TW201113051A - Oral disintegrating tablet and manufacturing method thereof - Google Patents

Abstract

The present invention provides an oral disintegrating tablet having excellent formability for being disintegrating tablet and excellent disintegrating property, and its manufacturing method. The oral disintegrating tablet of this invention contains pharmaceutical granulation particles, characterized in that the pharmaceutical granulation particles are formed by adding glycose-containing aqueous solution to the drug-containing powder, following by a wet granulation process granulation.

Description

[Technical Field] The present invention relates to an orally disintegrating ingot which is excellent in formability and disintegration property as an orally disintegrating ingot, and a method for producing the same. [Prior Art] A method for producing an intra-oral collapsed ingot is a method in which a suspension is introduced into a mold and dried under reduced pressure or freeze-dried as a method using a special manufacturing apparatus (refer to Patent Documents 1 and 2). A method in which the particles are wetted and dried by tableting (refer to Patent Documents 3 and 4), and a method in which an in-oral collapsed ingot is obtained by performing an injection step of temperature management after dry-type tableting (refer to Patent Document 5' 6) Wait. However, when a special manufacturing apparatus is used, it is possible to have both tablet physical properties and disintegration properties, but a large amount of excipients are required, and investment equipment is required. As for the method of forming a tablet, a method of producing an orally disintegrating ingot by a general dry tableting method is known (methods 7 to 10), and sugar is used. In the method of the sugar alcohol, it is known that a saccharide having high formability is used as an excipient having moldability and disintegration property for granulating a saccharide having low formability (see Patent Document 1 1). A method of producing an excipient using a lubricant which is highly soluble in water by a binding force of citric acid to avoid a lubricant/adhesion preventive agent for tableting (see Patent Document 12). However, these methods require a disintegrating agent or the like due to the large amount of excipients, and in the case of a tablet having a large amount of active ingredient, there is a problem that the mass of the tablet increases and the size is increased. Based on the above, it is desirable that a special device is not required, and even a small amount of excipients can be used as a technique for forming an orally disintegrating ingot which is excellent in formability and disintegration as an intraoral disintegrating tablet. [Patent Document 1] [Patent Document 1] International Publication No. 93/12.769 [Patent Document 2] Japanese Patent Publication No. Sho 62-50445 (Patent Document 3) Japanese Patent Publication No. Hei 8-19589 [Patent Document 5] Japanese Laid-Open Patent Publication No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. No. Hei. [Patent Document No. 1 pp. [Problem to be Solved by the Invention] The present invention has been made in view of the above circumstances, and an object thereof is to provide an oral cavity collapse without requiring a special device. Orally disintegrating ingots, which are excellent in the formability and disintegration of the ingots, and the method for producing the same. [Means for Solving the Problems] -6- 201113051 The inventors and the like have actively reviewed the results for the above purposes and found that By adding an aqueous solution containing a monosaccharide to a powder containing a drug and passing it through a wet type The granulated particles of the granules are formulated into an orally disintegrating ingot, and the orally disintegrating ingot which is excellent in formability and disintegration as an orally disintegrating ingot is obtained without a special device, thereby completing the present invention. . Accordingly, the present invention provides the following methods for producing an orally disintegrating ingot and an orally disintegrating ingot. [1] An intraoral disintegrating tablet which is an intraoral disintegrating tablet containing a drug granulated particle, characterized in that the drug granule is an aqueous solution containing a monosaccharide added to a powder containing a drug and wetted Granulated granulated particles. [2] The orally disintegrating ingot according to [1], wherein the monosaccharide is fructose or glucose. [3] The orally disintegrating ingot of the above-mentioned [1] or [2] wherein the content of the monosaccharide is from 1 to 30% by mass based on the granulated particles of the drug. [4] The intraoral disintegrating ingot as described in [1], [2] or [3] wherein the content of the drug is 45 to 99% by mass relative to the granulated particles of the drug » [5] such as [1]~[ 4] The intraoral collapsed ingot according to any one of the invention, wherein the content of the granulated particles of the drug is 1 〇 to 1 〇〇 mass% relative to the intragranular disintegrating ingot 〇 [6] as [1]~[5] The intraoral disintegrating tablet of any of the above, wherein the granulated particles of the drug further comprise crystalline cellulose. [7] A method for producing an orally disintegrating ingot according to [1], which comprises the steps of: spraying or dropping an aqueous solution containing a monosaccharide 201113051 in a powder containing a drug, followed by stirring and granulation, followed by drying. The step of obtaining the granulated particles of the drug, the step of ingoting the obtained drug granulated particles or a mixture of the drug granulated particles and other tablet ingredients. [Effect of the Invention] According to the present invention, it is possible to provide an orally disintegrating ingot which is excellent in both the properties (weariness) and disintegration of an orally disintegrating ingot, which does not require a special device, and a method for producing the same. [Embodiment] Hereinafter, the present invention will be described in detail. The intraoral collapsed tablet of the present invention is added to a powder containing a drug

I. A drug granulated particle obtained by adding an aqueous solution of a monosaccharide and being wet granulated [Powder containing a drug]

The drug to be formulated in the granulated particles of the drug used in the orally disintegrating tablet of the present invention is not particularly limited, and various drug powders (drugs, powders, and powders can be used as a drug). The pharmaceutical raw material for granulation such as drug particles on the particles is supported. The above drugs are listed as tannins, scutellaria extract (Scopolia extract), scutellaria extract, sorghum extract, eucalyptus powder, eucalyptus dry extract, allioxaluene, lycopene hydrochloride (be rberine chloride), bismuth nitrate, pseudoephedrine 201113051 pseudoephedrine hydrochloride, phenylephrine hydrochloride, d-maleic acid chlorpheniramine (<1-maleic acid chlorpheniramine) ), dl-chlorpheniramine maleate, 'Belladonna total alkaloid', aspirin, Acetaminophen, Ethenzamide, isopropyl anti-piles Isopropyl antipyrine, Ibuprofen, ketoprofen, naproxen, loxoprofen sodium, diphenhydramine hydrochloride, chlorpheniramine maleate Carbinoxamine Maleate, dextromethorphan hydrobromide 'anhydrocaffeine, sucralfate water and substance, synthetic water slippery , albumin tannate, cork, Gerani um thunbergii, yellow lotus, Swertia, Loperamide hydrochloride, copper chlorophyllin #5, red bud (Mallotus Japonicus), licorice, glycyrrhizic acid and its salts, pseudoephedrine sulfate, subcutaneous extract, Noscapine, dried extract of peony. These may be used alone or in combination of two or more. Among them, since the ratio of insoluble particles is high, the disintegration effect is high, so water insoluble or water-resistant such as tannins, ibuprofen, allantoin aluminum, naproxen, sucralfate water, and synthetic hydrotalcite are synthesized. The soluble one (the amount of the solvent required to dissolve 1 g or 1 m 1 is 100 mL or more, preferably 100 mL or more, more preferably 100 OOmL or more; and the 15th revised Japanese Pharmacopoeia) is preferable. The content of the drug is not particularly limited, and the drug granulated particles, that is, the drug granulated particles are preferably 45 to 99% by mass or more, and the lower limit is formulated in the oral cavity collapse 201113051. It is preferably 50% by mass or more, and more preferably 55% by mass or more. The upper limit is preferably 95% by mass or less, preferably 90% by mass or less. Further, the orally disintegrating ingot is preferably 10% by mass or more, more preferably 20% by mass or more, and most preferably 30% by mass or more from the viewpoint of blending more drugs into the orally disintegrating ingot. The upper limit is preferably 99% by mass or less, more preferably 95% by mass or less, still more preferably 90% by mass or less. In the present invention, a small amount of excipients can also be obtained.

I is an intraoral disintegration ingot which is excellent in formability and disintegration of an intraoral collapsed tablet, and can be formulated with a large amount of drug in an orally disintegrating ingot. [Aqueous Solution Containing Monosaccharide] The aqueous solution containing a monosaccharide of the present invention is a monosaccharide-containing one. By subjecting the powder containing the drug to wet granulation in an aqueous solution containing a water-soluble monosaccharide, excellent formability and disintegration property as an orally disintegrating tablet can be obtained. The monosaccharide is exemplified by glucose, fructose, galactose, and arabinose, and they may be used alone or in combination of two or more. Among them, in terms of the binding force and the degree of equilibrium of the saturated aqueous solution, glucose and fructose are preferred, and fructose is more preferable from the viewpoint of binding strength. The monosaccharide concentration is preferably from 0.01 to 75% by mass, more preferably from 1 to 55% by mass, most preferably from 4 to 40% by mass, based on the solution containing the monosaccharide, insofar as the kneaded product is not formed. The content of the monosaccharide in the granulated particles of the drug is preferably from 1 to 30% by mass, more preferably from 2 to 25% by mass, and most preferably from 3 to 10% by mass, based on the granulated particles of the drug. /. . When the content of the monosaccharide in the granulated particles of the drug is too small, the combination of the drug is insufficient, and there is a possibility that the granulation property and the disintegration property are not balanced. 2011-10-201113051, when the blending ratio is 3% by mass or more, the tablet can be further improved. Wear degree. When the content is too large, there is a tendency to cause collapse, and the tablet becomes hard and the solubility is deteriorated. The aqueous solution containing a monosaccharide may be added with other ingredients within a range not impairing the effects of the present invention. Other components include polysaccharides, sugar alcohols, water-soluble polymers, stabilizers, coloring matters, flavoring agents, and the like. The polysaccharides are exemplified by oligosaccharides, lactose, maltotriose, maltose, sucrose, and the like. The sugar alcohol is exemplified by a water-soluble polymer compound such as erythritol, xylitol, sorbitol, mannitol or the like. The viscosity of a low concentration in a 50% by mass aqueous solution or a saturated aqueous solution is l〇〇〇mPa. *s below (BL type viscometer (for example, Toki Sangyo Co., Ltd. RB80L type), 36 ° C, rotor number 2, 30 rpm), water-soluble cellulose derivative (hydroxypropyl cellulose, hydroxypropyl group A) Cellulose, hydroxymethylcellulose, etc.), polyvinyl alcohol, polyvinylpyrrolidone, and the like. The stabilizer is exemplified by ethylenediaminetetraacetic acid (EDTA) sodium or benzoic acid. The pigments are exemplified by titanium oxide, ferric oxide, and edible yellow No. 5. Flavoring agents are listed as aspartame, sucralose, acesulfame potassium, saccharin, sodium saccharin, trehalose, sweetener (Thaumatin) and other sweeteners, malic acid, Acidic agents such as tartaric acid. The content of the other components may be added within a range that does not impair the effects of the present invention, but is preferably 30% by mass or less relative to the aqueous solution containing a monosaccharide -11 - 201113051. Further, the amount of the monosaccharide is preferably 50% by mass or less, more preferably 40% by mass or less. The solvent of the aqueous monosaccharide solution may be a mixed solvent of water and a hydrophilic solvent (preferably ethanol) in addition to water alone. In this case, a range of water/hydrophilic solvent = 1/0 to 1/1 (mass ratio) is preferred. When the viscosity of the aqueous solution containing a monosaccharide is measured by a BL type viscosity meter (for example, Toki Sangyo Co., Ltd. RB80L type) (measurement condition: 36 ° C, rotor number 2 '60 rpm) is preferably 500 MPa·s or less. More preferably below 300mpa.s, and better below lOOmPa.s. [Pharmaceutical granules] The granules of the drug are obtained by adding an aqueous solution containing a monosaccharide to a powder containing a drug and granulating it by zen, but the powder containing the drug can be used without impairing the effects of the present invention. Add other particle components inside. Other particle components are listed as inorganic powder such as magnesium metasilicate aluminate, synthetic hydrotalcite, cellulose such as crystalline cellulose, ethyl cellulose, low-substituted hydroxypropyl cellulose, and derivatives thereof, corn starch, Starch such as potato starch or hydroxypropyl starch, and a derivative thereof, a sugar such as lactose or mannitol, a sugar alcohol or the like, may be used alone or in combination of two or more. Among them, a poorly soluble component in which the amount of the solvent of lg or 1 ml of the solution is 100 mL or more is preferable, and from the viewpoint of improving the manufacturability, crystalline cellulose, corn starch, and more preferably crystalline cellulose are preferable. In particular, when a small amount of crystalline cellulose is blended, it can be preferably used because it has a property of improving the degree of wear of the tablet. The crystalline cellulose is preferably one having a diameter (Φ) of 11 πιη, and a hardness of 60 N or more when the powder is ingots of -12-201113051 500 mg under a tableting pressure of lkN. Specific examples are CEOLUS KG-IOOO (IOON), CEOLUS KG-802 (78N) (made by Asahi Kasei Chemicals Co., Ltd.) or corresponding products, and more preferably CEOLUS KG- 1 000 » Other particle components can be formulated in granulated particles. The content thereof is preferably 〇3 to 35 mass%, more preferably 3 to 25 mass%, based on the granulated particles of the drug. When the content of other particle components is too small, there is a tendency that mechanical adhesion and manufacturing problems are likely to occur, and when there is too much, the collapse time becomes long. The average particle diameter of the granulated particles of the drug is preferably from 1 to ΙΟΟΟμηι, more preferably not more than 550 μm. Further, the average particle diameter is a 50% particle diameter of the mass cumulative particle size distribution, and can be measured, for example, by Robot Sifter RPS-95C (manufactured by SEISHIN Co., Ltd.). If the average particle size is too small, the grading and uniformity may be impaired, and when it is too large, the particles may be rough when taken. [Method for Producing Drug Granulating Particles] The granulated particles of the drug can be obtained by spraying or dropping an aqueous solution containing a monosaccharide while stirring and granulating the powder containing the drug, followed by drying. The apparatus is a stirring apparatus used for granulation, and for example, a high-speed stirring granulator, a rotary flow granulation apparatus, or the like can be used. Suitable manufacturing conditions are, for example, when a high speed mixer granulator LSF-2 (manufactured by Fukae Powtec Co., Ltd.) is used, the number of rotations of the agitator is 200 to 1500 rpm, preferably 500 to 2000 rpm, and a chopper is used. 500 to 4000 rpm, preferably 2000 to 3000 rpm. The spray or drip of the aqueous solution containing the monosaccharide was adjusted to a liquid speed of 20 to 50 g/min, and added while stirring. After stirring, it is dried. Drying can be carried out in a general drying method such as drying in a shed type or drying in a flowing layer, -13-201113051, but it is not limited thereto. For example, if it is a shed type dryer, it is dried at 60 to 80 ° C. The moisture content of the granulated particles is 〇~10% by mass. Then, using a suitable pulverizer or the like, a granulated object of a target particle size is obtained through a sieve or the like.

I. However, the method for producing the granulated particles of the present invention is not limited to the above, and can be produced by a method known to those skilled in the art. Further, when other particle components are blended in the granulated particles of the drug, the powder containing the drug may be mixed with other particle components, and then granulated by an aqueous solution containing a monosaccharide or added to a monosaccharide-containing material. The other components in the aqueous solution are added to the aqueous solution, and the method of granulating the powder containing the drug is added by this. [Intraoral collapse ingot]

I The intraoral collapsed tablet of the present invention is one containing the above granulated particles. So-called

I Intraoral disintegration means a tablet which can be taken in the oral cavity by chewing or using saliva to disintegrate, and which has a rapid disintegration function in the oral cavity after administration in a tablet. The content of the granulated particles of the drug in the oral cavity may be appropriately selected depending on the content of the drug or the monosaccharide, preferably from 10 to 100% by mass, more preferably from 20 to 100% by mass, even more preferably from 30 to 100%. quality%.

I The intraoral disintegrating tablet may be formulated with other excipients other than the granulated particles and the disintegrating disintegrating agent, etc., within the range which does not impair the effects of the present invention. The excipients are listed as inorganic powders such as magnesium metasilicate aluminate, synthetic hydrotalcites, crystalline cellulose, ethyl cellulose, low-substituted hydroxypropyl cellulose, and the like, corn starch, Starch and a derivative thereof such as potato starch, hydroxypropyl-14-201113051-based starch, sugars such as lactose and mannitol, and sugar alcohols may be used alone or in combination of two or more. The excipient may also be contained in the orally disintegrating ingot, and is preferably from 40 to 25% by mass, more preferably from 10 to 25% by mass, based on the orally disintegrating ingot. When the excipient exceeds 40% by mass, there is a possibility that the disintegration property is affected. Further, the content thereof contains an excipient contained in the granulated particles of the drug. By using the granulated particles of the drug of the present invention, excellent formability and disintegration as an orally disintegrating ingot can be obtained even with a small amount of excipients, and as a result, the amount of the drug in the orally disintegrated ingot can be increased. Disintegrators are listed as crospovidone, Carmellose Calcium, cross-linked residual methylcellulose sodium, low-substituted hydroxypropylcellulose, carboxymethylcellulose, carboxyl Methyl starch sodium, hydroxypropyl starch, etc. may be used alone or in combination of two or more. Among them, crospovidone is preferred. Commercially available products of crospovidone are listed, such as Kollidon CL and Kollidon CL-SF (all manufactured by BASF (Germany)). Although the disintegration agent may not be contained in the intraoral disintegration ingot, in the present invention, by disintegrating the disintegrating agent, the disintegration from the inside of the tablet can be obtained, so that the effect of rapid disintegration inside the particle by the monosaccharide can be obtained. The effect of multiplication. The content of the disintegrating agent is preferably 〇 20% by mass, more preferably 0 to 10% by mass, still more preferably 2.5 to 10% by mass, based on the orally disintegrating ingot. If the content of the disintegrator is too much, the wear will deteriorate. The orally disintegrating agent can use a commonly used additive within a range not detracting from the effects of the present invention. Listed as, for example, aspartame, acesulfame lactone, sugar -15-201113051 fine, saccharin sodium and other sweeteners, tartaric acid, malic acid, succinic acid, fumaric acid and other sour agents, mannitol, camphor, sputum A monoterpene such as borneol or limonene, which contains flavoring agents such as essential oils such as grapefruit flavor, apple flavor, peach flavor, etc., ferric oxide, yellow ferric oxide, titanium oxide, and edible yellow 5 A coloring agent such as magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid or the like. The converted wear degree of the orally disintegrating ingot can be obtained by the method shown in the item of the converted abrasion in the embodiment described later, and preferably less than 1.0% by mass, more preferably less than 5% by mass, and further Good is less than 0.2% by mass. Moreover, the disintegration time in the oral cavity is to place the tablet in the oral cavity, and the tablet is broken by the rotation of the tongue until the time when the tablet completely collapses, preferably less than 40 seconds, preferably less 30 seconds, preferably less than 20 seconds. The quality of the in-oral collapsed ingot is preferably 20 to 2000 mg/ingot. The shape of the tablet is not particularly limited, and may be a round shape, a caplet type, a donut type, an elliptical shape or the like, a laminated ingot, a nucleus ingot, or the like, and may be provided with an identification P mark and a character. And the dividing line used for segmentation. Preferably, the tablet is in the form of a tablet having a diameter of a powder which is conventionally used in the field of pharmaceutical preparations, and is tableted in such a manner as to achieve the target tablet strength. Further, the tablet strength can be measured by using a tablet breakage strength measuring device TH203 CP (manufactured by Toyama Industries Co., Ltd.). [Manufacturing Method of Intraoral Disintegrated Ingot] The intraoral disintegrating tablet can be obtained by ingoting a mixture of the obtained drug granulated particles or a mixed drug, and the particles and other tablet components. -16- 201113051 Ingots can be used in the molding of general tablets. For example, a single-shot tableting machine and a rotary tableting machine. The molding pressure at the time of tableting can be appropriately selected in accordance with the manner of the hardness of the target tablet. The hardness varies depending on the size of the tablet, and is preferably 3 kgf or more (a tablet hardness tester (manufactured by YAMATO Scientific)). [Examples] The present invention will be specifically described by the following examples and comparative examples, but the present invention is not limited by the following examples. Further, the amount in the table is the component amount in the component name, and the product name in the () is used. The aqueous solution containing the monosaccharide in the table is the amount necessary for the production, and is not contained in the tablet because it evaporates during drying. [Examples 1-22, Comparative Examples 1 and 2] [Preparation of granulated particles] First, an aqueous solution containing the monosaccharides of Tables 1 to 6 or a solution for granulation was prepared for 1 000 pieces. The component 1 〇〇〇 ingot in the column of the granulated particles other than the aqueous solution containing the monosaccharide or the solution for granulation is placed in a High Speed Mixer LFS-2 (manufactured by Fukae Powtec Co., Ltd.) to carry out premixing 1 After the minute, the number of revolutions was set to a stirrer l rpm, a knife was 2,000 rpm, and an aqueous solution containing a monosaccharide or a granulation solution was added dropwise thereto over two minutes. Subsequently, stirring was carried out for 2 minutes. The obtained granules were lapped and ventilated and dried at 80 ° C for 5 hours in a shed type dryer DN-93 (manufactured by Yamato Scientific Co., Ltd.) (Example 20 was at 60 ° C for 7 hours). Repeat the same operation and combine the obtained granules with a mesh of 1 000 Mm to obtain the drug granulation -17-201113051 particles (average particle size 150~3 00μπ〇. [Intraoral disintegration Preparation of ingots] The obtained granules of the drug and the components other than the lubricant are placed in a polyethylene bag in a ratio of 2000 parts, and the mixture is shaken by hand for about 20 times, and then a lubricant (2000 parts) is added. Further, the mixed powder was mixed 10 times using a Clean Press 12HUK (manufactured by Kikusui Seisakusho Co., Ltd.), and an ingot was obtained by an open feed type tableting machine to obtain a round ingot of φ 9.0 mm in parts of the mass shown in the table. In the case of the tableting damage strength measuring device TH-203CP (manufactured by Toyama Industrial Co., Ltd.), the tableting pressure is adjusted so that the hardness becomes 3 to 5 kgf (the number of turns of the turntable: 20 rpm, the number of the roots: 1 The obtained tablets were subjected to the following evaluations. The results are shown in the table. [Example 23] [Preparation of granulated particles] 1875 g of tannins and 1125 g of sorghum extract were mixed 3 times. Mixing granulator (Deep River Industry Co., Ltd., High Sp Eed Moxer FS · GS_ 10J type. After the introduction, stirring was started at a stirrer of 400 rpm and a cutter of 2,500 rpm. After mixing for 1 minute, a 7 mass% aqueous solution of fructose was added at a flow rate of 1 700 g/min. The stirring operation was continued for 8 minutes, and the agitated granules (temperature 401) were discharged from the granulator, and the obtained agitated granules were preliminarily heated at an inhalation temperature of 80 ° C and the temperature of the ejector was 50 ° C. Spiraflow SFC-5 (manufactured by FREUND Industries), starting the flow layer drying operation at an inhalation temperature of 80° (:, exhaust air volume of 2.51113/min, rotor rotation • 18-201113051, 200 rpm). After about 30 minutes, when the exhaust gas temperature reached 45 ° C, it was discharged from the Spiraflow SFC-5 type to obtain a granulated dried product (temperature: 55 ° C.) The granulated dried product was sieved through a mesh of a mesh of 850 μm. The particles passing through the screen are crushed by a doctor blade on the sieve to obtain granulated particles. [Mixing step] As shown in Table 7, the components are measured to have a total amount of 3,500 g. Ingredients other than magnesium humate are put into the mixer (shou Industrial (manufactured), Bohle Condenser 20L LM-20 type). After mixing for 20 minutes at 20 rpm, magnesium stearate was added and mixed for 5 minutes under conditions of 20 rpni. [Ingoting step] Using a mounting diameter of 1 1 mm (隅角平) 杵 臼 回转 回转 回转 回转 回转 ( 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊 菊Next, the mixture obtained in the aforementioned mixing step is tableted to obtain a tablet. The result of measuring the hardness of the obtained tablet was 5 kgf by the tablet damage strength measuring device TH-203 CP (manufactured by Toyama Industries Co., Ltd.). Other evaluations were carried out in the same manner as in Examples 1 to 22, and the results are shown in Table 7. [Example 24] The same procedure as in Example 23 was carried out except that in the case of the tableting step, the 直径•臼-19-201113051 having a mounting diameter of 9 mm (the angle of the flat surface) was used, and the tablet was pressed under the conditions of the pre-pressed lkN and the pressure of 5 kN. , obtaining a lozenge. The hardness of the obtained tablet was measured by a tablet breaking strength measuring device TH-203 CP (manufactured by Toyama Industries Co., Ltd.) to be 7 kgf. Other evaluations were carried out in the same manner as in the examples 1 to 22, and the results are shown in the table [ΪΙ例25] [Preparation of granulated particles] 1 500 g of tannin linolenic acid, 900 g of sorghum extract 3 times and 3 60 g of peony dried The extract was put into a stirring granulator (manufactured by Shenjiang Industrial Co., Ltd., High Speed Mixer FS.GS. 10J type). After the introduction, the mixture was stirred at 400 rpm with a stirrer at 2,500 rpm, and after mixing for 1 minute, a 7 mass% aqueous solution of fructose was added at a flow rate of 1 136 g/min. Thereafter, the stirring operation was continued for 1 minute, and the granulated product was discharged from the granulator (temperature: 40 ° C). The obtained agitated granules were preliminarily preheated at an induction temperature of 80 ° C, and put into a Spiraflow SFC-5 type (FREUND Industrial Co., Ltd.) so that the temperature of the discharger became 50 ° C, and the inhalation temperature was 80 ° C. The flow layer drying operation was started under conditions of an exhaust air volume of 2.5 m 3 /min and a rotor rotation number of 200 rpm. The drying operation was continued for about 50 minutes, and the mixture was discharged from the Spiraflow SFC-5 type at a temperature of 60 ° C to obtain a granular dried product (temperature: 72 ° C). The granulated dried product (the particles which have not passed through the sieve are pulverized by a doctor blade on the sieve) is sieved in a mesh of a mesh of 850 μm to obtain granulated particles. [Mixing step and tableting step] -20- 201113051 The obtained granulated particles were mixed in the same manner as in Example 23 to obtain a tablet. As a result of measuring the hardness of the obtained tablet by the tablet breaking strength measuring device TH-203 CP (manufactured by Fusei Co., Ltd.), other evaluations were carried out in the same manner as in the examples 1 to 22, and the results are shown in Table 7. [Converted Wear Degree] 曰 This Pharmacopoeia reference material is based on the wear test of the tablet. The preparation was placed in a simultaneous test chamber with the degree of wear test to determine the change in mass. Self-wearing degree minus mass The calculated degree of wear was evaluated on the basis of the following criteria. △ above. ◎: less than 0.2% by mass 〇: 0.2% by mass or more is less than 〇. 5 mass% Δ: 0.5% by mass or more and less than 1 · 〇% by mass X: 1. 0% by mass or less is less than 6 · 0% by mass XX : 6.0% by mass or more [Breakage time in the mouth] The adult male three-person and the female female surname were evaluated for the time when the tablet in the mouth was placed in the oral cavity while the tongue was rotated to cause the tablet to collapse and completely collapse. It was evaluated by the flat benchmark of the five people's collapse time. △ The above is the allowable range. <Standard> And ingot, won 5kgf of Shanshan Industry. Test with the experimental method and measure the rate of change, and set the allowable vanity. Will 'measure the tablet evenly, the following - 21 - 201113051 ◎: less than 20 seconds 〇: more than 20 seconds or less than 30 seconds △: more than 30 seconds or less than 40 seconds X: 40 seconds or more [Table 1 Intraoral Disintegration Ingot (Component Ingredient/Spin) EXAMPLES EXAMPLES EXAMPLES Example 1 2 3 4 5 Tannic Acid Huangliansu 100 100 100 100 100 Medicinal Paste Extract 3 times Dispersion 60 60 60 60 60 Excipients Corn Starch 40 40 40 40 40 Particles Containing Fructose 12 12 12 Monosaccharide Glucose 12 Glucose Glucose Oligosaccharide Mixture 12 Water Red Alcohol 4.8 Solvent Im Titanium Oxide 4.2 Liquid Pure Water (95) (95) (95) (95) (95) Lubricant magnesium stearate 0.9 0.9 0.9 0.9 0.9 Total (mg) 212.9 212.9 212.9 217.7 217.1 Monosaccharide content for pharmaceutical granules 5.7 5.7 5.4 5.5 5.6 (% by mass) i Aqueous solution of sugar 11.2 11.2 10.7 10.7 10.8 Drug content on granulated particles of the drug 56.6 56.6 56.6 55.4 55.5 (% by mass): sharpness in the oral cavity 56.4 56.4 56.4 55.1 55.3 The content of the granulated particles of the drug (% by mass) is broken in the oral cavity Ingot 99.6 99.6 99 .6 99.6 99.6 Breaking time in the mouth ◎ 〇〇 ◎ ◎ Measured degree of wear in the top ◎ ◎ ◎ -22- 201113051 [Table 2] Intraoral disintegrating ingot (component mass parts / lake) Example 6 Example 7 Implementation Example 8 Example 9 Medicine Tannins Huangliansu 100 100 100 100 Dongzhi Extract 3 times Dispersion 60 60 60 60 Excipient Corn Starch 40 40 40 40 Industry Monosaccharide Monosaccharide Single Candy Sugar 4 6 21 51 Subsolution Pure water (95) (95) (95) (95) Lubricant magnesium stearate 0.9 0.9 0.9 1.1 Total (mg) 204.9 206.9 221.9 252.1 Monosaccharide content on pharmaceutical granules 2.0 2.9 9.5 20.3 (% by mass) Aqueous solution of monosaccharide 4.0 5.9 18.1 34.9 Drug content on granulated particles of the drug 58.8 58.3 54.3 47.8 (% by mass) For intraoral disintegration 58.6 58.0 54.1 47.6 Pharmaceutical granulated particle content (% by mass) for intraoral disintegration ingot 99.6 99.6 99.6 99.6 Evaluation time of collapse in the mouth 〇 ◎ ◎ 磨损 Conversion degree of wear Δ 〇 ◎ ◎ -23- 201113051 [Table 3] Oral disintegrating ingot (component mass parts / rotation) Example 10 Example 11 Example 12 Drug Particle drug tannin huangliansu 100 100 100 East cockroach extract 3 times dispersion 60 60 60 Excipient 1 Corn starch 30 20 Crystalline cellulose (CEOLUS KG-1000 (钔)) 10 75 Crystalline cellulose (CEOLUS KG-802 ( Si2)) 20 aqueous solution containing monosaccharide 窜 candy sugar 6 6 12 pure water 0 〇〇) (125) (150) Lubricant magnesium stearate 0.9 0.9 1.1 Total (mg) 206.9 206.9 248.1 Monosaccharide containing halo (% by mass) For pharmaceutical granules 2.9 2.9 4.9 For aqueous solutions containing monosaccharides 5.7 4.6 7.4 Pharmaceutical bismuth (% by mass) For granulated particles of the drug 58.3 58.3 48.6 For intraoral disintegration 58.0 58.0 48.4 Pharmaceutical granulated particle content (% by mass) For the intraoral disintegration ingot 99.6 99.6 99.6 Evaluation of the collapse time in the mouth ◎ ◎ 〇 Conversion wear degree ◎ ◎ ◎ Mia 1) Asahi Kasei Chemical (stock) manufacturing: Use the diameter (♦) 11mm 杵, press the lkN 500mg powder hardness when the spindle is 100N) 眯2) Asahi Kasei Chemical Co., Ltd.: Use the diameter (Φ) 11mm, the hardness of the 500mg powder when ingot nkN is 78N) -24- 201113051 m 4] Intraoral disintegration ingot (component mass parts / ingot) Example 13 Example 14 Example 15 Example 16 Example 17 Example 18 Tannin acid huangliansu 100 100 150 100 100 150 Pharmacy scorpion extract 3 times dispersion 60 60 60 60 60 corn starch 40 40 40 10 10 5 Excipient Crystalline Cellulose (CEOLUS KG-100(Pn) 40 Industry Contains Single Fructose 5.0 10.0 12 12 12 10 Fruit Sugar Water Solution Pure Water (95) (130) (95) (90) (9〇) (90) Collapser cross-linked povidone 10 6.3 Excipient D-mannitol 40 40 70 Lubricant magnesium stearate 0.9 1.2 1.1 1.0 1.0 1.0 Total (mg) 215.9 297.5 263.1 223.0 253.0 166.0 Monosaccharide content on pharmaceutical granulation particles 2.4 4.0 4.6 6.6 6.6 6.1 (% by mass) For aqueous solutions containing monosaccharides 5.0 7.1 11.2 11.8 11.8 10.0 Drug content for granulated particles of the drug 58.5 48.0 64.9 65.9 65.9 90.9 (% by mass) For intraoral disintegration 55.6 40.3 64.6 53.8 47.4 90.4 Drug granulated particle content (% by mass) for intraoral disintegration ingots 95.0 84.0 99.6 81.6 71.9 99.4 Evaluation of collapse time in the mouth ◎ ◎ ◎ ◎ 〇 ◎ Conversion of wear 〇 ◎ ◎ ◎ ◎ ◎ ◎ (※) manufactured by Asahi Kasei Chemical Co., Ltd.: Using a diameter of (Φ) 11mm, the hardness of 100mg powder is 100N by tableting lkN -25- 201113051 [Table 5] Intra-aggregate ingot (ingredient parts by mass/ingot) Example 19 Example 20 Example 21 Example 22 Anhydrous caffeine 80 Noscapine 20 Pharmaceutical drug synthesis hydrotalcite 100 Ibuprofen 100 Allantoin aluminum 120 tablets of excipients crystalline cellulose (CEOLUSKG-1000_) 30 30 40 40 containing monosaccharide water single candy 6.4 6.4 6.4 8.0 solution pure water (65) (14〇) (65) (65) lubricant hard fat Magnesium sulphate 0.9 0.9 0.9 0.9 Total (mg) 117.3 157.3 147.3 168.9 Monosaccharide containing halo to granulated particles of the drug 5.5 4.1 4.4 4.8 (% by mass) Aqueous solution containing monosaccharide 9.0 4.4 9.0 11.0 Drug containing halo against granulated particles 72.7 80.0 71.4 75.0 (% by mass) For intraoral disintegration ingots 68.2 76.3 67.9 71.0 Pharmaceutical granules content (% by mass) for intraoral disintegration ingots 99.2 99.4 99.4 99.5 Evaluation of collapse time in the mouth ◎ ◎ ◎ ◎ Conversion Wear degree ◎ ◎ ◎ ◎ (※丨) Asahi Kasei Chemicals Co., Ltd.: Using a diameter of (Φ) 11 mm, the hardness of 100 mg of powder is 100 N by tableting lkN) -26- 201113051 [Table 6] Oral disintegrating tablets (ingredient parts by mass / ingot) Comparative Example 1 Comparative Example 2 Pharmaceutical granulated pine nut medicine Tannins huangliansu 100 100 East cockroach extract 3 times scattered 60 60 Excipient corn starch 40 40 Granulation solution red Alginol 10 HPC-L 10 Pure water (95) (95) Lubricant magnesium stearate 0.9 0.9 Total (mg) 210.9 210.9 Monosaccharide content (% by mass) For pharmaceutical granulation particles 0 0 For aqueous solutions containing monosaccharides _ • Drug content (% by mass) For drug granulation particles 57.1 57.1 For intraoral disintegration tablets 56.9 56.9 Drug granulation particle content (% by mass) For intraoral disintegration tablets 99.6 99.6 Evaluation of intraoral collapse time Δ X Conversion of wear XX 〇-27- 201113051 [Table 7] Oral Disintegrating Ingot (Component Ingredient/Spin) Example 23 Example 24 Example 25 Drug granulation ψ-L. Sub-drug tannin huangliansu 100 33.3 100 Extract 3 times scattered 60 20 60 peony dry extraction 24 Single sugar sugar solution with single sugar solution 6.3 2.1 4.8 Pure water (83.7) P7.9) (70.4) Collapsed cross-linked povidone (COLIDON CL-SF) 20 12 20 Crystalline cellulose (CEOLUS KG-IOOO^1) 45 40 45 D-mannitol 160 100 160 Corn starch 0.5 0.5 1 Flavoring agent Aspartame 7 10 6 1-Thinol 0.5 0.5 Grapefruit spice 1.5 Peach spice 0.4 Apple spice 1.0 Coloring agent Yellow ferric oxide 1.9 0.94 0 Lubricant magnesium stearate 1.6 0.9 1.7 Total (mg) 404.3 219.64 423.5 Monosaccharide wing (% by mass) granules for drug 3.8 3.8 2.5 Aqueous solution containing monosaccharide 7.0 7.0 6.4 Drug containing halo (% by mass) Drug granulation particles 72.2 72.1 76.3 For intraoral disintegration tablets 29.7 18.2 34.0 Pharmaceutical granulated particle content (% by mass) for intraoral disintegration ingots 41.1 25.2 44.6 Evaluation of collapse time in the mouth ◎ ◎ 〇 Conversion wear degree ◎ ◎ 〇 ( Milk) Asahi Kasei Chemicals Co., Ltd.: Using a diameter of (Φ) 11 mm, the hardness of 100 mg of powder is 100 N by tableting lkN. -28- 201113051 The materials used in the examples and comparative examples are as follows. &lt;Use raw materials&gt; Tannins huangliansu: ALPS pharmaceutical industry (shares) system, Japanese Pharmacopoeia suitable for Dongpu extract 3 times dispersion: ALPS pharmaceutical industry (shares) system, Dongpu extract 3 times scattered C (Dongyu Extract: corn starch = 1 : 2 mixture) Peony dry extract: Japanese powder medicine (stock), Japanese Pharmacopoeia suitable for water extract dry extract (7 times concentrated) Anhydrous caffeine: White Bird Pharmaceutical (shares) System, Japanese Pharmacopoeia suitable for Novos Cabin: White Bird Pharmaceutical (share) system, Japanese Pharmacopoeia suitable for synthetic hydrotalcite: Concord Chemical Industry Co., Ltd., VF, Japanese Pharmacopoeia suitable for ibuprofen: BASF company, Japanese Pharmacopoeia suitable Allantoin aluminum: PERMA CHEM (share) system, Japanese Pharmacopoeia suitable for fructose: Kato Chemical Co., Ltd., Japanese Pharmacopoeia Appropriate

Glucose: Sakamoto Food Chemical Co., Ltd., eclipse MEDICAL-LOSS, Japanese Pharmacopoeia Appropriate Glucose Oligosaccharide Mixture: JRS PHARMA, EMDEXR, (glucose 95% by mass, containing oligosaccharides as other ingredients) Eryditol: Cargill Celesta Group, erythritol (micronized powder), pharmaceutical additives specifications HPC-L: 曰本曹达(股), hydroxypropyl cellulose (HPC-L), 日-29- 201113051 This Pharmacopoeia Suitable for titanium oxide: FREUND industry (stock) system, Japanese Pharmacopoeia suitable for corn starch: Matsutake Chemical Industry Co., Ltd., Japanese Pharmacopoeia corn starch crystalline cellulose: CEOLUS KG- 1 000, Asahi Kasei Chemicals Co., Ltd., 曰本Pharmacopoeia Appropriate Crystalline Cellulose: CEOLUS KG-802, Asahi Kasei Chemicals Co., Ltd., Pharmacopoeia Pharmacopoeia Suitable for cross-linked povidone: BASF, Kollidon CL-SF, pharmaceuticals

I Additive Specifications Applicable

D-mannitol: Japan ROCKET Co., PEARLITOL 200SD, Japanese Pharmacopoeia Applicable Aspartame: ALPS Pharmaceutical Industry Co., Ltd., Japanese Pharmacopoeia Applicable 1-Menthol: Toyo Mint Industrial Co., Ltd., SUPER MENTOL 3003, Japanese Pharmacopoeia Appropriate product Grapefruit spice: Salt wild spice (stock), grapefruit powder SY-1512 Peach spice: Japanese Givaudan (stock), peach spice GIVO 5 5774 Apple flavor: Japanese Givaudan (stock), apple spice GIVO 5 5 772 Yellow ferric oxide: 癸巳化成(股), yellow ferric oxide, pharmaceutical additives Specifications Applicable: Magnesium citrate: Taiping Chemical Industry Co., Ltd., magnesium stearate, plant,曰This Pharmacopoeia is suitable for pure water: Otaru Pharmaceutical Co., Ltd., Japanese Pharmacopoeia Appropriate -30-

Claims (1)

201113051 VII. Patent application scope: 1. An intraoral disintegrating tablet, which is an intraoral disintegrating tablet containing drug granulated particles, characterized in that the granulated particles of the drug are added to a drug containing a monosaccharide. A drug granulated particle obtained by wet granulation in a powder. 2. In the case of an intraoral disintegration ingot of claim 1, wherein the monosaccharide is fructose or glucose. 3. The intraoral disintegrating tablet of claim 1 or 2, wherein the content of the monosaccharide is from 1 to 30% by mass based on the granulated particles of the drug. 4. The intraoral disintegrating tablet of claim 1, 2 or 3, wherein the content of the drug is 45 to 99% by mass relative to the granulated particles of the drug. The intraoral disintegration tablet according to any one of claims 1 to 4, wherein the content of the granulated particles of the drug is from 10 to 100% by mass relative to the orally disintegrating ingot. The intraoral disintegration tablet of any one of claims 1 to 5, wherein the drug granulated particles further comprise crystalline cellulose. 7. The method for producing an intraoral collapsed ingot according to the first aspect of the invention, which comprises the steps of: spraying or dropping an aqueous solution containing a monosaccharide in a powder containing a drug, stirring and granulating, and drying The step of obtaining the granulated particles of the drug, the step of ingoting the obtained drug granulated particles or a mixture of the drug granulated particles and other tablet ingredients. -31 - 201113051 IV. Designated representative map: (1) The representative representative of the case is: None. (II) Simple description of the symbol of the representative figure: None 201113051 V If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: none