JP4804737B2 - Calcium-containing rapidly disintegrating solid preparation - Google Patents

Description

  The present invention relates to a calcium-containing rapidly disintegrating solid preparation.

Osteoporosis is a social problem in the modern aging society. In order to maintain bone mass and prevent osteoporosis, it is essential to continue taking calcium.
In recent years, it has been desired to develop a tablet that can be taken without water as a dosage form considering the ease of taking by consumers. Usually, when taking solid preparations such as tablets, water is required, and there is a problem that it is not convenient. In addition, there is a problem that it is difficult to take a large tablet or a tablet with a large dose. In particular, patients who have difficulty swallowing, children, and elderly people may suffocate by using the throat. On the other hand, chewable tablets do not require water, but are not suitable for children and elderly people with weak chewing ability and teeth. In order to solve these problems, there are dosage forms that disintegrate rapidly in the oral cavity.
However, since the nutritional requirement of calcium is as high as 600 mg at the age of 30 years, for example, when trying to make a preparation that allows intake of half of it (300 mg), the number of grains becomes very large. When the number of grains is reduced, the calcium content increases and the disintegration property is delayed. Therefore, a fast disintegrating preparation containing a high amount of calcium has not yet been developed.

As a prior art, as a conventional patent relating to a rapidly disintegrating preparation, there are those relating to a rapidly disintegrating preparation containing erythritol or mannitol (Patent Document 1 and Patent Document 2). Patent Document 1 relates to a compressed composition imparted with fast disintegration by blending erythritol, and Patent Document 2 relates to a preparation imparted with rapid disintegration by blending mannitol. However, erythritol and mannitol have poor moldability, and many excipients are required for formulation, resulting in an increase in the number of grains.
There is also a patent relating to a solid pharmaceutical preparation (Patent Document 3). Patent document 3 gives quick disintegration by blending erythritol, crystalline cellulose, and a disintegrant into a pharmaceutical ingredient, but the disintegrant to be used is crospovidone which is a pharmaceutical additive. I can not use it.
There exists patent document 4 as a patent which provided quick disintegration by making a tablet porous. In Patent Document 4, sugar alcohol and starch are kneaded into an infiltrated lump, then rolled and molded, and further dried under reduced pressure to make it porous and impart quick disintegration. However, since the manufacturing method is complicated and a special apparatus is required, the manufacturing method is inferior in versatility.
Patents that devise the manufacturing method include Patent Document 5. Patent Document 5 imparts quick disintegration by adding water to a medicinal ingredient and a saccharide and moistening, compressing the wet powder, and then drying. However, there is a problem that it is difficult to use for an active ingredient that deteriorates when coexisting with water, and a special device for drying wet tablets is required.
On the other hand, regarding calcium-containing preparations, chewable tablets (Patent Document 6) containing acrylic acid polymers, chewable tablets (Patent Document 7) containing hydroxyalkyl celluloses having different viscosities, and chewable tablets containing povidone or copolyvidone. Although there is (Patent Document 8), acrylic acid polymers, hydroxyalkyl cellulose, povidone, and copolyvidone cannot be used for food.
Therefore, it is necessary to develop a high calcium-containing preparation that does not require complicated steps or special production facilities and is excellent in disintegration.

International Publication Number WO98 / 02185 JP 2001-58944 A Japanese Patent Laid-Open No. 10-182436 JP 2003-137815 A Japanese Patent No. 3069458 JP-A-9-194381 Japanese Patent No. 2995226 JP 2001-131076 A

  An object of the present invention is to provide a solid preparation containing a high amount of calcium and rapidly disintegrating when put in the oral cavity without requiring complicated processes and special production equipment.

  As a result of intensive studies to solve these problems, the present inventors granulated a calcium material with a galactomannan solution, and when compressed, a calcium-containing rapidly disintegrating solid that rapidly disintegrates when placed in the oral cavity. The inventors have found that a preparation can be obtained and have reached the present invention.

That is, the present invention is 1. A calcium-containing material is prepared using a solution containing 3 to 80 parts by mass of a calcium-containing material, 0.01 to 30.0 parts by mass of galactomannan and cellulose, and having a viscosity of a galactomannan solution of 80 mPa · s to 2000 mPa · s. A rapidly disintegrating tablet obtained by granulating a powder containing a calcium-containing material obtained by granulating and then tableting and then tableting , wherein the calcium-containing material comprises dolomite, eggshell calcium, scallop Shell calcium, oyster shell calcium, salmon calcium, sea urchin shell calcium, fossilized seaweed calcium, pearl calcium, beef bone calcium, fish bone powder calcium, fish scale calcium, etc. Or calcium carbonate, calcium phosphate, calcium lactate, calcium gluconate , Calcium citrate, rapidly disintegrating tablets be any or more of calcium salts such as calcium chloride, it oral disintegration time is within 34 seconds, and wherein,
2. 1 or 2 or more types chosen from carbohydrates and starches as an excipient | filler are characterized by the above-mentioned. The fast disintegrating tablets described,
3. 1. The particle size of the calcium-containing material is 250 μm or less. Or 2. The fast disintegrating tablet described.
4). 1. The average molecular weight of galactomannan is 100,000 Da or less. ~ 3. A rapidly disintegrating tablet according to any one of
5. 1. It is a food. ~ 4. The fast disintegrating tablet according to any one of the above.

According to the present invention, a calcium-containing rapidly disintegrating solid preparation having an extremely excellent disintegrating property can be easily produced by a widely used method without using a special apparatus or manufacturing method.
It is possible to provide a solid preparation containing a high amount of calcium excellent in disintegration.

The present invention is described in detail below.
The fast disintegrating solid preparation referred to in the present invention is a solid preparation that rapidly disintegrates when placed in the oral cavity.

Examples of calcium-containing materials used in the present invention include dolomite, eggshell calcium, scallop shell calcium, oyster shell calcium, salmon calcium, sea urchin shell calcium, fossilized seaweed calcium, pearl calcium, beef bone calcium, fish bone powder calcium, fish scale calcium, All commercially available products such as calcium calcium, calcium phosphate, calcium lactate, calcium citrate, calcium chloride, etc. Can be mentioned.
As a compounding quantity of a calcium containing raw material, 3-80 mass%, Preferably it is 4-70 mass%, Most preferably, 5-60 mass% is desirable. When the amount of the calcium material is less than this range, the amount of calcium decreases and a large amount of tablets must be taken. On the other hand, if this range is exceeded, the moldability will be poor and it will be difficult to obtain tablets that can withstand distribution.
The particle diameter of the calcium material is 250 μm or less, preferably 230 μm or less, particularly preferably 200 μm or less. When the particle size is large, roughness occurs in the oral cavity. Further, segregation occurs during production, resulting in a preparation lacking in content uniformity.

Galactomannan is a polysaccharide composed only of galactose and mannose, and has a structure in which galactose is bonded to the mannose main chain by α-1,6 as a substituent. In particular, it is known to be contained in a large amount in the endosperm portion of the legume seeds. Industrially, galactomannan can be isolated by first pulverizing endosperm from which seed coat has been removed, filtering a solution soaked in water or warm water, adding alcohol to precipitate, or freeze-drying. The obtained galactomannan can be enzymatically treated to produce a galactomannan degradation product having a small molecular weight, and any galactomannan can be used in the present invention.
The blending ratio of galactomannan is 0.01 to 30% by mass, preferably 0.01 to 25% by mass, particularly preferably 0.01 to 20% by mass. When the amount of galactomannan exceeds 30% by mass, the blending ratio of the calcium blending material decreases, and as a result, the intake increases and the burden on consumers and patients increases. If the blended amount of galactomannan is less than 0.01% by mass, the moldability becomes poor, and the tablet may be broken or worn.

Examples of the excipient used in the present invention include carbohydrates, starches, and celluloses.
Examples of the saccharides include all commercially available products such as sucrose, lactose, maltose, glucose, trehalose, reduced lactose, reduced maltose, sorbitol, mannitol, xylitol.

  Starches include corn starch, wheat starch, rice starch, potato starch, pregelatinized starch, partially pregelatinized starch, tapioca starch, high amylose starch, hydroxypropyl starch, starch hydrolysate, acetate starch, phosphate starch, octenyl succinate Examples include all commercially available products such as acid starch, carboxymethyl starch, phosphoric acid crosslinked starch, oxidized starch, dialdehyde starch, acid-treated starch, and sodium hypochlorite-treated starch.

Examples of celluloses include all commercially available products such as crystalline cellulose, powdered cellulose, methylcellulose, low-substituted hydroxypropylcellulose, carboxymethylcellulose calcium, and carboxymethylcellulose sodium.
These excipients can be used alone or in combination of two or more.

  The dosage form of the present invention is preferably a tablet or granule.

Moreover, the following inactive components can also be contained in order to improve manufacturability. Inactive ingredients in the present invention include dextrin, xanthan gum, sodium alginate, gum arabic, tragacanth gum, pullulan, carrageenan, agar, gelatin, soybean dietary fiber, vegetable hardened oil, vegetable oil powder, carnauba wax, cacao oil powder, sucrose fatty acid Listed are all commercially available products such as esters, magnesium stearate, calcium stearate, talc and the like.
Furthermore, fruit juice powder, a fragrance | flavor, etc. can be mix | blended for the purpose of improving seasoning and flavor as needed.

The tablet of the present invention is not affected by its shape and weight, and these are produced according to a general production method, and obtained by granulating a calcium-containing material using a galactomannan solution. A method of forming granules is desirable.
When galactomannan is dissolved in water, the solubility and viscosity of the resulting solution vary depending on the molecular weight of galactomannan.
The molecular weight of galactomannan is not particularly specified, but it is particularly desirable that galactomannan is treated with an enzyme to have a molecular weight of 100,000 Da or less.
Further, the viscosity of the aqueous solution is desirably 2000 mPa · s or less. When the viscosity is 2000 mPa · s or more, dispersibility is deteriorated during granulation, and the particle size and strength of the resulting granule are not uniform.
In consideration of versatility, the granulation method is preferably a fluidized bed granulation method, a stirring granulation method, an extrusion granulation method or the like.

  The rapidly disintegrating solid preparation of the present invention is, for example, obtained by granulating a calcium-containing material as it is or mixed with saccharides, starches, and celluloses using an aqueous galactomannan solution into granules. It can be produced by compression molding according to a conventional method. At this time, the above-mentioned excipients and inactive ingredients may be added.

The pressure at the time of compression molding may be arbitrarily set from the disintegration property in the oral cavity and the hardness of the tablet, but the oral disintegration time is sufficient even if the present invention is used to have physical properties that can withstand distribution. It doesn't have to be greatly damaged. Thus, the molding pressure and tablet hardness can be a conventional tablet comparable, compacting pressure 100~4000kg / cm ^2, preferably 100~3500kg / cm ^2, particularly preferably from 100~3000kg / cm ^2, tablet hardness Is 1 to 15 kgf, preferably 1 to 13 kgf, and particularly preferably 1 to 10 kgf. Further, the friability is 3.0% or less, preferably 2.5% or less, particularly preferably 2.0% or less.

The rapidly disintegrating food composition of the present invention obtained as described above is excellent in disintegration in the oral cavity or in water and has a hardness capable of withstanding circulation.
The disintegration time of the tablet obtained in the present invention in the oral cavity is desirably within 240 seconds, preferably within 210 seconds, and particularly preferably within 180 seconds. In addition, when tested in accordance with the evaluation method of “Disintegration Test Method (1) Tablet” described in the 14th revised Japanese Pharmacopoeia, it disintegrates within 480 seconds, preferably within 420 seconds, particularly preferably within 360 seconds. It is desirable to satisfy this sufficiently.
The calcium-containing rapidly disintegrating solid preparation of the present invention is a tablet that is particularly easy to take for children and the elderly.

  Examples of the present invention are shown below, but the present invention is not limited to these examples.

As a calcium-containing material, 2000 g of dolomite, 1000 g of trehalose, 750 g of corn starch, 750 g of crystalline cellulose, and 500 g of xylitol are put into a fluidized bed granulator (FLO-5M, manufactured by Freund Corporation) and decomposed by 10% by mass of galactomannan. After spraying the aqueous solution (80 mPa · s) to 10 parts by mass with respect to 100 parts by mass of the mixed powder, drying was performed at 80 ° C. so that the loss on drying was 2% or less. The granules obtained by drying and 15 g of sucrose ester were put into a V-type mixer (MIX WELL BLENDER V-20, manufactured by Deoksugakusho) and mixed for 5 minutes. Next, using a rotary tableting machine (AP-22, manufactured by Hata Seiko Co., Ltd.), 750 mg tablets were obtained with two types of tableting pressures.
The tableting pressure was adjusted so that the tablet hardness was 1.8 to 1.9 and 3.0 to 3.1.

  A tablet was obtained in the same manner as in Example 1 except that the solution to be sprayed was a 30% by mass galactomannan decomposition product aqueous solution (700 mPa · s).

  A tablet was obtained in the same manner as in Example 1 except that the solution to be sprayed was a 0.2% by mass galactomannan aqueous solution (2000 mPa · s).

  Tablets were obtained in the same manner as in Example 1 except that scallop shell calcium was used instead of dolomite as the calcium-containing material.

  A tablet was obtained in the same manner as in Example 4 except that the solution to be sprayed was a 30% by mass aqueous solution of galactomannan decomposition product (700 mPa · s).

  A tablet was obtained in the same manner as in Example 4 except that the solution to be sprayed was a 0.2% by mass galactomannan aqueous solution (2000 mPa · s).

[Comparative Example 1]
A tablet was obtained in the same manner as in Example 1 except that a 10% by mass dextrin aqueous solution was used instead of the 10% by mass galactomannan decomposition product aqueous solution.

[Comparative Example 2]
A tablet was obtained in the same manner as in Example 2 except that a 30% by mass trehalose aqueous solution was used instead of the 30% by mass galactomannan degradation product aqueous solution.

[Comparative Example 3]
A tablet was obtained in the same manner as in Example 3 except that a 0.2% by mass starch paste aqueous solution was used instead of the 0.2% by mass galactomannan aqueous solution.

[Comparative Example 4]
A tablet was obtained in the same manner as in Example 4 except that a 10% by mass dextrin aqueous solution was used instead of the 10% by mass galactomannan decomposition product aqueous solution.

[Comparative Example 5]
Tablets were obtained in the same manner as in Example 5 except that a 30% by mass trehalose aqueous solution was used instead of the 30% by mass galactomannan decomposition product aqueous solution.

[Comparative Example 6]
A tablet was obtained in the same manner as in Example 6 except that a 0.2% by mass starch paste aqueous solution was used instead of the 0.2% by mass galactomannan aqueous solution.

Test method 1. Hardness test Using a digital hardness tester (NEW SPEED CHECKER TS-75N, Okada Seiko), the hardness of 10 tablets was measured and the average value was displayed in Table 1.

Test method 2. Oral disintegration time measurement In the oral cavity of a total of 5 healthy adult men and women (25 to 40 years old), the time until the tablet completely disintegrates with saliva alone without water is measured, and the average value is shown in Table 1. It was shown to.

As shown in Table 1, in Examples 1 to 6, the oral disintegration time was fast although all had sufficient hardness. The speed is about 1/2 to 1/3 of the corresponding comparative example, which is a short time. Further, no problem occurred when tableting.
On the other hand, in the comparative example, the disintegration time in the oral cavity was slow even with the same tablet hardness as in the example. Further, the tableting powder of the comparative example had poor moldability, and in Comparative Examples 2 and 5, sticking was also observed.
That is, in the oral disintegration time, moldability, and tabletability, the results of Examples were better than those of Comparative Examples.

Claims (5)

A calcium-containing material is prepared using a solution containing 3 to 80 parts by mass of a calcium-containing material, 0.01 to 30.0 parts by mass of galactomannan and cellulose, and having a viscosity of a galactomannan solution of 80 mPa · s to 2000 mPa · s. A rapidly disintegrating tablet obtained by granulating a powder containing a calcium-containing material obtained by granulating and then tableting and then tableting , wherein the calcium-containing material comprises dolomite, eggshell calcium, scallop Shell calcium, oyster shell calcium, salmon calcium, sea urchin shell calcium, fossilized seaweed calcium, pearl calcium, beef bone calcium, fish bone powder calcium, fish scale calcium, etc. Or calcium carbonate, calcium phosphate, calcium lactate, calcium gluconate , Calcium citrate, a one or more calcium salts such as calcium chloride, rapidly disintegrating tablets that oral disintegration time is within 34 seconds, characterized by.   The rapidly disintegrating tablet according to claim 1, wherein the excipient comprises one or more selected from carbohydrates and starches.   The rapidly disintegrating tablet according to claim 1 or 2, wherein the calcium-containing material has a particle size of 250 µm or less.   The rapidly disintegrating tablet according to any one of claims 1 to 3, wherein the galactomannan has an average molecular weight of 100,000 Da or less. The rapidly disintegrating tablet according to any one of claims 1 to 4 , which is a food.