JP2000001428A - Tablet and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a process for surely producing an excellent tablet containing magnesium oxide as a principal drug (magnesium oxide tablet) and essentially free from darkening defect. SOLUTION: This process for the production of a magnesium oxide tablet comprises the tableting of a powdery mixture containing granular magnesium oxide, an excipient, talc and magnesium stearate or calcium stearate. The excipient is selected from lactose, crystalline cellulose, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, D-mannitol, starch and powdery cellulose.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for producing tablets containing magnesium oxide as a main drug (hereinafter referred to as "magnesium oxide tablets").

[0002]

2. Description of the Related Art Magnesium oxide (MgO) is mainly provided in the form of powder or fine granules as an antacid or laxative. On the other hand, magnesium oxide tablets in which magnesium oxide is in the form of a tablet are provided only slightly, despite the convenience of the tablet form. This is because, as is well known, even if magnesium oxide is tableted with an appropriate excipient or the like by a conventional method, a considerable amount of darkened magnesium oxide tablet is generated.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a method for producing an excellent magnesium oxide tablet having substantially no darkening.

[0004]

Means for Solving the Problems As a result of intensive studies, the inventors of the present invention have conducted tableting of mixed powder containing granular magnesium oxide, an excipient, and talc, and magnesium stearate or calcium stearate. As a result, the present inventors have found that the above problems can be solved, and have completed the present invention. Accordingly, one aspect of the present invention is a method for producing a magnesium oxide tablet, which comprises tablet-molding a granular magnesium oxide, an excipient, and talc, and a mixed powder containing magnesium stearate or calcium stearate. is there. Further, a magnesium oxide tablet produced by the production method, a magnesium oxide tablet, a magnesium oxide tablet containing an excipient, talc, and magnesium stearate or calcium stearate, which is substantially free from darkening ( Hereinafter, each of them is also referred to as “the magnesium oxide tablet of the present invention”).

[0005] The term "darkening" as used herein means that the surface of the tablet is totally or partially darkened, or has a black dot, line or surface. "Substantially no darkening"
This means that there is no darkening to such an extent that almost everyone can judge that no darkening is seen by a person skilled in the art.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION "Magnesium oxide tablets" are tablets mainly intended to exert the effects of magnesium oxide, and basically contain no medicinal ingredients other than magnesium oxide and are contained in tablets. It is a tablet having a high content of magnesium oxide. In the present invention, the tablet preferably contains magnesium oxide in a range of 50 to 95% by weight, more preferably 60 to 80% by weight.

[0007] "Granular" is a term distinguished from powdery, and is a term obvious to those skilled in the art. Usually, 90% or more of particles having a particle size of 74 μm or more are referred to.
The granules can be classified into fine granules or granules depending on the size of the particles, and any of them can be used in the present invention. In the present invention, the particle size is 74 to 50.
Preferably, 90% of the particles are present in the range of 0 μm, and more preferably, 98% or more of the particles are present in the range of 74 to 500 μm.

[0008] "Granular magnesium oxide" is usually
Powdered magnesium oxide is granulated into granules using an appropriate granulator. In the present invention, commercially available fine or granular magnesium oxide can be used as it is. The use of granular magnesium oxide is one of the features of the present invention.

The "excipient" applicable in the present invention is not particularly limited as long as it is a pharmaceutically acceptable excipient. Specifically, lactose, crystalline cellulose, calcium hydrogen phosphate,
Examples thereof include anhydrous calcium hydrogen phosphate, D-mannitol, starch, and cellulose powder. Two or more of these can be used in combination. Among them, for example, lactose and crystalline cellulose are preferred, and lactose for direct compression is more preferred. The content of the excipient in the tablet varies depending on the type and content of magnesium oxide and other additives,
The range of 3 to 48% by weight is suitable, and the range of 20 to 35% by weight is preferable.

The content of talc applicable in the present invention varies depending on the kind and content of magnesium oxide and other additives, but is suitably in the range of 2 to 20% by weight in the tablet. The range is preferably from 10 to 10% by weight, and more preferably from 3 to 8% by weight. This content is considered to be relatively high compared to the talc content in normal tablet formulations.

The magnesium stearate and the calcium stearate which can be used in the present invention can be used in combination with magnesium oxide, an excipient or the like, or both. The content of the magnesium stearate and the calcium stearate varies depending on the type and the content of the magnesium oxide and other additives, but it is appropriate that the total content is in the range of 0.1 to 2% by weight in the tablet. 3
It is preferably in the range of １1% by weight.

In the present invention, a disintegrating agent or a fluidizing agent can be optionally contained. These disintegrants and fluidizing agents are effective for improving the disintegration and abrasion resistance of the tablet and the moldability upon tableting, and those containing an appropriate amount of these are preferable.

The above-mentioned disintegrant is not particularly limited as long as it is a pharmaceutically acceptable disintegrant. Specifically, low-substituted hydroxypropyl cellulose, low-substituted carboxymethyl starch, crystalline cellulose, carmellose, carmellose calcium, Carmellose sodium, croscarmellose sodium and the like can be mentioned. These two
More than one species may be used in combination. Among these, for example, low-substituted hydroxypropylcellulose is preferable. The content of the disintegrant in the tablet varies depending on the type and the content of magnesium oxide and other additives, but is 0.5 to 10%.
% Is suitable, and preferably in the range of 1 to 5% by weight. By containing a disintegrant, the magnesium tablet of the present invention can be rapidly disintegrated in the stomach.

The above-mentioned fluidizing agent is not particularly limited as long as it is a pharmaceutically acceptable fluidizing agent, and specific examples thereof include calcium silicate, light silicic anhydride, and hydrous silicon dioxide. Two or more of these can be used in combination. The content of the fluidizing agent in the tablet varies depending on the type and content of magnesium oxide and other additives, but is preferably in the range of 0.1 to 3% by weight, and 0.5 to 3% by weight.
It is preferably in the range of 1.5% by weight. By containing a fluidizing agent, tableting trouble such as sticking can be further prevented, and the hardness of the tablet can be increased.

The mixing of magnesium oxide and other additives is carried out manually or by using a suitable mixer, for example, a general V-type mixer, a container-type mixer, a stirring-type mixer, a ribbon-type mixer. It can be carried out. The tableting method can be performed by a conventional direct compression method using a general tableting machine for pharmaceutical production. Examples of the tableting machine include a general rotary tableting machine and a single-shot tableting machine. The shape of the magnesium oxide tablet of the present invention is as follows:
Any of a corner R plane, a rounded corner plane, a corner plane, and the like may be used. Among them, the corner R surface is preferable.

[0016]

The present invention will be described in more detail with reference to comparative examples, examples and test examples. Comparative Example 1 300 g of commercially available fine-grained magnesium oxide (manufactured by Kyowa Chemical Industry Co., Ltd .; the same applies hereinafter) and 3 g of magnesium stearate were weighed out.
These were placed in a polyethylene bag and mixed for 2 minutes. This mixed powder was tableted to a tablet weight of 303 mg and a thickness of 3.35 mm using a rotary tableting machine CLEAN PRESSCORRECT 12HUK (manufactured by Kikusui Seisakusho, same hereafter) equipped with a flat punch with a corner of 8 mmφ, and tablets for comparative testing were prepared. Obtained.

Comparative Example 2 300 g of commercially available fine-grained magnesium oxide, crystalline cellulose (Avicel (registered trademark); manufactured by Asahi Kasei Corporation; the same applies hereinafter)
125 g, Macrogol 6000 20 g, and magnesium stearate 5 g were weighed and mixed with a V-type mixer FM-V-10 (manufactured by Fuji Sangyo Co., Ltd .; the same applies hereinafter) for 10 minutes. This mixed powder
Rotary tableting machine CLEA with 9.5mmφ, flat corner punch
The tablet was tableted with N PRESS CORRECT 12HUK to a weight of 450 mg per tablet and a thickness of 3.88 mm to obtain a tablet for comparative test.

Comparative Example 3 330 g of commercially available powdered magnesium oxide, lactose (Dilactose (registered trademark); manufactured by Freund Corporation; the same applies hereinafter) 16
7 g, low-substituted hydroxypropylcellulose (L-HPC;
Made by Shin-Etsu Chemical Co., Ltd. The same applies hereinafter) 10 g, talc 20 g, and magnesium stearate 3 g were weighed, placed in a polyethylene bag, and mixed for 2 minutes. This mixed powder is 9.5mmφ,
CLEAN PRESS CO, a rotary tablet press equipped with a corner R-face punch
Molding work was performed at RRECT 12HUK. However, since the mixed powder was bulky and had poor fluidity, poor filling into the mortar occurred, and molding was not possible.

Example 1 300 g of commercially available fine-grained magnesium oxide, crystalline cellulose 10
0 g, 50 g of talc, and 3 g of magnesium stearate were weighed, placed in a polyethylene bag, and mixed for 2 minutes.
This mixed powder was tableted to a weight of 453 mg per tablet and a thickness of 3.75 mm with a rotary tableting machine CLEAN PRESS CORRECT 12HUK equipped with a 9.5 mmφ, rounded flat punch to obtain the magnesium oxide tablet of the present invention.

Example 2 300 g of commercially available fine-grained magnesium oxide, crystalline cellulose 10
0 g, low-substituted hydroxypropylcellulose 10 g, talc 30 g, and magnesium stearate 3 g were weighed and mixed with a V-type mixer FM-V-10 for 10 minutes. This mixed powder is a rotary tableting machine equipped with a 9.5 mmφ, rounded flat punch.
Weight 443m per tablet at CLEAN PRESS CORRECT 12HUK
g, tablet compression to 3.67mm thickness, hardness 5kg or more, disintegration time within 1 minute (conforms to the disintegration test method published by Japan Pharmacopoeia 13, same hereafter)
Of the present invention was obtained.

Example 3 9,900 g of commercially available fine-grained magnesium oxide, crystalline cellulose
3,510 g, low-substituted hydroxypropylcellulose 300 g,
1,050 g of talc, 90 g of magnesium stearate, and 150 g of calcium silicate (FLORITE (registered trademark) RE, manufactured by Eisai Co., Ltd .; the same applies hereinafter) were weighed, and weighed with a Bohle container mixer PM100 (manufactured by Kotobuki Giken Kogyo Co., Ltd.). Mix for minutes. This mixed powder was formed into tablets with a weight of 500 mg and a thickness of 5.05 mm using a rotary tableting machine CLEAN PRESS CORRECT 12HUK equipped with a 9.5 mmφ, corner R-face punch, hardness of 5 kg or more, disintegration time within 1 minute, Friability 0.2% or less (USP
Based on 23 / NF18 general information chapter <1216>. The same applies to the following).

Example 4 330 g of commercially available fine-grained magnesium oxide, lactose 162 g, low-substituted hydroxypropylcellulose 10 g, talc 20 g, calcium stearate 3 g, and calcium silicate 5 g were weighed and placed in a polyethylene bag for 2 minutes. Mixed.
This mixed powder was tableted to a tablet weight of 530mg and a thickness of 5.47mm with a rotary tableting machine CLEAN PRESS CORRECT 12HUK equipped with a 9.5mmφ, corner R-face punch, hardness 5kg or more, disintegration time within 1 minute, A magnesium oxide tablet of the present invention having a friability of 0.2% or less was obtained.

Test Example 1 Various tablets according to the above Comparative Examples and Examples were visually observed by 10 ordinary persons skilled in the art, and the degree of darkening was determined by the determination method shown in Table 1 below (n = 10). Table 2 shows the results.

[0024]

[Table 1]

[0025]

[Table 2]

Test Example 2 Modification of Paddle Method, Second Method of Dissolution Test, published in Japanese Pharmacopoeia No. 13 (Test solution: 50 ml or 100 ml of 0.1N HCl, liquid temperature: 37)
), The number of revolutions: 50 rpm or 100 rpm, the height of the paddle: 1 cm from the bottom, the measurement time: 3 hours), and the dissolution test of the magnesium oxide tablet of the present invention of Example 4 was carried out. Agent). Fig. 1 (0.
Results with 50 ml of 1N HCl test solution) and Fig. 2 (0.1N HCl 100
(Results with ml test solution). As is clear from FIGS. 1 and 2, the magnesium oxide tablet of the present invention showed the dissolution characteristics equal to or higher than those of commercially available fine-grained magnesium oxide.

[0027]

According to the present invention, a magnesium oxide tablet substantially free from darkening can be produced with a yield of almost 100%, and an oxidized tablet which is excellent in hardness and disintegration and has low friability. It is possible to produce magnesium tablets.

[Brief description of the drawings]

FIG. 1 shows the results of a dissolution test of the magnesium oxide tablet of the present invention and a commercially available fine-grained magnesium oxide. The horizontal axis represents time (minutes), and the vertical axis represents liquidity (pH). -●-indicates the results at 100 rpm of the magnesium oxide tablet of the present invention according to Example 4, and -rpm- indicates the results at 50 rpm of the magnesium oxide tablet of the present invention according to Example 4. −
Indicates the results of a commercially available fine-grained magnesium oxide at a rotation speed of 100 rpm, and-□-indicates the results of a commercially available fine-grained magnesium oxide at a rotation speed of 50 rpm.

FIG. 2 shows the results of a dissolution test of the magnesium oxide tablet of the present invention and a commercially available fine-grained magnesium oxide. The horizontal axis represents time (minutes), and the vertical axis represents liquidity (pH). -●-indicates the results at 100 rpm of the magnesium oxide tablet of the present invention according to Example 4, and -rpm- indicates the results at 50 rpm of the magnesium oxide tablet of the present invention according to Example 4. −
Indicates the results of a commercially available fine-grained magnesium oxide at a rotation speed of 100 rpm, and-□-indicates the results of a commercially available fine-grained magnesium oxide at a rotation speed of 50 rpm.

Claims (15)

[Claims] 1. A method for producing a tablet containing magnesium oxide as a main ingredient, which comprises tablet-forming a granular magnesium oxide, an excipient, talc, and a mixed powder containing magnesium stearate or calcium stearate. . 2. The method according to claim 1, wherein the excipient is lactose, crystalline cellulose, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, D-mannitol, starch or powdered cellulose. 3. The method for producing a tablet according to claim 1, wherein a mixed powder further containing at least one selected from the group consisting of a disintegrant and a fluidizing agent is tableted. . 4. The tablet according to claim 3, wherein the disintegrant is low-substituted hydroxypropylcellulose, low-substituted carboxymethyl starch, crystalline cellulose, carmellose, carmellose calcium, carmellose sodium or croscarmellose sodium. Manufacturing method. 5. The method according to claim 3, wherein the superplasticizer is calcium silicate, light anhydrous silicic acid or hydrous silicon dioxide. 6. A particulate magnesium oxide content of 50 to 50.
The method for producing a tablet according to any one of claims 1 to 5, which is in a range of 95% by weight. 7. The method for producing a tablet according to claim 1, wherein the content of talc is in the range of 2 to 20% by weight. 8. A tablet produced by the production method according to any one of claims 1 to 7. 9. A magnesium oxide, excipient, and talc,
A tablet containing magnesium oxide as a main ingredient, which contains magnesium stearate or calcium stearate and is substantially free of darkening. 10. The excipient is lactose, crystalline cellulose, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, D-mannitol, starch, or powdered cellulose.
Tablets as described. 11. The method for producing a tablet according to claim 9, wherein a mixed powder further containing at least one selected from the group consisting of a disintegrant and a fluidizing agent is tableted. . 12. The tablet according to claim 11, wherein the disintegrant is low-substituted hydroxypropyl cellulose, low-substituted carboxymethyl starch, crystalline cellulose, carmellose, carmellose calcium, carmellose sodium or croscarmellose sodium. 13. The tablet according to claim 11, wherein the superplasticizer is calcium silicate, light anhydrous silicic acid, or hydrous silicon dioxide. 14. A particulate magnesium oxide content of 50.
14. A tablet according to any of claims 9 to 13, which is in the range of ~ 95% by weight. 15. The tablet according to claim 9, wherein the content of talc is in the range of 2 to 20% by weight.