JP2011037840A - Orodispersible tablet and process for manufacturing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an orodispersible tablet excellent in formability and disintegration ability as an orodispersible tablet and a process for manufacturing the same. <P>SOLUTION: The orodispersible tablet include granulated drug particles. The granulated drug particle is obtained by adding an aqueous solution containing a monosaccharide to the powder containing a drug and wet-granulating the powder. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to an orally disintegrating tablet excellent in moldability and disintegrating property as an orally disintegrating tablet and a method for producing the orally disintegrating tablet.

  As a method for producing an orally disintegrating tablet, as a method using a special production apparatus, a suspension is poured into a mold and dried under reduced pressure or freeze-dried (see Patent Documents 1 and 2). There are a method of tableting and drying (see Patent Documents 3 and 4), a method of obtaining an orally disintegrating tablet through an aging process that requires temperature control after dry tableting (see Patent Documents 5 and 6), and the like. However, when a special production apparatus is used, it is possible to achieve both tablet physical properties and disintegration properties, but many excipients are required, and further capital investment is required. As a method for producing an orally disintegrating tablet by a general dry tableting method as a tablet forming method, a method of combining excipients with high disintegration and solubility (see Patent Documents 7 to 10), sugar or sugar alcohol As a method to be used, a method in which a saccharide having a low moldability is granulated with a saccharide having a high moldability and used as an excipient having both moldability and disintegration (see Patent Document 11), a beating by the binding strength of citric acid A method for producing an excipient using a sugar that is extremely soluble in water is known as a lubricant and an anti-adhesive agent for avoiding a lock failure (see Patent Document 12). However, these methods have a problem that the tablet mass increases and the tablet size increases in the case of a tablet having a large amount of active ingredients, such as an increase in the amount of excipient and the need for a disintegrant. From the above, there has been a demand for a technique for obtaining an orally disintegrating tablet excellent in moldability and disintegration as an orally disintegrating tablet without requiring a special device and using a small amount of excipient.

International Publication No. 93/12769 Pamphlet Japanese Examined Patent Publication No. 62-50445 JP-A-8-19589 JP-A-8-19590 JP 2001-342128 A JP-A-11-263723 Japanese Patent Laid-Open No. 10-182436 JP 2001-58944 A JP 2006-70046 A JP 2005-132788 A International Publication No. 95/20380 Pamphlet JP-T-2006-501234

  The present invention has been made in view of the above circumstances, and an object thereof is to provide an orally disintegrating tablet excellent in moldability and disintegrating property as an orally disintegrating tablet, and a method for producing the same, without requiring a special device. To do.

  As a result of intensive investigations to achieve the above-mentioned object, the inventors of the present invention have made drug-granulated particles obtained by wet granulation by adding an aqueous solution containing a monosaccharide to a drug-containing powder into an orally disintegrating tablet. By blending, it was found that an orally disintegrating tablet excellent in moldability and disintegration property as an orally disintegrating tablet can be obtained without requiring a special device, and the present invention has been made.

Therefore, the present invention provides the following orally disintegrating tablets and methods for producing the orally disintegrating tablets.
[1]. An orally disintegrating tablet containing drug granulated particles, wherein the drug granulated particles are drug granulated particles wet-granulated by adding an aqueous solution containing a monosaccharide to a drug-containing powder. An orally disintegrating tablet.
[2]. The orally disintegrating tablet according to [1], wherein the monosaccharide is fructose or glucose.
[3]. The orally disintegrating tablet according to [1] or [2], wherein the monosaccharide content is 1 to 30% by mass with respect to the drug granulated particles.
[4]. The orally disintegrating tablet according to [1], [2] or [3], wherein the content of the drug is 45 to 99% by mass with respect to the drug granulated particles.
[5]. The orally disintegrating tablet according to any one of [1] to [4], wherein the content of the drug granulated particles is 10 to 100% by mass with respect to the orally disintegrating tablet.
[6]. The orally disintegrating tablet according to any one of [1] to [5], wherein the drug granulated particles further contain crystalline cellulose.
[7]. Steps of granulating the powder containing the drug while stirring or dropping an aqueous solution containing a monosaccharide, followed by drying to obtain drug granulated particles, the obtained drug granulated particles or drug granulated particles and others The method for producing an orally disintegrating tablet according to [1], which comprises a step of tableting a mixture with the tablet component.

  According to the present invention, it is possible to provide an orally disintegrating tablet excellent in moldability (friability) and disintegrating property as an orally disintegrating tablet and a method for producing the same without requiring a special device.

Hereinafter, the present invention will be described in detail.
The orally disintegrating tablet of the present invention contains drug-granulated particles that are wet-granulated by adding an aqueous solution containing a monosaccharide to a drug-containing powder.

[Powder containing drug]
There are no particular limitations on the drug compounded in the drug granulated particles used in the orally disintegrating tablet of the present invention, and various drug powders (single drug powders, powdered drug powders, drug particles carried on supported particles) And the like that can be used as a drug raw material for granulation, etc.).

  Examples of the above-mentioned drugs include berberine tannate, funnel extract triple powder, funnel extract powder, funnel extract, engosaku powder, dried engosac extract, aldioxa, berberine chloride, bismuth nitrate, pseudoephedrine hydrochloride, phenylephrine hydrochloride, chlorpheny d-maleate Lamin, dl-chlorpheniramine maleate, belladonna total alkaloid, aspirin, acetaminophen, etenzamide, isopropylantipyrine, ibuprofen, ketoprofen, naproxen, loxoprofen sodium, diphenhydramine hydrochloride, carbinoxamine maleate, dexttomethorphan hydrobromide, anhydrous Caffeine, sucralfate hydrate, synthetic hydrotalcite, albumin tannate, buckwheat, ginger pepper, auren, Nburi, loperamide hydrochloride, copper chlorophyllin potassium, Mallotus japonicus, licorice, glycyrrhizic acid and its salts, pseudoephedrine sulfate, Belladonna, noscapine, include peony dry extract, and the like. These can be used individually by 1 type or in combination of 2 or more types. Among them, since the disintegrating effect is enhanced when the proportion of insoluble particles is high, water-insoluble or poorly water-soluble ones such as berberine tannate, ibuprofen, aldioxa, naproxen, sucralfate hydrate, synthetic hydrotalcite (1 g or 1 mL) The amount of the solvent required to dissolve is preferably 100 mL or more, preferably 1000 mL or more, more preferably 10,000 mL or more; the 15th revised Japanese Pharmacopoeia).

  Although the content of the drug is not particularly limited, it is preferably 45 to 99% by mass in the drug granulated particles, that is, based on the drug granulated particles, and the lower limit is 50 mass from the viewpoint of blending the drug more in the orally disintegrating tablet. % Or more is more preferable, and 55 mass% or more is further more preferable. The upper limit is more preferably 95% by mass or less, and still more preferably 90% by mass or less. Moreover, 10 mass% or more is preferable with respect to an orally disintegrating tablet from the point which mix | blends a drug more in an orally disintegrating tablet, 20 mass% or more is more preferable, and 30 mass% or more is further more preferable. The upper limit is preferably 99% by mass or less, more preferably 95% by mass or less, and still more preferably 90% by mass or less. In the present invention, an orally disintegrating tablet excellent in moldability and disintegration as an orally disintegrating tablet can be obtained even with a small amount of excipient, and a large amount of drug can be blended in the orally disintegrating tablet.

[Aqueous solution containing monosaccharides]
The aqueous solution containing the monosaccharide of the present invention contains a monosaccharide. By wet granulating a drug-containing powder with an aqueous solution containing a water-soluble monosaccharide, excellent moldability and disintegration as an orally disintegrating tablet can be obtained. Examples of the monosaccharide include glucose, fructose, galactose, and arabinose, which can be used alone or in combination of two or more. Among these, glucose and fructose are preferable from the viewpoint of the balance between the binding strength and the viscosity of the saturated aqueous solution, and fructose is more preferable from the viewpoint of the binding strength.

  The monosaccharide concentration is preferably 0.01 to 75% by mass, more preferably 1 to 55% by mass, and still more preferably 4 to 40% by mass with respect to the aqueous solution containing the monosaccharide within the range where no kneaded product is formed. The content of monosaccharides in the drug granulated particles is preferably 1 to 30% by mass, more preferably 2 to 25% by mass, and further preferably 3 to 10% by mass with respect to the drug granulated particles. If the content of monosaccharides in the drug granulated particles is too small, drug binding becomes insufficient, and there is a possibility that the balance between granulation and disintegration may not be maintained. The degree can be improved more. When there is too much content, there exists a possibility that disintegration may be affected, there exists a possibility that a tablet may become hard and solubility may worsen.

  Other components can be added to the aqueous solution containing monosaccharides as long as the effects of the present invention are not impaired. Examples of other components include polysaccharides, sugar alcohols, water-soluble polymer compounds, stabilizers, pigments, and flavoring agents.

  Examples of the polysaccharide include oligosaccharide, lactose, maltotriose, maltose, and sucrose. Examples of the sugar alcohol include erythritol, xylitol, sorbitol, mannitol and the like.

  As a water-soluble polymer compound, the viscosity of the lower concentration of 50% by mass aqueous solution or saturated aqueous solution is 1000 mPa · s or less (BL type viscometer (eg, Toki Sangyo Co., Ltd. RB80L type), 36 ° C., rotor No. 2, 30 rpm) can be used, and water-soluble cellulose derivatives (hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, etc.), polyvinyl alcohol, polyvinylpyrrolidone and the like can be mentioned.

Examples of the stabilizer include sodium edetate and benzoic acid.
Examples of the dye include titanium oxide, iron sesquioxide, and edible yellow No. 5.
Examples of the corrigent include sweeteners such as aspartame, sucralose, acesulfame potassium, saccharin, sodium saccharin, trehalose and thaumatin, and sour agents such as malic acid and tartaric acid.

  The content of the other components can be added within a range not impairing the effects of the present invention, but is preferably 30% by mass or less with respect to the aqueous solution containing a monosaccharide. Moreover, it is preferable to set it as 50 mass% or less with respect to the quantity of a monosaccharide, More preferably, it is 40 mass% or less.

  As the solvent of the monosaccharide aqueous solution, water alone or a mixed solvent of water and a hydrophilic solvent (preferably ethanol) can be used. In this case, the range of water / hydrophilic solvent = 1/0 to 1/1 (mass ratio) is preferable.

  The viscosity of an aqueous solution containing a monosaccharide is 500 mPa · s or less when measured with a BL type viscometer (eg, Toki Sangyo Co., Ltd. RB80L type) (measuring conditions: 36 ° C., rotor No. 2, 60 rpm). Is preferred. More preferably, it is 300 mPa * s or less, More preferably, it is 100 mPa * s or less.

[Drug granulated particles]
The drug granulated particles are those obtained by wet granulation by adding an aqueous solution containing a monosaccharide to a drug-containing powder. However, the drug-containing powder does not impair the effects of the present invention. Other particle components can be blended. Other particle components include inorganic powders such as magnesium aluminate metasilicate, synthetic hydrotalcite, celluloses such as crystalline cellulose, ethyl cellulose, low-substituted hydroxypropyl cellulose and derivatives thereof, corn starch, potato starch, hydroxypropyl Starches such as starch and derivatives thereof, sugars such as lactose and mannitol, sugar alcohols and the like can be mentioned, and these can be used alone or in combination of two or more. Among them, a hardly soluble component having a solvent amount required to dissolve 1 g or 1 mL of 100 mL or more is preferable, and crystalline cellulose and corn starch are preferable, and crystalline cellulose is more preferable from the viewpoint of improving productivity. In particular, crystalline cellulose can be suitably used because it has a property of improving the friability of the tablet with a small amount. The crystalline cellulose is preferably one having a hardness of 60 N or more when 500 mg of powder is tableted with a tablet having a diameter (φ) of 11 mm at a tableting pressure of 1 kN. As specific examples, Theolas KG-1000 (100N), Theolas KG-802 (78N) (manufactured by Asahi Kasei Chemicals Co., Ltd.) or an equivalent product are preferable, and Theolas KG-1000 is more preferable.

  Other particle components may not be blended in the granulated particles, and the content thereof is preferably 0 to 35% by mass, more preferably 3 to 25% by mass with respect to the drug granulated particles. If the content of other particle components is too small, there is a risk that problems such as adhesion to the machine are likely to occur in productivity, and if it is too much, the disintegration time may be prolonged.

  The average particle size of the drug granulated particles is preferably 1-1000 μm, more preferably 500 μm or less. The average particle diameter is 50% of the mass cumulative particle size distribution, and can be measured by, for example, Robot Shifter RPS-95C (manufactured by Seishin Enterprise Co., Ltd.). If the average particle size is too small, the particles may be classified and the uniformity may be impaired. If the average particle size is too large, the particles may feel rough when taken.

[Method for producing drug granulated particles]
The drug granulated particles can be obtained by stirring and granulating an aqueous solution containing a monosaccharide on a drug-containing powder and then drying. As the apparatus, a stirring apparatus used for granulation, for example, a high-speed stirring granulator, a rolling fluidized granulator or the like can be used. Suitable production conditions include, for example, when a high-speed agitation granulator high speed mixer LFS-2 (manufactured by Fukae Pautech Co., Ltd.) is used, the rotation speed of the agitation is 200 to 1500 rpm, preferably 500 to 2000 rpm, and the chopper 500 to 4000 rpm. , Preferably it is 2000-3000 rpm. The aqueous solution containing monosaccharides is sprayed or added dropwise with stirring while adjusting the liquid speed to 20 to 50 g / min. Dry after stirring. For drying, methods commonly used for drying, such as shelf-type drying and fluidized bed drying, can be employed, and are not particularly limited. For example, if a shelf-type dryer, the drug granulated particles at 60 to 80 ° C. It is good to dry so that the moisture content of may become 0-10 mass%. Thereafter, using a pulverizer or the like as appropriate, a granulated product having a desired particle size is obtained with a sieve or the like. However, the manufacturing method of the granulated particle of this invention is not limited to this, It can manufacture by a method well-known to those skilled in the art.

  In addition, when other particle components are added to the drug granulated particles, a method of granulating with an aqueous solution containing a monosaccharide after mixing the powder containing the drug and other particle components, or an aqueous solution containing a monosaccharide The other components that can be added to the aqueous solution are added to the aqueous solution, and the drug-containing powder is granulated.

[Orally disintegrating tablets]
The orally disintegrating tablet of the present invention contains the granulated particles. An orally disintegrating tablet refers to a tablet that has the function of being disintegrated by chewing or saliva in the oral cavity and rapidly disintegrating in the oral cavity after taking the tablet. The content of the drug granulated particles in the orally disintegrating tablet is appropriately selected according to the content of the drug or monosaccharide, but is preferably 10 to 100% by mass, more preferably 20 to 100% by mass, and 30 to 100%. More preferred is mass%.

  In addition to the granulated particles, other tablet components such as an excipient and a disintegrant imparting disintegration can be blended with the orally disintegrating tablet within a range not impairing the effects of the present invention.

  Excipients include magnesium aluminate metasilicate, inorganic powders such as synthetic hydrotalcite, celluloses such as crystalline cellulose, ethyl cellulose, low-substituted hydroxypropyl cellulose and derivatives thereof, corn starch, potato starch, hydroxypropyl starch And the like, and sugars such as lactose and mannitol, sugar alcohols, and the like. These can be used singly or in appropriate combination of two or more.

  The excipient may not be contained in the orally disintegrating tablet, and is preferably 0 to 40% by mass, and more preferably 10 to 25% by mass with respect to the orally disintegrating tablet. If the excipient content exceeds 40% by mass, the disintegration property may be affected. This content includes excipients contained in the drug granulated particles. By using the drug granulated particles of the present invention, it is possible to obtain excellent moldability and disintegration property as an orally disintegrating tablet even with a small amount of excipient, resulting in a large amount of drug in the orally disintegrating tablet. can do.

  Examples of the disintegrant include crospovidone, carmellose calcium, croscarmellose sodium, low-substituted hydroxypropyl cellulose, carboxymethyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch and the like. They can be used in combination. Of these, crospovidone is preferred. As crospovidone, a commercially available product can be used, and examples include Kollidon CL, Kollidon CL-SF (both manufactured by BASF (Germany)), and the like.

  Although the disintegrant may not be included in the orally disintegrating tablet, in the present invention, by further disintegrating the disintegrant, it is possible to obtain disintegration from the inside of the tablet. Synergistic effects can be obtained. 0-20 mass% is preferable with respect to an orally disintegrating tablet, as for content of a disintegrating agent, 0-10 mass% is more preferable, and 2.5-10 mass% is further more preferable. If the content of the disintegrant is too large, wear may be deteriorated.

  In the orally disintegrating tablet, commonly used additives can be used as long as the effects of the present invention are not impaired. For example, sweeteners such as aspartame, acesulfame potassium, saccharin, sodium saccharin, sour agents such as tartaric acid, malic acid, succinic acid, fumaric acid, monoterpenes such as menthol, camphor, borneol, limonene, and essential oils containing them Flavoring agents (grapefruit flavoring, apple flavoring, peach flavoring, etc.), iron sesquioxide, yellow sesquioxide, titanium oxide, edible yellow No. 5 coloring agent, magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearin Examples include lubricants such as acids.

  The converted friability of the orally disintegrating tablet is determined by the method shown in the item of converted friability in the examples described later, preferably less than 1.0 mass%, more preferably less than 0.5 mass%, and more preferably 0.2 mass. More preferably less than%. The disintegration time of the orally disintegrating tablet is the time until the tablet is disintegrated while the tablet is put into the oral cavity and rolled with the tongue, and the tablet is completely disintegrated, preferably less than 40 seconds, more preferably less than 30 seconds. Preferably, less than 20 seconds is more preferable.

  The mass of the orally disintegrating tablet is desirably 20 to 2000 mg / tablet. The shape of the tablet is not particularly limited, but may be a round shape, a caplet shape, a donut shape, an oblong shape or the like, a laminated tablet, a dry-coated tablet, etc. A secant line may be attached. It is preferable to use a tablet with a diameter based on the amount of powder commonly used in the pharmaceutical preparation field, and tableting is performed so as to achieve the desired tablet strength. The tablet strength can be measured with a tablet breaking strength measuring instrument TH203CP (manufactured by Toyama Sangyo Co., Ltd.).

[Method for producing orally disintegrating tablets]
An orally disintegrating tablet can be obtained by tableting the obtained drug granulated particles or a mixture of the drug granulated particles and other tablet components. For tableting, an apparatus generally used for tablet formation is used. For example, a single tableting machine or a rotary tableting machine is used. The molding pressure at the time of tableting is appropriately selected so as to achieve the target tablet hardness. The hardness varies depending on the tablet size, but is preferably about 3 kgf (tablet hardness measuring device (manufactured by Yamato Kagaku)) or more.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not restrict | limited to the following Example. The amount in the table is the amount of the component in the case of the component name, and the name in parentheses is the product name used. The purified water in the aqueous solution containing the monosaccharides in the table is the amount required at the time of manufacture, and is not contained in the tablet because it evaporates when dried.

[Examples 1 to 22, Comparative Examples 1 and 2]
[Preparation of granulated particles]
In advance, 1000 tablets of an aqueous solution or a granulating solution containing the monosaccharides shown in Tables 1 to 6 were prepared. After putting 1000 tablets of the ingredients described in the drug granulation particle column other than the aqueous solution containing granule or the granulation solution into the high speed mixer LFS-2 (manufactured by Fukae Pautech Co., Ltd.) and premixing for 1 minute The number of revolutions was set to 1000 rpm for the agitator and 2000 rpm for the chopper, and the mixture was stirred while dropping an aqueous solution or a granulating solution containing a monosaccharide over 2 minutes. Thereafter, stirring was performed for 2 minutes. The obtained granulated material was spread on a vat and air-dried with a shelf dryer DN-93 (manufactured by Yamato Kagaku) at 80 ° C. for 5 hours (60 ° C. for 7 hours for Example 20). Granules obtained by repeating the same operation were combined and sieved with a sieve having an opening of 1000 μm to obtain drug granulated particles (average particle size of 150 to 300 μm).

[Preparation of orally disintegrating tablets]
The obtained drug granulated particles and ingredients other than the lubricant are taken in the prescribed ratio (for 2000 tablets), put in a plastic bag and shaken by hand about 20 times, and then mixed with the lubricant (for 2000 tablets). ) And mixed 10 times. This mixed powder was tableted with an open feed shoe using a clean press 12HUK (manufactured by Kikusui Seisakusho) to obtain a circular tablet (tablet) having a component mass part shown in the table and a total amount of φ9.0 mm. In addition, the tableting pressure was adjusted with a tablet breaking strength measuring instrument TH-203CP (manufactured by Toyama Sangyo Co., Ltd.) so that the hardness was 3 to 5 kgf (rotary plate rotation speed: 20 rpm, number of bottles: 12). The following evaluation was performed about the obtained tablet. The results are also shown in the table.

[Example 23]
[Preparation of granulated particles]
1875 g of berberine tannate and 1125 g of funnel extract 3 times were added to a stirring granulator (Fukae Kogyo Co., Ltd., high speed mixer FS.GS.10J type). After the addition, stirring was started under conditions of agitator 400 rpm and chopper 2500 rpm, and after mixing for 1 minute, 1700 g of a 7 mass% aqueous solution of fructose was added at a flow rate of 1700 g / min. Then, stirring operation was continued for 8 minutes and the stirring granulated material (temperature of 40 degreeC) was discharged | emitted from the granulator. The obtained agglomerated granule is preheated at an intake air temperature of 80 ° C., and is introduced into Spiraflow SFC-5 type (manufactured by Freund Sangyo Co., Ltd.) having an exhaust temperature of 50 ° C. Fluidized bed drying operation was started under the conditions of an air volume of 2.5 m ³ / min and a rotor rotation speed of 200 rpm. The drying operation was continued for about 30 minutes, and when the exhaust temperature reached 45 ° C, the product was discharged from Spiraflow SFC-5 type to obtain a granular dried product (temperature 55 ° C). The granular dried product was all sieved using a sieve having an aperture of 850 μm (particles that did not pass through the sieve were ground with a spatula) to obtain granulated particles.

[Mixing process]
Each component was measured with a total amount of 3500 g so that the composition shown in Table 7 was obtained. Among these, components other than magnesium stearate were charged into a blender (manufactured by Kotobuki Industries Co., Ltd., Boule Container Mixer 20L LM-20 type). After mixing for 20 minutes at 20 rpm, magnesium stearate was added and mixed for 5 minutes at 20 rpm.

[Tabletting process]
Using the rotary tableting machine (LIBRA2 manufactured by Kikusui Seisakusho Co., Ltd.) equipped with a 11 mm (Sumi Kakudaira) punch and mortar, the mixture obtained in the mixing step was opened at a turntable rotation speed of 20 rpm. Tableting was performed under the conditions of a feed shoe, a preload of 1 kN, and a main pressure of 7 kN to obtain tablets. It was 5 kgf as a result of measuring the hardness of the obtained tablet with a tablet breaking strength measuring instrument TH-203CP (manufactured by Toyama Sangyo Co., Ltd.). Other evaluations were performed in the same manner as in Examples 1 to 22, and the results are shown in Table 7.

[Example 24]
A tablet was obtained in the same manner as in Example 23, except that tableting was performed using a 9 mm diameter (sumi square flat) punch and die under the conditions of a preload of 1 kN and a main pressure of 5 kN. It was 7 kgf as a result of measuring the hardness of the obtained tablet with a tablet breaking strength measuring instrument TH-203CP (manufactured by Toyama Sangyo Co., Ltd.). Other evaluations were performed in the same manner as in Examples 1 to 22, and the results are shown in Table 7.

[Example 25]
[Preparation of granulated particles]
1500 g of berberine tannate, 900 g of funnel extract, and 360 g of dried peonies were charged into a stirring granulator (Fukae Industrial Co., Ltd., High Speed Mixer FS.GS.10J type). After the addition, stirring was started under the conditions of an agitator of 400 rpm and a chopper of 2500 rpm. After mixing for 1 minute, 1136 g of a 7 mass% aqueous solution of fructose was added at a flow rate of 1136 g / min. Thereafter, the stirring operation was continued for 10 minutes, and the stirred granulated product (temperature 40 ° C.) was discharged from the granulator. The obtained agglomerated granule is preheated at an intake air temperature of 80 ° C., and is introduced into Spiraflow SFC-5 type (manufactured by Freund Sangyo Co., Ltd.) having an exhaust temperature of 50 ° C. Fluidized bed drying operation was started under the conditions of an air volume of 2.5 m ³ / min and a rotor rotation speed of 200 rpm. The drying operation was continued for about 50 minutes, and when the exhaust temperature reached 60 ° C., the product was discharged from Spiraflow SFC-5 type to obtain a granular dried product (temperature 72 ° C.). The granular dried product was all sieved using a sieve having an aperture of 850 μm (particles that did not pass through the sieve were ground with a spatula) to obtain granulated particles.

[Mixing process and tableting process]
The obtained granulated particles were mixed and tableted in the same manner as in Example 23 to obtain tablets. The hardness of the obtained tablets was measured with a tablet breaking strength measuring instrument TH-203CP (manufactured by Toyama Sangyo Co., Ltd.) and found to be 5 kgf. Other evaluations were performed in the same manner as in Examples 1 to 22, and the results are shown in Table 7.

[Equivalent friability]
JP Reference Information The test was conducted in accordance with the tablet friability test method. In parallel with the friability test, the formulation was newly left in the same time and in the same measurement laboratory, and the mass change was measured. The mass change rate was subtracted from the friability to calculate the converted friability and evaluated according to the following criteria. △ or more is the allowable range.
<Standard>
◎: Less than 0.2% by mass ○: 0.2% by mass or more and less than 0.5% by mass Δ: 0.5% by mass or more and less than 1.0% by mass X: 1.0% by mass or more and less than 6.0% by mass XX: 6.0% by mass or more

[Mouth disintegration time]
Oral disintegration was evaluated by three adult men and two adult women. The tablet was placed in the mouth, and the tablet was disintegrated while rolling with the tongue, and the time until the tablet was completely disintegrated was measured. Evaluation was made based on the following criteria from the average value of the disintegration time of five people. △ or more is the allowable range.
<Standard>
◎: Less than 20 seconds ○: 20 seconds or more and less than 30 seconds △: 30 seconds or more and less than 40 seconds ×: 40 seconds or more

The raw materials used in Examples and Comparative Examples are as follows.
<Raw materials>
Berberine tannate: Alps Yakuhin Kogyo Co., Ltd., Japanese Pharmacopoeia compatible funnel extract triple powder: Alps Yakuhin Kogyo Co., Ltd.
Peonies dried extract: NIPPON POWDER PHARMACEUTICAL CO., LTD., Japanese Pharmacopoeia compatible product Peonies water extract (7 times concentrated)
Anhydrous caffeine: manufactured by Shiratori Pharmaceutical Co., Ltd., Japanese Pharmacopoeia compatible product Noscapine: manufactured by Shiratori Pharmaceutical Co., Ltd., Japanese Pharmacopoeia compatible synthetic hydrotalcite: manufactured by Kyowa Chemical Industry Co., Ltd., VF, Japanese Pharmacopoeia compatible product Ibuprofen: BASF, Japan Pharmacopoeia Aldioxa: Permachem Asia Co., Japan Pharmacopoeia Fructose: Kato Chemical Co., Japan Pharmacopoeia Glucose: Nippon Shokuhin Kako Co., Ltd. eclipse Medica loin, Japanese Pharmacopoeia Compliant glucose oligosaccharide mixture: JRS PHARMA Ltd., EMDEX ^R, (95 wt% glucose, comprising an oligosaccharide other components)
Erythritol: Cargill Selestar Group, Erythritol (fine powder), chemical additive standard compliant product HPC-L: Nippon Soda Co., Ltd., hydroxypropyl cellulose (HPC-L), Japanese Pharmacopoeia compliant titanium oxide: Freund Industries Co., Ltd., Japan Pharmacopoeia compatible corn starch: Matsutani Chemical Industry Co., Ltd., Japanese Pharmacopoeia corn starch crystalline cellulose: Theolas KG-1000, Asahi Kasei Chemicals Co., Ltd., Japanese Pharmacopoeia compatible crystalline cellulose: Theolas KG-802, manufactured by Asahi Kasei Chemicals Corporation, Japanese Pharmacopoeia compatible product Crosspovidone: manufactured by BASF, Kollidon CL-SF, chemical additive standard compatible product D-mannitol: manufactured by Rocket Japan Co., Pearitol Japanese Pharmacopoeia Aspartame: Alps Pharmaceutical Industries Co., Ltd., Japan Pharmacopoeia compatible product l-Menthol: Toyo Hikaru Kogyo Co., Ltd., Super Menthol 3003, Japan Pharmacopoeia compatible product Grapefruit flavor: Shiono Koryo Co., Ltd., Flapefruit Powder SY-1512
Peach flavor: Peach flavor GIVO 55774, manufactured by Givaudan Japan
Apple fragrance: Givadan Japan KK, Apple flavor GIVO 55772
Yellow ferric oxide: manufactured by Kasei Kasei Co., Ltd. Yellow ferric oxide, chemical additive standard compliant magnesium stearate: manufactured by Taihei Chemical Sangyo Co., Ltd. Magnesium stearate Plant, Japanese Pharmacopoeia purified water: Kominato Made by Pharmaceutical Co., Ltd., Japanese Pharmacopoeia compatible product

Claims (7)

  An orally disintegrating tablet containing drug granulated particles, wherein the drug granulated particles are drug granulated particles wet-granulated by adding an aqueous solution containing a monosaccharide to a drug-containing powder. An orally disintegrating tablet.   The orally disintegrating tablet according to claim 1, wherein the monosaccharide is fructose or glucose.   The orally disintegrating tablet according to claim 1 or 2, wherein the content of monosaccharide is 1 to 30% by mass with respect to the drug granulated particles.   The orally disintegrating tablet according to claim 1, 2 or 3, wherein the content of the drug is 45 to 99 mass% with respect to the drug granulated particles.   The orally disintegrating tablet according to any one of claims 1 to 4, wherein the content of the drug granulated particles is 10 to 100 mass% with respect to the orally disintegrating tablet.   The orally disintegrating tablet according to any one of claims 1 to 5, wherein the drug granulated particles further contain crystalline cellulose.   Steps of granulating the powder containing the drug while stirring or dropping an aqueous solution containing a monosaccharide, followed by drying to obtain drug granulated particles, the obtained drug granulated particles or drug granulated particles and others The manufacturing method of the orally disintegrating tablet of Claim 1 which has the process of tableting the mixture with the tablet component of this.