JP2002128661A - Method for producing rapidly collapsing tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an intraoral rapidly collapsing tablet which can rapidly be collapsed or dissolved in an oral cavity to facilitate the administration of the tablet and can accurately be administered with single dose in comparison with a liquid agent such as a syrup, because dosage forms sufficiently considering the easy administrations to patients are few and further because the development of an easily administrable oral preparation is requested, despite that tablets, capsules, granules, powders, troches, chewable agents, and the like, have been known as oral solid preparation forms in a medicine field. SOLUTION: It was found that the rapid collapsing tablet could be produced by tableting and drying a mixture containing a solvent-adsorbed carrier. A tablet-molding device used in the production method of the present invention does not require a special device. The tablet is characterized by having a sufficient strength and being simultaneously rapidly collapsed in an oral cavity, in a washing machine in which water or warm water is placed, or in a bathroom.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing a tablet and a tablet produced by the method.

[0002]

2. Description of the Related Art Tablets, capsules, granules, powders, troches, chewables and the like are known as oral solid preparations in the pharmaceutical field. However,
There are few dosage forms that fully consider the ease of taking by patients, and there is a need for the development of oral dosage forms that are easy to take, especially for children, the elderly, and those who have difficulty swallowing. Above all, quick-disintegrating buccal tablets that disintegrate or dissolve quickly in the oral cavity are easy to take and can be taken even more accurately than liquid solutions such as syrups. I have.

[0003] For example, Japanese Patent Publication No. 58-24410 discloses that the contents of a tablet are -30 to 30 which are inert to the contents of the tablet.
Mix with a solvent that freezes at + 25 ° C (eg, water, cyclohexane, benzene), with the solvent being 5 to 80% of the total mixture.
% By weight, solidified by placing the mixture in an inert cooling medium, compressed into a tablet at a temperature lower than the freezing point of the solvent, and then the solvent was volatilized by freeze-drying or air-drying to obtain a porous material with good disintegration properties. A method for producing a dispersible tablet is described. Further, JP-A-5-27054 discloses that a mixture containing a medicinal ingredient, a saccharide, and water enough to moisten the surface of saccharide particles is tableted and dried to have a moderate strength and to have a sufficient strength in the oral cavity. It is described that an orally dissolving tablet having a porous structure that rapidly disintegrates and dissolves is obtained.

[0004] However, tablets manufactured by the method described in Japanese Patent Publication No. 58-24410 have excellent disintegration and solubility in the oral cavity, but have insufficient tablet strength. As a result, difficulties have arisen when taking out the preparation. In addition, Japanese Patent Application Laid-Open No. H5-271054
In the method described in the publication, filling a wet powder having poor fluidity with a rotary tableting machine that is generally used widely,
When compressed, there is a drawback in that the filling variation and wet powder are likely to cause tableting troubles sticking to the dies and punches of the tableting machine.

[0005] In the field of detergents, powders, granules, and liquids are mainly used as detergents. These detergents need to be weighed at the time of use. There is a drawback that the liquid may splatter, causing discomfort to the user. Various attempts have been made to solve these problems. JP-A-4-
Japanese Patent No. 161498 discloses a tablet detergent containing potassium carbonate in a specific weight ratio. However, the present composition has a problem that it is not possible to obtain sufficient strength to withstand transfer.

[0006] In the field of bath salts as well, as in the case of detergents, there is a demand for various forms of tablets, which have the advantage of being accurate in a single use, being compact and easy to handle. For example, in JP-A-8-319228 and JP-A-9-2942, disintegration is enhanced by imparting foaming property by blending a carbonate or hydrogen carbonate with an organic acid, but it is satisfactory. It was not something.

[0007]

Means for Solving the Problems The inventors of the present invention have made intensive studies to solve the above-mentioned problems, and as a result, have obtained a tablet containing a carrier having a solvent adsorbed thereon, and having a quick disintegration property by drying. It has been found that tablets can be manufactured. The tablet molding device used in the production method of the present invention does not require a special device, and for example, a generally used rotary tableting machine can be used. The tablet produced by the production method of the present invention has sufficient strength at the time of transportation and does not hinder removal from a PTP package or the like, and is promptly taken in the mouth, a washing machine containing water or hot water and a bath water. Collapse.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The carrier in the present invention means all carriers acceptable in the fields of pharmaceuticals, quasi-drugs, cosmetics, foods and the like. Oil absorption capacity 80ml / 100g
It is more preferable to have the above (based on the JIS-K6220 test method). As such a carrier, for example, calcium silicate, light anhydrous silicic acid, hydrous silicon dioxide,
Silicon dioxide, aluminum oxide, magnesium carbonate,
Precipitated calcium carbonate, crystalline cellulose, synthetic aluminum silicate, magnesium silicate, magnesium aluminate metasilicate, dextrin, carmellose calcium and the like can be mentioned. These carriers may be used alone or in combination of two or more.

The solvent in the present invention means all solvents acceptable in the fields of pharmaceuticals, quasi-drugs, cosmetics, foods and the like. For example, water, methanol, ethanol,
i-propanol, n-propanol, chloroform,
Hexane, propylene glycol, diethyl ether,
Acetone, acetonitrile and the like can be mentioned. Among them,
Volatile substances such as low molecular weight water, methanol, and ethanol having the property of vaporizing at room temperature are more preferable.

In the present invention, the amount of the solvent adsorbed on the carrier can be appropriately selected within the range of 0.01 to 4.0 parts by weight per 1 part by weight of the carrier, but is preferably 0.3 to 2.0.
0 parts by weight, more preferably 0.5 to 1.0 parts by weight. In the tablet according to the present invention, the compounding ratio of the carrier capable of adsorbing the solvent is not particularly limited, but is preferably 1
0.1-20% by weight in the tablet, more preferably 0.5-10%
%, Particularly preferably 1.0 to 8% by weight.

In the production method of the present invention, tablet compression is performed by
Although it is carried out at a low pressure in consideration of the disintegration property, it is preferably 1 to 1000
kg / cm ² , more preferably 5 to 700 kg / cm ² ,
Particularly preferably, it is 10 to 500 kg / cm ² .

The method for drying tablets in the production method of the present invention is not particularly limited, but hot air drying such as a commonly used shelf dryer or aeration dryer is preferable in terms of equipment.
The drying temperature at that time is not particularly limited, and is appropriately set depending on the physical properties of the components used and the physical properties and amount of the solvent used.

The tablet of the present invention may contain various components depending on the intended use. In the pharmaceutical field, for example, as a medicinal ingredient, as a nourishing tonic health drug, a gastrointestinal drug, an antipyretic analgesic and anti-inflammatory drug, a psychotropic drug, an anxiolytic, an antidepressant, a hypnotic sedative, an antispasmodic, an antitussive expectorant, an antihistamine, arrhythmia Preparations, diuretics, antihypertensives and the like. Others
In addition to excipients such as sugars and sugar alcohols, additives such as disintegrants, binders, sour agents, artificial sweeteners, lubricants, coloring agents, and flavors may be used alone or in combination of two or more. it can.

[0014] The nourishing health agents, for example, vitamin A, vitamin D, vitamin E, vitamin B _1, vitamin B _2, vitamin B _6, vitamin C, vitamin such as vitamin B _12; calcium, magnesium, such as iron Minerals; proteins; amino acids; oligosaccharides;

The gastrointestinal drugs include, for example, stomachic digesters such as diastase, pepsin, funnel extract, lipase AP, and calyx oil; intestinal preparations such as berberine chloride, lactic acid bacteria, and bifidobacteria.

As the antacid, for example, it exerts its effect by neutralizing gastric acids such as sucralfate, magnesium carbonate, sodium hydrogen carbonate, magnesium metasilicate aluminate, synthetic hydrotalcite, precipitated calcium carbonate and magnesium oxide. And H ₂ -receptor antagonists such as ranitidine, cimetidine, famotidine, nizatidine, and roxatidine acetate.

Examples of antipyretic analgesics and anti-inflammatory drugs include aspirin, acetaminophen, etensamide, ibuprofen, diphenhydramine hydrochloride, dl-chlorpheniramine maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, caffeine , Serrapeptase, lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin and the like. As psychotropic drugs, for example, chlorpromazine,
Reserpine and the like. Examples of anxiolytics include chlordiazepoxide, diazepam and the like.

Examples of the antidepressant include imipramine, maprotiline, amphetamine and the like.
Hypnotic sedatives include, for example, estazolam, nitrazepam, diazepam, phenobarbital sodium and the like. Antispasmodics include, for example, scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride and the like.

Examples of antitussive expectorants include cloperastine hydrochloride, dextromethorphan hydrobromide, theophylline, potassium guaiacol sulfonate, guaifenesin and the like. Examples of the antihistamine include diphenhydramine hydrochloride, promethazine, isotipendyl hydrochloride, dl-chlorpheniramine maleate, and the like.

Examples of the agent for arrhythmia include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like.

As diuretics, for example, isosorbide,
Furosemide and the like. Examples of the antihypertensive include delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, methyldopa and the like.

As the sugar or sugar alcohol, for example,
Examples include sucrose, glucose, lactose, sorbitol, erythritol, xylitol, mannitol, maltitol and the like, with erythritol, xylitol and mannitol being particularly preferred.

Examples of the disintegrant include carmellose,
Examples include carmellose calcium, carmellose sodium, polyvinyl alcohol, low-substituted hydroxypropylcellulose, agar powder and the like. Examples of the binder include polyvinylpyrrolidone, hydroxypropylcellulose, gelatin, pullulan and the like. As the sour agent, for example, citric acid, tartaric acid, malic acid and the like can be mentioned. Examples of the artificial sweetener include saccharin sodium, aspartame, stevia, dipotassium glycyrrhizinate, and the like.

Examples of the lubricant include magnesium stearate, calcium stearate, polyethylene glycol, talc, stearic acid, sucrose fatty acid ester and the like. Examples of the coloring agent include food colors such as Food Yellow No. 5, Food Red No. 2, Food Blue No. 2, and the like;
Edible lake dyes; Examples of the flavor include lemon, lime, orange, strawberry, and menthol.

As the detergent, one or a combination of two or more of a surfactant, a washing builder, a fluorescent agent, an enzyme, a bleaching agent, a bulking agent, a reducing agent, a fragrance and the like can be used.

Examples of the surfactant include an anionic surfactant, a nonionic surfactant, a cationic surfactant, and a double-sided surfactant. Examples of the surfactants include, as anionic surfactants, linear alkyl benzene sulfonates, alkyl sulfates, alkenyl sulfates,
Alkyl ether sulfate, alkenyl ether sulfate,
Examples thereof include an alkyl ether carboxylic acid, an alkenyl ether carboxylate, an α-sulfofatty acid salt, an α-sulfofatty acid ester salt, and a soap. The anionic surfactant is preferably an alkali metal salt such as a sodium salt and a potassium salt.

Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyethylene glycol fatty acid ester, and polyoxyethylene polyoxypropylene. Examples thereof include alkyl ether, polyoxyethylene castor oil, polyoxyethylene hardened castor oil, polyoxyethylene alkylamine glycerin fatty acid ester, higher fatty acid alkanolamide, alkyl glycoside, and alkylamine oxide.

Examples of the cationic surfactant include a dialkyl type quaternary ammonium salt and a monoalkyl type quaternary ammonium salt. Examples of the surfactant include carboxybetaine and sulfobetaine. Examples of the builder include inorganic builders such as sodium tripolyphosphate and sodium pyrophosphate; aluminosilicates;
Calcium ion-trapping builders such as sodium citrate, sodium ethylenediaminetetraacetate, nitrilotriacetate, sodium polyacrylate, sodium acrylate-sodium maleate anhydride copolymer, polyacetal carboxylate; sodium carbonate, potassium carbonate,
Alkaline builders such as silicates are included. Examples of the fluorescent agent include 4,4′-bis- (2-sulfostyryl) -biphenyl salt, 4,4′-bis- (4-chloro-3-sulfostyryl) -biphenyl salt, and 2- (styrylphenyl) ) Naphthothiazole derivatives, 4,4'-bis- (triazol-2-yl) stilbene derivatives and the like.

Examples of the enzyme include protease, esterase, lipase, nuclease, cellulase, amylase, pectin and the like. Examples of the bleaching agent include sodium percarbonate, sodium perborate,
And sodium hydrogen sulfate adduct. Examples of the extender include sodium sulfate, potassium sulfate and the like. Examples of the reducing agent include sodium sulfite and potassium sulfite. Examples of the flavor include d-limonene, geraniol, linalool, citral, and the like.

In the bath preparation, in addition to various medicinal ingredients,
Excipients, binders, disintegrants, lubricants, fragrances and the like can be used alone or in combination of two or more. Examples of the excipient include monosaccharides such as glucose, sucrose, lactose, and sorbitol, disaccharides, and starch. Examples of the binder include dextrin, carrageenan, cellulose derivatives such as methylcellulose, polyethylene glycol and the like. Examples of the disintegrant include carboxymethyl cellulose, carboxymethyl starch, hydroxypropyl cellulose, hydroxypropyl starch, crystalline cellulose and the like. Examples of the lubricant include magnesium stearate, calcium stearate, and talc. Examples of the flavor include citrus and woody.

The hardness of the tablet obtained by the production method of the present invention is determined by the tablet diameter, the tablet weight, the tablet shape and the like.
It is appropriately selected according to the characteristics of each field of medicines, detergents and bath salts.

[0032]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, which do not limit the present invention.

[0033]

Example 1 Acetaminophen 300 parts by weight Erythritol 350 parts by weight D-mannitol 200 parts by weight Aspartame 10 parts by weight Hydroxypropylcellulose 50 parts by weight Calcium silicate 50 parts by weight Water 100 parts by weight Magnesium stearate 39 parts by weight Lemon flavor 1 Parts by weight Acetaminophen, erythritol, D-mannitol, aspartame, and hydroxypropylcellulose are granulated by a fluid bed granulator. Next, the calcium silicate to which the water has been adsorbed is mixed with the granules, and finally, a lemon flavor and magnesium stearate are mixed to obtain a tableting powder. This tableting powder is molded at a tablet weight of 1000 mg, a diameter of 15 mm, and a tableting pressure of 0.3 ton / cm ² to obtain a tablet. The tablets were dried in a through-air dryer at 70 ° C. for 2 hours.

[0034]

Example 2 Meclizine hydrochloride 25 parts by weight D-mannitol 250 parts by weight Erythritol 600 parts by weight Aspartame 10 parts by weight Calcium silicate 70 parts by weight Ethanol 100 parts by weight Magnesium stearate 44 parts by weight Lemon flavor 1 part by weight The adsorbed ethanol is mixed with meclizine hydrochloride, D-mannitol, erythritol, and aspartame. Finally, magnesium stearate is added and mixed to obtain a tableting powder. The tableting powder is molded at a tablet weight of 500 mg, a diameter of 12 mm, and a tableting pressure of 0.3 ton / cm ² to obtain a tablet. The tablets were dried at 40 ° C. for 2 hours in a through-air dryer.

[0035]

Example 3 200 parts by weight of polyoxyethylene doresyl ether (average number of moles of ethylene oxide added = 8) 4 parts of zeolite 4A 300 parts by weight 70 parts by weight of calcium silicate 100 parts by weight of sodium 100 parts by weight of sodium carbonate 200 parts by weight of sodium acetate Polyethylene glycol 10 parts by weight Sodium polyacrylate 30 parts by weight Protease 5 parts by weight Cellulase 5 parts by weight Lipase 5 parts by weight Perfume 2 parts by weight Sodium sulfate 73 parts by weight Calcium silicate with ethanol adsorbed in advance and components other than enzymes and flavors The granules, enzymes, and flavors are mixed to obtain a tableting powder. This tableting powder is 7000 mg per tablet,
A tablet is obtained by molding with a diameter of 25 mm and a tableting pressure of 0.2 ton / cm ² . The tablets were dried in a through-air dryer at 40 ° C. for 30 minutes.

[0036]

Example 4 Sodium hydrogen carbonate 250 parts by weight Sodium carbonate 200 parts by weight Fumaric acid 350 parts by weight Polyethylene glycol 6000 50 parts by weight Dextrin 50 parts by weight Calcium silicate 90 parts by weight Ethanol 150 parts by weight Fragrance 10 parts by weight The tablet adsorbed with ethanol is mixed with other components to obtain a tableting powder. Each tableting powder has a weight of 10 g, a diameter of 25 mm, and a tableting pressure of 0.2 ton /
Mold in cm ² to obtain tablets. The tablets were dried in a through-air dryer at 40 ° C. for 1 hour.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) C11D 3/43 C11D 3/43 11/00 11/00 F term (reference) 4C076 AA36 BB01 DD24 DD25 DD27 DD37 DD38 DD41 DD42 DD67 EE09 EE23 EE30 EE32. ED15 FA32

Claims (9)

[Claims] 1. A method for producing a tablet, comprising tableting and drying a mixture containing a carrier to which a solvent has been adsorbed. 2. The method according to claim 1, wherein the tablet is a rapidly disintegrating tablet in the oral cavity. 3. The method according to claim 1, wherein the tablet is a detergent. 4. The method for producing a tablet according to claim 1, wherein the tablet is a bath agent. 5. The method according to claim 1, wherein the solvent is water or ethanol or a mixture of water and ethanol. 6. The carrier has an oil absorption of 80 ml / 100 g (JIS).
The method for producing a tablet according to claim 1, wherein the substance is the above substance (by K6220 test method). 7. The method according to claim 1, wherein sugar or sugar alcohol is used as the excipient. 8. The method according to claim 7, wherein the sugar alcohol is selected from erythritol, xylitol and mannitol. 9. A tablet produced by the production method according to claim 1.