KR102271734B1 - Pharmaceutical composition for dry-granulation process comprising multivitamins as active pharmaceutical ingredient - Google Patents

Abstract

The present invention relates to a multi-vitamin pharmaceutical composition for a dry granulation process, and more specifically, to a multi-vitamin pharmaceutical composition for a dry granulation process, which contains vitamins and minerals as active ingredients, and contains talc and kaolin as antistatic agents. The present invention is suitable for use in tablet manufacturing by the dry granulation process, as the flowability deterioration and fine powder generation due to the generation of static electricity are remarkably improved even in the dry granulation process performed in a dry environment.

Description

Multivitamin pharmaceutical composition for dry granulation process {PHARMACEUTICAL COMPOSITION FOR DRY-GRANULATION PROCESS COMPRISING MULTIVITAMINS AS ACTIVE PHARMACEUTICAL INGREDIENT}

The present invention relates to a multivitamin pharmaceutical composition for dry granulation process.

Many vitamins such as vitamins A, C, D, E and B vitamins and many minerals such as iron, zinc, calcium and chromium are essential compounds for maintaining good health, but most of these compounds are not synthesized in the human body. Many compounds, commonly referred to as vitamins and minerals, are known to provide significant benefits in treating certain diseases while maintaining an individual's health, even when supplied in relatively small amounts.

Accordingly, these essential vitamins and minerals must be ingested from external sources, and food alone does not guarantee such intake, so the use of vitamin and mineral nutritional supplements, although not absolutely essential to maintaining health, has a significant effect on maintaining health. known to provide

However, in the case of these vitamin and mineral nutritional supplements, especially, due to decomposition by various external conditions such as light, temperature, humidity, etc., stability is lowered and there is a high risk of commercialization due to this, and in the case of general multivitamin tablets, trace ingredients That is, a variety of low-dose essential ingredients are included. In this case, the need to maintain uniformity of content of the corresponding ingredient is very high.

Accordingly, in general, in the preparation of a pharmaceutical composition of a multivitamin preparation, in order to increase the content uniformity of the low-dose main ingredient, the wet granulation method is generally used despite the decrease in productivity. The prior art for this will be understood with reference to Republic of Korea Patent Registration No. 10-1389061 B1 (Patent Document 1) and the like. Accordingly, all of the contents of Patent Document 1 are cited and incorporated as prior art in this specification.

However, when the wet granulation method is used, when the temperature of the main ingredients vulnerable to heat, such as vitamin B1, vitamin B2, and vitamin C, is raised to remove the solvent, the content of the heat-sensitive component is lowered.

In addition, according to the wet granulation method, it is difficult to obtain uniform granules, the granule dispersibility is not good, and a large amount of excipients are required during the granulation process, which increases the tablet weight and makes it difficult to take the tablet.

In order to solve the problems of wet granulation, a dry granulation method can be used, but in the case of dry granulation method, due to the lack of moisture, the problem of reduced flowability and content uniformity of particles due to static electricity generation and content due to particle scattering There is a problem in that a problem of deterioration and the like occur.

Accordingly, the researchers of the present invention disperse the multivitamin preparation with lactose, crospovidone, light anhydrous silicic acid, or a combination thereof, and then add and mix a specific pharmaceutically acceptable additive to the embryo product, thereby preventing static electricity and content It has been found that uniformity can be improved and the present invention has been completed.

KR 10-1389061 B1 (2014.04.18.)

An object of the present invention is to provide a multivitamin pharmaceutical raw material composition very suitable for the dry granulation process by solving problems such as static electricity generation and fine powder generation in the dry granulation method described above.

The present invention has been devised to solve the problems of the prior art described above,

Contains vitamins and minerals as active ingredients,

It provides a multivitamin pharmaceutical composition for dry granulation process, characterized in that it contains talc and kaolin as antistatic agents.

In the present invention, the antistatic agent, based on the total weight of the composition, provides a multivitamin pharmaceutical composition for the dry granulation process, characterized in that it is included in 0.5 to 2% by weight.

In the present invention, the antistatic agent, talc: kaolin = 1: provides a multi-vitamin pharmaceutical composition for the dry granulation process, characterized in that it is included in a weight ratio of 0.5 to 2.

In the present invention, there is provided a multivitamin pharmaceutical composition for the dry granulation process, characterized in that it further comprises at least one selected from a pharmaceutically acceptable diluent, disintegrant, and lubricant.

In the present invention, the diluent provides a multivitamin pharmaceutical composition for dry granulation process, characterized in that lactose, microcrystalline cellulose, or a combination thereof.

In the present invention, the disintegrant provides a multivitamin pharmaceutical composition for the dry granulation process, characterized in that crospovidone.

In the present invention, the lubricant provides a multivitamin pharmaceutical composition for dry granulation process, characterized in that light anhydrous silicic acid.

The present invention is suitable for use in tablet manufacturing by the dry granulation process, as the flowability deterioration and fine powder generation due to the generation of static electricity are remarkably improved even in the dry granulation process performed in a dry environment.

1 is a graph showing the relative standard deviation with respect to the weight of Examples of the present invention.

Hereinafter, the present invention will be described in detail.

The present invention is

Contains vitamins and minerals as active ingredients,

It is a multivitamin pharmaceutical composition for dry granulation process, characterized in that it contains talc and kaolin as antistatic agents, and may further include one or more selected from pharmaceutically acceptable diluents, disintegrants, and lubricants. have.

The diluent may be lactose, microcrystalline cellulose, or a combination thereof.

The disintegrant may be a pharmaceutically acceptable and widely used disintegrant without limitation, but is preferably crospovidone.

The lubricant may include, but is not limited to, a pharmaceutically acceptable and widely used lubricant, preferably light anhydrous silicic acid.

In particular, in the present invention, the antistatic agent uses a combination of talc and kaolin. Dry granules using a roller compactor. When manufactured using lactose or MCC (microcrystalline cellulose-101), static electricity is generated due to the nature of the series, so fluidity is reduced and static electricity is generated a lot due to fine powder, resulting in loss of main ingredients. However, to solve this problem, talc and kaolin are added to minimize the dust generated during roller compactor granulation while having properties similar to wet granulation.

As can be understood through Examples and Experimental Examples to be described later, by adding such talc and kaolin in an appropriate ratio and content, the anti-electrostatic effect and the flowability of the granules can be greatly improved.

The antistatic agent, based on the total weight of the composition, is included in 0.5 to 2% by weight, talc: kaolin = 1: 0.5 to 2 weight ratio is preferably included, and is included, and talc: kaolin = 1: 0.8 to 1.2 weight ratio. It is more preferable to be The talc and kaolin may exhibit a synergistic effect in antistatic, scattering, and sticking prevention through interaction, and the recovery rate of granules is high in this range. In addition, from the same viewpoint, it is preferable that the content of talc and kaolin, respectively, does not exceed 2% by weight. A more detailed understanding of this may be made through examples to be described later.

Hereinafter, the present invention will be described in more detail by way of examples. However, it is made clear that the following examples are only for the detailed description of the invention and are not intended to limit the scope of the rights by this.

Example

One. distribution ( sieve selection)

The sieve used for distribution is carried out with a sieve ranging from 20 to 80 mesh.

If a sieve of less than 20 mesh is used, the particle size of the raw material increases and the surface area is reduced, so there is a disadvantage that mixing unevenness occurs. If a sieve of more than 80 mesh is used, there is a risk of loss of main components due to static electricity due to fine powder. Thereafter, a mixing process is performed on the waste product.

2. Selection of mixing conditions

The homogeneity is improved through the process of mixing the waste product using a double-cone mixer (Jitech).

<primary mix>

If it is set to less than 10 rpm, it causes mixing unevenness due to the slow mobility of the mixture, and if it is performed at more than 30 rpm, the mixture sticks to the inside of the double cone mixer due to scattering, resulting in mixing unevenness.

If it is less than 5 minutes, the uniformity is lowered, and if it is mixed for more than 15 minutes, polarization of the main component occurs due to specific gravity.

<Secondary Mixing>

If the secondary mixing is set to less than 20 rpm, it causes mixing unevenness due to the slow mobility of the mixture, and if it is performed at more than 50 rpm, the mixture sticks to the inside of the double cone mixer due to scattering, resulting in mixing unevenness.

If it is less than 10 minutes, the uniformity is lowered, and if it is mixed for more than 20 minutes, polarization of the main component occurs due to specific gravity.

3. Manufacturing method

The table below shows the preparation of multivitamin tablets. After distributing the vitamin main component, lactose, crospovidone, and light anhydrous silicic acid by 1/2 mass each, put it in a double cone mixer and mix at 16rpm for 10 minutes. In addition, add talc and kaolin and mix at 22rpm for 15 minutes. This mixture is set for tableting with a rectangular punch, and the standard amount is 700 mg. The obtained tablets were film-coated with a mixture of 552.0 g of Opadry 85F62001 and 2208.0 g of water using a coating machine.

Specific prescription details were shown in Tables 1 and 2 below (the numerical values in parentheses indicate the content test result value (%) for the corresponding main ingredient).

< Comparison of content >

[Examples 1 to 5] of Table 1 showed the content results suitable for each main component standard.

[Example 6] of Table 2 shows the case where talc and kaolin were not added at all, and due to the generation of static electricity and the lack of lubricity, a sticking phenomenon of sticking to the equipment occurred, resulting in unevenness in the content of the main component added in a small amount. became [Example 7] is a case where only talc was added, and the antistatic effect was insufficient, so that the content of some main components was decreased due to the generation of static electricity. [Example 8] shows the case where talc and kaolin were added at 2% or more, respectively, and the content of each main component met the standard, but as a result of the disintegration test, the uncoated tablet was 32 minutes 24 seconds and the film-coated tablet 68 minutes 08 seconds. It did not meet the standards (within 30 minutes for uncoated tablets, within 60 minutes for coated tablets).

< flow comparison >

In [Examples 3 to 5, Example 8], the flowability of the granules was good, and among them, [Example 8] showed the best flowability. However, in the case of [Example 8] in which 2% or more of talc and kaolin were added, respectively, it was confirmed that the disintegration time was affected. As in [Examples 1 and 2], when 0.5% or more of the lubricant was not added, relatively low flow properties were observed. [Example 6] in which talc and kaolin were not added had the lowest flowability, and in [Example 7] using only talc, flowability was not as good as when kaolin was added.

< Recovery rate comparison >

For each prescription, 2100 g of a 3000T amount of the mixture was prepared and then roller compacted granules to measure the weight of the mixture before roller compaction and the granulate after roller compaction, respectively. The calculated recovery rate results are as follows.

In [Examples 3 to 5, 8], it was possible to secure a recovery rate of 99% or more, but in [Example 8], the tablets were not suitable for disintegration standards, and as a result, [Examples 3 to 5] were judged to be the most suitable.

Through this, it was confirmed that by adding 0.5% to 1.0% of talc and kaolin, respectively, static electricity could be prevented and dust could be minimized.

< Mass Deviation Comparison >

The values obtained by taking 10 tablets each and weighing them on a precision scale to obtain the relative standard deviation (%RSD) were as shown in the graph shown in FIG. 1 .

As can be seen from the graph of FIG. 1, the lowest mass deviation was shown in [Example 8], but the tablets did not meet the disintegration standards. Next, [Examples 3 to 5] showed a relatively low mass deviation, and among them, [Example 5] showed the lowest mass deviation. When talc and kaolin were added in a ratio of 0.86%, respectively, it was possible to produce tablets with the most uniform weight. Thus, the optimal ratio of excipients suitable for dry granulation was selected.

Claims (7)

Contains vitamins and minerals as active ingredients,
As an antistatic agent, the multivitamin pharmaceutical composition for dry granulation process, characterized in that it contains 0.5 to 2% by weight of talc and 0.5 to 2% by weight of kaolin, based on the total weight of the composition. delete The multivitamin pharmaceutical composition for dry granulation process according to claim 1, wherein the antistatic agent is included in a weight ratio of talc: kaolin = 1: 0.5 to 2 by weight. The multivitamin pharmaceutical composition for the dry granulation process according to claim 1, further comprising at least one selected from a pharmaceutically acceptable diluent, disintegrant, and lubricant. The multivitamin pharmaceutical composition for dry granulation process according to claim 4, wherein the diluent is lactose, microcrystalline cellulose, or a combination thereof. [Claim 5] The multivitamin pharmaceutical composition for dry granulation process according to claim 4, wherein the disintegrant is crospovidone. The multivitamin pharmaceutical composition for dry granulation process according to claim 4, wherein the lubricant is light anhydrous silicic acid.

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