JP2005306770A - Oral rapidly disintegrating preparation and method for producing the same - Google Patents

Abstract

[Problem] To provide an intraoral rapidly disintegrating preparation that does not require special processes, facilities and equipment, and has both a good feeling of administration, moderate hardness and excellent disintegration.
The following components (A), (B) and (C):
(A) Hydroxypropyl starch 40-80% by mass,
(B) 15 to 50% by mass of D-mannitol obtained by spray drying,
(C) An intraoral rapidly disintegrating preparation containing a physiologically active ingredient, and a method for producing the same.
[Selection figure] None

Description

  The present invention relates to a tablet manufactured so as to disintegrate easily and rapidly in the oral cavity (hereinafter referred to as “oral rapidly disintegrating preparation”) and a method for producing the same.

  Tablets are the most frequently used dosage form for oral administration of pharmaceutical products. Tablets have advantages such as “capable of counting and dispensing” and “convenient to carry”, but “difficult to swallow for elderly patients and children with weak swallowing power”, “does need water for taking”, etc. There are disadvantages. Therefore, if it is a tablet that disintegrates and dissolves rapidly in the oral cavity, water is not required at the time of taking, and it can be taken easily even by patients with reduced swallowing ability. Such tablets are called intraoral rapidly disintegrating preparations, and it is considered practically preferable that they disintegrate completely within 30 seconds in the saliva in the oral cavity of healthy adult males. In general, the hardness and disintegration of a tablet are in a mutually contradictory relationship, and the hardness must be lowered to increase the disintegration.

  However, tablet hardness is an important factor in production packaging and distribution processes, as well as removal from packaging when taking. Tablets with insufficient hardness will not be able to maintain their shape during each process and will be difficult to handle as well as lack accuracy in dosage during counting dispensing. It is generally said that a hardness of 29.4 N or more is necessary in order to prevent the tablet from being damaged in the process of manufacture and transportation and causing no problem in practical use. Therefore, development of a method for producing an intraoral rapidly disintegrating preparation having an appropriate hardness and excellent disintegration is desired.

  As a method for producing an intraoral rapidly disintegrating preparation with appropriate hardness and disintegration, a suspension of drug, saccharide and gelling agent is filled in a PTP (Press Through Package) blister and freeze-dried or dried under reduced pressure. A method of removing moisture and forming a tablet in a blister is known (see Patent Documents 1 and 2). In addition, a method of compressing and drying wet granules mainly composed of sugars granulated with water (see Patent Document 3) and a method of tableting a mixture containing moisture at a wet level on the particle surface (see Patent Document 4) are reported. These methods are generally known as wet manufacturing methods. Furthermore, after compression-molding a powder mainly composed of saccharides and added with a water-soluble binder at a low pressure, a tablet is placed under humidification to be wetted and dried to produce an intraoral rapidly disintegrating preparation ( Patent Documents 5 and 6), a powder to which a water-soluble fusible binder such as polyethylene glycol is added is compression-molded at a low pressure and then melted at a temperature higher than the melting point of the binder, and then the water-soluble fusible binder is used. A tablet manufacturing method (see Patent Document 7) in which strength is improved by solidification is disclosed. Recently, a method (see Patent Documents 8 to 10) in which a shear foam matrix of amorphous cotton candy is formed into tablets as granules having excellent fluidity is also disclosed. However, since these manufacturing methods require special processes, facilities, and equipment, there is a problem that the manufacturing cost increases.

  Furthermore, a method in which a physiologically active ingredient is mixed with crystalline cellulose having good moldability or low-substituted hydroxypropylcellulose and compression-molded with a low compression force (100 to 300 kgf) (see Patent Document 11), a physiologically active ingredient is crystalline cellulose, A method of compression molding by mixing with lactose, agar powder and low-substituted hydroxypropyl cellulose or hydroxypropyl starch is disclosed (see Patent Document 12). These methods can be manufactured using ordinary equipment and equipment, but contain a lot of water-insoluble fibrous components in the composition, which causes a sense of discomfort in the oral cavity and impairs the feeling of dosing. There is a drawback of being.

On the other hand, D-mannitol (91% by weight) obtained by spray drying, crospovidone (5% by weight) and an active ingredient as a disintegrant are mixed, and molded by a rotary tableting machine with a compression pressure of 6000 N to obtain tablet hardness. A method for producing a rapidly disintegrating preparation in the oral cavity having 37.1 N and a disintegration time of 19.1 seconds is disclosed (see Patent Document 13). Moreover, although the said document also mentions hydroxypropylcellulose as a suitable example of a disintegrating agent, the compounding quantity of a disintegrating agent is about 0.1 to 30 weight% in an intraoral quick disintegration type preparation. It is preferred.
JP 53-44619 A International Publication No. 93/12769 Pamphlet International Publication No. 93/15724 Pamphlet Japanese Patent Laid-Open No. 5-271054 JP-A-8-291051 JP-A-9-48726 International Publication No. 93/13758 Pamphlet International Publication No. 95/34290 Pamphlet International Publication No. 95/34293 Pamphlet JP-A-8-38138 JP-A-9-48726 JP 2000-119175 A International Publication No. 02/069934 Pamphlet

  Accordingly, an object of the present invention is to provide an intraoral rapidly disintegrating preparation and a method for producing the same, which do not require special processes, equipment and equipment, and have a good feeling of administration, moderate hardness and excellent disintegration. is there. In particular, from the point of practicality, an intraoral quick disintegrating preparation having disintegration property that disintegrates within 25 seconds in the oral cavity and hardness of 30N or more is provided.

In view of such circumstances, the present inventors have conducted intensive studies on a rapidly disintegrating preparation in the oral cavity having hardness that has no practical problem while maintaining rapid disintegration and good feeling in the oral cavity. It was found that by incorporating a specific amount of hydroxypropyl starch and specific D-mannitol into the active ingredient, an intraoral rapidly disintegrating preparation satisfying the above requirements was obtained, and the present invention was completed.
That is, the present invention comprises the following components (A), (B) and (C):
(A) Hydroxypropyl starch 40-80% by mass,
(B) 15 to 50% by mass of D-mannitol obtained by spray drying,
(C) An intraoral rapidly disintegrating preparation containing a physiologically active ingredient is provided.

  The present invention also provides a method for producing an intraoral rapidly disintegrating preparation characterized by mixing hydroxypropyl starch, D-mannitol obtained by spray drying, a physiologically active ingredient, and a disintegrating agent, followed by compression molding.

The intraoral rapidly disintegrating preparation of the present invention has a rapid disintegration property that completely disintegrates in the oral cavity within 25 seconds, preferably about 15 seconds, and a practically sufficient hardness that does not cause damage in the process of production and transportation. In addition, it has an excellent feeling of taking such as moderate sweetness, coolness and smooth mouthfeel.
Moreover, the intraoral quick-disintegrating preparation of the present invention containing 40 to 80% by mass of hydroxypropyl starch and 15 to 50% by mass of D-mannitol obtained by spray drying was formulated with 30% by mass of hydroxypropyl starch. Compared with intraoral rapidly disintegrating preparations, it has rapid disintegration and excellent feeling of administration.
Furthermore, since the intraoral rapidly disintegrating preparation of the present invention can be produced from commercially available raw materials by general equipment and processes, it is advantageous from the viewpoint of production cost as compared with the conventional production method.

  As the hydroxypropyl starch (hereinafter referred to as “HPS”) used in the intraoral rapidly disintegrating preparation of the present invention, a commercially available water-soluble HPS for adding pharmaceuticals can be used. Unlike hydroxypropylcellulose (hereinafter referred to as “HPC”), which is generally used as a binder / excipient, HPS is nearly spherical and has a relatively smooth surface. Good fluidity can be imparted to a smooth mouth-breaking and tableting powder at the time of taking. Moreover, content of HPS is 40-80 mass% in 1 tablet of the intraoral quick disintegration preparation of this invention from the point of sufficient hardness of an intraoral quick disintegration preparation, and the outstanding disintegration, 45-45 mass%. 70 mass% is preferable, and 45-65 mass% is especially preferable.

  It is known that D-mannitol usually promotes friction with the mortar wall surface when subjected to compression molding, leading to a decrease in fluidity of the tableting raw material. Therefore, D-mannitol is known in which physical properties such as moldability and fluidity are improved by a method such as reducing the average particle diameter. As a method for producing such D-mannitol, for example, a spray drying method described in JP-A-61-85330, a fine mill using a hammer mill, a jet mill described in WO 97/47287, etc. And rolling granulation described in JP-A-2001-10979.

  Among such improved D-mannitols, D-mannitol obtained by spray drying is used in the present invention. D-mannitol obtained by spray drying has a smooth surface compared to normal D-mannitol, in addition to the sweetness and coolness that D-mannitol originally has, and is preferable in terms of taking feeling. In addition, by using D-mannitol obtained by spray drying in combination with HPS, the tableting raw material is given better fluidity, which is advantageous in terms of production. In this specification, “D-mannitol obtained by spray drying” (hereinafter referred to as “spray-dried D-mannitol”) is obtained by spray-drying a solution and / or suspension of D-mannitol. It means what was done.

  Spray dried D-mannitol has a mass median particle diameter of 75-300 microns, an angle of repose of 25-45 degrees, a loose density of 0.35-0.75 g / ml and a zero density. Preferably having a tapped density of 45 to 0.85 g / ml, more preferably a median diameter of 75 to 300 microns, an angle of repose of 25 to 40 degrees, 0.40 to 0.60 g / having a loose density of ml and a tap density of 0.50 to 0.75 g / ml, in particular a mass median diameter of 75 to 250 microns, an angle of repose of about 31 degrees, a loose density of about 0.51 g / ml and about Those having a tap density of 0.60 g / ml are preferred. Such spray-dried D-mannitol can be produced, for example, according to the method described in WO 97/39739.

  Here, the “mass median diameter” refers to the particle size when the total mass of particles larger than a certain particle size occupies 50% of the mass of the total powder in the particle size distribution of the powder. The particle size distribution can be measured by a screening method, a light scattering / diffraction method, a sedimentation method, an electrical resistance test method, and the like. “Repose angle” is the method defined by ISO4324, which represents the angle at which the side slope of the conical sediment formed on the horizontal plane forms with the horizontal plane when the powder is gently dropped and deposited from the funnel to the horizontal plane. Can be measured. “Loose density” and “tap density” both indicate the apparent density of the powder. “Loose density” is a value obtained by dividing the weight of a powder sample by adding the powder sample to a fixed volume container, scraping the powder surface and weighing it, and dividing it by the internal volume of the container. It can be measured by a defined method. “Tap density” refers to the apparent density obtained by tapping a container a specified number of times in the stage of adding a powder sample into the container and filling the nectar with the powder in the container. DIN EN ISO787-11 It can be measured by the method defined in

The spray-dried D-mannitol may further contain 0.1 to 20% by mass of a sugar alcohol other than D-mannitol based on the total amount of sugar alcohol in order to improve the physical properties. The content of the sugar alcohol other than D-mannitol in the spray-dried D-mannitol is preferably 0.5 to 2.0 mass%, particularly preferably about 1 mass%. Examples of sugar alcohols other than D-mannitol include sorbitol, erythritol, xylitol, and lactitol, and sorbitol is preferred.
Such spray-dried D-mannitol is commercially available from Merck Ltd. under the trade name Partech M-200.

  The content of spray-dried D-mannitol is 15 to 50% by mass, preferably 20 to 50% by mass, and particularly preferably 20 to 40% by mass in one tablet of the intraoral rapidly disintegrating preparation of the present invention. In addition, the ratio [(A) / (B)] of the content of HPS (A) and the content of spray-dried D-mannitol (B) in the intraoral rapidly disintegrating preparation of the present invention is sufficient for the formulation. It is 1 or more from the point which provides the outstanding disintegration, 1-3 are preferable, and 1.3-2.3 are especially preferable.

  The intraoral rapidly disintegrating preparation of the present invention may further contain crospovidone or low-substituted HPC, preferably crospovidone, as a disintegrant. The content of the disintegrant is preferably 3 to 15% by mass, and particularly preferably 5 to 10% by mass, in one tablet of the intraoral quick disintegrating preparation of the present invention.

  In addition to the above-mentioned components, additives of the type normally used for tablet production may be added to the intraoral rapidly disintegrating preparation of the present invention as long as it does not affect the compression moldability and disintegration property. Examples of such additives include lubricants, flavoring agents, sweeteners, fragrances, and coloring agents.

  Examples of the lubricant include magnesium stearate, light anhydrous silicic acid, talc, sucrose fatty acid ester and the like. Examples of the corrigent include citric acid, malic acid, adipic acid, ascorbic acid and the like. Examples of the sweetening agent include aspartame, saccharin, glycyrrhizin, reduced maltose syrup and the like. Examples of the fragrances include pineapple, mint, menthol, lemon and orange. Examples of the colorant include yellow ferric oxide, red ferric oxide, and tar dyes. In addition, these additives can be used individually or in combination of 2 or more types, Furthermore, you may add in any step of a manufacturing process.

  The physiologically active ingredient used in the intraoral rapidly disintegrating preparation of the present invention is not particularly limited as long as it is intended for oral administration. For example, drugs for central and peripheral nerves, drugs for circulatory organs, drugs for respiratory organs, Examples include digestive organ agents, blood agents, antihistamines, antidiabetic agents, antifungal agents, antibiotics, and vitamins.

  Examples of the drugs for central and peripheral nerves include hypnotic sedatives such as estazolam, nitrazepam, and phenobarbital sodium; anxiolytics such as chlordiazepoxide and diazepam; agents for psychoneurosis such as chlorpromazine hydrochloride and reserpine; trihexyphenidyl hydrochloride, Anti-Parkinson drugs such as carbidopa, pergolide, levodopa; aspirin, aminopyrine, acetaminophen, ibuprofen, ketoprofen, ethenamide, diphenhydramine hydrochloride, dl-chlorpheniramine maleate, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, serrapeptase, lysozyme chloride, Tolfenamic acid, flufenamic acid, mefenamic acid, diclofenac sodium, salicylamide, indomethacin, pentazocine, noscapine, bucolome, Antipyretic analgesics, anti-inflammatory drugs such as phosphate dihydrocodeine; skeletal muscle relaxants such as methocarbamol; diphenhydramine hydrochloride, papaverine hydrochloride, and the like anticonvulsants such as scopolamine hydrobromide.

  Cardiovascular drugs include, for example, cardiotonic drugs such as aminophylline, ethylephrine hydrochloride, caffeine, digoxin, docarpamine, and pimobendan; arrhythmic drugs such as amiodarone hydrochloride, carteolol hydrochloride, procainamide hydrochloride, propafenone hydrochloride, propranolol hydrochloride, and pindolol Diuretics such as acetazolamide, isosorbide, chlorthalidone, spironolactone, trichloromethiazide, furosemide; nifedipine, delapril hydrochloride, captopril, labetalol hydrochloride, carvedilol, antihypertensive drugs such as hexamethonium bromide, hydralazine hydrochloride, methyldopa; phenylephrine hydrochloride, Vasoconstrictors such as midodrine hydrochloride, dihydroergotamine mesylate; isosorbide mononitrate, etaphenone hydrochloride, dilazep hydrochloride, isosorbide nitrate, trapidil Coronary vasodilators such as nicorandil, nisoldipine, nitrendipine, nitroglycerin, nifedipine, amlodipine besylate, carbochromene hydrochloride, molsidomine, verapamil hydrochloride; peripheral vasodilators such as inositol hexanicotinate, isoxsuprine hydrochloride, cinnarizine, hepronicart; clofibrate And drugs for hyperlipidemia such as colestimide, provocol, pravastatin, simvastatin and the like.

  Examples of respiratory organ drugs include antitussives such as dextrometrophan and codeine phosphate; expectorants such as L-methylcysteine hydrochloride, ambroxol hydrochloride and bromhexine hydrochloride; bronchodilators such as albuterol, procaterol and theophylline Is mentioned.

  Examples of digestive organ drugs include peptic ulcer drugs such as omeprazole, lansoprazole, cimetidine, famotidine, pirenzepine hydrochloride, and roxatidine acetate; healthy gastric drugs such as diastase; magnesium carbonate, sodium bicarbonate, Antacids such as magnesium aluminate and precipitated calcium carbonate; mucosal protective agents such as cetraxate hydrochloride and gefarnate; laxatives such as bisacodyl and picosulfate sodium; blocking agents such as loperamide, 5-aminosalicylic acid and sulfasalazine; itopride hydrochloride, Examples include gastrointestinal motility activators such as cisapride, metoclopramide, and trimebutine maleate.

  Examples of blood drugs include blood coagulation inhibitors such as warfarin potassium; antiplatelet drugs such as ethyl icosapentate, sarpogrelate hydrochloride, ticlopidine hydrochloride, and cilostazol.

  Examples of the antihistamine include diphenhydramine hydrochloride, chlorpheniramine maleate, clemastine fumarate, mequitazine, promethazine hydrochloride and the like.

  Examples of the antidiabetic agent include acarbose, acetohexamide, tolbutamide, desmopressin, glimepiride, glipizide, phenformin, zirclazide, glibenclamide, tolbutamide, voglibose and the like.

  Examples of antifungal agents include enoxacin, sparfloxacin, quinine hydrochloride, acyclovir, vidarabine, isoniazid, ethambutol hydrochloride and the like.

  Antibiotics include, for example, cephem, penem, carbapenem, macrolide, aminoglycoside, new quinolone, polypeptide antibiotics such as cephalexin, amoxicillin, pibmesilinum hydrochloride, cefotiam hydrochloride and the like.

Examples of vitamins include vitamin A such as retinol palmitate; vitamin B ₁ such as dibenzoylthiamine and fursultiamine hydrochloride; vitamin B ₂ such as riboflavin butyrate; vitamin B ₆ such as pyridoxine hydrochloride; and hydroxocobalamin acetate. Vitamin B ₁₂ ; vitamin C such as ascorbic acid and sodium L-ascorbate; vitamin D such as alphacalcidol; vitamin E such as d-α-tocopherol acetate; vitamin K such as phytonadione and menatoteren; nicotinamide and pantothenic acid Examples include calcium and folic acid.

  The physiologically active ingredient can be used as a free form or a pharmaceutically acceptable salt. Examples of such salts include inorganic acids (eg, hydrochloric acid, nitric acid, hydrobromic acid, sulfuric acid); organic acids (eg, succinic acid, acetic acid, p-toluenesulfonic acid, methanesulfonic acid, fumaric acid, lactic acid) , Trifluoroacetic acid); inorganic bases (for example, alkali metals such as sodium and potassium, alkaline earth metals such as calcium and magnesium); organic base compounds (for example, organic amines such as triethylamine, and basic amino acids such as arginine) ) And the like. Moreover, the said bioactive component can be used individually or in combination of 2 or more types. The content of the physiologically active ingredient varies depending on the type and dosage of the active ingredient, but is preferably 0.1 to 25% by mass, particularly 0.1 to 10% by mass, in one oral disintegrating preparation of the present invention. % Is preferred.

  The compression molding method is not particularly limited, but the direct tableting method is preferable from the viewpoint of simplicity and stability during granulation. In the case of the direct tableting method, as a tableting machine, a commonly used one such as a rotary tableting machine or a single-shot tableting machine can be used. Moreover, it is preferable to shape | mold with the compressive force of 3.92-7.84kN. In addition, when a lubricant is added to the intraoral rapidly disintegrating preparation of the present invention, an external lubricant type tableting machine may be used. The form of the tablet obtained by the production method of the present invention is not particularly limited, and for example, a circular shape having various surface shapes such as an ordinary R surface, a sugar-coated R surface, a corner plane, a corner plane, a two-step R surface, and the like. Any of irregular shape may be sufficient. The tablet can also be a split tablet with a score line. Furthermore, a multilayer tablet having two or more layers may be used.

  The intraoral rapidly disintegrating preparation of the present invention preferably has a tablet hardness of 30 N or more and an oral disintegration time of 25 seconds or less, particularly a tablet hardness of 30 to 80 N and an oral disintegration time of 25 seconds or less. Is preferred. Here, tablet hardness and disintegration time in the oral cavity can be measured by the methods shown in Examples below.

Hereinafter, the present invention will be described in detail with reference to Examples, Reference Examples and Comparative Examples, but the present invention is not limited thereto.
In addition, the preparations of Reference Examples 1 to 10 were manufactured without adding a physiologically active component among the components of the intraoral rapidly disintegrating preparation of the present invention.

Examples 1-5
The intraoral rapidly disintegrating preparations of the present invention shown in Table 1 below were produced and evaluated for tablet hardness, oral disintegration time, and ingestion feeling when used. The results are shown in Table 1.

(Manufacturing method) Each component shown in Table 1 is mixed to obtain a tableting powder, and using a universal tensile tester Autograph (manufactured by Shimadzu Corporation, Autogram AG-I type), the compression force is 4.41 kN and the diameter is 8 mm. A 200 mg tablet was obtained. For Examples 3 and 4, after making a tableting powder, a rotary type tableting machine (HT-AP6, manufactured by Hata Kogakusha Co., Ltd.) was used at a compression force of 600 kgf (5.88 kN), a diameter of 8 mm, and a mass of 200 mg. Pills were obtained.

(Evaluation methods)
(1) Fluidity of Tableting Powder and Adhesiveness to Axus At the time of tableting, the fluidity of tableting powder and adhesiveness to the punch were visually observed and evaluated.
(2) Tablet hardness The breaking strength in the diameter direction of the tablet was measured using a tablet physical property measuring apparatus (TM3-3 manufactured by Kikusui Seisakusho Co., Ltd.). The measurement was performed 5 tablets, and the average value was evaluated.
(3) Disintegration time in the oral cavity In a healthy adult male, the oral disintegration preparation of the present invention was included in the oral cavity without water, and the time until complete disintegration / dispersion with only saliva in the oral cavity was measured. . The test was performed by three people, and the average value was evaluated.
(4) Feeling of taking In accordance with the measurement of the oral disintegration time, the feeling of taking was evaluated according to the following 4 levels.

・ Evaluation criteria ×: Difficult to take with saliva alone △: Can be taken with saliva only, but there are problems with texture, taste, etc. ○: Can be taken with saliva only, no problems with texture, taste, etc. ◎: With saliva only It can be taken, and the texture and taste are favorable.

Reference Examples 1-10
The intraoral rapidly disintegrating preparations shown in Table 2 below were produced and evaluated for tablet hardness, oral disintegration time, and ingestion feeling when used. The results are shown in Table 2.

(Manufacturing method) Each component shown in Table 2 is mixed to obtain a tableting powder. A universal tensile tester Autograph (manufactured by Shimadzu Corp., Autogram AG-I type) is used with a compressive force of 3.92 kN, a diameter of 8 mm, A tablet with a mass of 180 mg was obtained. Evaluation was performed in the same manner as in Example 1.

Comparative Examples 1-9
The intraoral rapidly disintegrating preparations shown in Table 3 below were produced by the same method as in Reference Example 1, and the tablet hardness, oral disintegration time, and ingestion feeling when this was used were evaluated. However, for Comparative Example 1, powder D-mannitol was used instead of spray-dried D-mannitol. The results are shown in Table 3.

  As is apparent from Table 1, all of the preparations of Examples 1 to 5 exhibited extremely excellent disintegration within 25 seconds and maintained practically sufficient hardness of 30 N or more. In addition, all of these preparations did not cause an unpleasant foreign body sensation and the like, and the dosage feeling was good. Therefore, the intraoral rapidly disintegrating preparation of the present invention has both strength and disintegration that have no practical problem even if it contains physiologically active ingredients, sweeteners, flavoring agents, fragrances, etc. It was confirmed that it could be manufactured. Further, the preparations of Examples 3 and 4 were manufactured using a rotary type tableting machine usually used in the tablet production process, but the flowability of the tableting powder was good, and the mortar was used at the time of tableting. Since no adhesion to the surface was observed, it was revealed that the product was excellent in productivity.

  As is clear from Table 2, all of the intraoral rapidly disintegrating preparations of Reference Examples 1 to 10 had practically excellent hardness and disintegration, and there was no problem or very good feeling of taking. It was also revealed that a preparation containing crospopidone as a disintegrant in spray-dried D-mannitol and HPS has particularly good moldability and disintegration.

  As is apparent from Table 3, the preparation of Comparative Example 1 showed a tablet hardness of 29 N or less, and was unable to obtain a practically sufficient hardness. Further, the preparation of Comparative Example 3 was found to have a problem in practical use as an orally disintegrating tablet because the disintegration time in the oral cavity was long. In addition, the preparations of Comparative Examples 2 and 3 had an unpleasant foreign body feeling and taste considered to be derived from an insoluble additive at the time of taking, or were difficult to take only with saliva, and there was a problem in taking feeling. Furthermore, none of the preparations of Comparative Examples 4 to 9 satisfied the hardness, the oral disintegration time, and the feeling of ingestion.

  According to the present invention, it is possible to provide an excellent intraoral quick disintegrating preparation that exhibits various disintegration properties of various physiologically active ingredients in the oral cavity, has sufficient strength, and does not collapse during handling. Can do. Moreover, since the intraoral rapidly disintegrating preparation of the present invention can be produced without going through complicated steps using commercially available raw materials and general-purpose mixers and tableting machines, the conventional oral cavity can be used from the viewpoint of production cost, production time, etc. It is extremely superior to the internal fast disintegrating preparation.

Claims (4)

The following components (A), (B) and (C):
(A) Hydroxypropyl starch 40-80% by mass,
(B) 15 to 50% by mass of D-mannitol obtained by spray drying,
(C) An intraoral rapidly disintegrating preparation containing a physiologically active ingredient.   Furthermore, the intraoral quick disintegration type preparation of Claim 1 which contains 3-15 mass% of crospovidone.   3. The intraoral fast disintegrating preparation according to claim 1 or 2, wherein the tablet hardness is 30N or more and the oral disintegration time is 25 seconds or less.   A method for producing an intraoral rapidly disintegrating preparation, comprising mixing hydroxypropyl starch, D-mannitol obtained by spray drying, a physiologically active ingredient and a disintegrating agent, followed by compression molding.