KR20240002123A - Oral disintegrating formulation containing rhubarb root extract and manufacturing method thereof - Google Patents

Abstract

Pertaining to an orally disintegrating preparation and a method for manufacturing the same, the orally disintegrating preparation comprising a rhubarb root extract and an orally disintegrating agent according to one aspect has excellent oral disintegration properties and has physical properties suitable for an orally disintegrating preparation. .

Description

Orally disintegrating formulation containing rhubarb root extract and manufacturing method thereof}

The present invention relates to orally disintegrating preparations and methods for their preparation.

Generally, tablets or capsules should be taken by swallowing them with water, but this method may be inconvenient or impractical. In particular, it is difficult to administer tablets in the usual way for the elderly, infants, children, people with difficulty swallowing, patients who need to limit water intake, and patients who are difficult to manage due to physical or mental reasons such as dementia or Parkinson's disease. .

Orally disintegrating preparations were developed to improve this inconvenience. Recently, technologies for manufacturing orally disintegrating preparations using various methods have been in the spotlight. Orally disintegrating preparations are rapidly disintegrated and dissolved by saliva in the oral cavity without water, forming a solution or suspension, and sequentially move to the absorption sites of the digestive tract, such as the oral cavity, esophagus, duodenum, and small intestine, along with saliva. These preparations are not only easy to take by allowing them to be taken without water, but also have the characteristic of allowing the active ingredients to be absorbed quickly.

To date, various manufacturing processes for orally disintegrating preparations have been developed, and one of the widely used methods is spray drying. The most representative method using spray drying is the WowTab technology from Yamanouchi Pharmaceutical Company of Japan. In this method, tablets are manufactured by mixing low-formability saccharides and high-formability saccharides in an appropriate ratio and then spray-drying them with the drug.

Sugar, sugar alcohol, etc. are used as main excipients in these orally disintegrating preparations. However, sugar or sugar alcohol has poor tabletting properties, so when using it as a main excipient, attempts are made to improve tableting properties by mixing functional excipients such as crystalline cellulose or increasing the amount of lubricant. However, in this case, when the orally disintegrating agent is administered, there are problems such as poor texture, foreign body sensation, and long disintegration time. Therefore, there is a need to develop a method for manufacturing an orally disintegrating preparation with superior disintegrability.

US Patent No. 5,576,014 US Patent No. 6,589,554

One aspect is to provide an orally disintegrating formulation comprising a rhubarb root extract and an orally disintegrating agent.

Another aspect includes the steps of i) mixing excipients and disintegrants and granulating to prepare an orally disintegrant;

ii) mixing the orally disintegrant and rhubarb root extract; and

iii) to provide a method for producing an orally disintegrating formulation containing a rubab root extract and an orally disintegrating agent, including the step of formulating the mixture.

One aspect provides an orally disintegrating formulation comprising a rhubarb root extract and an orally disintegrating agent.

The orally disintegrant refers to a mixture having disintegration properties used in the production of orally disintegrating preparations.

In one embodiment, the orally disintegrant may be granulated.

As long as the granulation is a process that improves the fluidity and tabletability of the orally disintegrant, the type of process is not particularly limited, and for example, the granulation may be performed by a dry method, a wet method, or a fluidized bed granulation method. Manufacturing processes using a double binder include a wet method and a fluidized bed assembly method, and manufacturing processes using only a binder without a binder include a dry method.

In one embodiment, the orally disintegrating agent is present in an amount of 1 to 95% by weight, 1 to 94% by weight, 1 to 93% by weight, 1 to 92% by weight, 1 to 91% by weight, 1 based on the total weight of the orally disintegrating agent. to 90% by weight, 1 to 89% by weight, 10 to 95% by weight, 20 to 95% by weight, 30 to 95% by weight, 40 to 95% by weight, 50 to 95% by weight, 60 to 95% by weight, 70 to 95% by weight Weight %, 80 to 95 weight %, 10 to 94 weight %, 20 to 93 weight %, 30 to 92 weight %, 40 to 91 weight %, 50 to 90 weight %, 60 to 89 weight %, 70 to 89 weight % Alternatively, it may be included at 80 to 89% by weight.

The orally disintegrant may include excipients and disintegrants.

In one embodiment, the excipients include mannitol, sorbitol, xylitol, isomalt, glucose, maltodextrin, trehalose, dextrose, sucrose, fructose, maltose, maltitol, methylcellulose, microcrystalline cellulose, lactose, low degree of substitution. Hydroxycellulose, carboxymethylcellulose or alkali metal salts of carboxymethylcellulose, carrageenan, galactomannan, tragacanth, pectin, chitosan or derivatives of chitin, gum arabic, xanthan gum, alginic acid or alkali metal alganate, polymethacrylic It may be one or more types selected from the group consisting of acids or salts thereof, methacrylate copolymers, polyvinyl alcohol, polyvinylpyrrolidone, copolymers of polyvinylpyrrolidone and vinyl acetate, polypropylene oxide, and polymers thereof. .

In one embodiment, the excipient may be mannitol. The average particle size of the excipient is not particularly limited, but is preferably 10 to 200 μm, more preferably 10 to 100 μm, and even more preferably 10 to 50 μm. To achieve the desired particle size, ground products are suitably used as needed.

The excipients are used in an amount of 1 to 80% by weight, 1 to 79% by weight, 1 to 78% by weight, based on the total weight of the orally disintegrating preparation for the purpose of improving disintegration, solubility, moldability, tabletability, stability, etc. 1 to 77% by weight, 1 to 76% by weight, 1 to 75% by weight, 10 to 80% by weight, 20 to 80% by weight, 30 to 80% by weight, 40 to 80% by weight, 50 to 80% by weight, 10 to 80% by weight It may be included at 79% by weight, 20 to 78% by weight, 30 to 77% by weight, 40 to 76% by weight, or 50 to 75% by weight.

In one embodiment, the disintegrant is corn starch, hydroxypropyl methylcellulose, bentonite, hydroxypropyl starch, sodium carboxymethyl cellulose, sodium alginate, sodium lauryl sulfate, silicic anhydride, 1-hydroxypropyl cellulose, Dex. Tran, ion exchange resin, polyvinyl acetate, formaldehyde treated casein and gelatin, alginic acid, amylose, guar gum, sodium bicarbonate polyvinylpyrrolidone, gum arabic, amylopectin, pectin, sodium polyphosphate, ethyl cellulose, It may be one or more types selected from the group consisting of white sugar and magnesium aluminum silicate.

In one embodiment, the disintegrant may be corn starch. There is no particular limitation on the average particle size of the disintegrant, but is preferably 10 to 200 μm, more preferably 10 to 100 μm, and even more preferably 10 to 50 μm. To achieve the desired particle size, ground products are suitably used as needed.

The disintegrants can be used alone or in combination.

The disintegrant is used in an amount of 1 to 25% by weight, 1 to 24% by weight, 1 to 23% by weight, 1 to 22% by weight, 1 to 21% by weight, 1 to 20% by weight, 5 to 5%, based on the total weight of the orally disintegrating preparation. It may be included at 25% by weight, 10 to 25% by weight, 15 to 25% by weight, 5 to 24% by weight, 10 to 23% by weight, 15 to 22% by weight, 15 to 21% by weight, or 15 to 20% by weight.

When the disintegrant is corn starch or hydroxypropyl starch, the disintegrant can be used in an amount of preferably 4 to 20% by weight, more preferably 4 to 15% by weight, and even more preferably 8 to 12% by weight. there is.

In one embodiment, the orally disintegrating preparation may further include additives such as sweeteners, acidulants, flavorings, pigments, antioxidants, stabilizers, surfactants, etc. for the purpose of shaping, stabilizing, improving taste, etc. These additives can be added in an amount that does not adversely affect the disintegration time or hardness of the orally disintegrating preparation.

Examples of the sweeteners include sugars and sugar alcohols such as xylitol, erythritol, sorbitol, trehalose, glucose, and sucrose, and aspartame, sucralose, sodium saccharin, dipotassium glycyrrhizinate, thaumatin, and stevia. Includes high-intensity sweeteners such as

Examples of the flavoring include strawberry, orange, pineapple, yogurt, peppermint, spearmint, menthol, etc.

Examples of the above-mentioned acidulants include citric acid, malic acid, tartaric acid, etc.

The preparation according to the present invention can be formulated for oral administration, such as tablets, films, suspensions, granules, gels, pills, tinctures. , decoction, infusion, spirit, fluidextract, elixir, extract, syrup, powder, aromatic It can be formulated in various forms such as water, lemonade, etc.

The tablets include, for example, orally disintegrating tablets, mucoadhesive tablets, dispersible tablets, sublingual tablets, buccal tablets, and chewable tablets. ), effervescent tablets, and solution tablets. In addition, a person skilled in the art can use the above various tablets by modifying them in various ways as needed. More preferably, it may be a liquid form or a dosage form that dissolves, disperses, or disintegrates in the oral cavity (i.e., orally disintegrable). For example, it may be an orally dispersible dosage form, such as an orally dispersible film, an orally disintegrating tablet, a suspension, a suspension tablet, a rapidly disintegrating tablet, an orally disintegrating granule, an orally disintegrating troche, a sublingual tablet, a powder, and/or a chewable tablet. . These formulations preferably allow more than 80% of the total formulation to be dissolved, dispersed, or disintegrated within 10 or 5 minutes after oral administration. The orally dissolving film can be used interchangeably with terms such as film, strip, and orally disintegrating film, and can be used interchangeably in the oral cavity such as on the tongue, oral mucosa, and sublingually. It refers to a dosage form that is taken by sticking it inside the body and dissolving it. The formulation for oral administration in the form of an orally disintegrating film and a fast-acting disintegrating tablet according to the present invention has the advantage of being able to be taken without water.

The orally disintegrating preparation may be one or more dosage forms selected from the group consisting of orally disintegrating film, orally disintegrating tablets, suspensions, suspension tablets, rapidly disintegrating tablets, orally disintegrating granules, orally disintegrating troches, sublingual tablets, powders, and chewable tablets. You can.

The orally disintegrating preparation may further include ingredients typically used in orally disintegrating preparations, and may further include a pharmaceutically acceptable carrier that can be typically added to pharmaceutical preparations. The pharmaceutically acceptable carrier includes excipients, plasticizers, disintegrants, diluents, solvents, penetration enhancers, preservatives, buffers, gel formers, lubricants, carriers, stabilizers, gels, dyes, and pigments commonly used in the pharmaceutical field. , surfactants, inert fillers, adhesives, texturizers, softeners, emulsifiers, and mixtures thereof.

In one embodiment, the orally disintegrating preparation may include rubab root extract. The rhubarb root extract may be included in an amount of 0.0001 to 60% by weight, for example, 0.13334 to 4% by weight, 0.2 to 3% by weight, 0.3 to 1% by weight, or 0.4 to 0.5% by weight, based on the total weight of the orally disintegrating preparation. there is.

The disintegration time of an orally disintegrating preparation is measured by placing gauze on a petri dish, placing the orally disintegrating preparation on it, and then injecting a certain amount of a solution containing a certain concentration of gardenia blue pigment with a dropper to measure the time until the tablet loses its shape. It can be obtained by doing this:

The time required for rapid disintegration in the oral cavity (disintegration time) varies slightly from person to person, but in the present invention, after placing the orally disintegrating agent in the oral cavity, it is administered within 180 seconds, preferably within 90 seconds, more preferably within 60 seconds. This can mean complete disintegration within seconds.

In one embodiment, the orally disintegrating preparation may have a disintegration time of within 180 seconds, within 90 seconds, or within 60 seconds.

The hardness of orally disintegrating preparations can be measured using a hardness tester TBH325 TD, Erweka, Germany.

In one embodiment, the orally disintegrating formulation has a hardness of 1 to 9kp, 1 to 8kp, 1 to 7kp, 1 to 6kp, 1 to 5kp, 2 to 9kp, 3 to 9kp, 4 to 9kp, 2 to 8kp, 3. It may be from 7 kp, 4 to 6 kp, or 4 to 5 kp.

Friability of orally disintegrating formulations can be obtained by the tablet friability measurement method described in the Tablet friability chapter of USP 1216.

In one embodiment, the orally disintegrating formulation has a friability of 0.01 to 0.8%, 0.01 to 0.7%, 0.01 to 0.6%, 0.01 to 0.5%, 0.01 to 0.4%, 0.1 to 0.8%, 0.2 to 0.8%, 0.3. to 0.8%, 0.2 to 0.7%, 0.3 to 0.6%, 0.3 to 0.5%, or 0.3 to 0.4%.

The orally disintegrating preparation according to the present invention can be used in health functional foods.

In this specification, the term "health functional food" refers to a food manufactured or processed using specific ingredients as raw materials or by extracting, concentrating, refining, or mixing specific ingredients contained in food raw materials for the purpose of health supplementation. It refers to food designed and processed to fully exert bioregulatory functions on the living body, such as biodefense, regulation of biorhythm, and prevention and recovery of disease. The health functional food composition can perform functions related to preventing and improving skin damage caused by fine dust.

There are no special restrictions on the types of foods above. Examples of foods to which the extract can be added include formulations selected from the group consisting of powders, granules, tablets, capsules, pills, gels, jellies, suspensions, emulsions, syrups, tea bags, leached teas, gums, candies, and health drinks. and includes all health foods in the conventional sense.

The health drink composition may include various sweeteners, flavoring agents, or natural carbohydrates as additional ingredients, like ordinary drinks. The sweetener may be a natural sweetener or a synthetic sweetener. The natural sweetener may be thaumatin or stevia extract, and the synthetic sweetener may be saccharin, sucralose, or aspartame.

The natural carbohydrate may be monosaccharide, disaccharide, polysaccharide, xylitol, sorbitol, or erythritol. The monosaccharide may be glucose or fructose, and the disaccharide may be maltose or sucrose. The polysaccharide may be a dextrin or cyclodextrin. The proportion of the natural carbohydrate may generally be about 0.01 to 10 g, for example, about 0.01 to 0.1 g per 100 ml of the composition of the present invention.

The health functional food may include food supplements that are foodologically acceptable, and may include an appropriate carrier commonly used in the manufacture of health functional foods.

In addition to the above, the composition of the present invention contains various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, It may include carbonating agents used in carbonated drinks. Additionally, the composition of the present invention may include pulp for the production of natural fruit juice, fruit juice beverages, and vegetable beverages. These ingredients can be used independently or in combination. The ratio of these additives is not very important, but is generally selected in the range of 0.01 to 0.1 parts by weight per 100 parts by weight of the composition of the present invention.

Another aspect includes i) mixing excipients and disintegrants and granulating to prepare an orally disintegrant;

ii) mixing the orally disintegrant and rhubarb root extract; and

iii) It provides a method for producing an orally disintegrating formulation containing a rubab root extract and an orally disintegrating agent, including the step of formulating the mixture.

In one embodiment, the granulation may be performed by mixing excipients and disintegrants and stirring.

The excipient and disintegrant may be mixed at a weight ratio of 1:0.1 to 1.

The stirring may be performed at 50 to 90°C, 60 to 80°C, or 70°C.

According to one aspect, an orally disintegrating preparation containing a rhubarb root extract and an orally disintegrating agent has excellent oral disintegration properties and has physical properties suitable for an orally disintegrating preparation.

Figure 1 is a diagram showing the process for manufacturing an orally disintegrant according to the present invention.
Figure 2 shows the results of evaluating the moisture absorption rate of Preparation Example 1, Comparative Preparation Example 1, and Comparative Preparation Example 3.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes only and the scope of the present invention is not limited to these examples.

The terms or words used in the specification and claims of the present invention are not to be construed as limited to their ordinary or dictionary meanings, and the inventor may appropriately define the concept of terms to explain his or her invention in the best way. It must be interpreted as meaning and concept consistent with the technical idea of the present invention based on principles.

Throughout the specification of the present invention, when a part is said to "include" a certain component, this means that it does not exclude other components but may further include other components, unless specifically stated to the contrary. .

Throughout the specification of the present invention, “A and/or B” means A or B, or A and B.

Example 1: Granulated Orally Disintegrant

Mannitol and modified starch were mixed at a ratio of 8:2 and dissolved to a Brix concentration of 50. It was stirred at 70°C for 60 minutes and sterilized by treatment at 95°C for 30 minutes. Afterwards, the plate was hot-air dried and pulverized to obtain granules. The obtained granules were sieved with 40 mesh.

Comparative Example 1: Simple mixed oral disintegrant

Mannitol and modified starch were mixed at a ratio of 8:2 and sieved through a 40 mesh.

Comparative Example 2: Sugar alcohol-based orally disintegrant 1

Mannitol was used as an orally disintegrant.

Comparative Example 3: Sugar alcohol-based orally disintegrant 2

Xylitol and polydextrose were mixed at a ratio of 9.5:0.5 and sieved with 40 mesh.

Manufacturing Example 1

An orally dispersible tablet containing the orally disintegrant of Example 1 was prepared.

Specifically, orally disintegrating tablets were prepared by mixing and compressing at the mixing ratio shown in Table 1 below.

Raw material name weight(%) Rhubarb root extract powder 0.4445 Orally disintegrant of Example 1 88.3155 malic acid 0.8200 citric acid 0.6000 Strawberry flavor powder 3.0000 Carboxymethylcellulose Calcium 2.5000 Strawberry flavor powder 1.5000 stevia 0.3200 bit red 0.3000 silicon dioxide 0.9000 Magnesium stearate 0.8000 stearic acid 0.5000 Sum 100.0000

Comparative Manufacturing Examples 1 to 3

Orally dispersible tablets containing the orally disintegrants of Comparative Examples 1 to 3 were prepared.

The composition was prepared in the same manner as in Preparation Example 1, except that Comparative Examples 1 to 3 were used as orally disintegrants.

Experimental Example 1: Dissolution time evaluation

The dissolution time of the orally dispersible tablets of Preparation Example 1 and Comparative Preparation Examples 1 to 3 containing the orally disintegrants of Example 1 and Comparative Examples 1 to 3 was evaluated. Specifically, a gauze was laid on a petri dish and an orally disintegrating tablet was placed on it. Then, a certain amount of a solution containing a certain concentration of gardenia blue pigment was instilled with a dropper, and the time until the tablet lost its shape was measured.

Experimental Example 2: Physical property evaluation

The physical properties of Preparation Example 1 and Comparative Preparation Examples 1 to 3 were evaluated. Specifically, a 300g portion was tableted and randomly sampled to evaluate the physical properties.

2.1. Angle of repose measurement

The test was conducted according to the powder angle of repose measurement method described in the Powder flow chapter of USP 1174. The angle of repose means that the smaller the measured angle, the greater the fluidity of the powder.

2.2. weight deviation

Samples of 10 orally disintegrating tablets after tableting were randomly collected were tested for weight deviation (%).

2.3. Hardness measurement

The hardness of the orally dispersible tablets was measured on six samples using a hardness tester TBH325 TD, Erweka, Germany, and the average value was recorded.

2.4. Friability measurement

The tablet friability measurement method described in the Tablet friability chapter of USP 1216 was tested.

2.5. Water absorption rate measurement

A certain amount of a solution containing a certain concentration of gardenia blue pigment was instilled into an orally dispersible tablet, and then the water absorption rate of the orally disintegratable tablet was measured using a moisture meter. Afterwards, the cross-section of the orally dispersible tablet that had been measured was checked and the degree to which moisture was absorbed into the tablet's interior was visually evaluated.

The results of Experimental Examples 1 and 2 are shown in Table 2 and Figure 2.

Oral disintegrant Dissolution time angle of repose
(°) weight deviation
(%) Hardness
(kp) Masondo
(%) Manufacturing Example 1 Granulated Orally Disintegrant 31 seconds 22.62 0.32 4.15 0.39 Comparative Manufacturing Example 1 Simple mixed oral disintegrator More than 60 seconds over 40 3% or more 1 or less 1 or more Comparative Manufacturing Example 2 Sugar alcohol base oral disintegrant 1 More than 60 seconds - 1.25 9.01 0.82 Comparative Manufacturing Example 3 Sugar alcohol base oral disintegrant 2 More than 60 seconds - 1.52 11.10 0.91

As shown in Table 2 and Figure 2, when the granulated orally disintegrant was used as in Preparation Example 1, it was found to have excellent disintegration properties and physical properties suitable for orally disintegrating tablets.

Specifically, in terms of dissolution time, Preparation Example 1 using a granulated orally disintegrant showed the fastest dissolution time at 31 seconds, showing excellent disintegrability. The angle of repose was found to be 22.62° in Preparation Example 1, which was smaller than that in Comparative Preparation Example 1, indicating better fluidity. In the case of weight deviation, it was found that in Preparation Example 1, the weight deviation was the least and tablets could be manufactured uniformly.

If the hardness is less than 1, the tablet may break easily, and if the hardness is more than 9, disintegration of the tablet may be delayed. In the case of Preparation Example 1, the hardness was 4.15 kp, indicating a value suitable for use in orally disintegrating tablets. In Preparation Example 1, the friability value was the lowest at 0.39%, indicating that it had the best mechanical stability.

As a result of evaluating the moisture absorption rate, Preparation Example 1 showed the highest value of 24.52%, showing that it is suitable for use in orally disintegrating tablets.

From the above results, it was found that by using a granulated orally disintegrating agent, it was possible to manufacture orally disintegrating tablets with excellent disintegration properties and physical properties suitable for orally disintegrating tablets.

Claims (16)

An orally disintegrating preparation containing rhubarb root extract and an orally disintegrating agent. According to paragraph 1,
The orally disintegrating agent is an orally disintegrating preparation that is granulated. According to paragraph 1,
The orally disintegrating agent is an orally disintegrating formulation that is contained in an amount of 1 to 95% by weight based on the total weight of the orally disintegrating formulation. According to paragraph 1,
The orally disintegrating agent is an orally disintegrating formulation containing an excipient and a disintegrant. According to clause 4,
The excipients include mannitol, sorbitol, xylitol, isomalt, glucose, maltodextrin, trehalose, dextrose, sucrose, fructose, maltose, maltitol, methylcellulose, microcrystalline cellulose, lactose, low-substituted hydroxycellulose, and carboxymethyl. Cellulose or alkali metal salts of carboxymethylcellulose, carrageenan, galactomannan, tragacanth, pectin, chitosan or chitin derivatives, gum arabic, xanthan gum, alginic acid or alkaline metal alganic acid, polymethacrylic acid or its salt, meta An orally disintegrating preparation comprising at least one selected from the group consisting of acrylate copolymer, polyvinyl alcohol, polyvinylpyrrolidone, copolymer of polyvinylpyrrolidone and vinyl acetate, polypropylene oxide, and polymers thereof. According to clause 4,
The excipient is mannitol, and the average particle size of the mannitol is 10 to 200 μm. According to paragraph 4,
The excipient is an orally disintegrating formulation that is contained in an amount of 1 to 80% by weight based on the total weight of the orally disintegrating formulation. According to paragraph 4,
The disintegrant includes corn starch, hydroxypropyl methyl cellulose, bentonite, hydroxypropyl starch, sodium carboxymethyl cellulose, sodium alginate, sodium lauryl sulfate, silicic anhydride, 1-hydroxypropyl cellulose, dextran, ion exchange resin, Made of polyvinyl acetate, formaldehyde-treated casein and gelatin, alginic acid, amylose, guar gum, polyvinylpyrrolidone sodium bicarbonate, gum arabic, amylopectin, pectin, sodium polyphosphate, ethyl cellulose, sucrose, and magnesium aluminum silicate. An orally disintegrating preparation comprising at least one selected from the group consisting of: According to paragraph 4,
The disintegrant is corn starch, and the average particle size of the corn starch is 10 to 200 μm. According to paragraph 4,
The disintegrant is an orally disintegrating formulation containing 1 to 20% by weight based on the total weight of the orally disintegrating formulation. According to paragraph 1,
An orally disintegrating preparation containing one or more additives selected from the group consisting of sweeteners, acidulants, flavorings, colorants, antioxidants, stabilizers, and surfactants. According to paragraph 1,
The orally disintegrating preparations include tablets, films, suspensions, granules, gels, pills, tinctures, decoctions, infusions, It is in the form of a spirit, fluidextract, elixir, extract, syrup, powder, aromatic water or lemonade. Phosphorus orally disintegrating formulation. According to clause 12,
The tablets include orally disintegrating tablets, mucoadhesive tablets, dispersible tablets, sublingual tablets, buccal tablets, chewable tablets, and effervescent tablets ( An orally disintegrating preparation in the form of an effervescent tablet or a solution tablet. According to paragraph 1,
The rhubarb root extract is an orally disintegrating preparation comprising 0.13334 to 4% by weight based on the total weight of the orally disintegrating preparation. According to paragraph 1,
An orally disintegrating preparation having a disintegration time of less than 180 seconds, hardness of 1 to 9 kp, and friability of 0.01 to 0.8%. i) mixing excipients and disintegrants and granulating to prepare an orally disintegrant;
ii) mixing the orally disintegrant and rhubarb root extract; and
iii) A method for producing an orally disintegrating formulation containing a rhubarb root extract and an orally disintegrant, including the step of formulating the mixture.