JP2010202579A - Acarbose-containing disintegrating preparation in oral cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide an acarbose-containing disintegrating tablet in an oral cavity, disintegrating quickly in the oral cavity by saliva and without having a crack at the side surface part of a tablet, and a method for producing the same. <P>SOLUTION: The disintegrating tablet contains the following granulated materials (A) and (B): (A) the granulated material containing the acarbose and a crystalline cellulose; and (B) the granulated material containing a disintegrating component. Thereby, the acarbose-containing disintegrating tablet has an excellent disintegrating property, and can realize within 30 sec disintegration time in the oral cavity. Further, by the method for producing the tablet, since it is possible to suppress the weight of the disintegrating tablet, the tablet not becoming a large size and easy for taking can be obtained, and also since it is possible to prevent binding, the acarbose-containing disintegrating tablet in the oral cavity, without having the crack at the side surface part of the tablet can be obtained. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to an orally disintegrating agent containing acarbose which is a postprandial hyperglycemia improving agent.

  Acarbose has the effect of suppressing postprandial blood glucose increase by inhibiting the activities of α-amylase and α-glucosidase (such as sucrase and maltase) involved in carbohydrate digestion and absorption in the intestinal tract. It is used in diabetic patients for the purpose of improving

The acarbose preparation currently marketed needs to be taken with an appropriate amount of water immediately before eating, but considering patient compliance, an orally disintegrating tablet that can be taken without water is preferred.
However, acarbose has a relatively high dose of 50-100 mg per adult, and the acarbose drug substance is highly hygroscopic (Pharmaceutical Research 20 (4) 769-783 (1989)). The knowledge about the orally disintegrating tablet to be found is hardly found except the following patent document 1 (WO99 / 37308).

  In the WO99 / 37308 publication, acarbose, crospovidone, microcrystalline cellulose, lactose, and magnesium stearate are produced by the direct compression method, but the oral disintegration time of this preparation is described as 2 minutes or less. It is highly questionable whether the level of orally disintegrating tablets with rapid disintegration has been reached.

In addition, regarding the technology of orally disintegrating tablets, JP-A-2004-2326 discloses a fluidized bed granulation method in which an α-glucosidase inhibitor and an aqueous solution of hydroxypropylcellulose are sprayed onto a mixed powder of saccharides, disintegrant and crystalline cellulose. A rapidly disintegrating solid preparation is disclosed.
However, since the production method of this patent document is a possible means because the main ingredient content is as small as 0.2 to 0.3 μg as in the examples, it should be applied to an orally disintegrating tablet containing at least 50 mg of acarbose. Is impossible.

  Acarbose is viscous when it contains water, so it has the same function as a binder. Therefore, when produced by a production method such as general kneading granulation or fluidized bed granulation, there is a problem that acarbose absorbs moisture during production and the preparation does not disintegrate.

  Thus, although an orally disintegrating tablet was desired for acarbose, it was not possible to produce an orally disintegrating tablet that rapidly disintegrated and was easy to take because the tablet was not large.

Pharmaceutical Research 20 (4) 769-783 (1989)

WO99 / 37308 Japanese Patent Laid-Open No. 2004-2326

  An object of the present invention is to provide an acarbose-containing orally disintegrating tablet that is rapidly disintegrated by saliva in the oral cavity and is easy to take in an appropriate size.

  As a result of intensive studies to solve the above problems, the present inventors have found that the above object can be achieved by containing a predetermined excipient in acarbose or by using a predetermined production method.

That is, the present invention
(1) Orally disintegrating tablets containing the granulated product of (A) and (B) below (A) Granulated product containing acarbose and crystalline cellulose (B) Granulated product containing a rapidly disintegrating component,
(2) In the said (1), it is related with the orally disintegrating tablet characterized by the granulated material of (A) being manufactured by the fluidized-bed granulation method.

  Since the acarbose-containing orally disintegrating tablet of the present invention has an excellent disintegration property, the oral disintegration time within about 30 seconds is realized. Therefore, the acarbose-containing orally disintegrating tablet of the present invention can be rapidly disintegrated by saliva in the oral cavity, and the patient's compliance can be improved. Moreover, since the weight of an orally disintegrating tablet can be suppressed according to the present invention, an orally disintegrating tablet that is easy to take without being enlarged can be obtained. Furthermore, in the production method of the present invention, since binding can be prevented, an acarbose-containing orally disintegrating tablet without scratches on the side surface of the tablet can be obtained.

  Hereinafter, embodiments of the present invention will be described.

The orally disintegrating tablet of the present invention is a tablet that disintegrates rapidly in the oral cavity.
The orally disintegrating tablet of the present invention can be disintegrated within about 30 seconds in the oral cavity without ingesting water.

The acarbose used in the present invention may be produced according to a known method.
The content of acarbose in the orally disintegrating tablet of the present invention is 10 to 60% by weight, preferably 20 to 50% by weight in the tablet. Moreover, when using the tablet of this invention as a postprandial hyperglycemia improving agent, it is good to mix | blend acarbose so that it may become preferably 150 mg-300 mg as a daily dose of an adult.

The orally disintegrating tablet of the present invention is an orally disintegrating tablet containing (A) a granulated product containing acarbose and crystalline cellulose and (B) a granulated product containing a rapidly disintegrating component.
The granulated product in the present specification means a product granulated by a method usually used in the field of pharmaceutical preparation. Examples include powders and granules defined in the Japanese Pharmacopoeia 15th revision.

In the present invention, the crystalline cellulose used in the granulated product (A) is 0.6 parts by weight or more, preferably 0.6-2 parts by weight, more preferably 1-1.4 parts by weight with respect to 1 part by weight of acarbose. Added in parts by weight. Here, when the addition amount is less than 0.6 parts by weight, the disintegration time in the oral cavity tends to be delayed, which is not preferable.
The crystalline cellulose in the present specification includes a so-called microcrystalline cellulose, and is not particularly limited as long as it is a substance generally used in pharmaceuticals.

  The rapidly disintegrating component used in the granulated product (B) of the orally disintegrating tablet of the present invention includes, for example, sugars such as lactose, sucrose, mannitol, erythritol, trehalose, xylitol, crystalline cellulose, powdered cellulose, corn starch , Excipients such as light anhydrous silicic acid, anhydrous calcium hydrogen phosphate, magnesium aluminate metasilicate, crospovidone, croscarmellose sodium, low substituted hydroxypropyl cellulose, sodium carboxymethyl starch, croscarmellose calcium, carmellose, etc. Disintegrants, binders such as hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, lubricants such as magnesium stearate, aspartame, saccharin, saccharin sodium Sucralose, sorbitol, potassium acesulfame, saccharose, glucose, sweetening agents such as maltitol and the like. Moreover, these quick disintegrating components may use one type, and may mix and use two or more types.

The orally disintegrating tablet of the present invention is produced by, for example, producing a granulated product containing (A) acarbose and crystalline cellulose and (B) a rapidly disintegrating component, mixing them, and then tableting. Can be manufactured.
The granulated product (A) is preferably produced by a fluidized bed granulation method. When manufactured by the kneading granulation method, the disintegration time in the oral cavity tends to be delayed, which is not preferable. As a specific example of the production of the granulated product of (A), it is generally used in the production of acarbose, crystalline cellulose and, if necessary, pharmaceutical products in a fluidized bed granulator [Multiplex MP-01: Paulek Co., Ltd.]. Add additives that are mixed, feed air from the lower part of the fluidized bed granulator, float the mixture and keep it in a fluid state, spray the granulation solvent on this with a spray nozzle, fluidized bed granulation The method of obtaining a uniform granulated material by drying in-machine is mentioned. Although the temperature of the fluid air at the time of spraying and adsorbing is not particularly limited, it is usually 50 to 80 ° C, preferably 60 to 70 ° C. Although the temperature at the time of drying is not specifically limited, It is preferable to dry at 60-70 degreeC. Examples of the granulation solvent used in this method include water, ethanol, or a mixed solvent of one or more of these.

  For the production of the granulated product (B), for example, a rapidly disintegrating component and, if necessary, additives commonly used in the production of pharmaceuticals are mixed, and agitation granulation method, fluidized bed granulation method And a method of obtaining a desired granulated product by granulation using various granulation methods such as rolling granulation method and kneading granulation method. Specifically, in accordance with a commonly used method, a planetary mixer (Iwata Iron Works Co., Ltd.), a vertical granulator (Paurec Co., Ltd.), a high speed mixer (Fukae Powtech Co., Ltd.), a multiplex MP-01 (Paurec Co., Ltd.) ), Using a high speed mixer or the like. Examples of the granulating solvent used in this method include water, ethanol, or one or more mixed solvents thereof.

  Each granulated product produced by the above method is 0.4 to 3 parts by weight, preferably 0.8 to 1.5 parts by weight of the granulated product of (B) with respect to 1 part by weight of the granulated product of (A). It is mixed in the ratio of parts by weight. You may add the additive generally used in manufacture of a pharmaceutical as needed to the said mixture. Mixing is performed using a V-type mixer VM-5 (Dalton Co., Ltd.) or the like according to a commonly used method.

  The orally disintegrating tablet of the present invention can be obtained by tableting the mixture produced by the above method by a conventional method. For example, a method of obtaining a target tablet by tableting the composition produced by the above-described method with a commonly used apparatus such as a single tableting machine (Kikusui Seisakusho Co., Ltd.) or a rotary tableting machine (VIRGO-512). Is mentioned. The tableting pressure of the tablet in this case is not particularly limited as long as it does not hinder the manufacture of the tablet, but is 200 to 800 kg / cm 2, preferably 250 to 740 kg / cm 2.

  The orally disintegrating tablet of the present invention may contain additives such as an excipient, a binder, a disintegrant, a lubricant, a surfactant, a sweetener, a corrigent, a fragrance, and a colorant as necessary. it can. For example, starches such as corn starch, lactose, sucrose, mannitol, xylitol, erythritol, sorbitol, maltitol, calcium citrate, calcium phosphate, crystalline cellulose, magnesium carbonate, calcium carbonate, magnesium aluminate metasilicate, light anhydrous silicic acid, Excipients such as anhydrous calcium hydrogen phosphate; sucrose, gelatin, gum arabic powder, methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyethylene glycol, carboxymethylcellulose, crystalline cellulose / sodium carboxymethylcellulose, dextrin, pullulan, Binding agents such as tragacanth, sodium alginate, pregelatinized starch; crospovidone, carmelo Disintegrants such as sodium, croscarmellose sodium, carmellose calcium, carmellose, low-substituted hydroxypropylcellulose, crosslinked carmellose sodium, crosslinked polyvinylpyrrolidone, sodium carboxymethyl starch; magnesium stearate, calcium stearate, talc, light anhydrous silica Lubricants such as acid, hydrous silicon dioxide, sucrose fatty acid ester, hydrogenated oil; glycerin fatty acid ester, sorbitan fatty acid ester, polyoxyethylene fatty acid ester, polyoxyethylene hydrogenated castor oil, polyoxyethylene alkyl ether, sodium lauryl sulfate, Surfactants such as polyoxyethylene polyoxypropylene glycol; aspartame, saccharin, saccharin sodium, acesulfame potassium Sweeteners such as sucralose, sorbitol, sucrose, glucose, maltitol; flavoring agents such as citric acid, sodium citrate, tartaric acid, DL-malic acid, glycine, DL-alanine; strawberry, lemon, lemon lime, orange, l- Examples include fragrances such as menthol and mint oil; and coloring agents such as yellow iron sesquioxide, iron sesquioxide, edible tar dyes, and natural dyes.

  The size and shape of the orally disintegrating tablet of the present invention are not particularly limited as long as it is pharmaceutically acceptable, but in the case of a circular tablet, the diameter is 7 to 12 mm and the thickness is 3.40 to 6.50 mm, preferably Diameter 8-11mm, thickness 3.65-6.15mm, in the case of deformed tablets, minor diameter: 4-8mm, major diameter 8-18mm, preferably minor diameter: 4-6.5mm, major diameter: 8-15mm, thickness The thickness is 3.00 mm to 6.50 mm, preferably 3.65 mm to 6.15 mm. Also, the hardness of the orally disintegrating tablet of the present invention is not particularly limited as long as it does not hinder the handling of the orally disintegrating tablet.

  EXAMPLES The present invention will be described in detail below with reference to examples, but the scope of the present invention is not limited to the following examples.

(1) Acarbose 164.96 g and crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] 160 g were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and the resulting mixture was obtained. The solution was granulated by spraying 109 g of purified water. The granulated product was dried at 70 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) 181.8 g of D-mannitol, 120 g of crystalline cellulose, 80 g of crospovidone, and 4 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and purified water was added to the resulting mixture. 218g / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) 101.55 g of the granules obtained in (1) above and 96.45 g of the granules obtained in (2) above were mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Further, 1.0 g of light anhydrous silicic acid and 1.0 g of magnesium stearate were added and mixed, and then using a single tableting machine (Kikusui Seisakusho Co., Ltd.), the tableting pressure was 3330 with a diameter of 8.5 mm and a rounded surface. Tableting was performed at -3820N to produce an orally disintegrating tablet weighing 200 mg containing 51.55 mg of the active ingredient per tablet.
The resulting tablet had an oral disintegration time of 25 seconds.

(1) Acarbose 164.96 g, crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] 160 g and crospovidone [Polyplastidon XL-10: IPS Japan Co., Ltd.] 32 g are fluidized bed granulator [Multi Plex MP-01: Paulek Co., Ltd.] and the resulting mixture was granulated by spraying 147 g of purified water. The granulated product was dried at 70 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) 177.25 g of D-mannitol, 200 g of crystalline cellulose, 100 g of crospovidone, and 5.0 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and the resulting mixture was mixed. 725 g of purified water / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) The granule 55.775g obtained by said (1) and the granule 43.225g obtained by said (2) were mixed using the mixer [V type mixer VM-5: Dalton Co., Ltd.]. Further, 0.5 g of light anhydrous silicic acid and 0.5 g of magnesium stearate were added and mixed, and then using a single tableting machine (Kikusui Seisakusho Co., Ltd.), the tableting pressure 1470 with a diameter of 8.5 mm and a rounded surface. Tableting was carried out at -1670 N to produce an orally disintegrating tablet weighing 200 mg containing 51.55 mg of the active ingredient per tablet.
The tablet disintegration time in the oral cavity was 23 seconds.

(1) Acarbose 206.2 g, crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] 160 g and anhydrous calcium hydrogen phosphate [Kyowa Chemical Industry Co., Ltd.] 80 g were fluidized bed granulator [Multiplex MP-01: The resulting mixture was granulated by spraying 240 g of a purified water / ethanol mixed solvent (w / w = 2/8). The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) 177.25 g of D-mannitol, 200 g of crystalline cellulose, 100 g of crospovidone, and 5.0 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and the resulting mixture was mixed. 725 g of purified water / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) The granule 55.775g obtained by said (1) and the granule 43.225g obtained by said (2) were mixed using the mixer [V type mixer VM-5: Dalton Co., Ltd.]. Furthermore, 0.5 g of light anhydrous silicic acid and 0.5 g of magnesium stearate were added and mixed, and then using a single tableting machine [Kikusui Seisakusho Co., Ltd.], the tableting pressure 1570 was applied with a 8.5 mm diameter punch on the R surface. Tableting was carried out at -1660 N to produce an orally disintegrating tablet with a weight of 200 mg containing 51.55 mg of the active ingredient per tablet.
The tablet disintegration time in the oral cavity was 26 seconds.

(1) 154.65 g of acarbose and 150 g of crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and the resulting mixture was obtained. The solution was granulated by spraying 151.2 g of a purified water / ethanol mixed solvent (w / w = 2/8). The granulated product was dried at 60 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) Erythritol 32.725 g, crystalline cellulose 5.0 g, crospovidone 10 g and sucralose 0.5 g were mixed in a mortar, and purified water / ethanol mixed solvent (w / w = 1/1) 21 g was added and kneaded. Combined. The obtained mixture was dried at 55 ° C. with a dryer [mini jet oven] and then sized with a No. 22 sieve to obtain granules.
(3) 25.4 g of the granules obtained in (1) above and 24.1 g of the granules obtained in (2) above were mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Furthermore, 0.25 g of light anhydrous silicic acid and 0.25 g of magnesium stearate were added and mixed, and then using a single tableting machine [Kikusui Seisakusho Co., Ltd.], the tableting pressure 1570 with a diameter of 8.5 mm and a rounded surface. Tableting was carried out at -1760N to produce an orally disintegrating tablet weighing 200 mg containing 51.55 mg of active ingredient per tablet.
The tablet disintegration time of the obtained tablet was 20 seconds.

(1) Acarbose 206.2 g and crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] 280 g were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and the resulting mixture was obtained. The resulting mixture was granulated by spraying 152 g of purified water. The granulated product was dried at 70 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) 133.8 g of D-mannitol, 88 g of crystalline cellulose, 80 g of crospovidone, and 4 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and purified water was added to the resulting mixture. 172.5 g of ethanol / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) The granule obtained in the above (1) and the granule obtained in the above (2) were mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Furthermore, after adding and mixing 4 g of light anhydrous silicic acid and 4 g of magnesium stearate, using a single tableting machine (Kikusui Seisakusho Co., Ltd.), punching at a tableting pressure of 2550-2840 N with a 8.5 mm diameter punch on the R surface. Tablets were produced, which were orally disintegrating tablets with a weight of 200 mg containing 51.55 mg of active ingredient per tablet.
The tablet disintegration time in the oral cavity was 31 seconds.

  From the results of Examples 1 to 5, an orally disintegrating tablet having good oral disintegration time was obtained. Further, since the content of the main ingredient of the orally disintegrating tablet was about 26%, an orally disintegrating tablet having a moderate size and easy to be taken was obtained.

(Comparative Example 1)
(1) 154.65 g of acarbose and 150 g of lactose hydrate [pharmatose (200M): DMV] were mixed using a fluidized bed granulator [Multiplex MP-01: Paulek Co., Ltd.] and purified to the resulting mixture. It granulated by spraying 103g of water. The granulated product was dried at 75 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(2) 181.8 g of D-mannitol, 120 g of crystalline cellulose, 80 g of crospovidone, and 4 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and purified water was added to the resulting mixture. 218g / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) 30.47 g of the granules obtained in (1) above and 28.94 g of the granules obtained in (2) above were mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Further, 0.3 g of light anhydrous silicic acid and 0.3 g of magnesium stearate were added and mixed, and then using a single tableting machine [Kikusui Seisakusho Co., Ltd.], a tableting pressure of 3430 with a diameter of 8.5 mm and a rounded surface. Tableting was performed at -4410N, and an orally disintegrating tablet with a weight of 200 mg containing 51.55 mg of active ingredient per tablet was produced.
The tablet disintegration time of the obtained tablet was 57 seconds.

  In Comparative Example 1, lactose was used instead of crystalline cellulose, but the oral disintegration time was delayed as compared with Examples 1 to 5, and a good oral disintegrating tablet was not obtained.

(Comparative Example 2)
154.65 g of acarbose, 180 g of crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.], 196.35 g of D-mannitol, 60 g of crospovidone and 3 g of aspartame [Multiplex MP-01: POWREC Co., Ltd. The obtained mixture was granulated by spraying 304 g of a purified water / ethanol mixed solvent (w / w = 2/8). The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules. 3 g of light anhydrous silicic acid and 3 g of magnesium stearate were added to the obtained granules and mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Thereafter, using a single tableting machine [Kikusui Seisakusho Co., Ltd.], the tablet was tableted with a punching pressure of 2450-3040N with a diameter of 8.5 mm and an R surface, and a weight of 200 mg containing 51.55 mg of active ingredient per tablet. An orally disintegrating tablet was produced.
The tablet disintegration time in the oral cavity was 55 seconds. In addition, binding was recognized at the time of manufacture.

(Comparative Example 3)
206.2 g of acarbose, 160 g of crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Co., Ltd.] and 80 g of anhydrous calcium hydrogen phosphate [Kyowa Chemical Industry Co., Ltd.] are pulverized by a rotor speed mill with a screen diameter of 0.5 mm punching type: FRITSCH ], And mixed using a fluidized bed granulator [Multiplex MP-01: Powrec Co., Ltd.]. The obtained mixture was granulated by spraying 221.8 g of purified water / ethanol mixed solvent (w / w = 2/8). The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules. 157.08 g of D-mannitol [Pairitol SD100: Rocket Japan Co., Ltd.], 48 g of crospovidone and 2.4 g of sucralose were added to 267.2 g of the obtained granules, and a mixer [V-type mixer VM-5: Dalton Co., Ltd.] And mixed. Further, 4 g of light anhydrous silicic acid and 4 g of magnesium stearate were added and mixed, and then tableted with a single tableting machine (Kikusui Seisakusho Co., Ltd.) with a punch of 8 mm in diameter and R-side with a tableting pressure of 1370-1470N. A 200 mg orally disintegrating tablet containing 51.55 mg of active ingredient per tablet was produced.
The tablet disintegration time of the obtained tablet was 57 seconds. In addition, binding was recognized at the time of manufacture.

(Comparative Example 4)
(1) 51.55 g of acarbose and 50 g of crystalline cellulose [Theolas (registered trademark) 101: Asahi Kasei Corporation] were mixed in a mortar, and 26 g of ethanol was added and kneaded. The obtained mixture was dried at 55 ° C. with a dryer [mini jet oven] and then sized with a No. 22 sieve to obtain granules.
(2) 181.8 g of D-mannitol, 120 g of crystalline cellulose, 80 g of crospovidone, and 4 g of sucralose were mixed using a fluid bed granulator [Multiplex MP-01: Paulek Co., Ltd.], and purified water was added to the resulting mixture. 218g / ethanol mixed solvent (w / w = 2/8) was sprayed and granulated. The granulated product was dried at 55 ° C. with the same machine and then sized with No. 22 sieve to obtain granules.
(3) 50.775 g of the granule obtained in the above (1) and 48.225 g of the granule obtained in the above (2) were mixed using a mixer [V-type mixer VM-5: Dalton Co., Ltd.]. Furthermore, 0.5 g of light anhydrous silicic acid and 0.5 g of magnesium stearate were added and mixed, and then using a single tableting machine [Kikusui Seisakusho Co., Ltd.], the tableting pressure was 3700-4300 N with a 8 mm diameter punch on the R surface. The tablet was tableted with an orally disintegrating tablet with a weight of 200 mg containing 51.55 mg of active ingredient per tablet.
The resulting tablet had an oral disintegration time of 52 seconds.

Although the comparative examples 2 and 3 were manufactured with the manufacturing method different from the manufacturing method of Examples 1-5, all had the oral disintegration time delayed and favorable oral disintegration time was not obtained. Further, binding occurred during the production, and scratches were confirmed on the side surface of the tablet.
In Comparative Example 4, as in Examples 1 to 5, (A) a granulated product containing acarbose and crystalline cellulose and (B) a granulated product containing a rapidly disintegrating component were produced, mixed, and compressed. However, in the production of the granulated product of (A), it is produced not by the fluidized bed granulation method but by the kneading granulation method. Thus, when the granulation method of the granulated product of (A) is other than the fluidized bed granulation method, it was confirmed that the oral disintegration time tends to be delayed.
In addition, about the granulated material of (B), even if it granulates by methods other than the fluidized-bed granulation method (In Example 4, it granulates by the kneading granulation method), a good oral disintegration time is obtained. An orally disintegrating tablet is obtained.

Claims (2)

Orally disintegrating tablets containing the granules (A) and (B) below (A) Granules containing acarbose and crystalline cellulose (B) Granules containing a rapidly disintegrating component The orally disintegrating tablet according to claim 1, wherein the granulated product of (A) is produced by a fluidized bed granulation method.