TWI468189B - Oral internal disintegrating tablet and its manufacturing method - Google Patents

Description

Oral collapsed ingot and method of manufacturing same

The present invention relates to an orally disintegrating ingot which is excellent in formability and disintegration property as an intraoral collapsed ingot and a method for producing the same.

The method for producing an orally disintegrating ingot is a method in which a suspension is poured into a mold by a method using a special manufacturing apparatus and dried under reduced pressure or freeze-dried (refer to Patent Documents 1 and 2) to wet the wet granulated product. Further, the method of drying after tableting (see Patent Documents 3 and 4) and the method of performing temperature management after the dry tableting are performed to obtain an orally disintegrating ingot (see Patent Documents 5 and 6). However, when a special manufacturing apparatus is used, both the physical properties and the disintegration properties of the tablet can be obtained, 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, a method of using a saccharide having high formability as an excipient having moldability and disintegration which granulates a mold having low moldability is known (refer to Patent Document 11). A method in which a binding force of citric acid is used to avoid a lubricant for a tableting barrier, an adhesion preventing agent, and an excipient which is extremely soluble in water to produce an excipient (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 ingredients, there is a problem that the mass of the tablet increases and the size is increased. Based on the above, it is desired that a special device is not required, and even a small amount of excipients can be used as a technique for obtaining an orally disintegrating ingot which is excellent in formability and disintegration of an orally disintegrating ingot.

[Previous Technical Literature] [Patent Literature]

[Patent Document 1] International Publication No. 93/12769

[Patent Document 2] Japanese Patent Publication No. 62-50445

[Patent Document 3] Japanese Patent Publication No. 8-19589

[Patent Document 4] Japanese Patent Publication No. 8-19590

[Patent Document 5] JP-A-2001-342128

[Patent Document 6] JP-A-11-263723

[Patent Document 7] Japanese Patent Publication No. Hei 10-182436

[Patent Document 8] JP-A-2001-58944

[Patent Document 9] JP-A-2006-70046

[Patent Document 10] JP-A-2005-132788

[Patent Document 11] International Publication No. 95/20380

[Patent Document 12] Japanese Patent Publication No. 2006-501234

The present invention has been made in view of the above circumstances, and an object thereof is to provide an orally disintegrating ingot which is excellent in formability and disintegration property of an intraoral collapsed ingot without requiring a special device, and a method for producing the same.

The inventors of the present invention have actively reviewed the results for the above-mentioned purposes, and found that the granulated particles of the drug which are added to the powder containing the drug and wet granulated are formulated into an oral cavity. The ingot can be obtained as an orally disintegrating ingot which is excellent in formability and disintegration property as an orally disintegrating ingot, without requiring a special device.

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 according to [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 orally disintegrating ingot according to [1], [2] or [3], wherein the content of the drug is 45 to 99% by mass based on the granulated particles of the drug.

[5] The orally disintegrating tablet according to any one of [1] to [4] wherein the content of the granulated particles of the drug is from 10 to 100% by mass based on the amount of the intragranular disintegrated ingot.

[6] The intraoral disintegration tablet according to any one of [1] to [5] wherein the drug granulated particles further comprise crystalline cellulose.

[7] The method for producing an orally disintegrating ingot according to [1], 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 granulating the 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.

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 intraoral collapsed ingot without requiring a special device, and a method for producing the same.

The invention is described in detail below.

The orally disintegrating tablet of the present invention is a drug granulated particle obtained by adding a solution containing a monosaccharide to a powder containing a drug and wet granulating it.

[Powder containing drugs]

The drug to be formulated in the granulated particles of the drug to be 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 support). A pharmaceutical raw material for granulation such as drug particles on a particle).

The above drugs are listed as tannins, scutellaria extract (Scopolia extract), scutellaria extract, sorghum extract, eucalyptus powder, eucalyptus dry extract, allioxaline, lycopene hydrochloride (berberine chloride), bismuth subnitrate, pseudoephedrine hydrochloride, phenylephrine hydrochloride, d-maleic acid chlorpheniramine, d1-maleic acid Chlorpheniramine, Belladonna total alkaloid, aspirin, Acetaminophen, Ethenzamide, isopropyl antipyrine, Ibuprofen ), ketoprofen, naproxen, loxoprofen sodium, diphenhydramine hydrochloride, carbinoxamine maleate, hydrogen bromide Dextromethorphan hydrobromide, anhydrous caffeine, sucralfate hydrate, synthetic hydrotalcite, albumin tannate, cork, Tong's old grass Geranium thunbergii), Huanglian, Swertia, Loperamide hydrochloride, copper calcium chlorophyllin, Mallotus japonicus, licorice, glycyrrhizic acid and its salts, pseudoephedrine sulfate, belladonna extract , Noscapine, dried extracts 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 poorly water-soluble such as tannins, ibuprofen, allantoin aluminum, naproxen, sucralfate hydrate, and synthetic hydrotalcite are used. (The amount of the solvent required to dissolve 1 g or 1 ml is 100 mL or more, preferably 1000 mL or more, more preferably 10000 mL or more; and the 15th revised Japanese Pharmacopoeia).

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 obtained from the viewpoint of blending more drugs in the orally disintegrating ingot. It is preferably 50% by mass or more, preferably 55% by mass or more. The upper limit is preferably 95% by mass or less, preferably 90% by mass or less. Moreover, it 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, an orally disintegrating ingot which is excellent in formability and disintegration property as an orally disintegrating ingot can be obtained with a small amount of excipients, and a large amount of a drug can be formulated 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 intra-oral collapsed ingot 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 viscosity 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, in the range in which 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, 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 the granulation property and the disintegration property are not balanced. When the blending ratio is 3% by mass or more, the wear of the tablet can be further improved. 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 contain other components 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. Sugar alcohols are exemplified by erythritol, xylitol, sorbitol, mannitol and the like.

The water-soluble polymer compound can be used in a low concentration of a 50% by mass aqueous solution or a saturated aqueous solution, and has a viscosity of 1000 mPa·s or less (BL type viscosity meter (for example, Toki Sangyo Co., Ltd. RB80L type), 36 ° C, rotor number 2,30 rpm), a water-soluble cellulose derivative (hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, etc.), polyvinyl alcohol, polyvinylpyrrolidone or the like.

The stabilizer is exemplified by ethylenediaminetetraacetic acid (EDTA) sodium, benzoic acid, and the like.

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 based on the aqueous solution containing a monosaccharide. 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 viscometer (for example, Toki Sangyo Co., Ltd. RB80L type) (measurement conditions: 36 ° C, rotor number 2, 60 rpm) is preferably 500 mPa ‧ or less. It is preferably less than 300 mPa‧s, and more preferably less than 100 mPa‧s.

[Pharmaceutical Granulation Particles]

The drug granulated particles are obtained by adding an aqueous solution containing a monosaccharide to a powder containing a drug and wet granulating, but the powder containing the drug can be added with other particle components within a range not impairing the effects of the present invention. 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 and derivatives thereof such as potato starch and hydroxypropyl starch, sugars such as lactose and mannitol, sugar alcohols, and 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 required to dissolve 1 g or 1 ml 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 of ( Φ ) of 11 mm and a hardness of 60 N or more when the powder of 500 mg of the ingot is tableted at a pressure of 1 kN. Specific examples are CEOLUS KG-1000 (100N), CEOLUS KG-802 (78N) (manufactured by Asahi Kasei Chemicals Co., Ltd.) or a counterpart, and more preferably CEOLUS KG-1000.

Other particle components may be blended in the granulated particles, and the content thereof is preferably from 0 to 35% by mass, more preferably from 3 to 25% by 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 a manufacturing property are likely to occur, and when the amount is too large, the collapse time may become long.

The average particle diameter of the granulated particles of the drug is preferably from 1 to 1,000 μm, more preferably not more than 500 μm. Further, the average particle diameter is 50% of the 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 of Manufacturing Pharmaceutical Granules]

The drug granulated particles can be obtained by spraying or dropping an aqueous solution containing a monosaccharide while stirring in a powder containing a drug, followed by stirring and granulation. 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 using a high speed mixer granulator, High Speed mixer LFS-2 (manufactured by Fukae Powtec), the number of rotations of the agitator is 200 to 1500 rpm, preferably 500 to 2000 rpm, and a chopper is used. 500~4000rpm, preferably 2000~3000rpm. The spray or drip of the aqueous solution containing the monosaccharide is adjusted to a liquid speed of 20 to 50 g/min, and added while stirring. After stirring, it is dried. Drying may be carried out in a general drying method such as drying in a shed type or drying in a flowing layer, but is not limited thereto. For example, in the case of a shed type dryer, it is dried at 60 to 80 ° C to water the granulated particles of the drug. The content of the portion is 0 to 10% by mass. Subsequently, a granulated product of a target particle size is obtained through a sieve or the like using a suitable pulverizer or the like. However, the method for producing the granulated particles of the present invention is not limited to these, 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]

The intraoral collapsed tablet of the present invention is one containing the above granulated particles. The term "intraoral collapse" means a tablet which can be taken by chewing or using saliva to collapse in the oral cavity, 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%.

The orally disintegrating tablet can be formulated with other excipients such as an excipient other than the granulated particles and a disintegrating disintegrating agent in a range that does not impair the effects of the present invention.

The excipients 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 and a derivative thereof such as potato starch and hydroxypropyl 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 in-oral collapsed ingot, and is preferably from 0 to 40% by mass, more preferably from 10 to 25% by mass, based on the in-orbital collapsed ingot. When the excipient exceeds 40% by mass, the disintegration property may be 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 with a small amount of excipients, and as a result, the amount of the drug in the orally disintegrated ingot can be increased.

The disintegrating agents are listed as crospovidone, carmelellose Calcium, croscarmellose 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. A commercially available product can be used for crospovidone, and it is exemplified by Kollidon CL, Kollidon CL-SF (all manufactured by BASF (Germany)), and the like.

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 from 0 to 20% by mass, more preferably from 0 to 10% by mass, even more preferably from 2.5 to 10% by mass, based on the orally disintegrating ingot. If the content of the disintegrating agent 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 sweeteners such as aspartame, potassium acesulfame, saccharin, sodium saccharin, acid agents such as tartaric acid, malic acid, succinic acid, fumaric acid, mannitol, camphor, borneol, a monoterpene such as limonene, which contains a flavoring agent such as an essential oil (such as grapefruit flavor, apple flavor, peach flavor, etc.), ferric oxide, yellow ferric oxide, titanium oxide, and edible yellow No. 5, and the like. Lubricating agents such as magnesium stearate, sucrose fatty acid esters, polyethylene glycol, talc, and stearic acid.

The converted wear degree of the intra-oral collapsed ingot can be obtained by the method shown in the item of the converted wear degree in the following-described embodiment, and preferably less than 1.0% by mass, more preferably less than 0.5% by mass, and even better. Up to 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 20~2000mg/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 a label or a text for identification. 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 a tablet breakage strength measuring device TH203CP (manufactured by Toyama Industries Co., Ltd.).

[Method of manufacturing oral cavity collapsed ingot]

The intraoral disintegration tablet can be obtained by ingoting a mixture of the obtained drug granulated particles or mixed drug granulated particles with other tablet ingredients. The tablet can be used in the molding of a conventional tablet. 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 invention is specifically illustrated by the following examples and comparative examples, but the invention is not limited by the following examples. Further, the amount in the table is the amount of the component in the component name, and the product name in the () is used. The pure water in the aqueous solution containing the monosaccharide in the table is an amount necessary for the production, and is not contained in the tablet due to evaporation upon drying.

[Examples 1 to 22, Comparative Examples 1, 2] [Modulation of granulated particles]

First, an aqueous solution containing the monosaccharides of Tables 1 to 6 or 1000 parts of a granulation solution was prepared. 1000 parts of the ingredients in the column of the granulated particles of the drug containing the monosaccharide or the solution for granulation were placed in a High Speed Mixer LFS-2 (manufactured by Fukae Powtec Co., Ltd.), and premixed for 1 minute. The number of revolutions was set to 1000 rpm in a stirrer, and the cutter was 2000 rpm, and the aqueous solution containing the monosaccharide or the 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). The same operation was repeated and the obtained granules were combined and sieved through a mesh of 1000 μm to obtain drug granulated particles (average particle diameter of 150 to 300 μm).

[Modulation of intraoral disintegration ingots]

The obtained granules of the drug and the components other than the lubricant were placed in a polyethylene bag at a ratio of 2000 parts, and the mixture was shaken by hand for about 20 times, and then a lubricant (2000 parts) was added and further mixed. Times. This mixed powder was opened in an open feed type tableting machine using Clean Press 12HUK (manufactured by Kikusui Seisakusho Co., Ltd.) to obtain a round ingot (tablet) of Φ 9.0 mm in parts by mass in the total amount shown in the table. In addition, the tableting pressure was adjusted so that the hardness was 3 to 5 kgf (the number of rotations of the turntable: 20 rpm, the number of the roots: 12) was measured by the tablet breaking strength measuring device TH-203CP (manufactured by Toyama Industries Co., Ltd.). The obtained tablet was subjected to the following evaluation. The results are combined and listed in the table.

[Example 23] [Modulation of granulated particles]

1875 g of linalic acid linolenic acid and 1125 g of sorghum extract were placed in a stirring granulator (manufactured by Shenjiang Industrial Co., Ltd., High Speed Moxer FS GS. 10J type). After the introduction, stirring was started at a stirrer of 400 rpm and a cutter at 2,500 rpm, and after mixing for 1 minute, a 7 mass% aqueous solution of fructose was added at a flow rate of 1,700 g/min. Subsequently, the stirring operation was continued for 8 minutes, and the agitated granules (temperature 40 ° C) were discharged from the granulator. The obtained agitated granules were preheated at an induction temperature of 80 ° C, and put into a Spiraflow SFC-5 type (FREUND Industries, Ltd.) in such a manner that the temperature of the discharger became 50 ° C, and the exhaust gas was exhausted at an intake temperature of 80 ° C. The flow layer drying operation was started under conditions of an air volume of 2.5 m ³ /min and a rotor rotation number of 200 rpm. The drying operation was continued for about 30 minutes, and when the exhaust gas temperature became 45 ° C, it was discharged from the Spiraflow SFC-5 type to obtain a granular dried product (temperature: 55 ° C). The granulated dried product was sieved in a full amount using a mesh of 850 μm (particles not passing through the sieve were crushed with a doctor blade on the sieve) to obtain granulated particles.

[mixing step]

As shown in Table 7, the components were measured to have a total amount of 3,500 g. In these, components other than magnesium stearate were put into a mixer (manufactured by Shou Industrial Co., Ltd., Bohle Condenser 20L LM-20 type). After mixing for 20 minutes at 20 rpm, magnesium stearate was added, followed by mixing at 20 rpm for 5 minutes.

[Ingoting step]

Use a rotary type ingot machine with a diameter of 11mm (隅角平), manufactured by Kikusui Co., Ltd. (LIBRA2), turn on the turntable at 20rpm, open feed type ingot machine, preload 1kN, this pressure The mixture obtained in the aforementioned mixing step was tableted under the conditions of 7 kN to obtain a tablet. The hardness of the obtained tablet was measured by a tablet breaking strength measuring device TH-203CP (manufactured by Toyama Industries Co., Ltd.) to be 5 kgf. Other evaluations were carried out in the same manner as in Examples 1 to 22. The results are shown in Table 7.

[Example 24]

In the same manner as in Example 23, a tablet was obtained in the same manner as in Example 23, except that in the tableting step, a mounting diameter of 9 mm (angular angle) was used, and the tablet was placed under the conditions of a pre-pressing pressure of 1 kN and a pressure of 5 kN. The hardness of the obtained tablet was measured by a tablet breaking strength measuring device TH-203CP (manufactured by Toyama Industries Co., Ltd.) to be 7 kgf. Other evaluations were carried out in the same manner as in Examples 1 to 22. The results are shown in Table 7.

[Example 25] [Modulation of granulated particles]

1500 g of linalic acid linoleum, 900 g of sorghum extract 3 times and 360 g of peony dried extract were 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 1136 g/min. Subsequently, the stirring operation was continued for 10 minutes, and the agitated granules (temperature: 40 ° C) were discharged from the granulator. The obtained agitated granules were preheated at an induction temperature of 80 ° C, and put into a Spiraflow SFC-5 type (FREUND industry manufacturing) in such a manner that the temperature of the discharger became 50 ° C, and the exhaust air volume was 80 ° C at an suction temperature. The flow layer drying operation was started under conditions of 2.5 m ³ /min and a rotor rotation number of 200 rpm. The drying operation was continued for about 50 minutes, and when the exhaust gas temperature was 60 ° C, it was discharged from the Spiraflow SFC-5 type to obtain a granular dried product (temperature: 72 ° C). The granulated dried product was sieved in a full amount using a mesh of 850 μm (particles not passing through the sieve were crushed with a doctor blade on the sieve) to obtain granulated particles.

[Mixing step and tableting step]

In the same manner as in Example 23, the obtained granulated particles were mixed and tableted to obtain a tablet. The hardness of the obtained tablet was measured by a tablet breaking strength measuring device TH-203CP (manufactured by Toyama Industries Co., Ltd.) to be 5 kgf. Other evaluations were carried out in the same manner as in Examples 1 to 22. The results are shown in Table 7.

[converted wear degree]

Japanese Pharmacopoeia Reference Materials Tests were carried out in accordance with the wear test method for tablets. In parallel with the wear test, the preparation was placed in the simultaneous test chamber and the mass change was measured. The mass change rate was subtracted from the wear degree, and the converted wear degree was calculated and evaluated based on the following criteria. △ The above is the allowable range.

◎: less than 0.2% by mass

○: 0.2% by mass or less and less than 0.5% by mass

△: 0.5% by mass or more and less than 1.0% by mass

×: 1.0% by mass or less and less than 6.0% by mass

××: 6.0% by mass or more

[Break time in the mouth]

The disability of the mouth was evaluated by three male adults and two female surnames. The tablet was placed in the oral cavity, and the tablet was broken by the rotation of the tongue, and the time until the tablet completely collapsed was measured. The average of the five people's collapse time was evaluated on the following basis. △ The above is the allowable range.

<base>

◎: Less than 20 seconds

○: less than 30 seconds in less than 20 seconds

△: less than 30 seconds and less than 40 seconds

×: 40 seconds or more

(※1) Asahi Kasei Chemicals Co., Ltd. Manufacturing:

Use a diameter of ( Φ ) 11mm, and use a spindle pressure of 1kN to compress 500mg of powder into 100mg.

(※2) Asahi Kasei Chemicals Co., Ltd. Manufacturing:

Use a diameter of ( Φ ) 11mm, and use a spindle pressure of 1kN to compress the 500mg powder to a hardness of 78N)

(※1) Asahi Kasei Chemicals Co., Ltd. Manufacturing:

Use a diameter of ( Φ ) 11mm, and use a spindle pressure of 1kN to compress 500mg of powder into 100mg.

(※1) Asahi Kasei Chemicals Co., Ltd. Manufacturing:

Use a diameter of ( Φ ) 11mm, and use a spindle pressure of 1kN to compress 500mg of powder into 100mg.

(※1) Asahi Kasei Chemicals Co., Ltd. Manufacturing:

Use a diameter of ( Φ ) 11mm, and use a spindle pressure of 1kN to compress 500mg of powder into 100mg.

The materials used in the examples and comparative examples are as follows.

<Use raw materials>

Tannic acid huangliansu: ALPS pharmaceutical industry (shares) system, Japanese Pharmacopoeia suitable products

Dongpu extract 3 times scattered: ALPS pharmaceutical industry (shares) system, Dongpu extract 3 times scattered C (sorghum extract: corn starch = 1: 2 mixture)

Peony dry extract: Japanese powder medicine (stock) system, Japanese Pharmacopoeia suitable for peony water dry extract (7 times concentrated)

Anhydrous caffeine: White Bird Pharmaceutical Co., Ltd., Japanese Pharmacopoeia Appropriate

Noscapin: White Bird Pharmaceutical Co., Ltd., Japanese Pharmacopoeia Appropriate

Synthetic hydrotalcite: Concord Chemical Industry Co., Ltd., VF, Japanese Pharmacopoeia Appropriate

Ibuprofen: BASF company, Japanese Pharmacopoeia suitable

Allantoin aluminum: PERMA CHEM (share) system, Japanese Pharmacopoeia suitable product

Fructose: Kato Chemical Co., Ltd., Japanese Pharmacopoeia Appropriate

Glucose: Japanese food chemical (share) system, eclipse MEDICAL-LOSS, Japanese Pharmacopoeia suitable products

Glucose oligosaccharide mixture: JRS PHARMA, EMDEX ^R , (glucose 95% by mass, containing oligosaccharides as other ingredients)

Erythritol: Cargill Celesta Group, erythritol (fine powder), pharmaceutical additives

HPC-L: made by Japan Caoda Co., Ltd., hydroxypropyl cellulose (HPC-L), suitable for Japanese Pharmacopoeia

Titanium oxide: FREUND industry (shares) system, Japanese Pharmacopoeia suitable products

Corn Starch: Matsutake Chemical Industry Co., Ltd., Japanese Pharmacopoeia Corn Starch

Crystalline cellulose: CEOLUS KG-1000, Asahi Kasei Chemicals Co., Ltd., Japanese Pharmacopoeia Appropriate

Crystalline cellulose: CEOLUS KG-802, Asahi Kasei Chemicals Co., Ltd., Japanese Pharmacopoeia Appropriate

Cross-linked povidone: manufactured by BASF, Kollidon CL-SF, applicable to pharmaceutical additives

D-mannitol: Japan ROCKET (shares), PEARLITOL 200SD, Japanese Pharmacopoeia Appropriate

Aspartame: ALPS Pharmaceutical Industry Co., Ltd., Japanese Pharmacopoeia Appropriate

1-Menthol: Toyo Mint Industrial Co., Ltd., SUPER MENTOL 3003, Japanese Pharmacopoeia Appropriate

Grapefruit spice: salt wild spices (stock), grapefruit powder SY-1512

Peach Spice: Givaudan, Japan, Peach Spice GIVO 55774

Apple Spice: Givaudan, Japan, Apple Spice GIVO 55772

Yellow ferric oxide: bismuth chemical (stock) system, yellow ferric oxide, pharmaceutical additives specifications

Magnesium stearate: Taiping Chemical Industry Co., Ltd., magnesium stearate, plant, Japanese Pharmacopoeia

Pure water: Otaru Pharmaceutical Co., Ltd., Japanese Pharmacopoeia Appropriate

Claims (6)

An intraoral disintegrating ingot, which is an intraoral disintegrating tablet containing drug granulated particles, characterized in that the drug is composed of tannic acid huangliansu, Scopolia extract 3 times scattered, and oriental extract extract , Dongpu extract, Corydalis powder, Corydalis dry extract, allioxa, berberine chloride, bismuth subnitrate, pseudoephedrine hydrochloride, phenylephrine hydrochloride ), d-maleic acid chlorpheniramine, d1-chlorpheniramine maleate, Belladonna total alkaloid, aspirin, etetaminophen , Ethenzamide, isopropyl antipyrine, Ibuprofen, ketoprofen, naproxen, loxoprofen sodium, hydrochloric acid Diphenhydramine hydrochloride, Carbinoxamine Maleate, dextromethorphan hydrobromide, anhydrous caffeine, sucralfate Compound, synthetic hydrotalcite, albumin tannate, Phellodendron, Geranium thunbergii, yellow lotus, Swertia, Loperamide hydrochloride, copper calcium chlorophyllinate , selected from the group consisting of Mallotus japonicus, licorice, glycyrrhizic acid and its salts, pseudoephedrine sulfate, belladonna extract, noscapine, and dried extracts of peony. The granulated particles will contain fructose. The aqueous solution is granulated by spraying or dropping the granulated particles of the drug in the powder containing the drug, and the granule is granulated. The fructose content in the child is 2.9 to 25% by mass, and the obtained drug granulated particles or a mixture of the granulated particles of the drug and other tablet components are obtained by tableting. For example, in the oral cavity collapsed ingot of claim 1, wherein the drug is made up of linalic acid, ibuprofen, aldioxa, naproxen, sucralfate (naproxen). Sucralfate) A drug selected from hydrates and synthetic hydrotalcites. For example, in the oral cavity collapsed ingot of claim 1 or 2, the content of the drug is 45 to 99% by mass based on the drug granulated particles. The intraoral disintegrating tablet of claim 1 or 2, wherein the content of the granulated particles of the drug is from 10 to 100% by mass based on the amount of the intragranular disintegrating ingot. An intraoral disintegrating tablet according to claim 1 or 2, wherein the granulated particles of the drug further comprise crystalline cellulose. A method for producing an intraoral collapsed ingot according to the first aspect of the invention, which comprises the steps of: spraying or dripping an aqueous solution containing fructose in a powder containing a drug, stirring and granulating, and drying to obtain a drug granulation The step of particles, the step of ingoting the obtained drug granulated particles or a mixture of the drug granulated particles and other tablet ingredients.