JP2000273038A - Orally dissolving tablets - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject tablet having excellent disintegrating properties and solubility in an oral cavity, readily administrable and having a suitable strength by including an active ingredient, a lactose, a crystalline cellulose and light silicic acid anhydride in a specific proportion. SOLUTION: This tablet is obtained by including (B) 20-70 mass % of a lactose (e.g. α-hydrous lactose, α-anhydrous lactose or β-anhydrous lactose), (c) 20-50 mass % of a crystalline cellulose and (D) 0.1-10 mass % of light silicic acid anhydride in (A) at least one kind of an active ingredient. A low-substituted hydroxypropyl cellulose, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, etc., may further be contained as a disintegrating agent in tablet. The above tablet is capable of exhibiting a disintegrating time within 30 sec in a disintegration test according to the Japanese Pharmacopeia and excellent disintegrating properties and solubility. The above tablet has 30-150 N tablet hardness without being damaged in production and distribution processes.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an orally dissolving tablet having rapid disintegration or dissolution in the oral cavity without water in the field of pharmaceuticals and foods.

[0002]

2. Description of the Related Art Tablets, capsules, granules, powders and the like are generally used as oral solid dosage forms in the fields of pharmaceuticals and foods, but there are few dosage forms that are easy to handle and easy to take. . Tablets and capsules are difficult to swallow in the case of large preparations, and even chewable tablets are not suitable for elderly or children with weak chewing ability. Under such circumstances, there is a demand for the development of an orally dissolving tablet that can be easily taken by a patient without water and that can be easily taken at any time.

[0003] As a technique for preparing an orally dissolving tablet, a conventional method involves dissolving or suspending a pharmaceutical ingredient in an aqueous solvent, filling the blister pack in a preformed pocket, and freeze-drying or vacuum-drying the solution. (Japanese Patent Laid-Open No. 53-44619, Japanese Patent Publication No. Sho 62)
-50445, JP-A-5-81269, etc.) and a method of compressing the moistened granules at a low pressure, followed by drying to produce the granules (JP-A-6-218028, JP-A-8-19589).
No.) is known. However, these methods use special production equipment and require a long time for production, and thus have the disadvantage of being inferior in industrial productivity. From this point of view, it can be produced by a normal dry tableting method, and exhibits excellent disintegrability and solubility in the oral cavity, and at the same time, has an adequate strength without being damaged in the preparation process and further in the distribution process. There is a demand for the development of a formulation having the same.

On the other hand, lactose is (1) inexpensive, (2) poor in reactivity with active ingredients, (3) has low hygroscopicity, (4) taste without habit, (5) moldability. It is the most widely used excipient because of its good quality, and many studies on lactose have been made. However, it is impossible to produce a tablet having both sufficient hardness and rapid disintegration with lactose alone, and an example of producing an orally dissolving tablet by ordinary dry tableting in combination with other additives. There was no.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a solid preparation which can be easily taken even without water, especially an orally dissolving tablet which disintegrates and dissolves rapidly in the oral cavity and has an appropriate strength. It is in.

[0006]

Means for Solving the Problems As a result of repeated studies based on lactose, the present inventors found that lactose was mixed with crystalline cellulose and light anhydrous silicic acid, and further, a disintegrant was added, and dry tableting was performed. Have surprisingly been found to have the property of disintegrating and dissolving rapidly in the mouth while having moderate strength, and have completed the present invention. That is, the present invention contains at least one active ingredient, lactose, crystalline cellulose, and light anhydrous silicic acid, and has a tablet content of 20 to 70% by mass of lactose and 20 to 50% of crystalline cellulose.
It is an orally dissolving tablet characterized in that it is 0.1% by mass and 0.1 to 10% by mass of light anhydrous silicic acid.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION Lactose that can be used in the present invention includes all of α-hydrated lactose, α-anhydrolactose, and β-anhydrolactose, and lactose for direct compression may be used. Lactose is blended in the tablet in an amount of 20 to 70% by mass, preferably 35 to 70% by mass. The crystalline cellulose that can be used in the present invention includes those called microcrystalline cellulose, and includes various grades such as Avicel PH101 and Avicel PH.
102, Avicel PH301 and the like can be used. The crystalline cellulose is blended in the tablet in an amount of 20 to 50% by mass, preferably 30 to 40% by mass. Light silicic anhydride can be incorporated in the tablet in an amount of 0.1 to 10% by mass, preferably 0.5 to 5% by mass.

In the present invention, besides the above-mentioned components, disintegrating agents which can be generally used in the field of pharmaceutical preparations can be used.
For example, low-substituted hydroxypropylcellulose, carmellose calcium, sodium carboxymethyl starch, croscarmellose sodium, crospovidone and the like can be used.

[0009] The active ingredient in the present invention is an ingredient used in medicines, health foods and the like, and these can be blended as long as the effects of the invention are not hindered. The range that can be blended varies depending on the efficacy of the active ingredient, other properties, and the like, but is preferably 30% by mass or less in the tablet. The amounts of lactose, crystalline cellulose, and light anhydrous silicic acid are adjusted depending on the amounts of the active ingredients.

The tablet of the present invention may contain commonly used additives as long as the effects of the present invention are not hindered. Commonly used additives include, for example, binders, flavoring agents, lubricants, coloring agents, fragrances and the like.

The production of the orally-soluble tablet of the present invention is carried out by an apparatus generally used in the production of a pharmaceutical preparation.
For compression molding, an apparatus generally used for tablet molding is used, and for example, a rotary tableting machine or the like can be used. The powder used for compression molding may be tableted by a direct tableting method after mixing the components, but if necessary, a general granulation method, for example, a stirring granulation method, a fluidized bed granulation method Alternatively, granulation may be performed by a dry granulation method or the like.

The orally-soluble tablet of the present invention exhibits excellent disintegration and solubility in the oral cavity, and has a disintegration time of 30 seconds or less in a disintegration test according to the Japanese Pharmacopoeia. In addition, it has an appropriate strength not to be damaged in the preparation process and further in the distribution process, and preferably has a hardness of 30 N or more and 150 N or less.

[0013]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but these do not limit the present invention.

The physical properties of the tablets obtained in Examples and Comparative Examples were measured by the following test methods. (1) Hardness test The hardness was measured using a tablet hardness tester (Schrouni gel). The test was performed 10 times, and the average value was shown. (2) Disintegration test Since it was found that there was a correlation between the dissolution time in the oral cavity and the disintegration time in the disintegration test, the solubility in the oral cavity was evaluated by the disintegration test by the Japanese Pharmacopoeia. The test was performed using a collapse tester without an auxiliary plate (manufactured by Toyama Sangyo Co., Ltd.). The test was performed on 6 tablets, and the average value was shown.

Examples 1 to 3 and Comparative Examples 1 and 2 Table 1 shows Comparative Examples 1 and 2 as formulations for comparison with Examples 1 to 3 which are formulations of the preparation of the present invention. Lactose (manufactured by DMV), white sugar (manufactured by Dainippon Meiji Seisakusho), crystalline cellulose (Avicel PH101, manufactured by Asahi Kasei Corporation), light anhydrous silicic acid (Esilyl 200, manufactured by Nippon Aerosil Co., Ltd.), crospovidone (Corydon CL) , BASF
After mixing and pulverizing (Yariya pulverizer, Yarya Kikai Co., Ltd.), magnesium stearate (Ohira Chemical Co., Ltd.) was added, mixed for 2 minutes, sieved through No. 22 sieve, and mixed for 2 minutes. Using a single-shot tableting machine (Autograph, manufactured by Shimadzu Corporation), one tablet 220 mg, 9 mmφ, tableting pressure 9 with a corner punch.
It was compressed with KN. The obtained tablet was subjected to a hardness test and a disintegration test, and the results are shown in Table 1.

[0016]

[Table 1] From this test result, it was found that lactose is essential for shortening the disintegration time, and that the amount of lactose is preferably 20% by mass or more in order to keep the disintegration time within 30 seconds.

Examples 4 to 6 and Comparative Examples 3 and 4 Table 2 shows Comparative Examples 3 and 4 as formulations for comparison with Examples 4 to 6 which are formulations of the preparation of the present invention. Lactose (tabletose, manufactured by Megre), crystalline cellulose (avicel PH101, manufactured by Asahi Kasei), crospovidone (colydone CL, manufactured by BASF), light anhydrous silicic acid (Esilyl 200, manufactured by Nippon Aerosil Co., Ltd.), stearic acid After mixing magnesium (Ohira Chemical Co., Ltd.) for 2 minutes,
After sieving through No. 2 sieve, the mixture was mixed for 2 minutes, and using a rotary tableting machine (manufactured by Kikusui Seisakusho), 1 tablet 220 mg, 9 mm
The tablets were tableted with a φ, corner punch at a tableting pressure of 9 KN. The obtained tablets were subjected to a hardness test and a disintegration test.
It was shown to.

[0018]

[Table 2] According to the test results, it was found that crystalline cellulose was indispensable for increasing the hardness, and in order to increase the hardness to 30 N or more, the blending amount was preferably 20% by mass or more. Further, when the blending amount of the crystalline cellulose is increased, an unfavorable texture is generated at the time of ingestion. Therefore, it is found that the blending amount is preferably 50% by mass or less.

Examples 7 to 9 and Comparative Examples 5 and 6 Table 3 shows Comparative Examples 5 and 6 as formulations for comparison with Examples 7 to 9 which are formulations of the preparation of the present invention. Lactose (tabletose, manufactured by Megre), crystalline cellulose (avicel PH101, manufactured by Asahi Kasei), crospovidone (colydone CL, manufactured by BASF), light anhydrous silicic acid (Esilyl 200, manufactured by Nippon Aerosil Co., Ltd.), stearic acid After mixing magnesium (Ohira Chemical Co., Ltd.) for 2 minutes,
After sieving through No. 2 sieve, the mixture was mixed for 2 minutes, and using a rotary tableting machine (manufactured by Kikusui Seisakusho), 1 tablet 220 mg, 9 mm
The tablets were tableted with a φ, corner punch at a tableting pressure of 9 KN. The obtained tablets were subjected to a hardness test and a disintegration test.
It was shown to.

[0020]

[Table 3] According to the test results, it is found that light silicic anhydride is essential for shortening the disintegration time, and in order to keep the disintegration time within 30 seconds, the compounding amount is preferably 0.1% by mass or more. Was. In addition, if the blending amount of the light silicic anhydride increases, tableting trouble occurs, so the blending amount is 10% by mass.
The following has been found to be preferred.

Examples 10 to 13 Table 4 shows Examples 10 to 13 which are formulations of the preparation of the present invention. For each formulation, the active ingredients, aspartame (manufactured by Ajinomoto Co.), lactose (manufactured by DMV), crystalline cellulose (Avicel PH101, manufactured by Asahi Kasei Corporation), light anhydrous silicic acid (Esilyl 200, manufactured by Nippon Aerosil Co., Ltd.), crospovidone (Coridone CL) , BASF), croscarmellose sodium (Ac-Di-Sol, manufactured by Asahi Kasei), magnesium stearate (manufactured by Ohira Chemical Co., Ltd.), pulverized (Yariya pulverizer, Yariya Kikai), dry granulation The mixture was granulated using a machine (manufactured by Freund Sangyo) and sized with a roll granulator (manufactured by Freund Sangyo). After the granulated product was sieved with a No. 22 sieve, the product was tableted using a rotary tableting machine (manufactured by Kikusui Seisakusho) under the conditions shown in Table 4 using a corner punch.
A hardness test and a disintegration test were performed on the obtained tablets, and the results are shown in Table 4.

[0022]

[Table 4] From these test results, it was found that the effects of the invention were not affected even if one or more active ingredients and additives of pharmaceuticals and foods were combined in the present invention.

[0023]

The orally-dissolving tablet of the present invention has excellent disintegration and solubility in the oral cavity, so that it is easy to take and has an appropriate strength. And storage stability in the distribution process. Therefore, it can be suitably used for the treatment and prevention of diseases of patients, particularly elderly or pediatric patients, which are applied according to the contained active ingredient. In addition, since it can be produced by an ordinary production method using inexpensive raw materials, it is excellent in productivity and can be provided to patients at low cost.

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Yasushi Nakagawa 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd. (72) Inventor Shinji Aoki 3-24-1, Takada, Toshima-ku, Tokyo Taisho Pharmaceutical Co., Ltd.

Claims (5)

[Claims] 1. A tablet comprising at least one active ingredient, lactose, crystalline cellulose and light anhydrous silicic acid, wherein the amount in the tablet is 20 to 70% by mass of lactose, 20 to 50% by mass of crystalline cellulose and light anhydrous silicic acid. 0.1 to 10% by mass of an orally soluble tablet. 2. The orally soluble tablet according to claim 1, which has a tablet hardness of 30 N or more and 150 N or less. 3. The orally soluble tablet according to claim 1, wherein the disintegration time is within 30 seconds in a disintegration test according to the Japanese Pharmacopoeia. 4. The orally soluble tablet according to claim 1, further comprising a disintegrant. 5. The method according to claim 1, which is produced by a dry tableting method.
The orally-soluble tablet according to any one of the above.