KR102018385B1 - Orally disintegrating tablet and process for production thereof - Google Patents

Abstract

The present invention provides an oral disintegrating tablet containing a dry powder extract which is disintegrated at a rapid orbital disintegration time, has a good texture, and also has excellent granulation properties of a drug-containing granulated product, wherein the dry powder extract has 40 to 75% by mass and silicon dioxide 15 The present invention relates to an orally disintegrating tablet comprising a crude drug-containing granulated product containing from 50% by mass to 5% by mass and a disintegrant 5-30% by mass.

Description

Disintegrating tablet in oral cavity and manufacturing method therefor {ORALLY DISINTEGRATING TABLET AND PROCESS FOR PRODUCTION THEREOF}

The present invention relates to an orally disintegrating tablet and a method for producing the same.

The herbal dry extract has been blended into tablets because it has excellent and various effects. In recent years, compounding into the intraoral disintegrating tablet which disintegrates only with a small amount of saliva secreted into the oral cavity is made | formed, and such an intraoral disintegrating tablet requires the outstanding disintegration property.

Patent Document 1: Japanese Patent Application Laid-Open No. 2007-297313 Patent Document 2: Japanese Patent Application Laid-Open No. 2007-176861 Patent Document 3: Japanese Patent Laid-Open No. 5-221853

The decayability of the orally disintegrating tablet containing the herbal dry extract was examined. When tableting containing the herbal dry extract was tableted, even if the herbal dry extract contained a small amount, it disintegrated as compared to the tablet containing no dry extract. A significant delay was found in time. Conventionally, in oral tablets formulated in tablets of ordinary type taken with water, there is a method of improving disintegration, but the disintegration time of tablets of normal type is considerably longer than the time required for oral disintegrating tablets, It is unsuitable for intraoral disintegrating tablets that are disrupted with only a small amount of saliva secreted into the oral cavity.

SUMMARY OF THE INVENTION The present invention has been made in view of the above circumstances, and provides an orally disintegrating tablet containing herbal dry extract which is disintegrated in a rapid oral disintegration time, has a good texture, and also has excellent granulation properties of a herbal-containing granulated product. The purpose.

MEANS TO SOLVE THE PROBLEM As a result of earnestly examining in order to achieve the said objective, it contains 40 to 75 mass% of (A) herbal dry extract, 15 to 50 mass% of (B) silicon dioxide, and 5 to 30 mass% of (C) disintegrants. It was confirmed that the above problems can be solved by preparing an orally disintegrating tablet containing a crude drug-containing granulated product and blending the granulated product, thereby achieving the present invention.

Accordingly, the present invention provides the following intraoral disintegrating tablets and a method for producing the same.

[1] An orally disintegrating tablet comprising 40 to 75% by mass of a dry drug extract, 15 to 50% by mass of silicon dioxide, and 5 to 30% by mass of (C) disintegrant .

[2] The oral disintegrating tablet according to [1], wherein the blended mass ratio represented by (A) herbal dry extract / (B) silicon dioxide is contained in the herbal medicine-containing granulated product.

[3] The orally disintegrating tablet according to [1] or [2], wherein the compounded mass ratio represented by (C) disintegrant / (B) silicon dioxide in the herbal-containing granulated product is 0.1 to 1.75.

[4] The orally disintegrating tablet according to any one of [1] to [3], in which the (C) disintegrant is crospovidone.

[5] (A) Medicinal herb extracts include Yedeok-tree, Yeonho-sak, Yellow-white, Yellow-white, Yellow-green, Green-jacho, Garana, Licorice, and Gil-kyung (,), Cinnamon, gentiana, dysparum, Japanese magnolia, peony, ginger, senega, senna, creation, donkey, carrot, belladonna, mokyang The intraoral disintegrating tablet according to any one of [1] to [4], which is a dry extract of a herb selected from 木香), lunatic grass, and oyster.

[6] The orally disintegrating tablet according to any one of [1] to [5], wherein the blended mass ratio represented by the disintegrating agent in the disintegrating agent / intraoral disintegrating tablet in the herbal-containing granulated product is 0.01 to 1.0.

[7] (B) To a wet granulated product obtained by adding (A) herbal dry extract to a mixed mixture of silicon dioxide and water, and stirring and mixing (C) a disintegrant, followed by drying to dry the crude drug-containing granulated product The manufacturing method of the orally disintegrating tablet as described in [1] which obtains water and mix | blends the obtained crude drug containing granulated material.

According to the present invention, it is possible to provide an orally disintegrating tablet containing a herbal dry extract which disintegrates at a rapid orbital disintegration time, has a good texture, and also has excellent granulation properties of a herbal containing granule.

EMBODIMENT OF THE INVENTION Hereinafter, this invention is demonstrated in detail in order of (I) herbal containing granulated material, (II) manufacturing method of herbal containing granulated material, and (III) orally disintegrating tablet.

The orally disintegrating tablet of the present invention includes a drug-containing granulated product containing (A) 40 to 75% by weight of the dry chemical extract, (B) 15 to 50% by weight of silicon dioxide, and (C) 5 to 30% by weight of the disintegrant. It is. "Intraoral disintegrating tablet" means to disintegrate with saliva in the oral cavity and take it. Since it is preferable to disintegrate rapidly in the oral cavity after taking the tablet, the expected disintegration time is less than 60 seconds, preferably less than 45 seconds, more preferably 30 without chewing in the oral cavity. Less than a second.

(I) herbal-containing granulated products

The herbal medicine-containing granulated material contains 40 to 75 mass% of the herbal dry extract, 15 to 50 mass% of silicon dioxide, and 5 to 30 mass% of the disintegrating agent.

(A): herbal medicine dry extract

The term "medicinal herb dry extract" refers to a concentrated extract obtained by concentrating an extraction extract extracted from a herbal medicine with a hydrophilic solvent (water or 40 vol% or less of ethanol aqueous solution, etc.), and drying by an appropriate method to form a powder. When such a herbal dry extract is blended as it is, the disintegration time in the mouth becomes long, and the problem is likely to occur in the disintegration property. Although the reason is not clear, when the tablet is dissolved in the mouth, it is dissolved in a small amount of water such as saliva, and the herbal dry extract becomes a high-viscosity liquid and covers the surface of the tablet, thereby preventing the intrusion of water into the tablet. It is thought that one of the reasons is that the collapse of the tablet is delayed.

It does not specifically limit as a herbal dry extract, It can select from well-known herbal medicines suitably according to the objective. Specifically, for example, Yedeok-tree, Yeonho-sak, Yellow-white, Hwang-ryong, Yellow-jacho, Garana, Licorice, Gil-kyeong , Cinnamon, Gentiana, Dried grass, Japanese magnolia, Peony, Ginger, Senega, Senna, Creation, Angelica, Carrot, Belladonna, Moorang And dry extracts such as lunatic grass and euphoric acid. These herbal dry extracts may use 2 or more types together in any 1 type independently, may use what was prepared by the daily method, and may use a commercially available thing.

Specific examples of very suitable herbal dry extract include Yeokdeok dry extract, soft-hosak dried extract, yellow-white dry extract, tarana dry extract, licorice dry extract, Gilt-dried extract Extract, dried grass extract, Japanese magnolia dried extract, peony dried extract, ginger dried extract, senna dried extract, dried dried extract, donkey dried extract, carrot dried extract, etc. Can be. In the present invention, among the above, one or two or more selected from peony dry extract and soft hoax dry extract are preferable, and peony dry extract is more preferable.

Content of the herbal dry extract is 40-75 mass% in a herbal-containing granulated material, 45-70 mass% is preferable, and 50-65 mass% is more preferable. As the content of the herbal dry extract decreases, the amount of silicon dioxide and disintegrant for compounding the prescribed amount of herbal medicine increases. Therefore, according to the prescription amount of a herbal medicine, the dosage amount as a formulation increases, and there exists a possibility that it may cause a fall of a dose. Moreover, since content of the herbal medicine is low, granulation becomes difficult to advance. On the other hand, the higher the content, the longer the disintegration time of the tablet is due to the peculiarity of the herbal dry extract, and the disintegration becomes insufficient.

(B): silicon dioxide

By blending silicon dioxide, stickiness peculiar to the herbal dry extract is avoided, the disintegration time is shortened, and the disintegration property is improved. Examples of the silicon dioxide include synthetic silicas such as hard silicic anhydride and hydrous silicon dioxide, and among them, silicon dioxide having an average pore diameter of 10 nm or more and less than 30 nm is preferable. Even if the pore diameter is too small or too large, water is hard to be impregnated, and there is a fear that the granulation property may deteriorate. And the measuring method of an average pore diameter is computed by the pressure in the median value of nitrogen adsorption total amounts. In addition, the oil absorption amount is preferably 300 ml / 100 g or more (measurement method according to JIS K5101). The higher the oil absorption amount, the better the effects of the present invention, in particular, the disintegration property and the granulation property. On the other hand, when oil absorption amount is too low, there exists a possibility that the effect of this invention may not fully be acquired. The upper limit of the adsorption capacity is not particularly limited, and there is no problem even if the upper limit is higher than the upper limit, but it is about 500 ml / 100 g or less. Examples of silicon dioxide that satisfies the above average pore diameter and oil absorption amount include 350 grade equivalent products of Cyrisia manufactured by Fuji-Sirisia Chemical Co., Ltd. and the like.

Content of silicon dioxide is 15-50 mass% in the herbal-containing granulated material, 20-42 mass% is preferable, and 25-35 mass% is more preferable. If the content of silicon dioxide is too small, the stickiness peculiar to the herbal dry extract cannot be suppressed, the mouth disintegration time is long, and the disintegration property is insufficient. On the other hand, when there is too much content of silicon dioxide, granulation property will deteriorate and a granulated material will not be produced.

(C): disintegrant

Examples of disintegrating agents include crospovidone (crosslinked homopolymer of 1-ethenylpyrrolidone-2-one), croscarmellose sodium, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch, and the like. It can be used individually by 1 type or in combination of 2 or more types. Among them, crospovidone is preferable in terms of disintegration and texture. Examples of the products of crospovidone include trade names: Coridone CL from BASF, Coridone CL-SF, Polyplusdon XL from ISP, and the like. As for the average particle diameter of a disintegrating agent, 5-50 micrometers is preferable. By using this average particle diameter, the texture in the mouth becomes good. In addition, an average particle diameter is a volume 50% diameter measured by the dry measurement (for example, LS13 320 type by Bekuman Coalta Co., Ltd.). As crospovidone which has such an average particle diameter, brand name: Corridone CL-SF by BASF, etc. are mentioned.

Content of a disintegrant is 5-30 mass% in the herbal-containing granulated material, 6.5-27 mass% is preferable, and its 8-20 mass% is more preferable. If the content of the disintegrant is too small, the tablet disintegration time is long, and the disintegration property is insufficient. On the other hand, when there is too much disintegrant content, a texture will worsen.

As for the compounding mass ratio represented by (A) herbal dry extract / (B) silicon dioxide in a herbal-containing granulated material, 0.8-4.5 are preferable at the point of the balance of the disintegration property of a tablet and the granulation property of a herbal-containing granulated material, and 1.1- 3.5 is more preferable, and 1.4-2.6 are still more preferable. When the ratio of the herbal dry extract with respect to silicon dioxide is too low, there exists a possibility that granulation property may deteriorate, and when too high, disintegration property will worsen.

Moreover, as for the compounding mass ratio represented by (C) disintegrant / (B) silicon dioxide in a herbal-containing granulated material, 0.1-1.75 are preferable, 0.17-1.35 are more preferable at the point of the balance of disintegration property and texture, 0.23 to 0.80 are more preferable. If the ratio of the disintegrant to silicon dioxide is too low, there is a fear that the disintegration is deteriorated. On the other hand, if it is too high, a texture will worsen.

An arbitrary component can be mix | blended with the herbal medicine containing granulated material in the range which does not impair the effect of this invention. Examples of such optional components include excipients, binders, lubricants, flavors, colorants, sweeteners, acidulants, and the like.

Examples of the excipient include cellulose such as crystalline cellulose and low-substituted hydroxypropyl cellulose and derivatives thereof, starch such as corn starch, potato starch and hydroxypropyl starch and derivatives thereof, lactose, Sugars such as mannitol, sugar alcohols, magnesium metasilicate aluminate, synthetic hydrotalcite and the like. These can be used individually by 1 type or in combination of 2 or more types.

Examples of the binder include water-soluble high molecular compounds, sugars, sugar alcohols, and the like. Examples of the water-soluble polymer include water-soluble cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose and hydroxymethyl cellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, ethyl Cellulose, gum arabic, starch and the like. Examples of sugars include glucose, fructose, sucrose, lactose, maltose, trehalose, maltotriose, oligosaccharides and the like. Examples of sugar alcohols include mannitol sorbitol, maltitol, xylitol, erythritol and the like. These can be used individually by 1 type or in combination of 2 or more types.

Examples of the lubricant include magnesium stearate, calcium stearate, sodium stearyl fumarate, polyethylene glycol, talc, stearic acid, and sucrose fatty acid ester. Examples of the fragrance include menthol, limonene, plant essential oils (mint oil, mint oil, lychee oil, orange oil, lemon oil, and the like). Examples of the sweetening agent include sodium saccharin, aspartame, stevia, dipotassium glycyrrhinate, acesulfame potassium, taumatin, sucralose and the like. As the acidulant, citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, lactic acid or salts thereof can be used.

(II) Manufacturing method of drug-containing granulated product

The crude drug-containing granulated material is, for example, a mixture of (B) silicon dioxide and water mixed with (A) a dry granulated product by adding a dry dry extract to the wet granulated product, and (C) a disintegrant and then stirred and mixed. After that, it can be obtained by drying. More specifically, the following method is mentioned.

The manufacturing method of the herbal-containing granules will be described in more detail.

Silicon dioxide is thrown into a high speed stirring granulator, and it adds, stirring 1.2-1.8 mass parts of purified water with respect to 1 mass part of silicon dioxide from a liquid input part. After adding purified water, high-speed stirring is carried out again for 10 minutes (5 to 15 minutes), and then the herbal dry extract is added and stirred for 1 to 2 minutes until it becomes uniform again. Thereafter, a disintegrating agent is added, and high-speed stirring is further performed for 10 minutes (5 to 30 minutes). The assembly generally uses an apparatus used for assembly, for example, a high speed stirring granulator. The obtained granulated material is suitably dried and used. For drying, a shelf-type dryer or a fluidized bed granulator, which are generally used devices, is used. The obtained particles may be used as granulated particles as they are, or may be appropriately treated with grains or the like. It is preferable to perform sizing in combination with the grinding | pulverization process using a grinder, etc., and a bodily fluid passage process. Grinding and passing can be performed by a well-known method, respectively.

Although the average particle diameter of a herbal-containing granulated material can be arbitrarily set in the range which does not have a problem in manufacturability, 30-500 micrometers is preferable and 100-350 micrometers is more preferable. In addition, the average particle diameter of this invention means a number average diameter, and can calculate it by the number% using the laser diffraction type particle size distribution measuring apparatus (for example, LS13 320 by BECKMAN COULTER company). .

(Ⅲ) intraoral collapse tablet

The oral disintegrating tablet of the present invention contains the above-mentioned herbal-containing granulated product, and it is also possible to use it as it is as a herbal-containing granulated product, but the content thereof is preferably 1 to 97 mass% in the oral disintegrating tablet, and is preferably 5 to 80. Mass% is more preferable, and 5-35 mass% is further more preferable.

In the orally disintegrating tablet of the present invention, any component can be blended within a range that does not impair the effects of the present invention. As optional components, drugs, additives, etc. other than a herbal dry extract are mentioned. As an additive, what is generally mix | blended with a tablet can be used, For example, an excipient, a binder, a disintegrating agent, a lubricant, etc. are mentioned. These can be used individually by 1 type or in combination of 2 or more types.

The drug for use in the oral disintegrating tablet of the present invention is not particularly limited, and the drug contained in particulate raw materials (drug particles: drug single product, dispersed drug particles, supported particles) Particulate state drugs such as particles). Examples of drugs include tannin acid berberine, maniac extract triplex, maniac extract acid, lunatic grass root, soft green horse, aldioxa, berberine chloride, bismuth diacid, phosphoidoephedrine hydrochloride, Phenylephrine hydrochloride, d-maleic acid chlorpheniramine, dl-maleic acid chlorpheniramine, belladonna total alkaloids, aspirin, acetaminophen, methenzamide, isopropyl antipyrine, ibuprofen, ketoprofen, naproxen, roxofene Na, diphenhydramine hydrochloride, maleic acid carbinoxamine, dextromethorphan embrittlement, caffeine anhydrous, sucralate hydrate, synthetic hydrotalcite, albumin tannin, yellow horse, heterozygous horse , Hualien horse, Senburi horse, Loperamide hydrochloride, Copper chlorophyllin K, Yeok wood horse, Licorice horse, Glyciridin Acid and its salts, Pedrin, belladonna, etc. are mentioned. Among them, water insolubility such as berberan tannin, ibuprofen, aldioxa, naproxen, sucralate hydrate, synthetic hydrotalcite is preferred. When the ratio of such insoluble particles is high, the disintegrating effect is increased.

In addition, these drugs and drug particles may be granulated using an excipient, a binder, a disintegrating agent, a lubricant, and the like to form an active ingredient granulated product.

Examples of the excipient include cellulose such as crystalline cellulose and low-substituted hydroxypropyl cellulose and derivatives thereof, starch such as corn starch, potato starch and hydroxypropyl starch and derivatives thereof such as lactose and mannitol. Sugars and sugar alcohols, magnesium metasilicate aluminate, synthetic hydrotalcite and the like. These can be used individually by 1 type or in combination of 2 or more types.

Examples of the binder include water-soluble high molecular compounds, sugars, sugar alcohols, and the like. Examples of the water-soluble polymer include water-soluble cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose and hydroxymethyl cellulose, polyacrylic acid, carboxyvinyl polymer, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, methyl cellulose, ethyl Cellulose, gum arabic, starch and the like. Examples of sugars include glucose, fructose, sucrose, lactose, maltose, trehalose, maltotriose, oligosaccharides and the like. Examples of sugar alcohols include mannitol, sorbitol, maltitol, xylitol, erythritol and the like. These can be used individually by 1 type or in combination of 2 or more types.

Content of an excipient and a binder is 0-90 mass% in intraoral disintegrating tablet, and 0-50 mass% is preferable. When there is too much compounding quantity, there exists a possibility that the quantity of the herbal dry extract which can be mix | blended with this invention may become small, but the minimum at the time of compounding is preferable 20 mass%.

Examples of the disintegrating agent include crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, hydroxypropyl starch and the like. These can be used individually by 1 type or in combination of 2 or more types. Among them, crospovidone is preferable.

Moreover, 0.01-1.0 are preferable and, as for the compounding mass ratio represented by the disintegrating agent in the disintegrating agent / intraoral disintegrating tablet in a herbal-containing granulated material, 0.05-0.45 are more preferable.

0-20 mass% in oral disintegrating tablet is preferable, as for content of disintegrating agents other than a crude drug containing granulated material, 2-15 mass% is more preferable, 3.5-12 mass% is further more preferable. A large content deteriorates the texture.

Examples of the lubricant include magnesium stearate, calcium stearate, sodium stearyl fumarate, polyethylene glycol, talc, stearic acid, and sucrose fatty acid ester. 0-7 mass% is preferable in oral disintegrating tablet, and, as for content of a lubricant, 0.1-1.0 mass% is more preferable.

In addition, in the range which does not impair the effect of this invention, a pigment | dye, a mating agent, a flavoring agent, a fragrance | flavor, a stabilizer, etc. can be used individually by 1 type or in combination of 2 or more types, respectively. Examples of the dye include titanium oxide, iron oxide 32, food yellow No. 5, and the like. Examples of the stabilizer include sodium edetate, benzoic acid, and the like. Examples of the mating agent include aspartame, sucralose, acesulfame potassium, saccharin, sodium saccharin, trehalose, etc., as sweeteners, citric acid, malic acid, tartaric acid, succinic acid, fumaric acid, and the like. As a flavoring agent, monoterpenes, such as menthol, camphor, borneo, limonene, essential oils containing them, etc. are mentioned.

The orally disintegrating tablet of the present invention can be obtained by blending a drug-containing granulated product, and more specifically, it can be obtained by mixing the drug-containing granulated product with the above-described optional components as necessary and tableting the mixture. . In tableting, the apparatus generally used for shaping | molding of a tablet is used. For example, a single tablet press and a rotary tablet press are used. The molding pressure at the time of tableting is adjusted from the hardness suitable for a molded object, and the collapsibility in the oral cavity. For example, the pressure is set in the range of 100 to 2000 kgf.

The tablet size of the orally disintegrating tablet of the present invention is not particularly limited and may be a tablet having a diameter based on the amount of conventional powders in the pharmaceutical formulation field. The mass per tablet of tablet is not specifically limited, What is necessary is just to set suitably according to a use, a taking method, etc. For example, it is preferable to set it as 100-2000 mg / tablet.

The strength of the tablet is set to the strength corresponding to the tablet size as the orally disintegrating tablet. For example, in the case of a circular tablet having a diameter of 11.0 mm, the range of 3 to 12 kgf is preferable, and 4 to 8 kgf is more preferable. In addition, tablet strength can be measured by tablet breakdown strength measuring apparatus TH203CP (made by Toyama Industries, Ltd.).

The dosage form of a tablet can be suitably selected from well-known dosage forms, such as a monolayer tablet, a laminated tablet, a nucleated tablet, and the like. The shape may be any shape such as circular tablets, caplet tablets, donut tablets, or oblong tablets. The intraoral disintegrating tablet may be marked with a mark, a letter for identification, and a dividing line for division.

EXAMPLE

Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to the following Example. In addition, in the following example, when there is no specification especially, "%" of a composition shows the mass%, and a ratio shows the mass ratio.

[Examples 1 to 19 and Comparative Examples 1 to 9]

By the following method, the herbal-containing granulated material, the active ingredient granulated product, and the tablet were prepared, and the following evaluation was performed. Record the results in the table.

Preparation Example: Preparation of Herb-Containing Granules

The silicon dioxide (hard silicic anhydride (Japan)) described in the herbal dry extract containing granulated column previously takes 33000 servings of the composition amount, and is a high speed mixer FS.GS.10J type (Fukae pautech ), The rotational speed was set to 300 rpm of agitator and 1500 rpm of chopper, and stirred for 2 minutes, and about 1.5 times the amount of purified water taken by the ratio described in the impregnation column was dripped over 3 minutes from the liquid input part. After stirring, the mixture was stirred for 10 minutes, and the herbal dry extract taken at a predetermined ratio was added thereto, stirred for 1.5 minutes, and then the disintegrating agent taken at the ratio described in the herbal medicine-containing granulated column was added thereto, and the current value of the agitator Stirring was performed for 17 minutes until it became 6.4 A. The obtained granulated material was spread on a batt, and air-dried for 3 hours at 105 degreeC with shelf dryer DN-93 (made by Yamato Scientific). Sieve of 500㎛ size And for the amount and chetong (particles not passed through the body is rubbed with a spatula on the material coming from broken) to obtain an average particle size of 200 to 400㎛ granules (crude drug-containing granulated product).

Preparation Example: Preparation of Active Ingredient Granules

1500 g of tannin acidberberine and 900 g of lunatic extract triplex C were put into a stirring granulator (manufactured by Fukae Industry Co., Ltd., high speed mixer FS.GS.10J type). After the addition, stirring was started under the conditions of an agitator 400 rpm and a chopper 2500 rpm, and 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. Then, stirring operation was continued for 10 minutes, and the stirring granulated material (temperature 40 degreeC) was discharged | emitted from the granulator. The agitated granulated material obtained is preheated to an intake temperature of 80 ° C in advance, and charged into a Spiral flow SFC-5 type (manufactured by Furo Into Industrial Co., Ltd.) whose exhaust temperature is 50 ° C. The fluidized bed drying operation was started under the conditions of 占 폚, exhaust air volume of 2.5 m 3 / min, and rotor rotational speed of 200 rpm. The drying operation was continued for about 50 minutes, and discharged from the Spiral flow SFC-5 type at the time when the exhaust temperature became 60 degreeC, and the granular dry matter (temperature 72 degreeC) was obtained. The granular dried material was passed through the whole body through a sieve having an eye size of 850 µm (particles that did not pass through the sieve were crushed by a spatula on the sieve) to obtain an active ingredient granulated product. In addition, lunatic extract triplex C is a granulated particle containing lunatic extract and an excipient (corn starch (corn starch)), which is a water-soluble concentrated extract which is concentrated by extracting the extract extracted from the herbal medicine and dried in an appropriate manner to form a powder. This differs from the "medicinal herb dry extract" of the present invention.

[Preparation of Tablets]

After taking the obtained crude drug-containing granulated material, other active ingredient granulated product, and other additive ingredients other than the lubricant, it is taken at a predetermined ratio so as to be 3000 g, put into a plastic bag and shaken by hand about 20 times, and then mixed with the lubricant. Put again and mix 10 times. Using this mixed powder, a circular tablet having a diameter of 11.0 mm was obtained using Ribura 2 (manufactured by Kikusui Co., Ltd.). The tableting pressure was adjusted to a hardness of 4 to 8 kgf by using a tablet hardness tester (manufactured by Yamato Scientific Co., Ltd.) (rotational speed: 20 rpm, number of balls: 12).

[Evaluation of Oral Collapse]

Three adult males and one adult female evaluated oral disintegration in the following order.

The tablets were placed in the oral cavity, the tablets collapsed while rolling with the tongue, and the time until the tablets completely collapsed was measured. From the average value of the disintegration time of four people, the orbital disintegration was evaluated based on the following evaluation criteria. (Triangle | delta) or more shall be an allowable range.

<Evaluation Criteria>

◎: less than 30 seconds

○: 30 seconds or more but less than 45 seconds

△: 45 seconds or more but less than 60 seconds

×: 60 seconds or more

[Evaluation of the texture]

The texture of the three adult males and one adult female was evaluated in the following order.

The tablets were placed in the oral cavity, the tablets were disintegrated while being rolled with the tongue, and the texture (powder feeling, kernel feeling) until the tablets completely collapsed was determined according to the following criteria. However, about the orbital disintegration property of 60 second or more, it evaluated after crushing and collapsing.

<Judge criteria>

5 points: very good

4 points: Good

3 points | pieces: I cannot say which way

2 points | piece: not good

1 point: not very good

From the average value of the judgment result of four people, the oral herbal taste was evaluated based on the following evaluation criteria. (Triangle | delta) or more shall be an allowable range.

<Evaluation Criteria>

◎: 4 or more points

(Circle): Less than four points Three or more points

△: less than 3 points or more 2 points

×: less than 2 points

[Assessment of Assembly]

400 g of silicon dioxide is mixed with High Speed Mixer FS. GS. It put in 10J type (made by Fukae Powder Co., Ltd.), the rotation speed was set to an agitator 300rpm and a chopper 1500rpm, and it stirred for 2 minutes. The mixture was stirred while dropping 1.5 times the amount of purified water over 3 minutes with respect to silicon dioxide, followed by stirring for 10 minutes. The current value of the agitator at this time is measured. The herbal dry extract taken in predetermined ratio was thrown into this, and it stirred for 1.5 minutes, a disintegrating agent was added again, and stirring is continued. The stirring time from the disintegrant to the agitator's current value rises 0.4A is measured.

After the disintegrating agent was added, the stirring time taken until the current value of the agitator rose by 0.4 A was evaluated based on the following evaluation criteria. (Triangle | delta) or more shall be an allowable range.

In addition, formation of the granulated material can be confirmed by the increase of the current value. If the stirring time is too long to form the granulated material, the granulation does not proceed, and if the stirring time is short, the granules become large granules immediately, making adjustment of the particle size difficult, and thus, the granulation is not good. Regarding the granulation of the present invention, the target granulated product can be obtained by setting the stirring time to 15 minutes or more and less than 20 minutes.

<Evaluation Criteria>

◎: stirring time 15 minutes or more but less than 20 minutes

○: stirring time 10 minutes to less than 15 minutes or 20 minutes to less than 25 minutes

△: stirring time 5 minutes or less, less than 10 minutes or 25 minutes or more, less than 30 minutes

×: stirring time less than 5 minutes or 30 minutes or more

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

** Powdery feeling and numbness feeling which are the judgment criteria of the texture were not a problem, but because there were many peony dry extracts, it felt a little cold.

* The quantity of purified water is the quantity required at the time of preparation of particle | grains, and since it evaporates at the time of drying, it is not included in the sum total of refinement | purification.

The raw material used by the said example is shown below. In addition, unless otherwise specified, the quantity of each component in a table | surface is a pure part conversion amount.

Corridone CL-SF: product name, BASF product, crospovidone, average particle diameter 17 탆.

L-HPC (Low Substituted Hydroxypropyl Cellulose): Shin-Etsu Chemical Co., Ltd.

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Calcium silicate: Eza food Chemical Co., Ltd. product, Flolite RE, Average particle diameter 28 micrometers.

Claims (10)

(A) 45 to 70 mass% of crude dry extract selected from peony dry extract and prunus dry extract, (B) 20 to 35 mass% of silicon dioxide and (C) 6.5 to 20 mass% of disintegrant selected from cross povidone An orally disintegrating tablet, characterized in that it comprises a drug-containing granulated product. The method of claim 1,
The compound mass ratio represented by (A) herbal dry extract / (B) silicon dioxide in a herbal-containing granulated material is 1.4-3.5, The oral disintegrating tablet characterized by the above-mentioned. The method according to claim 1 or 2,
The compound mass ratio represented by (C) disintegrant / (B) silicon dioxide in a herbal-containing granulated material is 0.23-0.80, The intraoral disintegrating tablet characterized by the above-mentioned. The method according to claim 1 or 2,
Intraoral disintegrating tablet characterized in that it comprises 5 to 35% by mass of the herbal containing granules in the oral disintegrating tablet. The method according to claim 1 or 2,
A disintegrating agent is added in addition to the herbal-containing granulated product, and the content is 2 to 20% by mass in the oral disintegrating tablet. The method of claim 5,
The compounding mass ratio represented by the disintegrating agent in the disintegrating agent / intraoral disintegrating tablet in the herbal-containing granulated product is 0.01 to 1.0, wherein the disintegrating tablet in the oral cavity. The method of claim 5,
An oral disintegrating tablet is also characterized in that an excipient and a binder are blended in addition to the crude drug-containing granulated material, and the content thereof is 20 to 90% by mass in the oral disintegrating tablet. (A) 45 to 70 mass% of crude dry extract selected from peony dry extract and prunus dry extract, (B) 20 to 35 mass% of silicon dioxide and (C) 6.5 to 20 mass% of disintegrant selected from cross povidone A method for producing an orally disintegrating tablet comprising a crude drug-containing granulated product, wherein the wet granulated product is added to a wet granulated product by adding a dry herbal extract to a mixed mixture of silicon dioxide and water, followed by stirring and mixing the disintegrating agent. After that, it is dried to obtain a herbal-containing granulated product, and an orally disintegrating tablet containing the obtained herbal-containing granulated product is produced. delete delete