JP2702325B2 - Granular calcium composition and tablet comprising the same - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to novel granular calcium compositions and tablets comprising them.

More specifically, the present invention relates to a granular calcium composition and a tablet comprising the same, which have an improved feel when chewed in the mouth and can be used for calcium supplementation.

[0003]

2. Description of the Related Art Calcium-containing compounds are orally administered to supplement calcium in order to promote the growth of bone teeth with weak constitutions and adenopathies and to prevent the fragility of bone teeth of pregnant and nursing women. Examples of such calcium-containing compounds include anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate monohydrate, calcium carbonate, calcium lactate, calcium glucuronate, calcium glycerophosphate, L-
Calcium aspartate and the like.

These compounds usually contain other excipients, dyes,
It is molded into tablets, granules, powders, etc. together with flavors, etc., but the target subjects are often children, women, or elderly people. is important.

[0005]

However, anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen monohydrate, calcium carbonate, calcium lactate, calcium glucuronate, calcium glycerophosphate, L-asparagine Any calcium acid or the like has a normal particle size (usually particles having a particle size within a range necessary for being formed into tablets or granules), specifically, 80% by weight of particles having a particle size of 37 μm or more are chewable. Sometimes it could not be disintegrated minutely in the mouth, and as a result, the feeling of powdery or gritty remained, and the feeling of taking it was not sufficient. Therefore,
Several devices have been devised to solve this problem.

First, the particle size of these calcium compounds remains at 80% by weight in the range of from 37 μm to less than 200 μm, that is, without modifying the calcium compounds themselves, other highly soluble components such as This is a method of diluting with saccharides such as mannitol and molding into tablets or granules. This makes the calcium composition "flourish"
Although sugar was improved by saccharides and the like, the amount of excipients with respect to a certain amount of calcium naturally increased, and it was unavoidable to increase the size of tablets, increase the number of tablets, or increase the total amount of granules and the like.

A second method is to reduce the particle size of these calcium compounds. A powder of these calcium compounds, in which 80% by weight usually used in the preparation is in a range of 37 μm or more and less than 200 μm, is crushed by a pulverizer or the like to obtain 90% by weight.
When the powder was crushed so as to fall within a range of less than 37 μm, the “powderiness” was almost solved. However, due to such pulverization, the fluidity and binding properties of these calcium compounds are reduced. For example, tablets that can be molded into tablets but have low hardness and are easily chipped have low mechanical strength.

Accordingly, the size of the tablet is increased, the number of tablets is increased,
Alternatively, there is a demand for a method that can simultaneously solve the increase in the amount of granules and the deterioration in moldability. That is, there is a need for a method of improving the feel during chewing while maintaining the calcium compound weight% in one dosage unit (for example, one tablet or one packet) of the preparation relatively high.

[0009]

The present inventors have conducted intensive studies on these problems of the prior art, and as a result, surprisingly, a certain calcium compound and 1 to 15% by weight based on the calcium compound have been found. And a rapid disintegration is observed only when the average particle size of the granular composition is within a certain range, and as a result, the feeling in the mouth during chewing is good. Was found.

Thus, the present invention relates to a method for producing calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, calcium dihydrogen monohydrate, calcium carbonate, calcium lactate, calcium glucuronate, calcium glycerophosphate, L
A granular composition comprising one or more calcium compounds selected from the group consisting of calcium aspartate and 1 to 15% by weight of polyvinylpyrrolidone based on the calcium compound, wherein the granular calcium composition 60% by weight or more of the granular calcium composition having a particle size of 37 μm or more, and a tablet comprising the granular calcium composition.

In the present invention, the composition comprises anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate monohydrate, calcium carbonate, calcium lactate, calcium glucuronate, calcium L-aspartate, and calcium glycerophosphate. One or more selected from the group is used as the calcium compound. Of these, anhydrous calcium hydrogen phosphate, calcium carbonate, and calcium lactate are preferred, and anhydrous calcium hydrogen phosphate is particularly preferred.

[0012] The polyvinylpyrrolidone of the present invention is generally used as a binder in pharmaceutical preparations, and has, for example, an average molecular weight of 10,000 to 1,200,00.
0 can be mentioned.

The amount of such polyvinylpyrrolidone is 1 to 15% by weight based on the above calcium compound. 1
If the amount is less than 15% by weight, granulation cannot be performed due to a low bonding strength.
Among them, the amount of polyvinylpyrrolidone is preferably 3 to 10% by weight.

The granular composition of the present invention is a granular calcium composition comprising the above-mentioned calcium compound and polyvinylpyrrolidone. The granular calcium composition can be granulated as follows, for example.

The above-mentioned calcium compound used in the present invention is preferably pulverized so that at least 80% by weight thereof has a particle size of less than 37 μm before granulation. The pulverization may be carried out by a usual pulverizer, for example, a hammer mill.
The finely divided calcium compound is then homogeneously mixed with the polyvinylpyrrolidone. In this case, the particle size of polyvinylpyrrolidone is desirably such that 90% by weight or more of all particles have a particle size distribution of less than 250 μm.

As the mixer, it is preferable to use the same apparatus as that for the later-described granulation step from the viewpoint of yield, and a fluidized bed granulation dryer or a high-speed mixing and stirring granulator is generally used. Water is sprayed on the mixture of the calcium compound and polyvinylpyrrolidone which is uniformly mixed and stirred in these apparatuses, and granulated into a granular composition. Usually, a mixture of a homogeneously mixed calcium compound and polyvinylpyrrolidone is taken in an apparatus, about 10% by weight of water is sprayed at a rate of 20 ml / min, and the whole quantity is sprayed. The drying is performed under the condition that the granulated material is dried until the temperature exceeds the limit. Next, after the obtained granular composition is sieved through a sieve having an opening of 350 μm, the particle size distribution is measured by an electromagnetic micro-type sieve shaker (manufactured by Tsutsui Physical and Chemical Instruments Co., Ltd.). However, a granular calcium composition having a particle size of 37 μm or more is obtained.

Thus, the granular calcium composition provided by the present invention is provided as it is as a granular preparation (granule) of a calcium compound having improved powderiness and hardness before mastication. . In this case, a small amount of a flavoring agent or a flavoring agent may be added for flavoring the granule.

Further, in the present invention, the granular calcium composition provided as above is used as a disintegrant, a lubricant,
Tableting together with flavoring agents, flavoring agents and the like to form tablets is also included in the embodiment of the present invention. In this case, it is preferable that the amount of components other than the granular calcium composition is as small as possible, usually 40% or less, more preferably 30% or less.

In order to maintain mechanical strength as a tablet,
Usually, it is preferable to form a tablet having a hardness of 4.0 kg or more.

Thus, according to the present invention, granules of a calcium compound having a high content of a calcium compound, sufficient mechanical strength, and having no feeling of powderiness, hardness or the like during chewing, that is, having improved mouth feel. Agents and tablets are provided, and since compliance is expected to be improved as a calcium supplement, it can greatly contribute to medical treatment.

[0021]

The present invention will be described in more detail with reference to the following Examples, which should not be construed as limiting the present invention.

[0022]

Example 1, Comparative Examples 1 to 6 665 g of finely powdered anhydrous calcium hydrogen phosphate (Kyowa Chemical Industry standard product: particle size distribution of 37 μm or more and 16.3%, less than 37 μm 83.7%) and polyvinylpyrrolidone (manufactured by BASF) , Kollidon
K-30) was placed in a fluidized bed granulator and uniformly mixed with an air stream. Next, the homogenous mixture is granulated by spraying about 10% by weight of water at a rate of 20 ml / min, and then dried until the exhaust temperature in the apparatus exceeds 40 ° C. to obtain the granular anhydrous phosphorus of the present invention. Calcium hydrogen oxyhydrate was obtained (Example 1). The particle size distribution of the obtained granules was 37 μm or more, 68.5%, and less than 37 μm, 31.5%.

At the same time, various binders listed in Table 1 were taken for comparison and granulated in the same manner as in Example 1 to obtain granules (Comparative Examples 1 to 6). In Comparative Example 1, a commercially available product (Rikamit (registered trademark) U-100, manufactured by Kyowa Chemical Industry Co., Ltd.) was used.

For these Example 1 and Comparative Examples 1 to 6, the particle size distribution of the obtained granules and the results of a test conducted by 20 volunteers on the feel during chewing are shown in Table 1.

[0025]

[Table 1]

From Table 1, it can be seen that when polyvinylpyrrolidone is used as a binder, granules having an excellent feeling without powdery feeling are obtained, but granules are not obtained with other commonly used binders. It can be seen that even if it was obtained, only granules with inferior feel of powderiness were obtained.

[0027]

Examples 2 to 4 and Comparative Examples 7 to 10 Fine powder of anhydrous calcium hydrogen phosphate (a standard product of Kyowa Chemical Industry Co., Ltd.) was taken in the same manner as in Example 1 and polyvinylpyrrolidone (KSF, manufactured by BASF) was used.
(Ollidon K-30) was changed as described in Table 2 and granulated in the same manner as in Example 1 (Examples 2 to 3).
4, Comparative Examples 7 to 10). Table 2 shows the particle size distribution of the obtained granules and the results of testing the feel during chewing by 20 volunteers.

[0028]

[Table 2]

According to Table 2, the amount of polyvinylpyrrolidone is 1 to
When the amount is 15% by weight, granules having a high feel can be produced. However, when the amount is less than 1% by weight, granulation cannot be performed.

[0030]

Example 5 Tablets were produced using the granules produced in Example 1 by the following method (Example 5). Granulated anhydrous calcium hydrogen phosphate 72.0% D-sorbitol 10.0% D-mannitol 16.8% Fragrance 0.2% Magnesium stearate 1.0%

According to the above formula, the weight is 50 with a 10 mm diameter mortar and punch.
0 mg tablets were produced on an Elweka single tablet press. The average hardness (n = 20) of the obtained tablets was 5.2 kg.

Next, the feeling when the tablet was chewed was examined for 20 volunteers, and the results are shown in Table 3.

For comparison, a commercially available product using sodium polyacrylate as a binder instead of polyvinylpyrrolidone (Comparative Example 1) was used to form a tablet in the same manner as above (Comparative Example 11). The average hardness of the tablet was 5.0 kg. As for the tablet, the feel during chewing was examined for 20 volunteers in the same manner as above, and the results are shown in Table 3.

[0034]

[Table 3]

Table 3 shows that the feeling of the tablet of the present invention before chewing is remarkably improved.

[0036]

Example 6 After mixing 1% by weight of magnesium stearate with the granules produced in Example 1, tablets of 500 mg in weight were produced with a 10 mm diameter mortar using an Elweka single punch tableting machine.

When the feeling of chewing the tablet was examined for 20 volunteers, none of the volunteers complained of poor feeling such as powdery feeling.

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Claims (3)

(57) [Claims] (1) a group consisting of anhydrous calcium hydrogen phosphate, calcium hydrogen phosphate dihydrate, calcium dihydrogen phosphate monohydrate, calcium carbonate, calcium lactate, calcium glucuronate, calcium glycerophosphate and calcium L-aspartate; One or more selected calcium compounds and 1 to 15
% By weight of a polyvinylpyrrolidone, comprising 60% by weight of the granular calcium composition.
A granular calcium composition having a particle diameter of 37% or more by weight or more. 2. A tablet comprising the granular calcium composition according to claim 1. 3. The tablet according to claim 2, wherein the granular calcium composition is contained in an amount of 60% by weight or more of the tablet.