rpm for 5 minutes, and were stirred for 5 more minutes while 38mℓ of the said colored water was added little by little. The two resulting mixtures were mixed together and stirred for 3 minutes. The resulting mixture was dried in a vacuum oven at 40°C/660 Pa (5mmHg) for 16 hours to produce foamable granules. (2) 1kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 10mℓ of the said colored water was added little by little. The resulting moisturized colored sodium bicarbonate was dried in a vacuum oven at 40°C/660 Pa (5mmHg) for 16 hours to produce colored sodium bicarbonate. (3) 600g of the colored sodium bicarbonate, 30g of saccharin sodium powder, 200g of sodium benzoate powder and 90g of cidercorton were mixed and sieved 3 times by a 0.5mm (32-mesh) sieve (JIS). 920g of the resulting mixture and 5,000g of the foamable granules obtained in (1) were stirred and mixed in a Vertical Granulator at 600rpm for 3 minutes in a room at 50% relative humidity. (4) A Stokes-B2 was used as a tableting machine. Dry compressed air (22°C, 10% relative humidity) was blown around the tableting table to keep the relative humidity near the pounding bed at 10%. Using a corner-rounded pounder having a 15mm diameter, the mixture obtained in (3) was tableted at 14rpm. The diameter, thickness, weight and hardness of the foamable tablets obtained, and their foaming time, foaming state, pH and taste when they are dissolved in 100 ml of water at 24°C under normal pressure, are as follows: Diameter (mm) Thickness (mm) Weight (g) Hardness (kg) Foaming time Foaming state pH Taste 15.15 6.11 1.60 7 1'10" Good 4.77 Slightly sour Example 3 Foamable tablets with the following composition (Composition-C) were produced. Composition-C C-97 515.5mg (500mg as vitamine C) Citric anhydride 450 mg Sodium bicarbonate 500 mg Saccharin sodium 5 mg Cidercorton (perfume) 22.5mg Sodium benzoate 50 mg Total 1,543 mg (per tablet) Production method (1) 5g of sunset yellow was dissolved in water to make 100mℓ of colored water. 1.8kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 18mℓ of the said colored water was added little by little. Separately,2.062kg of C-97 and 1.8kg of powdered citric anhydride were stirred in a Vertical Granulator at 600rpm for 5 minutes, and were stirred for 5 more minutes while 32mℓ of the said colored water was added little by little. The two resulting mixtures were mixed together and stirred for 3 minutes. The resulting mixture was dried in a vacuum oven at 40°C/660 Pa (5mmHg) for 16 hours to produce foamable granules. (2) 1kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 10mℓ of the said colored water was added little by little. The resulting moisturized colored sodium bicarbonate was dried in a vacuum oven at 40°C/660 Pa (5mmHg) for 16 hours to obtain colored sodium bicarbonate. (3) 200g of the colored sodium bicarbonate obtained in (2), 20g of powdered saccharin sodium, 200g of powdered sodium benzoate and 90g of powdered cidercorton, were mixed together and sieved 3 times by a 0.5mm (32-mesh) sieve (JIS). 451g of the resulting mixture and 5,000g of the foamable granules obtained in (1) were mixed together and stirred in a Vertical Granulator at 600rpm for 3 minutes in a room at 50% relative humidity. (4) A Stokes-B2 was used as a tableting machine. Dry compressed air (22°C, relative humidity: 10%) was blown around the tableting table of the machine to keep the relative humidity near the pounder bed at 10%. The mixture obtained in (3) was tableted at a rate of 14rpm, using a round-cornered pounder having a 15mm diameter. The diameter, thickness, weight and hardness of the foamable tablets obtained, and their foaming time, foaming state, pH and taste when they are dissolved in 100mℓ of water at 24°C under normal pressure, are as follows: Diameter (mm) Thickness (mm) Weight (g) Hardness (kg) Foaming time Foaming state pH Taste 15.12 6.12 1.569 7 1'25" Good 4.66 Sour Example 4 Foamable tablets having the following composition (Composition-D) were produced. Composition-D C-97 247mg (240mg as vitamine C) Finely-powdered Aspirin 400mg Citric anhydride 1,200mg Sodium bicarbonate 1,800mg Polyethylene glycol 6000 20mg Saccharin sodium 10mg Sodium benzoate 100mg Total 3,777mg (per tablet) Production Method (1) 1.8kg of sodium bicarbonate was stirred in a Vertical Granulator at 600rpm for 5 minutes, and was stirred for 5 more minutes while 20mℓ of water was added little by little. (2) Separately from (1), 247g of C-97, 400g of finely-powdered Aspirin, 1,200g of citric anhydride and 20g of polyethylene glycol powder were stirred in a Vertical Granulator at 600rpm for 5 minutes, and were stirred for 5 more minutes while 20mℓ of water was added little by little. The resulting mixture was mixed with the moisturized sodium bicarbonate obtained in (1), and stirred for 3 minutes. (3) The resulting mixture was dried in a vacuum oven at 40°C/5mmHg for 16 hours. (4) 3.5kg of the mixture sieved by a 32-mesh sieve after being dried, 9.3g of powdered saccharin sodium and 93g of powdered sodium benzoate were stirred in a Vertical Granulator at 600rpm for 3 minutes. The resulting mixture was tableted using a flat pounder having a 25mm diameter to produce foamble tablets (diameter: approx. 25mm; thickness: approx. 6mm; weight: 3,800mg per tablet). Their foaming time when they were dissolved in 100mℓ of water at 16°C under normal pressure was 1 minute 15 seconds. Example 5 Foamable tablets with the following composition (Composition-G) were produced. Production Method (1) 130g of powdered Sports Drink Takeda® and 130g of citric anhydride were mixed together, and 3mℓ of water was sprayed over the mixture. (2) Separately from (1), 1mℓ of water was sprayed over 50g of sodium bicarbonate. (3) The materials obtained in (1) and (2), after being mixed together, were dried in a forced-convection oven at 50°C for 2 hours. (4) 300g of the dried mixture and 4.3g of powdered sodium benzoate were mixed together. Using a flat pounder 20mm in diameter, the resulting mixture was tableted (diameter: 20.12mm; thickness: 7.41mm; weight: 3.15g; hardness: 6.5kg). Their foaming time when they were dissolved in 100mℓ of water at 25°C under normal pressure was 1 minute and 10 seconds. Example 8 Foamable tablets with the following composition (Composition-I) were produced as follows. Composition-I L-ascorbic acid 300 mg SA-99 (Note) 795.4 mg (700 mg as vitamin C) Citric anhydride 950 mg Sodium bicarbonate 950 mg β-lactose 574.6 mg Fumaric acid 250 mg Saccharin sodium 20 mg Aspartame 10 mg Cidercorton (perfume) 100 mg Total 3,950 mg (per tablet) (Note) SA-99: Granules containing sodium L-ascorbate and corn-starch in a ratio of 1% (w/w), produced according to "the method for producing granules by circulating granulation" shown in Japanese Unexamined Patent Laid Open No. 57-59803. Production method (1) 5 g of sunset yellow was dissolved in water to make 100 ml of colored water. 950 g of sodium bicarbonate was stirred in a Vertical Granulator at 600 rpm for 5 minutes and was stirred for 5 more minutes while 30 ml of the said colored water was added little by little. To the resulting mixture was added 795.4 g of SA-99 and was stirred for 10 minutes, then 374.6 g of β-lactose was added, stirred for 5 minutes and mixed. Separately, 300 g of C-97 and 950 g of citric anhydride were stirred in a Vertical Granulator at 600 rpm for 5 minutes and was stirred for 5 more minutes while 15 ml of the said colored water was added little by little. To the resulting mixture was added the colored and moistured mixture of sodium bicarbonate, SA-99 and β-lactose and was stirred for 3 minutes. The resulting mixture was dried in a vacuum oven at 40°C/5 mmHg for 16 hours to produce foamable granules. (2) 200 g of β-lactose, 250 g of fumaric acid, 20 g of powdered saccharin sodium, 10 g of aspartame and 100 g of cidercorton (perfume) were mixed together and sieved by a 60-mesh sieve (JIS). 516 g of the resulting mixture and 3000 g of the foamable granules obtained in (1) were mixed together and stirred in a Vertical Granulator at 600 rpm for 3 minutes in a room at 50% relative humidity. (3) A Kikusui No.8 F-3 (Kikusui factory, Japan) was used as a tableting machine. The mixture obtained in (2) was tableted at a rate of 14 rpm, using a normal pounder having a 23 mm diameter. The diameter, thickness, weight and hardness of the foamable tablets obtained in (2), and their foaming time, foaming state, pH and taste when they are dissolved in 100 ml of water at 24°C under normal pressure, are as follows: Diameter (mm) Thickness (mm) Weight (g) Hardness (kg) Foaming time Foaming state pH Taste 23.15 8.24 4.066 17.48 1'38" Good 4.52 Sweet Example 9 Foamable tablets with the following composition (Composition-J) were produced as follows. Composition-J C-97 309.3 mg SA-99 795.4 mg Citric anhydride 950 mg Sodium bicarbonate 950 mg β-lactose 525.3 mg Fumaric acid 250 mg Saccharin sodium 20 mg Cidercorton (perfume) 100 mg Total 3,900 mg (per tablet) Production method (1) 5 g of sunset yellow was dissolved in water to make 100 ml of colored water. 950 g of sodium bicarbonate was stirred in a Vertical Granulator at 600 rpm for 5 minutes and was stirred for 5 more minutes while 25 ml of the said colored water was added little by little. To the resulting mixture was added 795.4 g of SA-99 and was stirred for 10 minutes, then 325.3 g of β-lactose was added. Separately, 309.3 g of C-97 and 950 g of Citric anhydride were stirred in a Vertical Granulator at 600 rpm for 5 minutes, and was stirred for 5 more minutes while 20 ml of the said colored water was added little by little. To the resulting mixture were added the colored and moistured mixture of sodium bicarbonate, SA-99 and β-lactose and was stirred for 3 minutes. The resulting mixture was dried in a vacuum oven at 40°C/5 mmHg for 16 hours to produce foamable granules. (2) 200 g of β-lactose, 250 g of fumaric acid, 20 g of powdered saccharin sodium and 100 g of cidercorton (perfume) were mixed together and sieved by a 60-mesh sieve (JIS) three times. 514 g of the resulting mixture and 3000 g of the foamable granules obtained in (1) were mixed together and stirred in a Vertical Granulator at 600 rpm for 3 minutes in a room at 50 % relative humidity. (3) A Kikusui No.8 F-3 (Kikusui factory, Japan) was used as a tableting machine. The mixture obtained in (2) was tableted at a rate of 14 rpm, using a normal pounder having a 23 mm diameter. The diameter, thickness, weight and hardness of the foamable tablets obtained, and their foaming time, foaming state, pH and taste when they are dissolved in 100 ml of water at 27°C water under normal pressure, are as follows: Diameter (mm) Thickness (mm) Weight (g) Hardness (Kg) Foaming time Foaming state pH Taste 23.15 8.42 3.898 10.9 1'20" Good 4.45 Sweet

Claims: Method for producing foamable compositions comprising a solid alkali or alkaline earth metal salt of carbonic acid (component A), a solid aliphatic carboxylic acid (component B) and vitamine C (Component C) by (a) separately moisturizing component A with 0.5 to 5 % (w/w) water, (b) mixing vitamine C into component B, (c) moisturizing the resultant component B with 0.5 to 5 % (w/w) water, (d) mixing the moistured mixture of B + vitamine C with the component A, wherein the ratio of component A to component B being 1 : 1 to 1 : 2 and the ratio of component C to the total amount of component A and component B being 40 % by weight or less. A method according to claim 1, wherein the alkali or alkaline earth metal salt of carbonic acid is selected from sodiumbicarbonate, potassiumbicarbonate, calciumcarbonate, magnesiumcarbonate and mixtures thereof. A method according to claim 1, wherein the component B is at least one of glyoxylic acid, tartaric acid, fumaric acid, maleic acid, malonic acid, malic acid, succinic acid, citric anhydride, citric acid and isocitric acid. A method according to claim 1, wherein the amount of water used for moisturization is 1-3 % (w/w).

Inventors: KIMURA, HIROSHI, NISHIKAWA, HIROKAZU, YAMASHITA, JUNZOU
Applicants: TAKEDA CHEMICAL INDUSTRIES, LTD.
Application year: 1986
Main classification: A61K9
IPC codes: A01N25, A61K9, C12G3, A23L2