JP2010159289A - Compression molding preparation and method for producing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a compression molding preparation having quick disintegrability in the oral cavity or in an aqueous solvent, excellent in sense of use at taking, and retaining hardness required for circulation or other handling, and provide a method for producing the preparation. <P>SOLUTION: This quick disintegrable compression molding preparation has pullulan added to a base agent of the preparation. Saccharides are preferable as the base agent of the preparation, sugar alcohols and glutinous starch syrup are particularly preferable. The compression molding preparation is produced by granulating particulate matter including the base agent for the preparation and other formulation additives with a solution in which pullulan is dissolved in an aqueous solvent, or by granulating the particulate matter with an aqueous solvent together with pullulan, and compression-molding the resultant granules. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a compression molding preparation that rapidly disintegrates even with a small amount of water using a compression molding composition for medicine and food, and a method for producing the same.

  In recent years, in addition to the pharmaceutical field, many products have been provided as oral preparations in the fields of health foods and nutritional foods. Many of these oral preparations are dry preparations such as tablets, capsules, granules, and powders. It is currently provided as However, many of these oral preparations are difficult to take for the elderly, children and patients with difficulty swallowing.

  For this reason, dry syrup preparations that can be suspended in water and made into syrups are also provided for ease of taking, but in the case of powder or granules, for each dose Even if it is packaged, the contents may remain in the package, or a part of the contents may be spilled when opened, and there is a problem in taking an appropriate amount.

  Recently, tablets or lozenges that can be taken without water and quickly disintegrate in the oral cavity, or tablets that dissolve quickly in aqueous solvents even when taken in water for the purpose of solving this difficulty of taking. The development of lozenges is ongoing.

  For example, as a method for producing a tablet or a troche as described above, a method for producing an orally disintegrating tablet that compresses a mixture containing water at such a level that the particle surface is moistened (see, for example, Patent Document 1), amorphous Known is a method for producing an orally disintegrating tablet (see, for example, Patent Documents 2 and 3) obtained by compression-molding under low pressure, placing the tablet under humidification, moistening, and further drying. It has been. Also known is a rapidly disintegrating compressed composition using a composition obtained by spray drying a suspension in which an inorganic antacid having the same mass as a saccharide is uniformly dispersed (see, for example, Patent Document 4). Yes. Furthermore, a method for producing an orally rapidly disintegrating tablet by combining a physiologically active substance, a saccharide, and a low-substituted hydroxypropylcellulose under certain conditions (see, for example, Patent Document 5), crystallized sugar and amorphization Oral quick disintegrating tablets using the prepared sugar and its production method (see, for example, Patent Document 6), Oral quick disintegrating tablets using sugar coated with metasilicate aluminate (for example, refer to Patent Document 7), etc. Are known.

  Although the above-mentioned conventional techniques can provide a preparation that maintains quick disintegration in an aqueous solvent and the hardness required for portability, both handle water during the manufacturing process and leave it under high humidity. May cause a problem in stability due to the relationship with the physiologically active ingredient used, and it is not always satisfactory from the viewpoint of manufacturing process management. Furthermore, in an example using an inorganic antacid, since a large amount of the inorganic antacid must be used, there is a concern that the production process and the pH in the digestive tract may be affected. In addition, when preparing a preparation according to the prior art, it is necessary to make the pressure adjustment constant during compression molding, which may complicate the setting and operation of manufacturing conditions. Furthermore, even with such a conventional technique, there is room for further improvement in the feeling of use at the time of taking, such as a feeling of roughness and a powdery feeling remaining after disintegrating in the oral cavity.

Japanese Patent Laid-Open No. 5-271054 Japanese Patent Laid-Open No. 11-12162 JP 11-349475 A JP 2000-86537 A JP 2000-103731 A JP 2002-154988 A JP 2002-308760 A

  Therefore, the present invention provides tablets that have quick disintegration in the mouth and aqueous solvent by simple means, yet have excellent usability when taken, and maintain hardness required for carrying, An object of the present invention is to provide a compression-molded preparation such as a troche and a technique for producing such a compression-molded preparation.

As a result of studying to solve the problems of the prior art, the present inventors have included pullulan in a compression molding preparation such as a tablet or a troche so that it has a suitable strength and hardness and is worn out in the distribution process. In addition, a compression-molded product that can be rapidly disintegrated in a small amount of water is obtained. The present invention was completed by discovering that it also has a disintegrating property that rapidly disintegrates in water.

That is, the gist of the present invention is as follows.
(1) A rapidly disintegrating compression-molded preparation obtained by adding pullulan to a preparation base comprising a sugar selected from the group consisting of sugar, starch sugar, lactose, honey and sugar alcohol, and a silicate compound .
(2) The compression molding composition as described in (1) above , wherein the pullulan content is 0.0001 to 0.1 parts by mass with respect to the compression molding preparation.
(3) The rapidly disintegrating composition according to (1) or (2) above, wherein the content of pullulan is 0.0002 to 0.15 parts by mass with respect to 1 part by mass of the pharmaceutical base. Compression molding formulation.
(4) The rapidly disintegrating compression-molded preparation according to any one of (1) to (3) , further comprising a physiologically active substance.
(5) The rapidly disintegrating compression-molded preparation according to (4) , wherein the physiologically active substance is a pharmaceutically active ingredient.
(6) Granules containing a saccharide selected from the group consisting of sugar, starch sugar, lactose, honey and sugar alcohol, and a preparation base containing a silicate compound, and further containing other appropriate formulation aids. Granulated with a solution obtained by dissolving pullulan in an aqueous solvent, or granulated with an aqueous solvent together with pullulan in an aqueous solvent containing the formulation base and further suitable formulation aids. A method for producing a rapidly disintegrating compression-molded preparation characterized by compression-molding the granulated product.

  The compression-molded preparation of the present invention dissolves rapidly with a small amount of water. For example, when the compression-molded preparation is included in the mouth, it disintegrates within 60 seconds, and the mouth feels rough after the disintegration. Does not remain. In addition, this molded product has an appropriate strength and hardness, and is less likely to lose its shape during distribution and storage.

The present invention relates to a composition for compression molding in which pullulan is added to a pharmaceutical base, a physiologically active ingredient is further added as necessary, and various other additives are further added as formulation aids as necessary. Are a rapidly disintegrating compression-molded preparation that can be disintegrated in a short time with a small amount of water, obtained by compression-molding the composition for compression molding, and a method for producing the same.

The pullulan used in the compression-molded preparation of the present invention is a natural polysaccharide in which maltotriose is regularly α-1,6-linked using starch as a raw material.
When pullulan is used, it is preferably 0.0001 to 0.1 parts by weight, more preferably 0.001 to 0.05 parts by weight, with respect to 1 part by weight of the compression-molded preparation. More preferably, the amount is 0.003 to 0.03 parts by mass. Moreover, it is preferable that it is 0.0002-0.15 mass part with respect to 1 mass part of bases for formulation, It is more preferable that it is 0.001-0.07 mass part, 0.003-0. More preferably, it is 05 mass parts. When gluconolactone and pullulan are used at the same time, it is preferable that gluconolactone: pullulan be blended so that the mass ratio is 0.1-10: 0.01-5.

  The pharmaceutical base used in the compression-molded preparation of the present invention is a base for making a solid molded preparation such as a tablet or troche, and a part or all of it contains an additive that dissolves in water. Any additive that is usually called an excipient is not particularly specified. Of these, saccharides are particularly preferred for the purposes of the present invention. Silicate compounds can also be preferably used.

  The saccharide used in the present invention is not particularly limited, and various saccharides are used. Examples of these saccharides include sugar, starch sugar, lactose, honey, sugar alcohol, and the like, and two or more of these may be used in an appropriate ratio. Examples of the sugar include sucrose, coupling sugar, fructooligosaccharide, palatinose and the like. Examples of starch sugar include glucose, maltose, powdered koji, starch syrup, and fructose. Examples of lactose include lactose, isomerized lactose (lactulose), and reduced lactose (lactitol). Examples of honey include various honeys that are generally used for food. Examples of the sugar alcohol include sorbitol, mannitol, maltitol, reduced starch saccharified product, xylitol, reduced palatinose, and erythritol. Of these, sugar alcohols and starch syrup are preferred, and saccharides such as mannitol, trehalose, xylitol, and sorbitol are particularly preferred.

  Examples of the silicic acid compound used in the present invention include silicic acid or alkali metal or alkaline earth metal salt of metasilicic acid. Specific examples include calcium silicate, magnesium silicate, and aluminum silicate, and magnesium metasilicate aluminate is preferable.

A physiologically active ingredient can be added to the rapidly disintegrating compression-molded preparation of the present invention as needed. Examples of the physiologically active ingredient include a pharmaceutically active ingredient, a preference ingredient, a nutritional supplement ingredient, and the like.
Among these physiologically active ingredients, examples of pharmaceutically active ingredients include nourishing tonic health drugs, antipyretic / analgesic / anti-inflammatory drugs, psychotropic drugs, anxiolytics, antidepressants, hypnotic sedatives, antispasmodics, gastrointestinal drugs, Acid, antitussive expectorant, dental and oral medicine, antihistamine, allergy, cardiotonic, arrhythmia, diuretic, antihypertensive, vasoconstrictor, coronary vasodilator, peripheral vasodilator, antibacterial, antibiotic One or more components selected from substances, chemotherapeutic agents, diabetic agents, osteoporosis agents, skeletal muscle relaxants and the like are used.

For example, vitamin A, vitamin D, vitamin E (such as d-α-tocopherol acetate), vitamin B ₁ (such as dibenzoylthiamine, fursultiamine hydrochloride), vitamin B ₂ (such as riboflavin butyrate) ), Vitamin B ₆ (such as pyridoxine hydrochloride), vitamin C (such as ascorbic acid, sodium L-ascorbate), vitamin B ₁₂ (such as hydroxocobalamin acetate); minerals such as calcium, magnesium, iron; protein; amino acids Oligosaccharides; herbal medicines and the like.

  Antipyretic / analgesic / anti-inflammatory drugs include, for example, aspirin, acetaminophen, ethenamide, ibuprofen, diphenhydramine hydrochloride, chlorpheniramine dl-maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, caffeine, Examples include serrapeptase, lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin, bucolome, pentazocine, and tranexamic acid.

  Examples of the psychotropic drug include chlorpromazine, reserpine and the like. Examples of anti-anxiety drugs include chlordiazepoxide, diazepam and the like. Examples of the antidepressant include imipramine, maprotiline, amphetamine and the like. Examples of the hypnotic sedative include estazolam, nitrazepam, diazepam, phenobarbital sodium, triazolam, brotizolam and the like. Antispasmodic agents include, for example, scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride, and the like.

  Gastrointestinal drugs include, for example, healthy gastrointestinals such as diastase, sugar-containing pepsin, funnel extract, lipase AP, and cinnamon oil; intestinals such as berberine chloride, resistant lactic acid bacteria, and bifidobacteria; and antiemetics such as domperidone. . Examples of the antacid include magnesium carbonate, sodium hydrogen carbonate, magnesium aluminate metasilicate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and the like. In addition, therapeutic agents for peptic ulcers such as gefarnate, cetraxate hydrochloride, teprenone, sofalcone, rebamipide, cimetidine, ranitidine hydrochloride, famotidine, nizatidine, omeprazole, lansoprazole and the like can also be mentioned. Further, laxatives such as sodium picosulfate, senna extract, bisacodyl and the like can be mentioned.

  Examples of the antitussive expectorant include cloperastine hydrochloride, dextromethorphan hydrobromide, theophylline, potassium guaiacol sulfonate, and guaifenesin. Examples of the dental and oral medicine include oxytetracycline, triamcinolone acetonide, chlorhexidine hydrochloride, lidocaine and the like.

  Examples of the antihistamine include diphenhydramine hydrochloride, promethazine, isothipentyl hydrochloride, dl-chlorpheniramine maleate, and the like. Examples of the cardiotonic agent include ethylephrine hydrochloride. Examples of allergic agents include oxamide, tranilast, mequitazine, ketotifen fumarate, epinastine hydrochloride, cetirizine hydrochloride and the like. Examples of the arrhythmic agent include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like. Examples of the diuretic include isosorbide and furosemide. Examples of the blood pressure lowering agent include delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, methyldopa, and the like.

  Examples of the vasoconstrictor include phenylephrine hydrochloride. Examples of the coronary vasodilator include carbochromene hydrochloride, molsidomine, verapamil hydrochloride and the like. Examples of the peripheral vasodilator include cinnarizine and the like. Examples of the astringent include dehydrocholic acid and trepibutone.

  Antibiotics include, for example, cephem, penem and carbapenem antibiotics such as cephalexin, amoxicillin, pibmesilinum hydrochloride and cefotiam hydrochloride. Examples of the chemotherapeutic agent include sulfamethizole and thiazosulfone. Examples of the diabetic agent include tolbutamide, voglibose and the like. Examples of the osteoporosis agent include ipriflavone. Examples of skeletal muscle relaxants include metocarbamol.

  Among the physiologically active ingredients described above, in the compression-molded preparation of the present invention, as the physiologically active ingredients that are preferably blended, for example, among the aforementioned ingredients, vitamins, herbal medicines, antipyretic / analgesic / anti-inflammatory drugs, anxiolytics, Hypnotic sedatives, antispasmodic drugs, gastrointestinal drugs, peptic ulcer drugs, antitussive expectorants, antihistamines, allergic drugs, antihypertensive drugs, diabetes drugs, osteoporosis drugs, skeletal muscle relaxants and the like. These active ingredients may be diluted with a diluent or the like generally used in the fields of medicine, food, and the like. In addition, at least one of the physiologically active ingredients in the compression-molded preparation of the present invention may be oily.

  The compression-molded preparation of the present invention obtained as described above is used as a troche, a tablet or the like in the pharmaceutical and food fields, and the shape and use of this compression-molded preparation are not particularly limited. However, it can be particularly preferably used for a compression-molded preparation intended to rapidly disintegrate in water, particularly with a small amount of water. That is, the compression-molded preparation of the present invention has a characteristic that it disintegrates in a short time upon contact with a small amount of water, and generally disintegrates in a short time of 1 to 60 seconds, preferably 1 to 30 seconds.

The compression molding preparation of the present invention is first prepared after obtaining a granule for compression molding. The granules for compression molding can be obtained by simply mixing the desired ingredients with the base for formulation, the physiologically active substance and other compression molding formulations of the present invention, but it is desirable to perform wet granulation. In wet granulation, a granular material containing one or more substances selected from physiologically active substances and other appropriate formulation aids, if necessary, in a formulation base, is a solution obtained by dissolving pullulan in an aqueous solvent. or granulated, more desirable to be granulated together with an aqueous solvent and pullulan. Moreover, you may mix other suitable formulation aids in the aqueous solution containing a pullulan . Alternatively, a granular material containing a pharmaceutical base and pullulan may be prepared as described above to obtain a granular material separately added with a physiologically active substance, and this may be compression molded.

  Further, as the aqueous solvent used for wet granulation, a water-miscible organic solvent may be used depending on the type of physiologically active substance to be used and other formulation aids. As the water-miscible organic solvent, ethanol, propanol and the like are preferable. The granulation method is not particularly limited as long as it is a generally used method, but stirring granulation, fluidized bed granulation, rolling granulation and the like can be raised, and fluidized bed granulation is particularly preferable.

  The granular material thus obtained is compression-molded by a conventional method such as tableting or other molding methods to obtain the compression-molded preparation of the present invention. The molding pressure at the time of this compression molding may be selected as appropriate so that a tablet that disintegrates within 1 to 60 seconds can be obtained with a small amount of water. -20,000N are preferable, and 3,000N-15,000N are more preferable. Although the compression-molded preparation of the present invention can be produced by tableting or other ordinary methods, the obtained molded product has an appropriate strength and hardness, and is deformed by handling during transportation and storage. Do not do.

  Furthermore, in the production of the compression-molded preparation of the present invention, as long as there is no hindrance to the effect of the present invention, various types generally used for the production of compression-molded preparations described as other formulation aids in the above part. The additive may be included.

  Examples of such additives that are formulation aids include disintegrants, binders, lubricants, taste-masking ingredients, fragrances, and adjuvants.

  Disintegrants include, for example, starch such as corn starch and potato starch, partially pregelatinized starch, sodium carboxymethyl starch, carmellose, carmellose calcium, croscarmellose sodium, polyvinyl alcohol, crospovidone, low-substituted hydroxypropylcellulose, crystals Examples include cellulose and hydroxypropyl starch. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, carmellose sodium, pregelatinized starch, polyvinylpyrrolidone, gum arabic powder, gelatin, pullulan and the like. Examples of the bulking agent include sucrose, glucose, lactose, mannitol, maltose, sorbitol, calcium phosphate, calcium sulfate and the like.

  Examples of the taste-masking component include citric acid, tartaric acid, malic acid and the like. Examples of the foaming agent include sodium bicarbonate. Examples of artificial sweeteners include saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia, and thaumatin. Examples of the masking agent include water-insoluble polymers such as ethyl cellulose and anti-salivary gastric polymers such as methyl methacrylate / butyl methacrylate / diethylaminoethyl methacrylate / copolymer.

  Examples of the fragrance include lemon, lemon lime, orange, menthol, mint oil, vanillin, and powdered fragrance obtained by adsorbing it on dextrin or cyclodextrin. Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid and the like.

  Examples of the auxiliary agent include a colorant, a physiologically active ingredient stabilizer, and a solubilizing agent. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 3 and edible blue No. 2; edible lake pigments; Stabilizers or solubilizers vary depending on the physiologically active components used, and examples include antioxidants such as ascorbic acid and tocopherol, and surfactants such as polysorbate 80.

EXAMPLES Next, although an Example and a test example are given and this invention is demonstrated in more detail, this invention is not restrict | limited at all by these Examples.
Production Example: Production of Granulated Product of Formulation Base 240 g of magnesium aluminate metasilicate (trade name: Neusilin FL2, manufactured by Fuji Chemical Industry Co., Ltd.) was suspended in 2,400 g of purified water. The above-mentioned Neusilin FL2 suspension (2,400 g) is used for 5,484 g of D-mannitol (trade name: Mannit P, manufactured by Towa Kasei Kogyo Co., Ltd.), and a fluidized bed granulator (FLO-5 type). Using a fluidized bed granulator: manufactured by Freund Sangyo Co., Ltd., a granulated product of a pharmaceutical base was produced.

Example 1: Production of a compression-molded preparation using pullulan
15.32 g of pullulan fine powder (trade name: Pullulan PI-21, manufactured by Hayashibara Co., Ltd.) was dissolved in 306.4 g of purified water. To this aqueous solution of pullulan , 800 g of the base granulated product for preparation produced in the above production example was added, and granulated by a fluidized bed granulator. To 46.79 g of the obtained granulated product, 2.92 g of a crosslinkable polyvinylpyrrolidone (trade name: Kollidon CL, crospovidone, manufactured by BASF Corp.) and magnesium stearate (magnesium stearate: manufactured by Nippon Oil & Fats Co., Ltd.) ) 0.29 g was added. Using these granules, tablets with a diameter of 8.0 mm were produced with an oil press at a tableting pressure of 2,500 N.

Example 2 : Production of a compression-molded preparation using gluconolactone and pullulan 7.66 g of gluconolactone ( trade name: Glucno δ lactone: manufactured by Fujisawa Pharmaceutical Co., Ltd. ) and 7.66 g of pullulan were added to 306.4 g of purified water. Dissolved. To this aqueous solution of glucunolactone and pullulan, 800 g of the granulated product of the preparation base prepared in the above production example was added, and granulated by a fluidized bed granulator. Kollidon CL was added to 46.79 g of the granulated product.
2.92 g and 0.29 g of magnesium stearate were added. The granules were tableted with an oil press at a tableting pressure of 15,000 N to produce tablets with a diameter of 8.0 mm.

Comparative Example 1:
Tableting was performed according to the same conditions as in Example 1 except that 15.32 g of gluconolactone in Example 1 was changed to 15.32 g of propylene glycol alginate (trade name: Kimiroid, manufactured by Kimika Co., Ltd.), and the diameter was 8 0.0 mm tablets were produced.

Comparative Example 2:
According to the same conditions as Example 1 except that 15.32 g of gluconolactone of Example 1 is 15.32 g of polyoxyethylene polyoxypropylene glycol (trade name: Adeka Pluronic F68, manufactured by Asahi Denka Kogyo Co., Ltd.). Tableting was performed to produce a tablet having a diameter of 8.0 mm.

Comparative Example 3:
Tableting is performed according to the same conditions as in Example 1 except that 15.32 g of gluconolactone of Example 1 is 15.32 g of dextrin (trade name: dextrin, manufactured by Matsutani Chemical Co., Ltd.), and the diameter is 8. 0 mm tablets were produced.

Comparative Example 4:
Tableting was performed according to the same conditions as in Example 1 except that 15.32 g of gluconolactone in Example 1 was changed to 15.32 g of syrup (brand name: Minamata, manufactured by Nippon Shokuhin Kako Co., Ltd.). 0 mm tablets were produced.

Test example:
Using each tablet produced in Example 1 to Example 2 and Comparative Example 1 to Comparative Example 4,
The disintegration property was evaluated by three panelists. Specifically, each panel included a sample tablet in the oral cavity, and the disintegration time and the state of disintegration in the oral cavity were evaluated. Table 1 shows the average results of the evaluation of each panel.

Example 3 :
As active pharmaceutical ingredients, 100 g of famotidine and 45 g of lactose (trade name: lactose DMV200M: manufactured by DMV Co., Ltd.) in 2 L of purified water, hydroxypropylcellulose (trade name: HPC-ssL, manufactured by Nippon Soda Co., Ltd.) 10.5 g Granulation was carried out by an ordinary method using an aqueous solution dissolved together. 46.4 g of ethyl acrylate / methyl methacrylate copolymer emulsion (trade name: Eudragit NE30D, manufactured by Rohm Co., Ltd.) and talc (trade name: manufactured by Talkan Hayashi, Hayashi Kasei Co., Ltd.) 8.4 g Was used to prepare famotidine-containing granules by a conventional method. Tablets were produced by compressing 6.089 g of this famotidine-containing granule together with 40.7 g of the granule obtained in Example 1 by the method of Example 1.

Example 4 :
Instead famotidine 100g of Example 4 to lansoprazole 100g, further methyl ethyl methacrylate acrylate copolymer emulsion methacrylic acid copolymer LD: instead of (trade name Eudragit L30D-55, Rohm Co., Ltd.) and the other embodiment Tablets were produced in the same manner as in Example 3 .

Example 5 :
A tablet was produced in the same manner as in Example 3 except that 100 g of famotidine in Example 3 was replaced with 100 g of triazolam.

Example 6 :
Tablets were produced according to Example 3 , except that starch syrup was added when producing the granulated product of Example 1.

All of the tablets obtained in Examples 3 to 6 disintegrated in the oral cavity within 60 seconds, and the touch was smooth.

  The rapidly disintegrating compression-molded preparation of the present invention is a tablet or troche type containing various drug components as a molded preparation that rapidly disintegrates with a small amount of water in the oral cavity and does not remain after the disintegration. It is useful as a pharmaceutical product.

Claims (6)

A rapidly disintegrating compression-molded preparation comprising pullulan added to a preparation base containing a sugar selected from the group consisting of sugar, starch sugar, lactose, honey and sugar alcohol, and a silicate compound . The compression molding composition according to claim 1 , wherein the content of pullulan is 0.0001 to 0.1 parts by mass with respect to the compression molding preparation. The rapidly disintegrating compression-molded preparation according to claim 1 or 2 , wherein the content of pullulan is 0.0002 to 0.15 parts by mass with respect to 1 part by mass of the preparation base. The rapidly disintegrating compression-molded preparation according to any one of claims 1 to 3 , further comprising a physiologically active substance. The rapidly disintegrating compression-molded preparation according to claim 4 , wherein the physiologically active substance is a pharmaceutically active ingredient. A granular material containing a formulation base containing a saccharide selected from the group consisting of sugar, starch sugar, lactose, honey and sugar alcohol, and a silicate compound, and further containing a formulation aid, pullulan as an aqueous solvent granulated either in solution dissolved in, or, further comprises a formulation for base granules contain other formulation aids, pullulan and both granulated with an aqueous solvent, the granules obtained A method for producing a rapidly disintegrating compression molding preparation, characterized by compression molding.