JP2001139461A - Quickly collapsable tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a quickly collapsable tablet which has dosage form very easy to orally administer for an aged person, dysphagia patient, or infant patient, does not require a special machine device, a special installation or the like, can be produced by a conventional tableting machine, and has an appearance and hardness equal to those of ordinary tablets. SOLUTION: This quickly collapsable tablet prepared by tableting a mixture of specific lactose, crystal cellulose and a medicinal ingredient.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a rapidly disintegrating tablet, and more particularly, to a rapidly disintegrating tablet which can be produced with a conventional tableting machine without using a special tableting machine. .

[0002]

2. Description of the Related Art Pharmaceutical oral dosage forms include tablets, capsules, powders, granules and liquids. Above all, the combination of tablets and capsules accounts for more than 60% of the dosage form,
It is the centerpiece of oral preparations.

On the other hand, tablets and capsules cannot be taken.
Alternatively, there are many patients who are difficult to take. In particular, patients who are older and have reduced swallowing ability, patients who cannot swallow solids, children, and the like often have difficulty in taking tablets prescribed by a doctor. For these patients, there are other dosage forms, namely syrups, solutions, granules and powders, but very few facilities have these dosage forms at the same time, except for large hospitals and pharmacies. There are various reasons for this on the medical front side, such as the problem of space for storing medicines and the economical problem of preparing multiple drugs. Often have. It is ideal for a medical society where patients who can take tablets and capsules and those who cannot drink can choose a dosage form. Can not be expected in the future.

[0004] From the viewpoint of the supply of pharmaceuticals, it is necessary to develop a preparation that can be easily taken by any patient. One of the reasons is that tablets are easily disintegrated in the oral cavity. Tablets with added ingestibility, such as powders and dry syrups, are being developed. However, up to now, quick dissolving tablets by freeze drying, heated drying, and quick disintegrating tablets by special manufacturing machines have been applied to only a few formulations, but all of them are compatible in terms of manufacturability and manufacturing cost. There are many pharmaceutical ingredients that cannot be used. In addition, even if a pharmaceutical preparation can be made, there are many pharmaceutical ingredients that have low productivity or cannot cope with the production process, and there are very many that cannot produce a rapidly disintegrating tablet of the required pharmaceutical ingredient.

[0005] Under these circumstances, patients who can take tablets and those who cannot take tablets can be taken together without selecting them, and any pharmaceutical ingredient can be used without using a special manufacturing method or manufacturing machine.
There is a need for a formulation technique capable of mass-producing rapidly disintegrating tablets at low cost by ordinary tableting, but such a technique has not yet been developed.

[0006]

The present invention does not require any special manufacturing method and equipment, can be manufactured by an ordinary method, does not select a pharmaceutical ingredient, and is different from conventional tablets in use. An object of the present invention is to provide a rapidly disintegrating tablet which is excellent in ingestibility and free of disintegration.

[0007]

Means for Solving the Problems The inventors of the present invention have conducted intensive studies to solve the above-mentioned problems, and as a result, the use of granulated lactose and crystalline cellulose as a base of tablets has made it possible to obtain a conventional tablet. The present inventors have found that the above-mentioned tablets can be rapidly disintegrating tablets by the tableting method and completed the present invention.

That is, the present invention is as follows. (1) A rapidly disintegrating tablet produced by tableting a mixture of granulated lactose, crystalline cellulose, and a pharmaceutical ingredient. (2) The rapidly disintegrating tablet according to (1), wherein the granulated lactose particles are sized to 100 to 1500 μm. (3) The rapidly disintegrating tablet according to (1) or (2), wherein the crystalline cellulose is microcrystalline cellulose. (4) The weight mixing ratio of the granulated lactose and crystalline cellulose is:
3: 2 to 19: 1 (1) to
It is a rapidly disintegrating tablet according to any one of (3).

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION <1> Raw Material Composition of Fast Disintegrating Tablet of the Present Invention The base in the fast disintegrating tablet of the present invention is not particularly limited as long as it is granulated lactose and crystalline cellulose.

The lactose granulated in the present invention is lactose obtained by granulating lactose to an appropriate particle size. Various particle sizes can be obtained by granulating lactose, and any of them can be used for the rapidly disintegrating tablet of the present invention. Preferably those having a particle diameter of 100 to 1500 μm are used, more preferably those having a particle diameter of 150 to 1200 μm, and still more preferably those having a particle diameter of 200 to 800 μm.

In the present invention, the “particle size” is a weight average particle size.

In order to measure the particle size, a sieving method can be used. Specifically, an automatic particle size distribution analyzer (for powder) or the like can be used.

The method for granulating lactose is not particularly limited, and examples thereof include stirring granulation and fluidized bed granulation.

Lactose is not particularly limited as long as it is generally used as a base for tablets, and for example, tabletose manufactured by Megre and the like can be used.

In the present invention, the crystalline cellulose includes:
There is no particular limitation as long as it is generally used as a tablet base. For example, Avicel manufactured by Asahi Kasei Corporation can be used.

The crystalline cellulose is more preferably microcrystalline cellulose. Microcrystalline cellulose is obtained by pulverizing crystalline cellulose.

The crystalline cellulose or microcrystalline cellulose is not particularly limited, but those having a particle size of 100 μm or less, more preferably 50 μm or less, are preferably used. In this case, the volume average particle size measured by a wet type particle size distribution analyzer (for example, a laser diffraction type) is shown.

In the rapidly disintegrating tablet of the present invention, the weight mixing ratio of granulated lactose and crystalline cellulose is 3: 2 to 19:
1, more preferably 7: 3 to 9:
1, more preferably from 8: 2 to 9: 1.

These are 50 parts of the total amount of the rapidly disintegrating tablet.
% By weight or more, more preferably,
70% by weight or more is used.

The pharmaceutical component contained in the rapidly disintegrating tablet of the present invention can be used without particular limitation as long as it is a pharmaceutical component contained in a usual oral pharmaceutical composition.

Examples of such a pharmaceutical component include agents for the nervous system, agents for the circulatory system, agents for the digestive system, agents for the respiratory system and the like.

The content of the pharmaceutical ingredient in the rapidly disintegrating tablet may be such that when the prescribed amount of the composition is taken, the dosage becomes suitable for each active ingredient. . Further, in addition to the above-mentioned components, various orally administrable optional components which are acceptable as additives for pharmaceuticals can be added to the rapidly disintegrating tablet of the present invention as required. As such additives, for example, stabilizers, solubilizers, antioxidants, sweeteners, fragrances and the like can be added as desired.

Further, in the rapidly disintegrating tablet of the present invention,
Based on granulated lactose and crystalline cellulose, flavors, sweeteners and the like can be added to make it easier to take. <2> Method for Producing Rapidly Disintegrating Tablet of the Present Invention The method for producing the rapidly disintegrating tablet of the present invention is not particularly limited, and examples thereof include ordinary tablet producing methods.

For example, each of the above-mentioned raw material compositions for the rapidly disintegrating tablet is appropriately weighed and mixed. These can be obtained by tableting with a rotary tableting machine (for example, HT-AP45 manufactured by Hata Ironworks Co., Ltd.) used in the production of ordinary tablets at a compression pressure of 0.3 to 1.5 t.

[0025]

The present invention will be specifically described below with reference to examples.

[0026]

Example 1 <Basic prescription> The raw material compositions shown in Table 1 are weighed and mixed. This powdered granule is converted into a single-shot tableting machine (N30E
(Trade name, manufactured by Okada Seiko Co., Ltd.) with a pressing force of 0.5 t or 1.0 t to obtain a flat-cornered tablet having a diameter of 7 mm and a weight of 100 mg.

The granulated lactose used as the raw material composition was prepared by sieving tablace (manufactured by Megre) to a particle size of 70 to 500 μm. As the crystalline cellulose, Avicel PH102 (manufactured by Asahi Kasei Corporation) having a particle size of 30 μm was used.

[0028]

[Table 1]

[0029]

Example 2 <Basic prescription> The raw material compositions shown in Table 1 are weighed and mixed. This powder was pressed with a single-shot tableting machine in the same manner as in Example 1 at a pressing force of 0.5 t or 1.0 t to obtain a flat-cornered tablet having a diameter of 7 mm and a weight of 100 mg.

[0030]

Example 3 <Basic prescription> The raw material compositions shown in Table 2 are weighed and mixed. This powder was pressed with a single-shot tableting machine in the same manner as in Example 1 at a pressing force of 0.5 t or 1.0 t to obtain a flat-cornered tablet having a diameter of 7 mm and a weight of 100 mg. The crystalline cellulose has a particle size of Avicel PH301 (made by Asahi Kasei Corporation)
The thing of 0 μm was used.

[0031]

[Table 2]

[0032]

Example 4 <Basic prescription> The raw material compositions shown in Table 2 are weighed and mixed. This powder was pressed with a single-shot tableting machine in the same manner as in Example 3 with a pressing force of 0.5 t or 1.0 t to obtain a flat-cornered tablet having a diameter of 7 mm and a weight of 100 mg.

[0033]

Example 5 <Production by rotary tableting machine> The components shown in Table 3 are weighed and mixed. This granule was tableted with a rotary tableting machine (HT-AP45, manufactured by Hata Ironworks Co., Ltd.) to obtain a flat corner tablet having a diameter of 7 mm and a weight of 100 mg. In addition,
The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0034]

[Table 3]

[0035]

Example 6 <Study of tablet size and weight> The components shown in Table 4 are weighed and mixed. A tableting machine (N30)
E type, manufactured by Okada Seiko Co., Ltd.)
Three corner flat tablets having a diameter of 8 mm and weighing 150, 180 and 200 mg, and three corner flat tablets having a diameter of 9 mm and a weight of 200, 22
A total of 6 kinds of three kinds of angled flat tablets of 0 and 250 mg were obtained.
The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0036]

[Table 4]

[0037]

Example 7 <Nicorandil rapidly disintegrating tablet> Components shown in Table 5 are weighed and mixed. This powder is pressed with a single-shot tableting machine at a pressing force of 0.5t or 0.75t, and the diameter is 7m.
m and a weight of 100 mg were obtained. The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0038]

[Table 5]

[0039]

Example 8 <cisapride rapidly disintegrating tablet> Components shown in Table 6 are weighed and mixed. This granule is tableted with a single-shot tableting machine at a compression pressure of 1.25 t, and has a diameter of 8 mm and a weight of 200 m.
g corner flat tablets were obtained. The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0040]

[Table 6]

[0041]

Example 9 <Famotidine disintegrating tablet> Components shown in Table 7 are weighed and mixed. The powder is pressed with a single-shot tableting machine at a pressing pressure of 0.75 t or 1.0 t, and the diameter is 9 m.
m, a flat tablet with a corner weight of 250 mg was obtained. The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0042]

[Table 7]

[0043]

Example 10 <Famotidine disintegrating tablet> Components shown in Table 7 are weighed and mixed. The powder is pressed with a single-shot tableting machine at a pressing pressure of 0.75 t or 1.0 t, and the diameter is 9 m.
m, a flat tablet with a corner weight of 250 mg was obtained. The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0044]

Example 11 <Simvastatin fast-disintegrating tablet (1)>
The components shown in Table 8 are weighed and mixed. The granules were tableted with a single-shot tableting machine at a compression pressure of 0.5 t to obtain flat corner tablets having a diameter of 7 mm and a weight of 130 mg. The same crystalline cellulose and granulated lactose as in Example 3 were used.

[0045]

[Table 8]

[0046]

Example 12 <Simvastatin rapidly disintegrating tablet (2)>
The components shown in Table 9 are weighed and mixed. The powder was granulated and sized by a stirring granulation method to obtain granules a. Next, granules a
The components shown in Table 10 containing are weighed and mixed. The granules were tableted with a single-shot tableting machine at a pressing force of 0.75 t or 1.0 t to obtain flat-cornered tablets having a diameter of 9 mm and a weight of 250 mg.

[0047]

[Table 9]

[0048]

[Table 10]

[0049]

Example 13 <Evaluation of rapidly disintegrating tablet of the present invention> A tablet hardness test and a disintegration test were performed on the rapidly disintegrating tablets obtained in the above Examples. Disintegration was evaluated by a weighted disintegration test. <1> Tablet hardness test With respect to the various rapidly disintegrating tablets prepared in Examples 1 to 4 and 7 to 12, the load when the tablet was crushed by applying a weight in the diameter direction of the tablet, that is, the hardness of the tablet was measured. <2> Weighted Disintegration Test For the rapidly disintegrating tablets prepared in Examples 1 to 4 and 7 to 12, for example, in order to test the rapid disintegration of various tablets in the oral cavity, a method as shown in FIG. The time required for the tablet to disintegrate was measured by a weighted disintegration test.

That is, the tablets are placed on a platform in the container. This platform is grooved with a width smaller than the diameter of the tablet, and when purified water is added, water can easily enter from the lower part of the tablet. Next, as shown in FIG. 1B, a weight of 50 g is applied to the tablet, and then purified water is poured into the container so that the tablet is covered. From the time when purified water was added, the time when the collapse completely occurred and the weight change of the pressurized portion appeared was measured and defined as the collapse time.

The above results are expressed as the relationship between tablet hardness and disintegration time, and are shown in FIGS.

Table 1 summarizes the results.
It is shown in FIG.

[0053]

[Table 11] The target evaluation standard value is a tablet hardness of 3 kg or more required for extrusion from a PTP (press-through package) package, and a weighted disintegration time of about 10 seconds as a measure of disintegration in the oral cavity and the like. From the results, it was found that the quick disintegrating tablet of the present invention clears the set evaluation standard value, can be easily pushed out of the PTP package, and can be disintegrated in about 10 seconds even when clogged in the throat or the like. .

As shown in Tables 12 and 13 below, the weighted disintegration test apparatus used in the weighted disintegration test in the present example was based on the disintegration time due to oral disintegration (without water and with 30 ml of water). Satisfies the correlation. Disintegration time due to oral disintegration is the average value measured by three volunteers.

[0055]

[Table 12] 崩 壊 Oral disintegration Weighted disintegration test Without water 37 ℃ ─────────── ────────────── Sample 1 13.67 12.77 Sample 2 17.10 14.50 Sample 3 21.63 19.68 Sample 4 13.45 12.73 Sample 5 17. 02 15.87 Sample 6 20.89 19.01 Sample 7 15.21 12.06 Sample 8 16.34 12.90 Sample 9 18.67 15.43 Sample 10 78.08 55.74 Sample 11 136.45 96 .65 sample 12 117.87 88.44 sample 13 14.35 11.46 sample 14 15.34 12.20 ─

[0056]

[Table 13] 崩 壊 Oral disintegration Weighted disintegration test With water 37 ℃ ─────────── ────────────── Sample 1 14.70 12.77 Sample 2 18.86 14.50 Sample 3 23.27 19.68 Sample 4 14.21 12.73 Sample 5 19. 22 15.87 Sample 6 19.91 19.01 Sample 7 12.49 12.06 Sample 8 13.99 12.90 Sample 9 17.73 15.43 Sample 10 70.26 55.74 Sample 11 120.87 96 .65 sample 12 111.25 88.44 sample 13 11.22 11.46 sample 14 12.12 12.20 ─

[0057]

According to the present invention, it is possible to provide a rapidly disintegrating tablet which is very easy to take even for elderly patients and patients with dysphagia. In addition, the rapidly disintegrating tablet of the present invention can be produced very simply by setting the base to a specific composition, and can be produced by exactly the same method (equipment) as in the past, and is usually a tablet having the same appearance and hardness. Because there is no inferiority to ordinary PT
P packaging is available. Furthermore, since the rapidly disintegrating tablet of the present invention disintegrates quickly even when it adheres to the throat or the like, it is possible to overcome the problem that the tablet stays in the throat or the like to cause inflammation.

[Brief description of the drawings]

FIG. 1 is a diagram illustrating a weighted collapse test in the present invention.

FIG. 2 shows the relationship between the tablet tests of Examples 1 to 4 and the disintegration time.

FIG. 3 shows the relationship between tablet hardness and disintegration time in Example 7.

FIG. 4 shows the relationship between tablet hardness and disintegration time in Example 8.

FIG. 5 shows the relationship between tablet hardness and disintegration time in Examples 9 and 10.

FIG. 6 shows the relationship between tablet hardness and disintegration time in Example 11.

FIG. 7 shows the relationship between tablet hardness and disintegration time in Example 12.

[Explanation of symbols]

 a: fast disintegrating tablet b: table c: purified water d: container e: weighting means

 ──────────────────────────────────────────────────続 き Continuing on the front page (72) Mitsuhiro Saito 51-sanjo-cho, Omiya-shi, Saitama Ota Pharmaceutical Co., Ltd. Reference) 4C076 AA37 BB01 DD67 EE31 FF06

Claims (4)

[Claims] 1. A rapidly disintegrating tablet produced by tableting a mixture of granulated lactose, crystalline cellulose and a pharmaceutical ingredient. 2. The method according to claim 1, wherein the particles of the granulated lactose are 100 to 150.
The rapidly disintegrating tablet according to claim 1, which is sized to 0 µm. 3. The rapidly disintegrating tablet according to claim 1, wherein the crystalline cellulose is microcrystalline cellulose. 4. The rapidly disintegrating tablet according to claim 1, wherein the weight mixing ratio of the granulated lactose and the crystalline cellulose is 3: 2 to 19: 1.