WO2007029376A1

WO2007029376A1 - Orally rapidly disintegrating tablet

Info

Publication number: WO2007029376A1
Application number: PCT/JP2006/309706
Authority: WO
Inventors: Tadashi Fukami; Yoshiro Nagai; Kanemasa Takado; Hitoshi Machimura
Original assignee: Fuji Chemical Industry Co., Ltd.
Priority date: 2005-09-02
Filing date: 2006-05-16
Publication date: 2007-03-15
Also published as: JP5074190B2; JPWO2007029376A1

Abstract

[PROBLEMS] To provide an orally rapidly disintegrating tablet which has sufficient level of hardness and molding property not to cause problems such as chipping or dusting during production or transport and also shows a good disintegrability in the oral cavity, while maintaining a high content of an active ingredient; and a process for producing an orally rapidly disintegrating tablet comprising shaping under compression using a conventional drug preparation facility. [MEANS FOR SOLVING PROBLEMS] The following ingredients (a) to (d) are mixed with one another: (a) a granulated particle comprising (i) an inorganic substance and (ii) a disintegrating agent dispersed homogenously in (iii) a composite particle made of at least two saccharides, which is optionally contains an active ingredient; (b) a lubricant; (c) at least one ingredient selected from an auxiliary disintegrating agent, an excipient and/or a binder; and (d) the active ingredient, and then the resulting mixture is shaped under compression by using a conventional drug preparation facility or by using a method in which a lubricant is previously coated onto the surfaces of a pestle and a mortar (external lubricating method). Thus, an orally rapidly disintegrating tablet can be prepared which has an excellent molding property, a good disintegrability and a satisfactory level of hardness even at a high active ingredient content.

Description

Specification

Orally rapidly disintegrating tablets

Technical field

[0001] The present invention relates to an intraoral rapidly disintegrating tablet having rapid and powerful disintegration property and appropriate hardness in the oral cavity, and a method for producing the same with high productivity. The intraoral rapidly disintegrating tablet of the present invention can be used in the field of medicine.

Background art

[0002] Intraoral rapidly disintegrating tablets have a disintegration time of about 60 seconds or less in the oral cavity, and need to have a certain degree of hardness so that the tablets are not chipped or pulverized during manufacture or transportation. Hardness and disintegration time are contradictory elements. If disintegration time is increased, the hardness decreases, and if the hardness is increased, the disintegration time decreases. In order to solve the problem of disintegration time and hardness, several methods are known for producing a rapidly disintegrating tablet in the oral cavity, including a wet tableting method, a tableting warming method, and a direct tableting method. In the wet tableting method and the tableting warming method, the usual preparation equipment for compression molding cannot be used, and a heating device, a humidifying device, and a drying device are required, and special equipment is required. In addition, the process involves processes such as humidification, warming, and drying in addition to normal compression molding, so there is a problem in productivity and it is not suitable for water-soluble active ingredients.

[0003] On the other hand, a method for producing an orally rapidly disintegrating tablet by the direct tableting method can use a normal preparation facility. However, in the direct tableting method, it is difficult to have both moldability, moderate hardness and disintegration while increasing the content of the active ingredient, and methods for improving these are known. For example, there is a method in which an active ingredient, spray-dried mannitol, crospovidone, and excipients that can be used for pharmaceuticals are dry mixed and then compression molded to produce an orally rapidly disintegrating tablet (see Patent Document 1). .

Tablets made by using spray-dried mannitol suitable for direct compression and crospovidone, a super disintegrant, have moderate moldability and disintegration, but can be used as an orally rapidly disintegrating tablet. However, there was a problem that the tolerance between the oral disintegration time and the hardness of the obtained tablets was not always sufficient.

[0004] Medicinal properties, mantle with an average particle size of 5 μm to less than 90 μm, average particle size of 90 After fluidized bed granulation of μπι ～ 500 / ζ m of mantle, disintegrant and crystalline cellulose

There is a method of producing an intraorally rapidly disintegrating tablet formed by compression molding (see Patent Document 2). This method required a complicated process in which two types of particles with different particle sizes were fluidized, granulated, and then compression molded. In addition, the particles by fluidized bed granulation are non-spherical granules bound by the raw material-derived particle force S binder, and the components of the particles are not evenly dispersed in the particles, so the oral cavity rapidly disintegrates. However, it was not enough to satisfy the moldability and disintegration properties suitable for the active tablets.

[0005] In addition, the present inventors previously invented a composition for a rapidly disintegrating tablet in the oral cavity, wherein a disintegrant and an inorganic substance are uniformly dispersed in water in saccharide composite particles (Patent Document). (Refer to 3, 4). These are granulated particles that have been spray-dried, so that they have good meterability in a compression molding machine and are particles in which disintegrants and inorganic substances are homogeneously dispersed. Indicated. However, tablets obtained by mixing and compressing active ingredients and spray-dried granules in Examples of Patent Documents 3 and 4 can obtain the desired disintegration but have insufficient hardness (30-40N), and tablet manufacture Sometimes, problems such as chipping and powdering of tablets occurred during transportation. In addition, if the active ingredient content is high, tableting troubles such as sticking to the bag may occur.

Patent document 1: International publication 00Z57857 pamphlet

Patent Document 2: Japanese Patent Laid-Open No. 2001-58944

Patent Document 3: International Publication 2005Z037319 Pamphlet

Patent Document 4: International Publication 2005Z037254 Pamphlet

Disclosure of the invention

Problems to be solved by the invention

[0006] The present invention eliminates problems that occur when the content rate of the active ingredient is high compared to the above-described prior art oral disintegrating tablets, and has sufficient hardness that does not cause problems during production and transportation and the oral cavity. It is an object of the present invention to provide an intraoral rapidly disintegrating tablet having good disintegration property and a method for producing an intraoral rapidly disintegrating tablet having high productivity.

Means for solving the problem

[0007] As a result of intensive studies to achieve the above object, the present inventors have found that (a) two or more sugars Granulated particles made by spray drying a specific ratio of minerals, minerals and disintegrants, or by further adding active ingredients and spray drying, (b) lubricants, (C) excipients, disintegration aids At least one or more selected from agents and Z or binders, and (d) tablets containing the active ingredient are surprisingly free from problems that occur when the active ingredient content is high. It has been found that the production method has sufficient hardness that does not cause erosion, good disintegration property in the oral cavity, and high productivity.

[0008] The "orally-fast disintegrating tablet" in the present invention means a tablet that can disintegrate rapidly in the oral cavity, for example, within 40 seconds, more preferably within 30 seconds, and even more preferably within 20 seconds. To do. The oral disintegration time here is the time obtained by the conditions of the intraoral quick disintegrating tablet described later and the methods of the examples. The disintegration time in the oral cavity varies depending on the tablet size and tablet shape, and this is also included in the present invention.

The invention's effect

[0009] The tablet obtained by using the composition for rapidly disintegrating tablets in the oral cavity of the present invention has a higher active ingredient content than conventional quick disintegrating tablets, causing problems during production and transportation. It has the feature of having a good disintegration time in the oral cavity despite having a sufficient hardness. Therefore, the intraoral rapidly disintegrating tablet of the present invention obtained by blending a medicinal component with the composition is suitable for a pharmaceutical product that requires rapid or powerful disintegration in the oral cavity.

BEST MODE FOR CARRYING OUT THE INVENTION

[0010] The rapidly disintegrating tablet in the oral cavity of the present invention is (a) a structure in which an inorganic substance and a disintegrant are homogeneously dispersed in a composite particle of two or more saccharides, and further contains an active ingredient. (B) Lubricant, (c) At least one or more selected from excipients, disintegration aids and Z or binders, and (d) an orally rapidly disintegrating tablet comprising an active ingredient is there.

[0011] The granulated particles used in the present invention are described below. The granulated particle used in the present invention is a granulated particle in which an inorganic substance and a disintegrant are homogeneously dispersed in a composite particle having mannitol and other saccharide power, or further containing an active ingredient. These granulated particles can be obtained by spray-drying (i) saccharides, (mouth) disintegrants, and (c) inorganic substances in water and then spray-drying, or further dispersing active ingredients and spray-drying. Specifically, the method described in International Publication 2005Z 037319 or International Publication 2005Z037254 Therefore, it is a composition for intraoral rapidly disintegrating tablets manufactured. Several types of these compositions are manufactured and sold by Fuji Chemical Industry Co., Ltd. as F-M ELT [trademark], and any type can be used.

In the present invention, the saccharide refers to sugar and sugar alcohol. The saccharide contained in the granulated particles used in the present invention is a combination of mannitol and saccharides other than mannitol. The saccharides other than mannitol are at least one or more selected from forces such as xylitol, sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, palatinit and palatinose. The weight ratio of mannitol to saccharides other than mannitol is: mannitol: saccharides other than mannitol = 98 to 67: 2-33, preferably mannitol: saccharides other than mannitol = 97 ~ 87: 3-13, more preferably man-tol: saccharides other than man-tol = 96-89: 4-11. Among these saccharides, those having an average particle size that are readily soluble in water can be used.

[0013] As the inorganic substance contained in the granulated particles of the present invention, a pharmaceutically acceptable inorganic acid containing at least one of aluminum, magnesium and strength aluminum is preferred. For example, aluminate metasilicate Magnesium, Magnesium aluminate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granules, Hyde mouth talcite, aluminum silicate, calcium phosphate, calcium carbonate, calcium silicate, magnesium silicate, Magnesium oxide, magnesium hydroxide, alumina hydroxide, magnesium hydroxide, aluminum hydroxide gel, magnesium carbonate, etc. At least one selected. More preferably, magnesium aluminate metasilicate, magnesium aluminate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granule, hydrated talcite, calcium carbonate, calcium silicate and dried At least one selected from hydroxyaluminum gel strength, more preferably at least one selected from magnesium aluminate metasilicate, hydrated talcite, anhydrous calcium hydrogen phosphate and calcium carbonate. The average particle diameter of these inorganic substances is 0.1 to 100 / ζ πι, preferably 1 to 60 / ζ πι, and more preferably 1 to 40 m. In order to obtain a desired average particle size, a product pulverized by a conventional method can be used! [0014] As the disintegrant contained in the granulated particles of the present invention, at least one selected from crospovidone, croscarmellose sodium, low-substituted hydroxypropylcellulose, and crystalline cellulose strength is preferred. May be used alone, but it is more preferable to use them as a mixture. Of these, crospovidone and crystalline cellulose are more preferably used. When using crospovidone and crystalline cellulose, the weight ratio of crospovidone and crystalline cellulose is 5-15: 8-22, preferably 5-14: 10-22, more preferably 6-13: 12-21. Ah. The above disintegrant preferably has an average particle size of 0.1 to: LOO / zm, more preferably 1 to 1 in order to prevent uniform dispersibility in the composition of the present invention and roughness in the oral cavity. The thickness is 60 μm, more preferably 1 to 40 μm. In order to obtain a desired average particle size, those obtained by pulverization by a conventional method can be used.

[0015] The blending amount of each component of the granulated particle of the present invention is 40 to 90 parts by weight of saccharide, 1 to 30 parts by weight of an inorganic substance, and 5 to 40 parts by weight of a disintegrant with respect to 100 parts by weight of the entire granulated particle. Preferably, the amount is 50 to 80 parts by weight of saccharide, 2 to 15 parts by weight of an inorganic substance, and 10 to 36 parts by weight of a disintegrant with respect to 100 parts by weight of the whole granulated particles. More preferably, it is 62 to 78 parts by weight of saccharide, 3 to 8 parts by weight of an inorganic substance, and 18 to 34 parts by weight of a disintegrant with respect to 100 parts by weight of the whole granulated particles.

[0016] The granulated particles of the present invention have a structure in which a disintegrant and an inorganic substance are homogeneously dispersed in composite particles having man-tol and saccharide power other than man-tol. By making the saccharide, which is a component, into composite particles, high moldability, fast disintegration, and tablet hardness suitable for a composition for a rapidly disintegrating tablet in the oral cavity can be provided. Furthermore, by having a structure in which the disintegrant and the inorganic substance are homogeneously dispersed, a minute amount of moisture in the oral cavity can be introduced into the tablet more rapidly and more quickly. In other words, the water-conducting pores of a specific inorganic substance attract minute water into the tablet and effectively act on the disintegrant dispersed together, thereby giving good rapid disintegration in the oral cavity. Can do.

[0017] The granulated particles used in the present invention can contain an active ingredient described later and other ingredients that can be added to a pharmaceutical within a range not impairing the disintegration property described later. The amount is 0.01 to 80 parts by weight, preferably 0.05 to 70 parts by weight, more preferably 0.1 to 60 parts by weight, based on 100 parts by weight of the saccharide, inorganic substance and disintegrant. It is. As will be described in detail later, the active ingredient is not contained in the granulated particles. Good.

[0018] The granulated particles used in the present invention can be produced by a production method capable of obtaining desired physical properties. Commonly used methods such as a spray drying method, a fluidized bed granulation drying method, and a stirring granulation method are used. It can be produced by a wet granulation method such as a wet extrusion granulation method. The spray drying method is preferred from the standpoint of ease of production and easy acquisition of desired physical properties.

[0019] The spray drying method will be specifically described below. It can be produced by spray-drying an aqueous solution or dispersion containing a saccharide, an inorganic substance and a disintegrant according to a conventional method. More specifically, after a saccharide is previously dissolved or dispersed in an aqueous solvent, a dispersion obtained by uniformly dispersing a disintegrant and an inorganic substance can be produced by spray drying. In addition to the above-mentioned components, those containing an active component may optionally contain an active component, and are one of the other components that can be added to the pharmaceuticals described below as long as they do not impair disintegration. It can be produced by spray-drying a dispersion in which more than seeds are added and homogeneously dispersed.

[0020] Examples of the solvent include water, ethanol, methanol and the like as long as they are pharmaceutically acceptable solvents without affecting the characteristics of the granulated particles. The dispersion can be prepared by a known method, and examples thereof include ordinary stirring, colloid mill, high-pressure homogenizer, ultrasonic irradiation, etc., but a method capable of highly dispersing particles in an aqueous dispersion. If it is. The concentration in the dispersion is not particularly limited as long as it can be spray-dried with clay of the dispersion, that is, 5 to 50% by weight, preferably 10 to 45% by weight, more preferably 25 to 45% by weight. .

[0021] The conditions for spray drying are not particularly limited, but it is preferable to use a disk-type or nozzle-type spray dryer as the spray dryer. As the temperature at the time of spray drying, the inlet temperature is preferably about 120 to 220 ° C, and the outlet temperature is preferably about 80 to 130 ° C. The concentration of the solid matter in the aqueous dispersion during spray drying may be in a range that allows spray drying.

[0022] The average particle size of the granulated particles used in the present invention thus obtained can be appropriately adjusted depending on the concentration of the aqueous solution or dispersion, the spray drying method, the drying conditions, and the like. m, preferably 5 to 300 μm, more preferably 10 to 200 μm, even more preferred 30 to 200 μm is preferable because it can prevent roughening in the oral cavity! /.

[0023] The static specific volume of the granulated particles is preferably 1.5 to 4. Og / ml, more preferably 1.

It is 5 to 3.5 gZml, more preferably 1.5 to 2.5 gZml. Since the granulated particles have such a static specific volume, they can be easily filled into a mortar when they are formed into tablets, so that the formulation process proceeds smoothly, the tablets are uniformly compressed, and excellent punching is achieved. Can show lockability. The static specific volume can be measured according to standard methods. In addition, since the particles have good fluidity, excellent tableting properties can be shown in the formulation process.

[0024] Examples of the lubricant used in the present invention include gum arabic powder, cacao butter, carnauba roux, carmellose calcium, carmellose sodium, caropeptide, hydrous carbon dioxide, dry hydroxide-aluminum gel, Glycerin, magnesium silicate, light anhydrous carboxylic acid, light liquid paraffin, crystalline cellulose, hydrogenated oil, synthetic aluminum silicate, sesame oil, wheat starch, white beeswax, magnesium oxide, dimethylpolysiloxane, sodium tartrate, sucrose fatty acid ester , Glycerin fatty acid ester, silicone resin, aluminum hydroxide gel, stearyl alcohol, stearic acid, aluminum stearate, calcium stearate, polyoxyl stearate, magnesium stearate, cetanol, zera Chin, Talc, Magnesium carbonate, Precipitated calcium carbonate, Corn starch, Lactose, No, Dop fat, Sucrose, Potato tempo, Hydroxypropyl cellulose, Fumaric acid, Sodium stearyl fumarate, Polyethylene glycol, Polyoxyethylene Polyoxypropylene glycol , Polysorbate, beeswax, magnesium aluminate metasilicate, methyl cellulose, mole, glyceryl monostearate, sodium lauryl sulfate, calcium sulfate, magnesium sulfate, liquid paraffin, and phosphoric acid.

Preferably, stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid ester, polyethylene glycol, sodium stearyl fumarate, talc

[0025] The excipient, disintegration aid, and binder in the present invention are components that can improve the disintegration and moldability of the rapidly disintegrating tablet in the oral cavity of the present invention. , Binder However, it is not particularly limited to these applications.

The excipient in the present invention includes, for example, starch acrylate, L-aspartic acid, aminoethinolesnorephonic acid, aminoacetic acid, candy (powder), gum arabic, gum arabic powder, anoregic acid, sodium alginate, alpha-1 Modified starch, inositol, ethyl cellulose, ethylene acetate butyl copolymer, erythritol, sodium chloride, olive oil, kaolin, strength kaolin, casein, fructose, pumice grains, carmellose, carmellose sodium, hydrous diacid Yeast, dry hydroxyaluminum gel, dry sodium sulfate, dry magnesium sulfate, agar, agar powder, xylitol, citrate, sodium citrate, disodium citrate, glycerin, calcium glycephosphate, sodium dalconate, L- Dartami , Clay, clay grains, croscarmellose sodium, aluminum silicate, synthetic aluminum carbonate, hydroxypropyl starch, crystalline cellulose, magnesium aluminate, calcium silicate, magnesium silicate, light anhydrous key acid , Light liquid paraffin, coffee powder, crystalline cellulose, crystalline cellulose 'carmellose sodium, fine crystalline cell mouth, pearl millet, synthetic aluminum silicate, synthetic hydrotalcite, sesame oil, wheat flour, wheat starch, wheat germ powder , Rice (rice flour), rice starch, potassium acetate, calcium acetate, cellulose acetate phthalate, safflower oil, honey beeswax, zinc oxide, titanium oxide, magnesium oxide, j8-cyclodextrin, dihydroxyaluminum aminoacetate, 2, 6 —T-Butyl-4 Methylphenol, dimethylpolysiloxane, tartaric acid, potassium hydrogen tartrate, calcined gypsum, sucrose fatty acid ester, hydroxyalumina magnesium, hydroxyaluminum gel, hydroxyaluminum sodium bicarbonate Precipitate, magnesium hydroxide, squalane, stearyl alcohol, stearic acid, calcium stearate, polyoxyl stearate, magnesium stearate, purified gelatin, purified saccharose, purified white sugar, purified white sugar spherical granules, purified montan wax Zein, sesquioleate sorbitan, cetanol, gypsum, cetostearyl alcohol, shellac, gelatin, sorbitan fatty acid ester, D-sorbitol, tricalcium phosphate, soybean oil, soybean oil unsaponifiable matter, soybean lecithin, defatted Milk, talc, carbonate ammonium - © beam, calcium carbonate, magnesium carbonate, sodium neutral anhydrous sulfate, low-substituted hydroxypropyl cell row , Dextran, dextrin, natural aluminum silicate, corn syrup, corn starch, trehalose, tragacanth, silicon dioxide, calcium lactate, lactose, hyde mouth talcite, maltose, white shellac, white petrolatum, white, kuddo, white sugar, white sugar Starch spherical granules, green leaf extract, green leaf green juice powder, honey, palatin, palatinose, paraffin, potato starch, semi-digested starch, human serum albumin, hydroxypropyl starch, hydroxypropylcellulose, phytic acid , Glucose, glucose hydrate, partially alpha starch, pullulan, propylene glycol, powdered maltose starch, powdered cellulose, pectin, bentonite, sodium polyacrylate, polyester Polyethylene glycol, polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene 'polyoxypropylene' glycol, sodium polystyrene sulfonate, polysorbate, polyvinylacetal jetylaminoacetate, polybutyropyrrolidone, maltitol, Maltose, D-manntol, starch, isopropyl myristate, anhydrous lactose, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate calcium granulated product, magnesium aluminate metasilicate, methylcellulose, cottonseed powder, cottonseed Oil, molasses, aluminum monostearate, glyceryl monostearate, sorbitan monostearate, anhydrous caustic acid, medicinal charcoal, peanut oil, aluminum sulfate, calcium sulfate, granular limestone, granular corn One or more of starch, liquid paraffin, dl-malic acid, calcium monohydrogen phosphate, calcium hydrogen phosphate, potassium hydrogen phosphate, sodium hydrogen phosphate, and any of these may be used alone Two or more types can be blended.

Preferably, crystalline cellulose, powdered cellulose, croscarmellose sodium, magnesium aluminate metasilicate, magnesium aluminate silicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate granule, hyde mouth tar Sight, bentonite, aluminum silicate, calcium phosphate, calcium carbonate, calcium silicate, magnesium silicate, magnesium oxide, magnesium hydroxide, magnesium hydroxide magnesium, dried hydroxyaluminum gel, magnesium carbonate, wheat starch, rice Open rice (rice starch), corn starch (corn starch), potato starch ゝ Partial alpha-unified starch, hydroxypropyl starch, man-toll, xylitol And sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, palatinit, palatinose, agar, shellac and tragacanth. More preferably, crystalline cellulose, croscarmellose sodium, magnesium metasilicate aluminate, magnesium aluminate, calcium hydrogen phosphate, anhydrous hydrogen phosphate power, anhydrous calcium hydrogen phosphate granules, calcium silicate, These are aluminum silicate, anhydrous hydrate, and hydrated talcite.

Examples of the disintegration aid in the present invention include adipic acid, alginic acid, sodium alginate, alpha-monoized starch, erythritol, fructose, carboxymethyl starch sodium, carmellose, carmellose calcium, carmellose sodium, hydrous silicon dioxide, Kantene, Xylitol, Guar gum, Calcium citrate, Croscarmellose sodium, Crospovidone, Synthetic aluminum silicate, Magnesium aluminate, Low-substituted hydroxypropinolecellulose, Crystalline cellulose, Crystalline cellulose 'Power normelose sodium, Wheat starch , Rice starch, cellulose acetate phthalate, dioctyl sodium sulfosuccinate, sucrose fatty acid ester, hydroxyalumina magnesium, calcium stearate , Polyoxyl stearate, sorbitan sesquioleate, gelatin, cerac, sorbitol, sorbitan fatty acid ester, talc, sodium bicarbonate, magnesium carbonate, precipitated calcium carbonate, dextrin, sodium dehydroacetate, corn starch, tragacanth, trehalose, lactose, Maltose, sucrose, hydrated talcite, honey, palatinit, palatinose, potato starch, hydroxyethyl methylcellulose, hydroxypropyl starch, hydroxypropylcellulose, glucose, bentonite, partially alpha-monoized starch, monosodium fumarate, polyethylene dalcol, Polyoxyethylene hydrogenated castor oil, polyoxyethylene 'polyoxypropylene' glycol, polysorbate, polybiethylene 1 type of substances such as rucetal jetylaminoacetate, polybutyrrolidone, maltitol, D-manntol, anhydrous citrate, anhydrous silicate, magnesium metasilicate aluminate, methylcellulose, glyceryl monostearate, sodium lauryl sulfate Any one of these may be used alone, but two or more of them can be blended.

Preferably, low substituted hydroxypropyl cellulose, crystalline cellulose, carmellose, Croscarmellose sodium, sodium carboxymethyl starch, crospovidone, magnesium aluminate metasilicate, magnesium aluminate, synthetic aluminum carbonate, precipitated calcium carbonate, hydroxyalumina magnesium carbonate, magnesium carbonate, wheat starch , Rice starch, corn starch, potato starch, partially alpha starch, hydroxypropyl starch, mannitol, xylitol, sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, paranit, palatinose , Kanten, Shellac, Tragant.

More preferably, low-substituted hydroxypropyl cellulose, crystalline cellulose, carmellose, croscarmellose sodium, sodium carboxymethyl starch, rice starch, corn starch, crospovidone, magnesium aluminate metasilicate, magnesium alginate, Synthetic aluminum silicate.

The binder in the present invention includes, for example, ethyl acrylate 'methyl methacrylate copolymer emulsion, acetyl glycerin fatty acid ester, aminoalkyl methacrylate copolymer E, aminoalkyl methacrylate copolymer RS, aminoethyl sulfonic acid, candy ( Flour), gum arabic, gum arabic powder, sodium alginate, propylene glycol alginate, alpha starch starch, ester gum H, ethyl cellulose, ovata powder, hydrolyzed gelatin powder, sodium caseinate, fructose, caramel, carragham powder, carboxy Bull polymer, carboxymethylethyl cellulose, carboxymethyl starch sodium, carmellose, carmellose sodium, hydrous silicon dioxide, agar, ume powder, xanthan gum, beef tallow Oil, Guar gum, Glycerin, Synthetic aluminum silicate, Light anhydrous carboxylic acid, Hydroxypropylcellulose containing light anhydrous carboxylic acid, Crystalline cellulose, Hardened oil, Copolyvidone, Sesame oil, Wheat flour, Wheat starch, Rice coconut (rice flour), Rice starch, Vinegar Acid burr, cellulose acetate phthalate, white beeswax, oxidized starch, dioctyl sodium sulfosuccinate, dihydroxyaluminum aminoacetate, potassium sodium tartrate, sucrose fatty acid ester, stearyl alcohol, stearic acid, calcium stearate, stearin Acid polyoxyl, sorbitan sesquioleate, cetanol, gelatin, shellac, sorbitan fatty acid ester, D-sorbitol, soybean lecithin, carbonated lucyme, simple syrup, dextrin, Npun (soluble), corn starch, tragacanth , Paraffin, potato starch, hydroxyethyl cellulose, hydroxyethyl methylenoresellose, hydroxypropinorestarch, hydroxypropenoresenorelose, hydroxypropylmethylcellulose, hydroxypropylmethylcellulose acetate succinate, hydroxypropinoremethinolecellulose phthalate, pipette Mouth-rubbutoxide, butylphthalyl glycolate, glucose, partially alpha-monoized starch, fumaric acid, pullulan, polypropylene alcohol, pectin, sodium polyacrylate, partially neutralized polyacrylic acid, polyethylene glycol, polyoxyethylene . Polyoxypropylene. Glycol, Polysorbate, Polybulacetal Jetylaminoacetate, Polybulu alcohol ( Completely saponified product), polyvinyl alcohol (partially saponified product), polyvinyl pyrrolidone, polybutene, sodium polyphosphate, D-manntol, starch, light anhydrous caustic acid, magnesium metasilicate aluminate, etc. Any of these may be used alone, but two or more of them may be blended.

[0029] The active ingredient used in the present invention is not particularly limited, and is a central nerve agent such as a peripheral nerve agent, an antipyretic analgesic / antiinflammatory agent, a hypnotic sedative, or a neuropsychiatric agent; a skeletal muscle relaxant, an autonomic god Peripheral nerve drugs such as transdermal drugs; Cardiovascular drugs such as cardiotonic drugs, arrhythmia drugs, diuretics, vasodilators; respiratory drugs such as bronchodilators and antitussives; Digestives such as digestives, intestinal drugs, and antacids Tube drugs; metabolic drugs such as hormones, antihistamines and vitamins; anti-ulcer agents; antibiotics; chemotherapeutic agents; herbal extracts;

[0030] As the active ingredient, those processed by a known method such as coating can be used for the purpose of concealing bitterness and controlling release. Moreover, in order to release in the digestive tract, the release may be controlled by a known method. If the active ingredient is rough in the oral cavity, it can be blended in order to enhance the feeling of taking, and an average particle size of 0.1 to LOO m is preferred.

The active ingredient should be contained in either or both of the above and outside of the granulated particles. If not included in the granulated particles, (a) the granulated particles, (b) the lubricant, and ( c) What is necessary is just to mix | blend at the time of mixing with at least 1 or more types chosen from an excipient | filler, a disintegration aid, and Z or binder.

[0031] The rapidly disintegrating tablet in the oral cavity of the present invention comprises (a) granulated particles 1 to 98 with respect to 100 parts by weight of the whole tablet. Parts by weight, (b) lubricant 0.01 to 5 parts by weight, (c) at least one selected from excipients, disintegration aids and Z or binders 1 to 98 parts by weight, (d) active ingredient 0. Consists of 01-60 parts by weight. More preferably, for 100 parts by weight of the whole tablet, (a) 5 to 90 parts by weight of granulated particles, (b) 0.1 to 3 parts by weight of lubricant, (c) excipient, disintegration aid and At least one selected from Z or a binder is 5 to 90 parts by weight, and (d) the active ingredient is 0.1 to 50 parts by weight.

[0032] The intraoral rapidly disintegrating tablet of the present invention can be blended with other components that can be blended with pharmaceuticals as long as the disintegration property is not impaired. Surfactants that do not impair disintegration that can be incorporated into the rapidly disintegrating tablet of the present invention include surfactants (for example, polyoxyethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene glycol, sorbitan fatty acid ester, Polysorbate, glycerin fatty acid ester, sodium lauryl sulfate, etc.)

, Acidulants (eg, citrate, tartaric acid, malic acid, ascorbic acid), foaming agents (eg, sodium bicarbonate, sodium carbonate), sweeteners (sodium saccharin, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin), flavoring (E.g. lemon oil, orange oil, menthol, etc.), colorants (e.g. edible red No. 2, edible blue No. 2, edible yellow No. 5, edible lake dye, ferric trioxide, etc.), stabilizers (e.g. Edetate sodium, tocopherol, cyclodextrin, etc.), flavoring agents, and flavoring agents.

[0033] The rapidly disintegrating tablet in the oral cavity of the present invention is at least one or more selected from (a) granulated particles, (b) a lubricant, (c) an excipient, a disintegration aid and Z or a binder. And (d) It can be produced by mixing the active ingredient and other ingredients that can be blended with pharmaceuticals, followed by compression molding. The compression molding is preferably performed by the direct tableting method. The tableting pressure at that time depends on the size of the tablet and can be selected within the range of tableting pressure that can be formulated.

[0034] The other production methods include (a) granulated particles, (b) lubricant, (c) excipient, disintegration aid and at least one selected from Z or binder, and d) The active ingredient may be subjected to compression molding after wet granulation. Examples of wet granulation methods include spray drying, fluidized bed granulation drying, stirring granulation, and wet extrusion granulation. In addition, after compression molding, aging such as heating and humidification can be performed according to a conventional method to impart desired hardness' disintegration property.

[0035] In the production of an orally rapidly disintegrating tablet in the present invention, as described above, the lubricant may be mixed with other ingredients and then mixed with other ingredients, and then compression molded. The other It is possible to manufacture by the method of pre-coating and compression molding (external lubrication method) on the surface of the punch and the wall of the mortar without mixing with the ingredients of the mold, giving the desired hardness and disintegration can do. The method of applying the lubricant to the mortar can be performed by a conventionally known method or machine.

[0036] The intraorally rapidly disintegrating tablet of the present invention has a hardness of usually 40 to 200N, preferably 40 to 150N, more preferably 40 to 120N. In addition, since the tableting pressure varies depending on the size of the tablet, the tableting pressure can be adjusted as appropriate to achieve the above-mentioned hardness. When a 200 mg tablet is compressed using a 8 mm diameter punch, it has a hardness of 40 to 70 N when the tableting pressure is 300 to 2400 kgf.

[0037] In the present invention, it is unclear that the drug content has sufficient hardness, good disintegration property, and good moldability, but the properties (structure and shape) of the granulated particles are maintained. And the synergistic effect with the granulated particles due to the characteristics of certain excipients, disintegration aids and Z or the binder itself.

[0038] The rapidly disintegrating tablet in the oral cavity of the present invention can also be used as other solid preparations such as molding into tablets other than those intended for rapid disintegrating (for example, tabletable tablets).

Since the rapidly disintegrating tablet in the oral cavity of the present invention disintegrates immediately with a small amount of water, it can be used not only for pharmaceuticals but also for foods, health foods, specific function foods, pet foods, feeds and agricultural chemicals.

Example

[0039] In the following, the present invention will be described by way of examples. These examples do not limit the scope of the present invention.

Each tablet obtained in the examples was evaluated by the following method.

[Oral disintegration time]

The time from when 3 to 8 subjects put tablets (n = 6 each) into the oral cavity until they completely disintegrate was measured, and the average value was taken as the oral disintegration time.

[Tablet hardness]

It was measured using a load cell type tablet hardness meter [PC-30, manufactured by Seida Okada Co., Ltd.]. [Tabletting disorder] The mortar of the tableting machine and the tablet after tableting were observed to evaluate the stateking and cabbing.

[0040] [Comparative Example 1] Tableting after dry mixing

Spray-dried granulation D-Mann-Toll (Pearlitol 200 SD, Roquette) 51.2 parts by weight, Xylitol (Xylit XC, Towa Kasei Kogyo Co., Ltd.) 3.2 parts by weight, Crospovidone (Coridon CL, BASF Takeda Vitamin Co., Ltd.] 7.2 parts by weight, crystalline cellulose (Ceras PH-101, manufactured by Asahi Kasei Co., Ltd.) 13.6 parts by weight, magnesium aluminate metasilicate (Neusilin UFL2, manufactured by Fuji Chemical Industry Co., Ltd.) ] 4. Mix 8 parts by weight, add 20 parts by weight of aspirin, mix with appropriate amount of magnesium stearate in V, and then press rotary tableting machine [HT-API 8SS-II, Hata Tekko Co., Ltd.] The product produced by force was subjected to force-stamping during tableting with a tablet having a weight of 200 mg, a diameter of 8 mm, and a 9R tablet with a set hardness of 50 N, and the tablet could not be obtained.

[0041] [Reference Example 1] Production of granulated particles

Mantol (Mannit p, manufactured by Towa Kasei Kogyo Co., Ltd.) 64 parts by weight, 4 parts by weight of xylitol, 9 parts by weight of crospovidone, 17 parts by weight of crystalline cellulose, 6 parts by weight of magnesium metasilicate aluminate in water And then spray-dried at an outlet temperature of 90 ° C using a spray dryer (L-8 type, manufactured by Okawara Kako Co., Ltd.). Good fluidity! White spherical granulated particles Got.

[0042] [Comparative Example 2]

After mixing 5 parts by weight of aspirin with 95 parts by weight of the granulated particles obtained in Reference Example 1, and then mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, weight 200 mg, diameter 8mm, 9R tablets were obtained.

[0043] [Example 1]

88 parts by weight of the granulated particles obtained in Reference Example 1 5 parts by weight of aspirin, low-substituted hydroxypropylcellulose [LH-Bl, manufactured by Shin-Etsu Chemical Co., Ltd.] 1 part by weight, magnesium aluminometasilicate 1 part by weight And croscarmellose sodium (Kiccolate ND200, manufactured by Asahi Kasei) After mixing 5 parts by weight and mixing an appropriate amount of magnesium stearate, the tablet was tableted using a rotary tableting machine with a set hardness of 50N, and weighed 200mg, diameter 8mm, 9R. Tablets were obtained. [0044] [Example 2]

88 parts by weight of the granulated particles obtained in Reference Example 1 and 5 parts by weight of aspirin, 1 part by weight of polyvinylpyrrolidone (Collidon 30, manufactured by BASF Takeda Vitamin Co., Ltd.), 1 part by weight of magnesium aluminate metasilicate and 5 parts by weight of crospovidone The parts were mixed and mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets with a weight of 200 mg and a diameter of 8 mm ゝ 9R.

[0045] [Example 3]

88 parts by weight of the granulated particles obtained in Reference Example 1 5 parts by weight of aspirin, 1 part by weight of hydroxypropyl methylcellulose [TC-5R, manufactured by Shin-Etsu Chemical Co., Ltd.], 1 part by weight of magnesium aluminate metasilicate Then, 5 parts by weight of crospovidone was mixed and an appropriate amount of magnesium stearate was mixed, and then tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets having a weight of 200 mg, a diameter of 8 mm, and 9R.

[Example 4]

88 parts by weight of the granulated particles obtained in Reference Example 1 and 5 parts by weight of aspirin, 1 part by weight of hydroxypropylcellulose (HPC SL, Nippon Soda Co., Ltd.), calcium silicate (FLORITE RE, Eisai Food Chemical) (Made by Co., Ltd.) 1 part by weight and 5 parts by weight of croscarmellose sodium were mixed, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50 N, weight 200 mg, diameter 8 mm, 9R tablets were obtained.

[0047] [Comparative Example 3]

After mixing 20 parts by weight of aspirin with 80 parts by weight of the granulated particles obtained in Reference Example 1, and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, and the weight was 200 mg, diameter. 8mm, 9R tablets were obtained.

[0048] [Example 5]

60 parts by weight of the granulated particles obtained in Reference Example 1 were mixed with 20 parts by weight of aspirin and 20 parts by weight of crystalline cellulose, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0049] [Example 6]

60 parts by weight of the granulated particles obtained in Reference Example 1 and 20 parts by weight of aspirin and corn denp [Made by Nippon Corn Starch Co., Ltd.] After mixing 20 parts by weight and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets with a weight of 200mg and a diameter of 8mm ゝ 9R. It was.

[0050] [Comparative Example 4]

After mixing 60 parts by weight of the granulated particles obtained in Reference Example 1 with 40 parts by weight of aspirin and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, weight 200 mg, diameter 8mm, 9R tablets were obtained.

[0051] [Example 7]

50 parts by weight of the granulated particles obtained in Reference Example 1 are mixed with 40 parts by weight of aspirin and 10 parts by weight of crystalline cellulose, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0052] [Table 1]

[0053] Since Comparative Example 1 caused tableting trouble and was unable to obtain a tablet, it can be seen that the granulated particles used in the present invention play an important role. From Examples 1 to 7 and Comparative Examples 2 to 4, by adding at least one or more selected from excipients, disintegration aids and Z or binders in the present invention, good disintegration and good molding The higher the hardness and the higher the hardness.

[0054] [Reference Example 2] Production of granulated particles

Mantol 65 parts by weight, xylitol 4 parts by weight, crospovidone 9 parts by weight, crystal cell port 17 parts by weight and 5 parts by weight of anhydrous calcium hydrogen phosphate were uniformly dispersed in water, and then the outlet temperature was 90 ° using a spray dryer (L-8 type, manufactured by Okawara Chemical Co., Ltd.). Spray drying with C gave white spherical granulated particles with good fluidity.

[0055] [Comparative Example 5]

Mix 90 parts by weight of the granulated particles obtained in Reference Example 2 with 10 parts by weight of aspirin, mix with an appropriate amount of magnesium stearate, and then press the tablet with a set hardness of 50 N using a rotary tableting machine. 8mm, 9R tablets were obtained.

[0056] [Example 8]

70 parts by weight of the granulated particles obtained in Reference Example 2 are mixed with 10 parts by weight of aspirin and 20 parts by weight of low-substituted hydroxypropyl cellulose, mixed with an appropriate amount of magnesium stearate, and then set using a rotary tableting machine. Tableting was performed with a hardness of 50 N, and tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0057] [Example 9]

Croscarmellose sodium (Ac-D To Sol, manufactured by Asahi Kasei Co., Ltd.) 50 g and light anhydrous caeic acid (Fad Solida 101, manufactured by Freund Sangyo Co., Ltd.) 50 g were kneaded in a mortar while adding an appropriate amount of water. . This was granulated with a 22 mesh sieve, dried at 60 ° C. for 18 hours, and then granulated with a 22 mesh sieve to obtain granules A.

80 parts by weight of the granulated particles obtained in Reference Example 2 were mixed with 10 parts by weight of aspirin and 10 parts by weight of granules A, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0058] [Comparative Example 6]

After mixing 20 parts by weight of aspirin with 80 parts by weight of the granulated particles obtained in Reference Example 2 and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, and the weight was 200 mg, diameter. 8mm, 9R tablets were obtained.

[Example 10]

Mix 70 parts by weight of the granulated particles obtained in Reference Example 2 with 20 parts by weight of aspirin and 10 parts by weight of croscarmellose sodium, mix with an appropriate amount of magnesium stearate, and then set the hardness to 50 N using a rotary tableting machine. Tablet, weight 200mg, diameter 8mm, 9R tablet Got.

[0060] [Example 11]

60 parts by weight of the granulated particles obtained in Reference Example 2 are mixed with 20 parts by weight of aspirin and 20 parts by weight of carmellose (NS-300, manufactured by Gotoku Pharmaceutical) and mixed with an appropriate amount of magnesium stearate, followed by rotary tableting. Tableting was performed using a machine with a set hardness of 50 N, and tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0061] [Example 12]

60 parts by weight of the granulated particles obtained in Reference Example 2 were mixed with 20 parts by weight of aspirin and 20 parts by weight of crystalline cellulose, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0062] [Example 13]

Mix 32 parts by weight of the granulated particles obtained in Reference Example 2 with 20 parts by weight of aspirin and 48 parts by weight of crystalline cellulose, mix with an appropriate amount of magnesium stearate, and then tablet with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0063] [Example 14]

70 parts by weight of the granulated particles obtained in Reference Example 2 are mixed with 20 parts by weight of aspirin and 10 parts by weight of corndenpene, mixed with an appropriate amount of magnesium stearate, and then tableted using a rotary tableting machine with a set hardness of 50N. As a result, a tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0064] [Comparative Example 7]

After mixing 70 parts by weight of the granulated particles obtained in Reference Example 2 with 30 parts by weight of aspirin and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a set hardness of 50 N using a rotary tableting machine, weight 200 mg, diameter 8mm, 9R tablets were obtained.

[0065] [Example 15]

60 parts by weight of the granulated particles obtained in Reference Example 2 were mixed with 30 parts by weight of aspirin and 10 parts by weight of crospovidone, mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0066] [Comparative Example 8] After mixing 60 parts by weight of the granulated particles obtained in Reference Example 2 with 40 parts by weight of aspirin and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, weight 200 mg, diameter 8mm, 9R tablets were obtained.

[0067] [Example 16]

Mix 50 parts by weight of the granulated particles obtained in Reference Example 2 with 40 parts by weight of aspirin and 10 parts by weight of carmellose, mix with an appropriate amount of magnesium stearate, and then press the tablet with a set hardness of 50 N using a rotary tableting machine. As a result, a tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0068] [Example 17]

40 parts by weight of the granulated particles obtained in Reference Example 2 are mixed with 40 parts by weight of aspirin and 20 parts by weight of corndenpene, mixed with an appropriate amount of magnesium stearate, and then tableted using a rotary tableting machine with a set hardness of 50N. As a result, a tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0069] [Example 18]

After mixing 40 parts by weight of the granulated particles obtained in Reference Example 2 with 40 parts by weight of aspirin and 20 parts by weight of rice starch (Micropearl, manufactured by Shimada Chemical Co., Ltd.), an appropriate amount of magnesium stearate is mixed. Then, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine to obtain tablets having a weight of 200 mg and a diameter of 8 mm ゝ 9R.

[0070] [Example 19]

After mixing 50 parts by weight of the granulated particles obtained in Reference Example 2 with 40 parts by weight of aspirin and 10 parts by weight of crospovidone, and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a set hardness of 50 N using a rotary tableting machine. A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0071] [Table 2] Tableting pressure Tablet hardness Tableting disorder Oral disintegration test

[kgf] [N] [sec]

Comparative Example 5 440-470 50.9 None 54.7

Example 8 540-635 40.9 None 37.8

Example 9 470-507 49.4 None 21.1

Comparative Example 6 360-380 41.6 None 98.9

Example 1 0 45.1 None 36.5

Example 1 1 560-595 41.0 None 18.0

Example 1 2 336-365 49.1 None 21.2

Example 1 3 205-225 44.6 None 23.2

Example 1 4 500-540 48.1 None 26.2

Comparative Example 7 425-460 48.0

Example 1 5 698-791 44.9 None 32.6

Comparative Example 8 425-460 48.0

Example 1 6 680-470 43.6 None 21.2

Example 1 7 890-960 49.2 None 22.8

Example 1 8 490-530 57.7 None 21.2

Example 1 9 580-610 41.6 None 1 9.1

[0072] From the results of Table 2, it is possible to increase the content of the drug by adding at least one selected from excipients, disintegration aids, and Z or binder force to the granulated particles in the present invention. It can be seen that good disintegration and good moldability can be obtained with higher hardness.

[0073] [Reference Example 3] Production of granulated particles

Mantol (Mannit p, manufactured by Towa Kasei Kogyo Co., Ltd.) 65 parts by weight, xylitol 5 parts by weight, crospovidone 8 parts by weight, crystalline cellulose 15 parts by weight, magnesium metasilicate aluminate 7 parts by weight in water And then spray-dried at an outlet temperature of 80 ° C using a spray dryer (L-8 type, manufactured by Okawahara Kako Co., Ltd.). Good fluidity! White spherical granulated particles Got.

[0074] [Comparative Example 9]

After mixing 70 parts by weight of the granulated particles obtained in Reference Example 3 with 30 parts by weight of acetaminophen and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0075] [Example 20]

65 parts by weight of the granulated particles obtained in Reference Example 3 and 30 parts by weight of acetaminophen and carmello After mixing 5 parts by weight and a suitable amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[0076] [Example 21]

50 parts by weight of the granulated particles obtained in Reference Example 3 are mixed with 30 parts by weight of acetaminophen and 20 parts by weight of hydroxypropyl cellulose, mixed with an appropriate amount of magnesium stearate, and then set to a hardness of 50 N using a rotary tableting machine. As a result, tablets having a weight of 200 mg and a diameter of 8 mmmm9R were obtained.

[0077] [Example 22]

50 parts by weight of the granulated particles obtained in Reference Example 3 are mixed with 30 parts by weight of acetaminophen and 20 parts by weight of carmellose, mixed with an appropriate amount of magnesium stearate, and then set to a hardness of 50 N using a rotary tableting machine. As a result, tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0078] [Comparative Example 10]

After mixing 50 parts by weight of acetaminophen with 50 parts by weight of the granulated particles obtained in Reference Example 3 and mixing an appropriate amount of magnesium stearate, the rotary tableting machine sets the hardness to 50 N, weight 200 mg, diameter. Force to try tableting as 8mm, 9R The upper limit pressure of the tableting machine exceeded 2400k gf, and the machine stopped, so it was impossible to obtain tablets.

[0079] [Example 23]

After mixing 50 parts by weight of the granulated particles obtained in Reference Example 3 with 40 parts by weight of acetaminophen and 10 parts by weight of crospovidone, mixing an appropriate amount of sodium stearyl fumarate, and then setting the hardness with a rotary tableting machine. Tableting was performed as 50N to obtain a tablet having a weight of 200 mg, a diameter of 8 mm, and 9R.

[0080] [Example 24]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 3 with 50 parts by weight of acetaminophen and 30 parts by weight of carmellose, mixing an appropriate amount of magnesium stearate, and setting the hardness to 50 N using a rotary tableting machine. As a result, tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained. [0081] [Example 25]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 3 with 50 parts by weight of acetaminophen and 30 parts by weight of comedenpene, mixing an appropriate amount of magnesium stearate, and setting the hardness to 50 N using a rotary tableting machine. Tableting was performed to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[Example 26]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 3 with 50 parts by weight of acetaminophen and 30 parts by weight of corn starch, mixing an appropriate amount of magnesium stearate, and then setting the hardness to 50 N using a rotary tableting machine. As a result, tablets having a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0083] [Example 27]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 3 with 50 parts by weight of acetaminophen, 20 parts by weight of comedenpene and 10 parts by weight of corn starch, and then mixing an appropriate amount of magnesium stearate, rotary Tableting was performed using a tableting machine with a set hardness of 50N, and a glaze having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0084] [Example 28]

Mix 60 parts by weight of acetaminophen and 30 parts by weight of crystal cell mouth with 10 parts by weight of the granulated particles obtained in Reference Example 3, mix with an appropriate amount of magnesium stearate, and set using a rotary tableting machine. Tableting was performed with a hardness of 50 N, and tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0085] [Example 29]

After mixing 10 parts by weight of the granulated particles obtained in Reference Example 3 with 60 parts by weight of acetaminophen, 10 parts by weight of carmellose and 20 parts by weight of rice starch, and then mixing an appropriate amount of magnesium stearate, Tableting was performed using a tableting machine with a set hardness of 50 N, and tablets with a weight of 200 mg and a diameter of 8 mm ゝ 9R were obtained.

[0086] [Example 30]

Mix 10 parts by weight of the granulated particles obtained in Reference Example 3 with 60 parts by weight of acetaminophen, 25 parts by weight of crospovidone and 5 parts by weight of crystalline cellulose, and add an appropriate amount of magnesium stearate. After mixing, the tablets were tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets having a weight of 200 mg and a diameter of 8 mm ゝ 9R.

[0087] [Table 3]

[0088] From the results shown in Table 3, the content of the drug can be increased by adding at least one selected from the group consisting of excipient, disintegration aid and Z or binder force to the granulated particles in the present invention. It can be seen that good disintegration and good moldability can be obtained with higher hardness.

[0089] [Reference Example 4] Production of granulated particles

After uniformly dispersing 65 parts by weight of mantol, 5 parts by weight of xylitol, 8 parts by weight of crospovidone, 18 parts by weight of the crystal cell mouth and 4 parts by weight of anhydrous calcium hydrogen phosphate, spray dryer [L — 8 type, manufactured by Okawara Chemical Industries Co., Ltd.] was spray-dried at an outlet temperature of 80 ° C. to obtain white spherical granulated particles with good fluidity.

[0090] [Comparative Example 11]

After mixing 20 parts by weight of acetaminophen with 80 parts by weight of the granulated particles obtained in Reference Example 4, and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0091] [Example 31]

The granulated particles obtained in Reference Example 4 are mixed with 64 parts by weight of acetaminophen 20 parts by weight and a crystal cell port. After mixing 16 parts by weight of the cellulose and an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[0092] [Comparative Example 12]

After mixing 70 parts by weight of the granulated particles obtained in Reference Example 4 with 30 parts by weight of acetaminophen and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a set hardness of 50 N using a rotary tableting machine, A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0093] [Example 32]

Mix 65 parts by weight of the granulated particles obtained in Reference Example 4 with 30 parts by weight of acetaminophen and 5 parts by weight of crospovidone, mix an appropriate amount of sodium stearyl fumarate, and then set the hardness with a rotary tableting machine. Tableting was performed as 50N to obtain tablets having a weight of 200 mg, a diameter of 8 mm, and 9R.

[0094] [Example 33]

After mixing 50 parts by weight of the granulated particles obtained in Reference Example 4 with 30 parts by weight of acetaminophen and 20 parts by weight of carmellose and mixing an appropriate amount of magnesium stearate, the set hardness is set to 50 N using a rotary tableting machine. As a result, tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0095] [Comparative Example 13]

After mixing 40 parts by weight of acetaminophen with 60 parts by weight of the granulated particles obtained in Reference Example 4, and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, A tablet having a weight of 200 mg, a diameter of 8 mm, and 9R was obtained.

[0096] [Example 34]

Mix 35 parts by weight of the granulated particles obtained in Reference Example 4 with 40 parts by weight of acetaminophen and 25 parts by weight of crystal cell mouth, mix with an appropriate amount of magnesium stearate, and set with a rotary tableting machine. Tableting was performed with a hardness of 50 N, and tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0097] [Example 35]

35 parts by weight of the granulated particles obtained in Reference Example 4 and 40 parts by weight of acetaminophen 25 parts by weight of the mixture was mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50 N to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[0098] [Example 36]

Mix 35 parts by weight of the granulated particles obtained in Reference Example 4 with 40 parts by weight of acetaminophen, 20 parts by weight of comedenpene and 5 parts by weight of crystalline cellulose, mix with an appropriate amount of magnesium stearate, and then perform rotary tableting. Tableting was performed using a machine with a set hardness of 50 N, and tablets with a weight of 200 mg and a diameter of 8 mm 9 R were obtained.

[0099] [Example 37]

Mix 35 parts by weight of the granulated particles obtained in Reference Example 4 with 40 parts by weight of acetaminophen, 20 parts by weight of comedenpene and 5 parts by weight of carmellose, mix with an appropriate amount of magnesium stearate, and then use a rotary tableting machine. Was tableted with a set hardness of 50N, and tablets with a weight of 200mg and a diameter of 8mm ゝ 9R were obtained.

[0100] [Example 38]

Mix 35 parts by weight of the granulated particles obtained in Reference Example 4 with 40 parts by weight of acetaminophen and 25 parts by weight of carmellose, mix with an appropriate amount of magnesium stearate, and then set the hardness to 50 N using a rotary tableting machine. To obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R

[0101] [Comparative Example 14]

After mixing 50 parts by weight of acetaminophen with 50 parts by weight of the granulated particles obtained in Reference Example 4 and mixing an appropriate amount of magnesium stearate, the hardness is set to 50 N with a rotary tableting machine, weight 200 mg, diameter. Force to try tableting as 8mm and 9R The upper limit pressure of the tableting machine exceeded 2400kgf and the machine stopped, so it was impossible to obtain tablets.

[0102] [Example 39]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 4 with 50 parts by weight of acetoaminophene and 30 parts by weight of comedenpene, and mixing an appropriate amount of magnesium stearate, the rotary tablet press sets the hardness to 50N. Tableting was performed to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R. [0103] [Example 40]

After mixing 20 parts by weight of the granulated particles obtained in Reference Example 4 with 50 parts by weight of acetoaminophen and 30 parts by weight of carmellose, and mixing an appropriate amount of magnesium stearate, the mixture is beaten to a set hardness of 50 N using a rotary tablet machine. Tablets to obtain tablets with a weight of 200mg, a diameter of 8mm, and 9R

[Example 41]

After mixing 10 parts by weight of the granulated particles obtained in Reference Example 4 with 60 parts by weight of acetaminophen, 10 parts by weight of carmellose and 20 parts by weight of rice starch, and combining two appropriate amounts of magnesium stearate, Tableting was performed with a tableting machine with a set hardness of 50 N, and tablets with a weight of 200 mg and a straightness of 8 mm 9 R were obtained.

[0105] [Example 42]

Mix 10 parts by weight of the granulated particles obtained in Reference Example 4 with 60 parts by weight of acetaminophen and 30 parts by weight of carmellose, mix with an appropriate amount of magnesium stearate, and then press the rotary tablet to set the hardness to 50N. Tablets were obtained with a weight of 200 mg, diameter 8 mm, and 9R.

[0106] [Table 4]

Tableting pressure Tablet hardness Tableting disorder Oral disintegration test [kgf] [N] [sec] Comparative example 1 1 620-650 55.9 None 84 Example 31 480-510 52.5 None 22 Comparative example 1 2 820-900 51.1 None 167 Example 32 1 1 10-1260 50.4 None 21 Example 33 1 180-1280 44.7 None 25 Comparative example 1 3 2280-2376 43.0 Sticking to heel 298 Example 34 680-730 55.2 None 18

Example 35 600-670 55.3 None 23

Example 36 580-630 50.0 None 22

Example 37 690-730 55.1 None 24

Example 38 660-730 58.2 None 21

Comparative example 1 4 Exceeding 2400-Untabletable-Example 39 760-900 49.3 None 24

Example 40 780-870 58.0 None 18

Example 41 800-899 48.9 None 1 9

Example 42 2000-2290 66.2 None 27 [0107] From the results shown in Table 4, it is possible to increase the content of the drug by adding at least one selected from excipients, disintegration aids and Z or binder force to the granulated particles in the present invention. It can be seen that very good disintegration and good moldability can be obtained with higher hardness.

[0108] [Reference Example 5] Production of granulated particles containing drug

Manthol 64.5 parts by weight, xylitol 5 parts by weight, crospovidone 8 parts by weight, crystalline cellulose 18 parts by weight, anhydrous calcium hydrogen phosphate 4 parts by weight, oral peramide hydrochloride (Japanese Pharmacopoeia Standards for Foreign Drugs) 0.5 After homogeneously dispersing parts by weight in water, using a spray dryer (L 8 type, manufactured by Okawahara Chemical Co., Ltd.), spray-drying at an outlet temperature of 90 ° C, and white spherical granule with good fluidity Particles were obtained.

[Comparative Example 15]

The granulated particles obtained in Reference Example 5 were mixed with an appropriate amount of magnesium stearate, and then tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[0110] [Example 43]

After mixing 20 parts by weight of hydroxypropyl starch with 80 parts by weight of the granulated particles obtained in Reference Example 5 and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a set hardness of 50 N using a rotary tableting machine, and the weight is 200 mg. A tablet with a diameter of 8 mm and 9R was obtained.

[0111] [Example 44]

After mixing 93 parts by weight of the granulated particles obtained in Reference Example 5 with 1 part by weight of hydroxypropyl cellulose, 1 part by weight of magnesium aluminate metasilicate and 5 parts by weight of crospovidone, and mixing an appropriate amount of magnesium stearate, Tableting was performed using a rotary tableting machine with a set hardness of 50 N, and tablets with a weight of 200 mg, a diameter of 8 mm, and 9R were obtained.

[0112] [Example 45]

Crospovidone 5 g, trehalose [manufactured by Asahi Kasei Co., Ltd.] 10 g and the granulated particles 85 g obtained in Reference Example 5 were kneaded in a mortar with ethanol (99.5%) in an appropriate amount. This was granulated with a 22 mesh sieve, dried at 60 ° C. for 18 hours, and then granulated with a 22 mesh sieve to obtain granules B. After mixing an appropriate amount of magnesium stearate with granule B, the tablet was tableted with a setting hardness of 50 N using a rotary tableting machine to obtain tablets of weight 200 mg, diameter 8 mm, 9R.

[0113] [Example 46]

Crospovidone (50 g) and maltitol (manufactured by Towa Kasei Kogyo Co., Ltd.) (10 g) were kneaded in a mortar while preparing an appropriate amount of ethanol (99.5%). This was granulated with a 22 mesh sieve, dried at 60 ° C. for 18 hours, and then granulated with a 22 mesh sieve to obtain granules C.

After mixing 88 parts by weight of the granulated particles obtained in Reference Example 5 with 12 parts by weight of granules C and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, weight 200 mg, diameter 8mm, 9R tablets were obtained.

[0114] [Example 47]

10 g of crospovidone and 90 g of the granulated particles obtained in Reference Example 5 were kneaded in a mortar while adding an appropriate amount of ethanol (99.5%). This was granulated with a 22-mesh sieve, dried at 60 ° C for 18 hours, and then sized with a 22-mesh sieve to obtain granules D.

After an appropriate amount of magnesium stearate was mixed with granule D, it was tableted with a rotary tableting machine with a set hardness of 50N to obtain tablets with a weight of 200 mg, a diameter of 8 mm, and 9R.

[0115] [Example 48]

50 g of crospovidone, 50 g of maltitol, and 10 g of magnesium aluminate metasilicate were kneaded in a mortar while adding an appropriate amount of ethanol (99.5%). This was granulated with a 22 mesh sieve, dried at 60 ° C for 18 hours, and then sized with a 22 mesh sieve to obtain granules E.

After mixing 1 part by weight of granule El with 89 parts by weight of the granulated particles obtained in Reference Example 5 and mixing an appropriate amount of magnesium stearate, the tablet was tableted with a set hardness of 50 N using a rotary tableting machine, and the weight was 200 mg. Tablets with a diameter of 8 mm and 9R were obtained.

[0116] [Example 49]

Crospovidone (5 g), maltitol (20 g), magnesium metasilicate aluminate (5 g) and hydroxypropyl starch (70 g) were mixed with an appropriate amount of ethanol (99.5%) in a mortar. This was granulated with a 22 mesh sieve, dried at 60 ° C for 18 hours, and then granulated with a 22 mesh sieve to obtain granules F.

Mix 90 parts by weight of the granulated particles obtained in Reference Example 5 with 10 parts by weight of granule F, After mixing the magnesium acid, the tablet was tableted with a set hardness of 50N using a rotary tableting machine to obtain tablets with a weight of 200mg, a diameter of 8mm and 9R.

[0117] [Table 5]

[0118] From the results of Table 5, it is preferable to add at least one selected from the group consisting of excipient, disintegration aid and Z or binder force to the granulated particles of the present invention, while achieving higher hardness. It can be seen that disintegration is obtained.

[0119] [Reference Example 6] Production of granulated particles

Mantol (Mannit p, manufactured by Towa Kasei Kogyo Co., Ltd.) 63 parts by weight, 6 parts by weight of xylitol, 7 parts by weight of crospovidone, 19 parts by weight of crystalline cellulose, 5 parts by weight of magnesium metasilicate aluminate in water And then spray-dried at an outlet temperature of 90 ° C using a spray dryer (L-8 type, manufactured by Okawara Kako Co., Ltd.). Good fluidity! White spherical granulated particles Got.

[0120] [Comparative Example 16]

After mixing 70 parts by weight of the granulated particles obtained in Reference Example 6 with 30 parts by weight of ascorbic acid and mixing an appropriate amount of magnesium stearate, the tablet is tableted with a set hardness of 50 N using a rotary tableting machine, and the weight is 200 mg. A tablet with a diameter of 8 mm and 9R was obtained.

[0121] [Example 50]

40 parts by weight of the granulated particles obtained in Reference Example 6 were mixed with 30 parts by weight of ascorbic acid and 30 parts by weight of rice starch, mixed with an appropriate amount of magnesium stearate, and then tableted using a rotary tableting machine with a set hardness of 50N. And obtained tablets with a weight of 200 mg, a diameter of 8 mm and 9R [0122] [Example 51]

After mixing 40 parts by weight of the granulated particles obtained in Reference Example 6 with 30 parts by weight of ascorbic acid, 20 parts by weight of rice starch and 10 parts by weight of corn starch, and mixing an appropriate amount of magnesium stearate, a rotary tableting machine is used. Was tableted with a set hardness of 50 N, and tablets with a weight of 200 mg and a diameter of 8 mm 9 R were obtained.

[0123] [Example 52]

After mixing 40 parts by weight of the granulated particles obtained in Reference Example 6 with 30 parts by weight of ascorbic acid, 20 parts by weight of rice starch and 10 parts by weight of crystalline cellulose, and mixing an appropriate amount of magnesium stearate, a rotary tableting machine is used. Tableting was performed with a set hardness of 50 N, and tablets with a weight of 200 mg and a diameter of 8 mm ゝ 9R were obtained.

[0124] [Example 53]

Mix 40 parts by weight of the granulated particles obtained in Reference Example 6 with 30 parts by weight of ascorbic acid and 30 parts by weight of crystal back cell mouth, mix an appropriate amount of magnesium stearate, and then set the hardness using a rotary tableting machine. Tableting was performed as 50N to obtain tablets having a weight of 200 mg, a diameter of 8 mm, and 9R.

[0125] [Table 6]

[0126] From the results shown in Table 6, it is preferable to add at least one selected from the group consisting of an excipient, a disintegration aid, and Z or a binder force to the granulated particles of the present invention, while attaining a higher hardness. It can be seen that disintegration is obtained.

[0127] [Reference Example 7] Production of granulated particles

After uniformly dispersing 65 parts by weight of Mantol, 5 parts by weight of lactose, 8 parts by weight of crospovidone, 18 parts by weight of crystalline cellulose, and 4 parts by weight of calcium hydrogen phosphate, the spray dryer [L-8 type, Okawara Kako Co., Ltd.) and spray dried at an outlet temperature of 90 ° C. Good white spherical particles were obtained.

[0128] [Comparative Example 17]

After mixing 80 parts by weight of the granulated particles obtained in Reference Example 7, 20 parts by weight of aspirin and an appropriate amount of magnesium stearate, a tableting machine (compact high-speed rotary tableting machine VIRGO, Kikusui Manufacturing Co., Ltd.) To obtain a tablet with a tablet weight of 200 mg, a diameter of 8 mm and a flat corner.

[Example 54]

20 parts by weight of aspirin is mixed with 80 parts by weight of the granulated particles obtained in Reference Example 7, and an appropriate amount of magnesium stearate is applied to the surface of the punch and the wall of the die before filling the granules into the die of the tablet machine. Tablet with external lubrication device (compact high-speed rotary tableting machine VIRGO, manufactured by Kikusui Seisakusho Co., Ltd.), tablet weight 200mg, diameter 8mm, flat corner angle tablet Manufactured.

[0130] [Table 7]

[0131] From the results in Table 7, oral disintegrating tablets that were tableted by the external lubrication method obtained good moldability and disintegration, and were rapidly mixed with the lubricant and tableted in advance. It can be seen that the disintegration time is shorter than tablets, and the disintegration is superior.

Industrial applicability

[0132] It can be provided as a tablet having sufficient hardness and good disintegration property in the oral cavity.

There are no problems that occur when the content of the active ingredient is high. In addition, there are no problems in manufacturing and transportation, and there are no problems! /, Sufficient hardness and high degree, and good moldability. It is possible to provide a method for producing an intraoral rapidly disintegrating tablet having a disintegrating property in the oral cavity and an intraoral rapidly disintegrating tablet obtained by compression molding using an ordinary preparation facility.

Claims

The scope of the claims

[1] (a) (i) Granulated particles in which (mouth) inorganic substance and (c) disintegrant are uniformly dispersed in composite particles of two or more saccharides, (b) lubricant, ( c) An orally rapidly disintegrating tablet comprising at least one selected from excipients, disintegration aids and Z or binders, and (d) an active ingredient.

[2] The intraorally rapidly disintegrating tablet according to claim 1, wherein the saccharide of the granulated particles is a composite particle having at least one kind selected from mannitol and the following group force;

Xylitol, sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, palatinit and palatinose.

[3] Inorganic strength of granulated particles Magnesium aluminate metasilicate, magnesium aluminate silicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate Aluminum Calcium Phosphate, Calcium Phosphate, Calcium Carbonate, Calcium Kaate, Magnesium Oxide, Magnesium Oxide, Magnesium Hydroxide, Hydroxy-Alumina Magnesium, Dry Hydroxy-Aluminum Gel, Magnesium Carbonate The orally rapidly disintegrating tablet according to claim 1 or 2.

[4] The intraoral fast disintegrating property according to claims 1 to 3, wherein the disintegrant of the granulated particles is at least one selected from crospovidone, low-substituted hydroxypropylcellulose, crystalline cellulose and croscarmellose sodium strength. tablet.

[5] Each component force of the granulated particles according to claims 1 to 4 (i) 40 to 90 parts by weight of sugar, (mouth) 1 to 30 parts by weight of an inorganic substance, (c) 5 to 40 parts by weight of a disintegrant, The total amount of ingredients (ii) to (iii) consists of 100 parts by weight, and the saccharide of (ii) is a granulated particle with a ratio of saccharides other than mantol: mannitol = 98 to 67: 2 to 33 The intraorally rapidly disintegrating tablet according to claim 1, comprising:

[6] Each component force of the granulated particles of claims 1 to 4 (i) 50 to 80 parts by weight of sugar, (mouth) 2 to 15 parts by weight of an inorganic substance, and (c) 10 to 36 parts by weight of a disintegrant. The total amount of ingredients (i) to (c) is 100 parts by weight, and the saccharide of (i) is a granulated particle with a ratio of saccharides other than mantol: saccharides other than mantol = 97 to 87: 3 to 13 The intraorally rapidly disintegrating tablet according to claim 1, comprising:

[7] The components of the granulated particles according to claims 1 to 4 are (i) 62 to 78 parts by weight of sugar, (mouth) 3 to 8 parts by weight of an inorganic substance, and (c) 18 to 34 parts by weight of a disintegrant. The total amount of components (i) to (c) is 100 parts by weight, and the saccharide of (i) is a saccharide other than man-tol: mann-tol = 96-89: 4-11 The intraorally rapidly disintegrating tablet according to claim 1, comprising granulated particles having a resultant force.

[8] The granulated particles according to claims 1 to 7, wherein the granulated particles are obtained by suspending (i) two or more saccharides, (mouth) inorganic substances, and (c) disintegrants in water, followed by spray drying. The intraoral rapidly disintegrating tablet according to claim 1, which is a particle.

[9] The rapidly disintegrating tablet in an oral cavity according to claims 1 to 8, wherein the granulated particles according to claims 1 to 8 are granulated particles containing an active ingredient.

[10] The lubricant is at least one selected from stearic acid, magnesium stearate, calcium stearate, sucrose fatty acid ester, glycerin fatty acid ester, polyethylene glycol, sodium stearyl fumarate, and talc power. 9 intraoral fast disintegrating tablets.

[11] The excipient is powdered cellulose, magnesium aluminate metasilicate, magnesium aluminate silicate, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, anhydrous calcium phosphate granule, hydrated talcite, Bentonite, Aluminum silicate, Synthetic aluminum silicate 'Hydroxypropyl starch' Crystalline cellulose, Calcium phosphate, Calcium carbonate, Calcium silicate, Magnesium silicate, Magnesium oxide, Magnesium hydroxide, Hydroxy-alumina magnesium, Dry water Acid aluminum gel, magnesium carbonate, mannitol, xylitol, sorbitol, erythritol, maltitol, lactose, sucrose, glucose, fructose, maltose, trehalose, palatinit, palatinose, agar, shellac, tragacanth Et intraorally rapidly disintegrating tablet agent of claim 1 to 10 is at least one selected.

[12] Disintegration aids are crystalline cellulose, crystalline cellulose 'carmellose sodium, carmellose, croscarmellose sodium, carboxymethyl starch sodium, crospovidone, low-substituted hydroxypropylcellulose, hydrous silicon dioxide, light anhydrous key acid, wheat The orally rapidly disintegrating tablet according to claim 1, wherein the tablet is at least one selected from starch, rice starch, corn starch, potato starch, partially alpha starch, and hydroxypropyl starch.

[13] Binder selected from carmellose sodium, hydroxypropylcellulose, hydroxypropyl methylcellulose, polybulurpyrrolidone, gum arabic powder, gelatin, pullulan, etc. The orally rapidly disintegrating tablet according to claim 1, wherein the tablet is at least one or more kinds.

[14] For 100 parts by weight of the whole tablet, (a) 1 to 98 parts by weight of granulated particles, (b) 0.01 to 5 parts by weight of lubricant, (c) excipient, disintegration aid and 14. Orally rapidly disintegrating tablet according to claim 1 to 13, wherein at least one or more selected from 1 to 98 parts by weight, (d) active ingredient is also added to 0.01 to 60 parts by weight.

[15] Based on 100 parts by weight of the whole tablet, (a) 5 to 90 parts by weight of granulated particles, (b) 0.01 to 3 parts by weight of lubricant, (c) excipient, disintegration aid and The orally fast disintegrating tablet according to any one of claims 1 to 13, comprising at least one or more selected from Z or binder power of 5 to 90 parts by weight, and (d) active ingredient of 0.1 to 50 parts by weight.

[16] After mixing (a) granulated particles, (b) lubricant, (c) at least one selected from excipients, disintegration aids and Z or binders, and (d) active ingredients The method for producing an orally rapidly disintegrating tablet according to claim 1 to 15, which is compression-molded.

[17] (b) Lubricant applied in advance to the mortar surface and mortar wall of the compression molding machine, and (a) granulated particles, (c) excipient, disintegration aid and Z or binder selected. The method for producing an orally rapidly disintegrating tablet according to claim 1, wherein at least one or more selected from the above and (d) active ingredients are mixed and filled and compression molded.