JPH10298062A - Rapidly dissolving type tablet in oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a rapidly dissolving type tablet in the oral cavity having such sufficient abrasion and strength as not to be broken at a packing operation of PTP(press through package) and an unsealing operation but as to be rapidly collapsed in the oral cavity, and further to provide a method for readily producing the tablet, without using a complex machine, capable of using a conventional machine for medical supplies and excellent in mass-productivity when producing the tablet. SOLUTION: This rapidly dissolving type tablet in the oral cavity is obtained by carrying out the wet granulation of a mixture of a pharmaceutical ingredient with a mannitol as a main vehicle, an auxiliary vehicle and a bondable disintegrator to provide granules, mixing a disintegrator powder with the granules and carrying out the compression molding of the granules. The tablet includes 65-96.4 wt.% main vehicle, 2-15 wt.% auxiliary vehicle, 0.3-5 wt.% bondable disintegrator and 0.3-8 wt.% disintegrator. The auxiliary vehicle is a crystalline cellulose, the bondable disintegrator is a carboxymethyl starch sodium and the disintegrator is at least one kind selected from the carboxymethyl starch sodium and a crosscarmellose sodium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a PTP (press thro
ugh package) It relates to a rapidly dissolving tablet in the oral cavity which has abrasion resistance and strength of a pharmaceutically acceptable degree without being damaged during packaging and opening. The present invention also relates to a method for producing such a rapidly dissolving tablet in the oral cavity by a simple process.

[0002]

2. Description of the Related Art Conventionally, many forms have been known as oral administration preparations. Recently, several dosage forms have been developed in consideration of the ease of drinking for patients. For example, International Publication WO93
/ 15724 discloses a method of manufacturing a tablet by compressing a wet kneaded product before drying in a conventional manufacturing method of tableting by a conventional wet granule compression method. International Publication WO95 / 20380 discloses an orally soluble compression-formed product containing a saccharide having low moldability and a saccharide having high moldability. JP-A-5-270154 discloses a method for producing an orally dissolving tablet in which a mixture containing a medicinal ingredient, a saccharide, and water to such an extent that the particle surface becomes wet is tableted.

[0003]

However, the rapid dissolving tablet in the oral cavity according to the prior art described above has a problem in the product such as insufficient abrasion resistance, mechanical strength and the like, or the manufacturing process thereof. Is complicated, the manufacturing machine is special,
There are manufacturing problems such as a low manufacturing yield.

[0004] Therefore, a rapidly dissolving tablet in the oral cavity which has sufficient friability and strength so as not to be damaged at the time of PTP packaging and opening and which disintegrates rapidly in the oral cavity is desired. Further, in the production of such tablets, a simple production method which is excellent in mass productivity and which can use a conventional granulator, dryer and tableting machine without using a complicated machine is desired.

[0005] Furthermore, there are many elderly patients who have reduced swallowing power which require such an oral dissolving-type preparation, and in these elderly people, half-dose administration is often desired due to the special pharmacokinetics thereof. However, the fast-dissolving tablets according to the prior art have low molding strength and are crushed at the time of division, or fall off partly from the split surface, making it difficult to accurately administer the dose. Absent. Therefore, a fast-dissolving tablet having high strength while maintaining rapid disintegration is desired.

[0006]

DISCLOSURE OF THE INVENTION The present invention provides a granule obtained by wet granulating a mixture containing a medicinal ingredient, mannitol as a main excipient, an auxiliary excipient and a binding disintegrant, into a granule obtained by wet granulation. The present invention provides a rapidly dissolving tablet in the oral cavity which is obtained by mixing powder and compression molding. In the present invention, the medicinal component is a granule obtained by wet granulating a mixture containing mannitol as a main excipient, an auxiliary excipient and a binding disintegrant, together with a powder containing a disintegrant. Can be added.

[0007] The present invention also relates to a method of mixing a disintegrant powder with granules obtained by wet granulating a mixture containing a medicinal ingredient, mannitol as a main excipient, an auxiliary excipient and a binding disintegrant. The present invention provides a method for producing a rapidly dissolving oral tablet, which is characterized by compression molding.

Hereinafter, the present invention will be described in detail. In the present invention, the “rapidly dissolving type in the oral cavity” means, when orally administered to a mammal such as a human, within 2 minutes, preferably within 1 minute, more preferably within 40 seconds without taking water. In which the tablet disintegrates and disperses quickly. Further, "sufficient mechanical strength" means that the friability is 0.8% or less, preferably 0.1% or less in a usual friability test.
5% or less, which means that the tablet hardly loses weight due to attrition in normal production and distribution processes.

The medicinal ingredient used in the present invention includes any medicinal ingredient which can be taken orally. In the present invention, those having no or little bitterness are preferred, but those having bitterness can also be used. Such medicinal ingredients include antifungal agents, for example, fluconazole; analgesics, for example, acetaminophen and acetylsalicylic acid; antihistamines, for example, diphenhydramine, doxylamine succinate and meclizine; decongestants, for example, pseudoephedrine hydrochloride; Antibiotics, for example,
Azithromycin and erythromycin; penicillin,
For example, saltamicilintosylate and amoxicillin trihydrate; enzyme inhibitors such as sulbactam sodium; antihypertensive agents such as nifedipine, doxazosin mesylate and amlodipine besylate; antidiabetic agents such as glipizide; For example, pyrbuterol hydrochloride and theophylline; anti-inflammatory agents such as piroxicam, ampiroxicam and tenidap;
Antidepressants such as sertraline hydrochloride; antipsychotics such as ziprasidone; anti-impotence drugs such as sildenafil citrate; antiulcer drugs such as cimetidine and famotidine; antacids such as calcium carbonate and magnesium oxide; Sedating antihistamines, such as
Cetirizine and the like can be mentioned. The medicinal ingredients used in the present invention include nutritional and food supplements, such as vitamins. These active ingredients can be used alone or in combination of two or more. In the tablet of the present invention, the active ingredient is preferably 0.01% of the total weight of the tablet.
To 15% by weight, more preferably 0.1 to 10% by weight.

[0010] In the tablet of the present invention, it is essential to use mannitol as a main excipient. Mannitol has moderate sweetness and coolness, and is advantageous in terms of palatability. In addition, since it has low hygroscopicity, it is advantageous from the viewpoint of storage stability. Other sugar alcohols (eg xylitol, erythritol, maltitol or sorbitol)
When used, the final tablet product cannot maintain rapid disintegration.

In the present invention, mannitol is preferably incorporated in an amount of 65 to 96.4% by weight, more preferably 77 to 94% by weight, based on the total weight of the tablet. Outside this range, satisfactory rapid disintegration may not be obtained.

In the present invention, an auxiliary excipient is added in addition to mannitol as a main excipient. Here, the "auxiliary vehicle" refers to a water-soluble or water-insoluble commonly used pharmaceutical additive excellent in moldability. The expression "excellent in moldability" means that when 200 mg is tableted at a tableting pressure of 200 kg / cm ² using a punch having a diameter (φ) of 8 mm, hardness is 3 kg or more. A preferred co-excipient used in the present invention is microcrystalline cellulose. "Crystalline cellulose" refers to α-cellulose partially depolymerized with a mineral acid and purified. In the tablet of the present invention, disintegration is significantly improved by adding crystalline cellulose. The crystalline cellulose used here is, for example, a conventionally used one or a commercially available one (for example, Avicel® P)
H-101, PH102, PH-301, PH-30
2, and CEOLUS KG-801 (trade name, Asahi Kasei Kogyo) or a crushed product thereof. These can be used alone or in combination of two or more.

An auxiliary excipient such as crystalline cellulose is preferably blended in an amount of 2 to 15% by weight, more preferably 3 to 10% by weight, based on the total weight of the tablet. Outside this range, the disintegration tends to decrease. If the amount exceeds 15%,
Since a large amount of water is required for disintegration, rapid disintegration may not be obtained with a small amount of saliva in the oral cavity.

Examples of the binding disintegrant used in the present invention include starch derivatives such as corn starch, potato starch and sodium carboxymethyl starch, and cellulose derivatives such as carboxymethyl cellulose calcium, low-substituted hydroxypropyl cellulose and croscarmellose sodium. And the like. Among these, sodium carboxymethyl starch is preferable from the viewpoint of a strong disintegration power and a small amount of water involved in the disintegration.

In the present invention, if a binding disintegrant is not incorporated into the inside of the granules, the granules are brittle and powder during the production process, which is a problem in production. Further, by incorporating the binding disintegrant mentioned in the present invention into the granules, it is possible to have a binding effect between the particles, so that the tablet can be rapidly disintegrated without using a generally known binder. The mechanical strength can be improved while maintaining the properties. Therefore, in the present invention, such a disintegrant is referred to as a binding disintegrant. More specifically, the `` binding disintegrant '' has a function as a binder for binding individual particles to form a granulated product when producing granules, and for oral administration of tablets, It refers to a disintegrant having a function of exhibiting rapid solubility.

In the tablet of the present invention, the binding disintegrant is
Preferably, 0.3 to 5% by weight, more preferably 0.4 to 4% by weight, most preferably 0.
5 to 3% by weight is blended. Outside of this range, the disintegration in the oral cavity may be reduced.

According to the present invention, a mixture is prepared by mixing the above-mentioned active ingredient, mannitol as the above-mentioned main excipient, the above-mentioned auxiliary excipient, the above-mentioned binding disintegrant and other additives as necessary. Is granulated by wet granulation.

The other additives to be blended here may be any as long as the effects on fast-solubility, hardness, abrasion and the like are acceptable. Such additives include:
For example, sour agents, foaming agents, artificial sweeteners, flavors, lubricants, and coloring agents can be used.

In the present invention, since the above-mentioned binding disintegrant has a weak binding function, a generally known binding agent is not used. Examples of the acidulant include citric acid, tartaric acid, malic acid, succinic acid, fumaric acid, and salts thereof. Examples of the foaming agent include sodium bicarbonate and sodium carbonate. As an artificial sweetener, for example,
Saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin and the like can be mentioned.
Examples of the flavor include lemon, lemon lime, orange, strawberry, menthol, grape, cola, and the like. Lubricants include magnesium stearate, talc and the like. As a coloring agent, for example,
Food dyes such as Food Yellow No. 5, Food Red No. 2, Food Blue No. 2 and the like, edible lake dyes, redwood, iron oxide and the like. These additives may be added, if necessary, in the total weight of the tablet.
0.1 to 10% by weight can be added.

As another additive, even if the agar is added to the formulation in a range of 4% or less, fast disintegrating tablets having almost the same properties without losing rapid disintegration and strength properties can be obtained. If the agar is added in excess of 4%, the water absorption increases, and the amount of saliva in the oral cavity loses rapid disintegration, which is not preferable.

In the present invention, a disintegrant powder is mixed with granules having the above composition, and the mixture is compression-molded to obtain a rapidly dissolving tablet in the oral cavity.

The disintegrant used in the present invention is at least one selected from sodium carboxymethyl starch, croscarmellose sodium, calcium carboxymethylcellulose, and low-substituted hydroxypropylcellulose. Among these disintegrants, croscarmellose sodium and sodium carboxymethyl starch are preferred from the viewpoint of quick disintegration and abrasion resistance.

In the present invention, the disintegrant is incorporated preferably in an amount of 0.3 to 8% by weight, more preferably 1 to 5% by weight, based on the total weight of the tablet. Outside this range, disintegration in the oral cavity tends to be poor.

In the present invention, a lubricant may be added to the granules in addition to the disintegrant in order to prevent tableting trouble during compression molding, for example, to prevent sticking. Examples of the lubricant used here include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid and the like. The lubricant is preferably added in an amount of 0.25 to 4% by weight, more preferably 0.5 to 3% by weight, based on the total weight of the tablet.

Next, the production method of the present invention will be described in detail.

In the production method of the present invention, first, the above-mentioned medicinal ingredient, mannitol as the above-mentioned main excipient, the above-mentioned auxiliary excipient, the above-mentioned binding disintegrant and other additives as necessary are mixed. A mixture is made and the mixture is wet granulated to prepare granules. The wet granulation method that can be used here may be a method for producing a wet granule that has been conventionally used. Stirring granulation, fluidized bed granulation, extrusion granulation, tumbling granulation, etc. Not limited.

More specifically, a medicinal ingredient, mannitol, an auxiliary excipient, a binding disintegrant and the like are charged in a stirring granulator, and a binding liquid (purified water or the like) is added in an appropriate amount (for example, based on all solid components). , 20% by weight) and granulate by dropping to obtain desired granules. The preferred rotation speed of the stirrer in this case (the agitator, which may also be referred to as a main blade, a rotor disk, etc.) varies depending on the model, the total capacity, etc.
The speed is particularly preferably 60 to 550 rpm, and the rotating speed of the pulverizer (which may be called a cross screw, a lamp breaker, or the like) varies depending on the model and the total capacity, but is 1200 to 4800 rpm.
Min, preferably 1800 to 4600 rpm. The production temperature does not need to be particularly adjusted, and may generally be room temperature (for example, 20 to 30 ° C.), but may be heated or cooled as necessary.

In the dry granulation method without using water, only tablets having poor mechanical strength can be obtained, or a large tableting pressure is required to cover the strength, which is not preferable in production.

The granules in the rapidly dissolving tablet in the oral cavity of the present invention can be produced by the stirring granulation method as described above, but are not limited thereto. It may be manufactured by a granulation method, a fluidized bed granulation method, or the like.

The granules thus obtained preferably have a particle size of not more than 1000 μm, more preferably not more than 15 μm.
It has an average particle size of 0 to 850 micrometers. Further, by sieving after drying, granules having a uniform particle size can be obtained. As a sieve to be used, for example, No. 20 (8
No. 30 (500 micrometers), No. 42 (355 micrometers), No. 50 (300 micrometers), No. 60 (250 micrometers), No. 83 (180 micrometers), 10
No. 0 (150 micrometers), No. 140 (106 micrometers), No. 200 (75 micrometers), and No. 330 (45 micrometers) sieves.

Incidentally, by adjusting the mixing ratio of each component and the rotation speed of a stirrer (agitator) and a pulverizer (chopper), it is possible to design granules having various particle diameters.

Then, the granules thus obtained are dried by a through-air tray dryer or a fluidized bed dryer.
The granules are mixed with a disintegrant powder together with additives such as lubricants, if necessary, and the resulting mixture is compression-molded to obtain tablets. Compression molding is performed using a conventional tableting machine (eg, a tableting machine YH-
BT type (Yonekura Seisakusho), single-shot tableting machine KT-2 (Niei Seiko Co., Ltd.) or rotary tableting machine Crimpress Collect 12HUK (Kikusui Seisakusho) can be used.

According to the production method of the present invention, a general-purpose granulator,
Since a dryer and a tableting machine can be used, a conventional apparatus can be used as it is. Therefore, the manufacturing method of the present invention has a simple manufacturing process and is excellent in mass productivity, and is advantageous in manufacturing cost, manufacturing time, manufacturing yield, and the like, as compared with the conventional method for manufacturing a rapidly dissolving tablet in the oral cavity.

The orally rapidly dissolving tablet according to the present invention has a high mechanical strength and can be processed into a desired shape such as a circle, an ellipse, a diamond, a capsule, and a triangle. Further, the tablet may be in the form of a divided tablet in which a score line for dividing the tablet is cut. Such a divided tablet has a score line formed of at least one groove for dividing the tablet on its upper surface and / or lower surface, and can be manufactured by a known method. The score line is easily engraved, for example, by using the shape of a punch for a tableting machine for a split tablet. The divided tablet can be formed into a known shape by a known method.

More specifically, the divided tablet that can be employed in the tablet of the present invention has one or both sides formed of a pair of flat surfaces, and the pair of flat surfaces is located inside the edge of the tablet toward the opposite tablet surface from the edge of the tablet. And an obtuse angle with each other, and a narrow groove may be engraved at the intersection of the planes (for example, see Japanese Utility Model Laid-Open No. 08-1012).

Further, the tablet of the present invention is a disc-shaped uncoated tablet provided with a scored line composed of at least one narrow groove extending in the diameter direction for facilitating the tablet division on the upper surface and / or the lower surface. The upper surface may be gradually depressed from the opposite edge portion toward the dividing line, and the lower surface may be thinner from the peripheral portion to the central portion (for example, Japanese Patent Application Laid-Open No. 08-053345). Reference).

Such a divided tablet is particularly useful, for example, for medical treatment of the elderly, for which administration of half tablets is desired. The present invention also has a high significance in that a rapidly dissolving tablet in the oral cavity is originally a dosage form suitable for elderly people with reduced swallowing power. The divided tablet of the present invention has good weight uniformity of the half tablet after division and is suitable for the weight deviation test of the Japanese Pharmacopoeia. Further, the weight loss from the fractured surface at the time of division is as small as about 0.1%. As described above, when the image is divided along the dividing line, a good dividing property is obtained.

Here, the diameter or the major axis of the tablet is
Usually, it is 6 mm to 15 mm, and the tablet weight is usually 150 mg to 1000 mg, but is not limited thereto.

According to the production method of the present invention, the disintegration time according to the Japanese Pharmacopoeia 13 disintegration test is within 1 minute and 30 seconds, and preferably within 1 minute; 0.5% or less; hardness by a hardness test described below is 2
Approximately 15 kg, preferably 3 to 12 kg of a rapidly dissolving oral tablet can be produced. Regarding the mechanical strength characteristics, a hardness of 3 kg or more and a friability of 0.5% or less are considered to be in a usual pharmaceutical packaging form (for example, PTP).
Packaging).

[0040]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to examples, comparative examples, and evaluation tests.

The evaluation test was performed by the following method. (Hardness test) The breaking strength in the diameter direction of the tablet was measured with a tablet hardness tester (manufactured by Toyama Sangyo Co., Ltd.) (n = 3). (Friability test) Twenty tablets were charged in a friability tester and rotated at 25 rpm for 4 minutes, and the reduction due to the abrasion was indicated in% by weight. (In Vitro Disintegration Test) The in vitro disintegration test was performed according to the Japanese Pharmacopoeia 13 Disintegration Test Method. However, water was used as the test solution, and no auxiliary panel was used (n = 3). (Intraoral disintegration test) The time required for a compressed adult product to completely disintegrate and disperse with only saliva in the oral cavity is measured by including the tablet in the oral cavity of the present invention without water in the oral cavity of a healthy adult male. did. The results were expressed as an average of five persons. (Split strength test) A tablet was placed on a tablet table with the score line part down, and the pressure when the tablet was split so that the score line was opened from above the pressure head was defined as the split strength (using a tablet hardness tester manufactured by Toyama Sangyo Co., Ltd.) n = 5). (Weight Deviation Test) The test was carried out and determined according to the Japanese Pharmacopoeia 13 Weight Deviation Test.

Hereinafter, examples of tablets and results of comparative tests are shown.

(Example 1) Sildenafil citrate (70 g, Pfizer Pharmaceutical), mannitol (791 g, Towa Kasei Kogyo) as medicinal ingredients, and crystalline cellulose (50 g, Asahi Kasei Kogyo) as co-excipient, sodium carboxymethyl starch ( 14 g, Matsutani Chemical Co., Ltd.) and aspartame (25 g, Ajinomoto) were charged into a stirring granulator (high speed mixer, LFS-2 type, Fukae Kogyo Co., Ltd.), and the rotation speed of the agitator and chopper was set to 200 rpm /
, And granulation was performed at room temperature while adding purified water (196 g) dropwise. The obtained granules are dried by a fluid bed dryer (Multiplex-01 type, Powrex), and then croscarmellose sodium (30 g, Asahi Kasei Kogyo) as a powder disintegrant outside the granules and magnesium stearate (20 g) as a lubricant. , Nippon Oil & Fats Co., Ltd., and then compression-molded with a single-shot tableting machine KT-2 (Nichiei Seiko) to obtain a rapidly dissolving intraoral tablet of the present invention having a diameter of 15 mm and a weight of 1000 mg. The composition of the components is shown in Table 1.

(Comparative Example 1) and (Comparative Example 2) Comparative tablets (15 mmφ, 1000 mg) were obtained according to the component compositions shown in Table 1 in the same manner as in (Example 1). Table 1

Table 2 shows the performance test results of the tablets. Table 2

As can be seen from Table 2, Example 1 containing mannitol as a main excipient has excellent characteristics as a fast-dissolving tablet such that the friability is 0.8% or less and the disintegration time is 1 minute 30 seconds or less. I was

(Example 2) Mannitol, crystalline cellulose, sodium carboxymethyl starch and aspartame were uniformly mixed in a mortar in the amounts shown in Table 3, and kneaded with 3.5 ml of purified water. The kneaded product was extruded and granulated with a No. 20 sieve, and dried at 50 ° C. for 4 hours in a ventilation dryer (SPH-201, Tabaispec). After the dried granulated product is sized with a No. 30 sieve, croscarmellose sodium, amlodipine besylate, and magnesium stearate are added and mixed with powder, and a Brinell-type tableting tester (YH-BT, Yonekura Seisakusho) is used. Tablet compression, diameter 1
A rapidly dissolving tablet of the present invention weighing 0.5 mm and weighing 500 mg was obtained.

Comparative Example 3 According to the composition shown in Table 3,
In the same manner as in (Example 2), a comparative tablet (diameter 10.
5 mm, weight 500 mg). Table 3

Table 4 shows the performance test results of the tablets. Table 4

Table 4 shows that Example 2 in which microcrystalline cellulose was added as a co-excipient was compared with Comparative Example 3 in which microcrystalline cellulose was not included.
The disintegration time was shortened (within 1 minute), and it had excellent properties as a fast-dissolving tablet.

(Comparative Examples 4 and 5) Comparative tablets (diameter 10.5 mm, weight 500 mg) were obtained in the same manner as in (Example 2) according to the component compositions shown in Table 5. Table 5

Table 6 shows the performance test results of the tablets. Table 6

From Table 6, it can be seen that, in Example 2, in which a binding disintegrant and a disintegrant were blended inside and outside the granules, fast dissolution (within 1 minute) having good mechanical strength and rapid disintegration with high abrasion resistance. A shaped tablet was obtained. In addition, unless a binding disintegrant was incorporated into the granules, the granules were brittle and powdered during the production process, which became a practical problem (Comparative Example 4).

(Example 3-5) According to the component composition shown in Table 7, a rapidly dissolving tablet (diameter 10.5 mm, weight 500 mg) of the present invention was obtained in the same manner as in (Example 2). Table 7

Table 8 shows the performance test results of the tablets. Table 8

From Table 8, it was found that the binding disintegrant inside the granules was 0.5
３3%, the disintegrant outside the granule had excellent properties as a fast-dissolving tablet, such as a disintegration time of 1 minute or less and a friability of 0.5% or less in a range of 1 to 5%.

Next, another embodiment of the present invention will be described.

(Example 6) 360 g of mannitol, 20 g of crystalline cellulose, 15 g of agar agar, aspartame 1
After mixing 0 g, the mixture was granulated with a fluidized bed granulator (Multiplex-01 type, Powrex) using 16 g of sodium carboxymethyl starch suspended and dispersed in 360 g of water. The granulation conditions at this time were a spray pressure of 0.5 kg / cm ² , a spray rate of 17.4 g / ml, an air temperature of 60 ° C. during spraying, and 80 ° C. after the end of spraying. After drying, doxazosin mesylate (1.0% by weight), croscarmellose sodium (3.0% by weight), and magnesium stearate (2.0% by weight) were added to the dried granules, and the mixture was treated in the same manner as in (Example 2). The tablet was compressed to obtain a rapidly dissolving tablet of the present invention having a diameter of 10.5 mm and a weight of 500 mg. Table 9 shows the component compositions, and Table 10 shows the performance test results of the tablets. Table 9

Example 7 A single-shot tableting machine (KT-2) was used to obtain a tableting powder having the same formulation as shown in Table 7 (Example 3).
(Neiei Seiko Co., Ltd.) to obtain a scored flat-type fast-dissolving tablet of the present invention having one groove having a diameter of 10.5 mm, a weight of 400 mg and a thickness of 4.8 mm. Table 1 shows the performance test results of tablets.
0 is shown. Table 11 shows the division characteristics.

(Example 8) A single-shot tableting machine (KT-2) was prepared using a tableting powder obtained by the same formulation as shown in Table 7 (Example 3).
Mold, Nichiei Seiko Co., Ltd.) to obtain a single-sided arched quick-dissolving tablet of the present invention having one groove with a diameter of 8.5 mm, a weight of 200 mg and a thickness of 3.2 mm. Table 10 shows the performance test results of the tablets. Table 11 shows the division characteristics. Table 10 Table 11

From these results, it can be seen that in Example 6 produced by the fluidized-bed granulation method and in Examples 7 and 8 in which split fast-dissolving tablets containing a score were formed, the friability was 0.5% or less and the disintegration time was 1 minute or less. As described above, the tablet had excellent characteristics as a fast-dissolving tablet. In addition, both types (flat type, single-sided arch type) quick-dissolving tablets with scored lines passed the weight deviation test before and after splitting, and the weight loss due to breakage during splitting was as small as 0.1%, achieving good splittability. Was done.

(Examples 9 and 10) According to the component compositions shown in Table 12, a rapidly dissolving tablet (diameter: 10.5 mm, weight: 500 mg) was obtained in the same manner as in (Example 2). Table 12

Table 13 shows the performance test results of the tablets. Table 13

Example 11 According to the composition shown in Table 14, a fast dissolving tablet (diameter 10.5 mm, weight 500 mg) was obtained in the same manner as in Example 2. Table 14

Table 15 shows the performance test results of the tablets.

[0066]

As described above, the present invention provides fast dissolving,
It is possible to provide an orally rapidly dissolving tablet excellent in both friability and hardness. Therefore, the tablet of the present invention
It can also be used preferably for PTP packaging. In addition, the production method of the present invention is a conventional granulator, a dryer, a simple process using a tableting machine, it is possible to produce a rapidly dissolving tablet in the oral cavity, compared with the conventional method, production cost, It is also advantageous in manufacturing yield and the like. Furthermore, application to divided tablets becomes possible, and it is particularly useful for medical care for the elderly, for which administration of half tablets is desired in many cases.

[0067]

Claims (10)

[Claims] 1. A disintegrant powder is mixed with granules obtained by wet granulation of a mixture containing a pharmaceutically active ingredient, mannitol as a main excipient, an auxiliary excipient and a binding disintegrant, followed by compression molding. Oral fast-dissolving tablet. 2. The main excipient is 65 to 96.4% by weight; the auxiliary excipient is 2 to 15% by weight; the binding disintegrant is 0.3 to 5% by weight; The oral fast-dissolving tablet according to claim 1, which is contained in an amount of 3 to 8% by weight. 3. The method according to claim 1, wherein the main excipient is 77 to 94% by weight.
3 to 10% by weight of the co-excipient; 0.4 to 4% by weight of the associative disintegrant;
The oral fast-dissolving tablet according to claim 2, which is contained by weight. 4. The co-excipient is crystalline cellulose,
2. The rapidly dissolving tablet in the oral cavity according to claim 1, wherein the binding disintegrant is sodium carboxymethyl starch, and the disintegrant is at least one selected from sodium carboxymethyl starch and sodium croscarmellose. 5. The medicinal component is an antifungal, an analgesic, an anti-inflammatory, an antihistamine, a decongestant, an antibiotic, a penicillin, an enzyme inhibitor, an antihypertensive, a hypotensive, an antidiabetic, a bronchodilator Drugs, anti-inflammatory drugs, antidepressants, antacids,
2. The oral fast dissolving tablet according to claim 1, wherein the tablet is selected from non-sedating antihistamines, nutritional supplements, therapeutic agents for urinary diseases, and food supplements. 6. The tablet according to claim 1, wherein the mixture before the wet granulation further contains a sweetener. 7. The orally rapidly dissolving tablet according to claim 1, wherein a lubricant is added to the granules in addition to the disintegrant powder. 8. The rapidly dissolving tablet in the oral cavity according to claim 1, wherein a score line comprising at least one groove for dividing the tablet is cut on the upper surface and / or the lower surface of the tablet. 9. A granule obtained by wet granulating a mixture containing mannitol as a main excipient, an auxiliary excipient and a binding disintegrant, mixing a powder containing a medicinal ingredient and a disintegrant, Oral fast-dissolving tablets formed by compression molding. 10. A disintegrant powder is mixed with granules obtained by wet granulating a mixture containing a medicinal ingredient, mannitol as a main excipient, an auxiliary excipient and a binding disintegrant, and compression-molded. A method for producing a rapidly dissolving tablet in the oral cavity.