JP2002154948A - Highly disintegrable tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain highly disintegrable tablets with stable runnability of the medicament therein, comprising powder prepared by formulating the medicament with crospovidone followed by granulation. SOLUTION: The tablets are obtained by formulating a disintegrant, a water- soluble vehicle or granulated powder thereof and a lubricant in powder prepared by formulating a medicament with crospovidone followed by granulation and then by making a compression of the resultant formulation.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a granulated powder obtained by blending a drug with crospovidone and granulating the disintegrant, a water-soluble excipient or its granulated powder, and a lubricant. Thereafter, the present invention relates to a tablet obtained by tableting and having excellent disintegration and drug dissolution characteristics.

[0002]

2. Description of the Related Art Conventionally, various disintegrants are often incorporated into tablets containing a drug in order to achieve rapid elution and absorption of the drug in a living body. For example,
Crospovidone is a disintegrant having a strong disintegration power, which is widely used in tablets requiring improvement in drug solubility and rapid disintegration, and is widely used in tablets. In general, a drug having a large efficacious dose and having unfavorable physical properties such as adhesiveness requires a larger amount of a disintegrant. However, when the compounding amount of the disintegrant is increased, the strength of the tablet tends to be weak and brittle, and phenomena such as sticking to a die or a punch at the time of tableting tend to occur. Furthermore, since the disintegrant is porous and has a high porosity, the apparent density of the tablet containing the disintegrant is low, and when the disintegration function of the disintegrant does not function sufficiently due to the interaction with the drug, the tablet may be dissolved in gastric juice or water. Tended to float, and the disintegration time was prolonged due to the decrease in the area of contact with water. For example, a benzimidazole compound or a physiologically acceptable salt thereof has a strong inhibitory effect of a so-called proton pump, and is widely used as a therapeutic agent for gastric ulcer, duodenal ulcer and the like by suppressing gastric acid secretion. However, they have the characteristics of being very unstable chemically and having high tackiness and hygroscopicity.
Therefore, various contrivances have been made with respect to tableting. For example, WO99 / 53918 discloses rabeprazole, a benzimidazole compound, or a physiologically acceptable salt thereof, 1) crospovidone and 2). Granulated powder containing sodium hydroxide, potassium hydroxide and / or sodium carbonate, or rabeprazole or a physiologically acceptable salt thereof is added to 1) crospovidone and 2) sodium hydroxide or potassium hydroxide. And / or rabeprazole or a physiologically acceptable salt thereof, comprising: 1) crospovidone and 2) sodium hydroxide, potassium hydroxide and / or Or, a core product containing sodium carbonate is coated with an intermediate film, and an enteric film is further coated on the core. Discloses to have the physical properties and stability.

[0003]

However, the stability of the pharmaceutical properties of tablets containing a drug, for example, tablets containing a benzimidazole compound or a physiologically acceptable salt thereof, is still insufficient by the above technique. is not. Tablets obtained by mixing a drug, for example, a benzimidazole-based compound or a physiologically acceptable salt thereof, with crospovidone and a lubricant such as magnesium stearate and tableting the same are used for powder granulation. In some cases, the disintegration time of the tablet may be prolonged or the dissolution may be delayed due to fluctuations in the production conditions of the tablet or storage conditions of the tablet. That is, the present invention aims to further stabilize the physicochemical properties, especially the disintegration and drug dissolution of tablets containing a powder obtained by mixing and granulating crospovidone with a drug. is there.

[0004]

Means for Solving the Problems The present invention relates to a method in which a disintegrating agent, a water-soluble excipient or a granulated powder thereof, and a lubricant are mixed with a powder obtained by mixing crospovidone with a drug and granulating. The tablet is then tableted. Usually, the compounding ratio of crospovidone is preferably 5 to 70% by weight based on the tablet. The water-soluble excipient is not particularly limited, and includes, for example, mannitol, erythritol, xylitol and / or lactose. The mixing ratio of the water-soluble excipient is not particularly limited, but is usually 5 to 20% by weight, preferably 10 to 20% by weight, based on the granulated powder obtained by mixing and granulating crospovidone. Department. The lubricant is not particularly limited, but is preferably magnesium stearate, calcium stearate, or sodium stearyl fumarate, and the compounding ratio thereof is usually 0.1 to the tablet weight.
The amount is 1 to 5% by weight, preferably 0.2 to 3% by weight, and more preferably 0.5 to 2% by weight.
Disintegrators include, but are not limited to, for example, crospovidone, carmellose sodium, carmellose calcium, croscarmellose sodium, and low substituted hydroxypropylcellulose.

[0005] In the present invention, the drug is not particularly limited. For example, a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof can be used.

Embedded image Examples of the benzimidazole-based compound include rabeprazole, omeprazole, pantoprazole, lansoprazole, and their sodium and potassium salts represented by (Formula 2). Formula 3 shows the structural formula of each compound.

Embedded image

That is, the present invention provides a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof, which is mixed with crospovidone and granulated to obtain a granulated powder.
It is a tablet obtained by blending a disintegrant, a disintegrant, mannitol or a granulated powder thereof, and magnesium stearate and then tableting. Further, the present invention is a tablet obtained by coating the tablet with an enteric coating, or a tablet obtained by coating the tablet with an intermediate coating and further coating with an enteric coating.

[0007] The present invention also provides a granulated powder obtained by blending a drug with crospovidone and granulating, after blending a disintegrant, a water-soluble excipient or its granulated powder, and a lubricant, This is a method for producing a tablet containing a drug, which is characterized by tableting. In particular, a disintegrating agent, a water-soluble excipient or a compound thereof is added to a granulated powder obtained by blending crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof and granulating the compound. This is a method for producing a tablet containing a benzimidazole compound or a physiologically acceptable salt thereof, which is characterized by tableting after blending a granular powder and a lubricant.

Further, the present invention relates to a benzimidazole compound represented by the following formula (1) or a physiologically acceptable salt thereof, mixed with crospovidone, and granulated to obtain a disintegrant, Containing a benzimidazole compound or a physiologically acceptable salt thereof, characterized in that an enteric excipient or a granulated powder thereof, and a lubricant are blended, and after tableting, an enteric film is coated. It is a manufacturing method of. When a benzimidazole compound is taken, it immediately decomposes upon contact with gastric acid in the stomach and loses its biological activity. Therefore, in order to prevent decomposition in the stomach, it is necessary to prepare a preparation that does not dissolve in the stomach, that is, a preparation in which a tablet containing a benzimidazole compound is coated with an enteric substance.

Also, the present invention provides a granulated powder obtained by blending crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof, and granulating the compound.
A disintegrant, a water-soluble excipient or a granulated powder thereof, and a lubricant, and after tableting, coating an intermediate film, and further coating an enteric film, or a benzimidazole compound or a benzimidazole compound thereof. This is a method for producing a tablet containing a physiologically acceptable salt. Because enteric coatings are generally acidic substances,
Direct contact with a benzimidazole compound is not preferred. Therefore, an inert intermediate film can be applied between the core containing the benzimidazole compound and the enteric film. Here, inactive is a substance that does not adversely affect the stability of the benzimidazole compound. The inert intermediate film is a water-soluble polymer, a water-soluble or water-dispersible substance,
Any of the water-insoluble substances may be specifically, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, aminoalkyl methacrylate copolymer E,
Lactose, mannitol, starch, crystalline cellulose, ethyl cellulose, vinyl acetate and the like can be mentioned. When an intermediate film is formed from a water-insoluble substance as disclosed in JP-A-1-290628, water-insoluble fine particles may be mixed in the film.

The benzimidazole compound in the present invention can be produced by a known method. For example,
JP-A-52-62275, JP-A-54-1417
No. 83, JP-A No. 1-6270 and the like.

[0011] Crospovidone in the present invention is a product listed in the standard of pharmaceutical excipients, and further contains magnesium stearate and calcium stearate as lubricants and mannitol, erythritol, xylitol and / or water-soluble excipients.
Alternatively, lactose is listed in the Japanese Pharmacopoeia and is easily available.

Tablets containing crospovidone added to a drug usually contain a lubricant at the time of tableting, but the disintegration is caused by fluctuations in manufacturing conditions and fluctuations in the granulation state of the powder such as over-granulation. During the test, a part of the disintegrated tablet may float on the interface of the disintegration test solution, prolong the disintegration time of the tablet, or delay the dissolution of the drug from the tablet. Further, when the tablet is stored under a heated or humidified condition, the disintegration time of the tablet may be prolonged and the elution delay of the drug from the tablet may be further accelerated. The present invention has surprisingly solved these problems, and has further improved the physicochemical stabilization of tablets containing a drug, particularly tablets containing a benzimidazole compound or a physiologically acceptable salt thereof. It is the purpose.
The tablet according to the present invention has a very remarkable effect of preventing a phenomenon in which a part of a disintegrated tablet floats on an interface of a disintegration test solution, and prevents a dissolution delay of a drug from a tablet and a prolonged disintegration of a tablet over time. ing. That is, by using a powder obtained by mixing and granulating crospovidone with the drug according to the present invention, regardless of the granulation state of the powder, for example, even when using an over-granulated powder, good disintegration can be achieved. Tablets having excellent stability and drug dissolution properties can be prepared. That is, even when using a compacted overgranulated powder obtained by compounding and granulating crospovidone into a drug, a disintegrant, a water-soluble excipient or its granulated powder, and a lubricant A tablet obtained by tableting after the compounding of the compound can be prepared into a tablet having good disintegration and drug dissolution and excellent stability.

Hereinafter, the benzimidazole compound or a physiologically acceptable salt thereof is referred to as a benzimidazole compound.

The granulated powder or preparation according to the present invention can be produced by a commonly used method. That is, for example, rabeprazole sodium, a benzimidazole compound, 10 g, crospovidone 15 g, mannitol 43.2 g, hydroxypropyl cellulose 1.5 g
The mixture is further mixed, and while stirring, 0.5 g of sodium hydroxide dissolved or dispersed in ethanol is gradually added, and the mixture is tumbled and granulated. The resulting mixture is dried at 50 ° C. using a shelf dryer, and then subjected to a speed mill (16 mesh). ). To this are added 4 g of crospovidone as a disintegrant, 10 g of mannitol as a water-soluble excipient, and 0.8 g of magnesium stearate as a lubricant, followed by tableting and tableting, and 85 mg per tablet containing 10 mg of rabeprazole sodium. Tablets can be obtained. The tablet is sprayed with an ethanol solution of hydroxypropylcellulose using a fluidized bed apparatus or a pan coating apparatus to form an intermediate film.Furthermore, an ethanol solution or an aqueous ethanol solution of hydroxypropylmethylcellulose phthalate or an enteric methacrylic acid copolymer is applied. By spraying, an enteric coated tablet provided with an intermediate film can be produced.

[0015]

According to the present invention, a tablet containing a powder obtained by mixing crospovidone with a drug and granulating the tablet can be formed into a tablet having excellent physicochemical properties such as disintegration and drug dissolution properties. it can.

(1) Effect of blending a water-soluble excipient to prevent disintegration of tablets and prevent floating: crospovidone is added to rabeprazole sodium,
To the powder obtained by adding ethanol and over-granulating by the tumbling granulation method, 24 tablets each of the following formulations of Examples 1 to 5 containing 8 mg of mannitol as a water-soluble excipient were used. Then, a disintegration test was performed according to the disintegration test method described in the Japanese Pharmacopoeia (Japanese Pharmacopoeia second liquid). Mannitol added in Example 1, Example 2, Example 3, Example 4 and Example 5 was mannitol powder, a water granulated product of mannitol, and a water production using 0.5% hydroxypropyl cellulose of mannitol, respectively. Granules, 1% of mannitol
A water-granulated product of hydroxypropylcellulose and a water-granulated product of mannitol with 2% hydroxypropylcellulose were used. In addition, as a control experiment, a tablet prepared in the same manner as in Example 1 except that mannitol was not added to the powdered portion was evaluated in the same manner (Control Example 1). Table 1 shows each formulation, and FIG.
The floating rate of each tablet after 0 minute (the number of tablets floating after 10 minutes / 24 × 100 (%)) was shown. The number of floating tablets refers to the number of tablets floating in the disintegration test solution 10 minutes after the start of the disintegration test, with the tablet appearance remaining or a part of the tablet disintegrated. Furthermore, for powder obtained by blending crospovidone with rabeprazole, adding ethanol and over-granulating by tumbling granulation,
The amount of mannitol water granulated product to be blended is 3 levels (6 mg
(Example 6), 8 mg (Example 2), and 10 mg (Example 7)), tablets were prepared, and 24 tablets each were used, and the disintegration test method (Japanese Pharmacopoeia No. 2) liquid)
A disintegration test was performed. As a control experiment, it was prepared in the same manner as in Example 2 except that mannitol was not added to the powdered part, and the same evaluation was performed (Control Example 1). Table 2
FIG. 1 shows the floating rate of each tablet after 10 minutes in the disintegration test solution.

[0017]

[Table 1]

[0018]

[Table 2]

As a result of a comparison experiment in the disintegration test of the tablets of Examples 1 to 5 and the tablet of Comparative Example 1, almost 100% was obtained for the tablet without mannitol added to the powdered part (Control Example 1).
Tablets floated, whereas in tablets containing mannitol, regardless of the difference in the state of mannitol powder (whether mannitol was granulated or not, the amount of hydroxypropylcellulose in the mannitol granulated powder) The proportion of tablets that disintegrated rapidly and floated with the tablet appearance remaining or a portion of the tablet disintegrated was very small.
In particular, the effect was remarkable in a tablet in which mannitol powder, a water-granulated product of mannitol, or a water-granulated product of mannitol with 0.5% hydroxypropylcellulose were added to the powdered portion. In addition, as a result of a comparison experiment of the tablets of Examples 2, 6 and 7, and Control Example 1, as the amount of mannitol added as a water-soluble excipient increases, the tablet appearance remains or a part of the tablet is reduced. The number of tablets floating at the interface of the disintegration test solution in a disintegrated state was reduced. In particular, when 8 mg (Example 2) and 10 mg (Example 7) were blended, almost no tablet floatation was observed, and favorable disintegration was shown. The "blending of a water-soluble excipient into a powder obtained by blending crospovidone with a drug and granulating" according to the present invention has a remarkable effect of prolonging disintegration and floating of the tablet in a disintegration test. It is clear that they give good disintegration properties. In particular, even when the powder obtained by mixing and granulating crospovidone with the drug is an overgranulated powder, the tablet has good disintegration properties, and the production conditions during powder granulation It is clear that the disintegration time is less susceptible to fluctuations and tablet storage conditions.

(2) Effect of Incorporation of Water-soluble Excipients to Promote Drug Elution from Tablets Enteric-coated tablets obtained in Example 8 shown below (20 mg of rabeprazole sodium mixed with crospovidone, and ethanol was added. Tablets prepared by preparing an over-granulated powder by the tumbling granulation method and blending 20 mg of mannitol powder to form tablets (core part)
, A tablet coated with an intermediate film and an enteric film) was subjected to a dissolution test according to the dissolution test method described in the Japanese Pharmacopoeia by using 6 tablets each (900 ml of the second liquid of the Japanese Pharmacopoeia, paddle method,
50 rpm). The amount of rabeprazole sodium in the eluate by the elution test was measured by high performance liquid chromatography. As a control experiment, a tablet prepared in the same manner as in Example 8 except that mannitol was not added to the powdered portion was evaluated in the same manner (Control Example 2). Table 3 shows each formulation. Table 4 and FIG. 3 show the results of the dissolution test of the enteric tablet of Example 8, and Tables 5 and 4 show the results of the dissolution test of the enteric tablet of Control Example 8, respectively.

[0021]

[Table 3]

[0022]

[Table 4]

[0023]

[Table 5]

As a result of a comparative experiment of dissolution of enteric tablets of Example 8 and Control Example 2, enteric tablets obtained by mixing and compressing and coating 20 mg of mannitol powder with the powder obtained by over-granulating the core were obtained. In Example 8, almost 1 minute after 20 minutes from the start of the dissolution test.
The dissolution of rabeprazole sodium of 00% was obtained, and the coefficient of variation of the dissolution rate of each of the six enteric coated tablets at each time was small, and the dissolution with little variation was obtained. On the other hand, in the case of a tablet containing no mannitol in the core (Comparative Example 2), the time to achieve 100% dissolution was as late as 30 minutes, and the coefficient of variation of the dissolution rate of each of the six enteric-coated tablets at each time was as follows. 10 and 20 minutes after the start of elution. The “blending of a water-soluble excipient into a powder obtained by blending crospovidone with a drug and granulating” according to the present invention has an effect of accelerating the dissolution of the drug from the tablet, and the dissolution rate over time. It is clear that the coefficient of variation is small and has an effect of achieving stable elution.

[0025]

EXAMPLES The present invention will be described in more detail with reference to the following Examples, but it should not be construed that the present invention is limited thereto.

Example 1 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). In A granules, 4 g of crospovidone,
8 g of mannitol, 0.8 g of magnesium stearate
After powdering, and tableting, rabeprazole sodium 10mg
One tablet of 83 mg was obtained. The formulation is shown in Table 1.

Example 2 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
Purified water was gradually added to perform stirring wet granulation, and the granules were dried and sized to prepare a water granulated product of mannitol. A
After adding 4 g of crospovidone, 8 g of a water granulated product of mannitol, and 0.8 g of magnesium stearate to the granules, the mixture is compressed and one tablet containing 10 mg of rabeprazole sodium 83
mg tablets were obtained. The formulation is shown in Table 1.

EXAMPLE 3 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
1 g of hydroxypropyl cellulose dissolved in purified water
Was slowly added, and the mixture was stirred and wet-granulated, and the granules were dried and sized to prepare a water-granulated product of mannitol containing 0.5% hydroxypropylcellulose. A granule A was powdered with 4 g of crospovidone, 8 g of an aqueous granulated product of mannitol containing 0.5% hydroxypropylcellulose, and 0.8 g of magnesium stearate, and the mixture was tableted to form 83 mg of one tablet containing 10 mg of rabeprazole sodium. Tablets were obtained. The formulation is shown in Table 1.

Example 4 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
Hydroxypropyl cellulose dissolved in purified water 0.1.
5 g is gradually added, and agitated wet granulation is performed, and the granules are dried.
The resulting mixture was sized to prepare an aqueous granulated product of mannitol containing 1% hydroxypropylcellulose. A granule A was powdered with 4 g of crospovidone, 8 g of an aqueous granulated product of mannitol containing 1% hydroxypropylcellulose, and 0.8 g of magnesium stearate. Obtained. The formulation is shown in Table 1.

Example 5 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
Hydroxypropyl cellulose dissolved in purified water 0.1.
5 g is gradually added, and agitated wet granulation is performed, and the granules are dried.
After sizing, an aqueous granulated product of mannitol containing 2% hydroxypropylcellulose was prepared. A granule A was powdered with 4 g of crospovidone, 8 g of an aqueous granulated product of mannitol containing 2% hydroxypropylcellulose, and 0.8 g of magnesium stearate, and the mixture was tabletted to form a tablet of 83 mg containing 10 mg of rabeprazole sodium. Obtained. The formulation is shown in Table 1.

Example 6 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
Purified water was gradually added to perform stirring wet granulation, and the granules were dried and sized to prepare a water granulated product of mannitol. A
One tablet containing 10 mg of rabeprazole sodium was added to the granules by adding 4 g of crospovidone, 6 g of an aqueous granulated product of mannitol, and 0.8 g of magnesium stearate, followed by tableting.
1 mg tablets were obtained. The formulation is shown in Table 2.

Example 7 Crospovidone 1 was added to 10 g of rabeprazole sodium.
5 g, 43.4 g of mannitol, and 1.5 g of hydroxypropylcellulose were each added to a stirring granulator, and mixed with 0.5 g of sodium hydroxide dissolved in ethanol.
g, slowly add and stir wet granulate, then dry the granules,
The granules were sized (A granules). Separately, to 100 g of mannitol,
Purified water was gradually added to perform stirring wet granulation, and the granules were dried and sized to prepare a water granulated product of mannitol. A
After adding 4 g of crospovidone, 10 g of an aqueous granulated product of mannitol, and 0.8 g of magnesium stearate to the granules,
Tablets containing 10 mg of rabeprazole sodium 1 tablet 8
5 mg tablets were obtained. The formulation is shown in Table 2.

Example 8 Crospovidone 3 was added to 20 g of rabeprazole sodium.
0 g, 86.4 g of mannitol, and 3 g of hydroxypropylcellulose were added to a stirring granulator, and while mixing, 1 g of sodium hydroxide dissolved in ethanol was gradually added, followed by stirring and wet granulation. Granulated. Add 8 g of crospovidone and 2 mannitol to the granules.
0 g and magnesium stearate (1.6 g) were powdered, and the mixture was compressed into tablets each containing 20 mg of rabeprazole sodium (17 tablets).
0 mg tablets were obtained. The tablets were coated with an ethanol solution containing ethyl cellulose, hydroxypropyl cellulose and magnesium stearate using a fluidized bed granulator, and 10 mg of an intermediate film was laminated. Next, hydroxypropyl methylcellulose phthalate,
A water-containing ethanol solution containing monoglyceride, talc, titanium oxide, iron sesquioxide and magnesium stearate is sprayed using a fluidized bed granulator, and the enteric coating 1
One tablet 197 mg enteric coated tablet containing 20 mg rabeprazole sodium coated with 7 mg was obtained. The formulation is shown in Table 3.

[0034]

[Brief description of the drawings]

[0035]

FIG. 1 shows the results of the tablet floating rates observed in the disintegration test for the tablets obtained in Examples 1 to 5.

[0036]

FIG. 2 shows the results of the tablet floating rate observed in a disintegration test for tablets (Examples 2, 6, and 7) tableted with varying amounts of mannitol.

[0037]

FIG. 3 shows the results of a dissolution test of the enteric coated tablet of Example 8.

[0038]

FIG. 4 shows the results of a dissolution test of the enteric coated tablet of Control Example 2.

Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat II (reference) A61K 47/26 A61K 47/26 47/32 47/32 A61P 1/04 A61P 1/04 F term (reference) 4C076 AA45 BB01 CC16 DD30 DD38 DD41 DD42 DD67 EE16 EE32 FF04 FF06 FF09 GG14 GG16 4C086 AA01 AA02 BC39 GA07 GA08 MA02 MA03 MA05 MA35 NA11 ZA68

Claims (13)

[Claims] A tablet obtained by mixing a disintegrating agent, a water-soluble excipient or its granulated powder, and a lubricant with a powder obtained by mixing crospovidone with a drug and granulating the mixture, and then tableting. 2. The tablet according to claim 1, wherein the water-soluble excipient is mannitol, erythritol, xylitol and / or lactose. 3. The tablet according to claim 1, wherein the lubricant is magnesium stearate or calcium stearate, or sodium stearyl fumarate or sodium stearyl fumarate. 4. The tablet according to claim 1, wherein the drug is a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof. 5. A disintegrant, mannitol or a granulated product thereof, which is obtained by blending crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof and granulating the compound. Tablets obtained by mixing powder and magnesium stearate and then tableting 6. A tablet obtained by coating the tablet according to claim 5 with an enteric coating. 7. A tablet according to claim 5, which is coated with an intermediate film.
Tablets further coated with an enteric coating. 8. The benzimidazole compound or a physiologically acceptable salt thereof is rabeprazole, omeprazole, pantoprazole, lansoprazole or a physiologically acceptable salt thereof. Tablets described in 9. The mixing ratio of the water-soluble excipient is 5 to 20% with respect to the granulated powder obtained by mixing and granulating crospovidone.
The tablet according to any one of claims 1 to 7, which is a part by weight. 10. Tableting after blending a disintegrating agent, a water-soluble excipient or its granulated powder, and a lubricant with a granulated powder obtained by blending a drug with crospovidone and granulating. For producing tablets containing a drug characterized by the following 11. A disintegrant, a water-soluble excipient and a granulated powder obtained by blending crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof and granulating the compound. Or a method for producing a tablet containing a benzimidazole-based compound or a physiologically acceptable salt thereof, which comprises tableting after blending the granulated powder thereof and a lubricant. 12. A disintegrant and a water-soluble excipient in a granulated powder obtained by mixing crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof and granulating the compound. Or a method for producing a tablet containing a benzimidazole-based compound or a physiologically acceptable salt thereof, wherein the tablet is mixed with a granulated powder thereof and a lubricant, and after tableting, is coated with an enteric film. 13. A disintegrant, a water-soluble excipient, and a granulated powder obtained by mixing crospovidone with a benzimidazole compound represented by the formula (1) or a physiologically acceptable salt thereof and granulating the compound. Or a granulated powder thereof, and after blending a lubricant and tableting, coating an intermediate film, and further coating a benzimidazole compound or a physiologically acceptable salt thereof, which is characterized by coating an enteric film. Method for producing tablets containing