JPH07187998A - Production of tablet - Google Patents

Abstract

PURPOSE:To provide a ready method for production of a tablet more excellent in stability. CONSTITUTION:An organic acid having 50 to 300mum average particle size and polyethylene glycol are heated and melt-blended at 60 to 100 deg.C in a mixer equipped with stirring blades while rotating them at a high speed within a range of 12 to 25 Froude number (Fr) which is defined by the formula described below. The molten mixture is subsequently cooled under stirring and powdered to prepare a coating powder containing particles of <=125mum particle size in an amount of <=15wt.% and particles of iota500mum in an amount of >=30wt.%. After addition of an alkaline agent thereto, it is subjected to compressing, thus obtaining the objective tablet. Fr=V/(RXg)<0.5> [Fr, V, R and g in the formula show respectively Froude number, peripheral speed (m/sec) of top of rotary blade, rotational radius (m) of rotary blade and acceleration (m/sec<2>) of gravity].

Description

Detailed Description of the Invention

[0001]

The present invention relates to a method for producing tablets,
Specifically, in the production of tablets with an effervescent composition that has good storage stability and is capable of quickly dissolving carbon dioxide in water while foaming it, it suppresses the reaction of coexisting organic acids and alkalis and maintains the storage stability of the tablet. Therefore, the present invention relates to a method for producing a tablet in which a uniform coating layer is formed on an organic acid.

[0002]

2. Description of the Related Art A compounding agent containing an alkaline agent such as carbonate or bicarbonate and an organic acid is molded by tableting or granulation to form an effervescent composition by using a cleaning agent, a bath agent or bath water. Cleaning agent,
It is applied to products such as pool fungicides. These products, when added to water, have the advantage that the components react quickly to generate carbon dioxide gas, and at the same time, they have the effect of increasing the commercial value because they give the consumer a pleasant feeling of use. Particularly in bath agents, the blood circulation promoting effect of generated carbon dioxide is positively utilized.

However, when a carbonate or bicarbonate and an organic acid are allowed to coexist, a reaction occurs with a small amount of water, so that
The generation of carbon dioxide gas increases the internal pressure of the packaging container, which may cause the container to swell or even be damaged. If such a situation occurs, not only the product value will be significantly impaired, but also the credibility of consumers may be impaired.

In order to obtain a stable product by mixing a carbonate or bicarbonate with an organic acid, it is most important to thoroughly prevent the contamination of water. Therefore, careful attention has been paid to strict control of raw materials and processes at the time of manufacture to prevent the entry of water. Furthermore, in order to keep the product stable from its manufacture to its use by consumers, it is hermetically sealed to prevent the product from absorbing moisture. Nevertheless, it was hard to say that the problem was solved.

In order to solve this, Japanese Patent Laid-Open No. 58-213714
In the publication, a method is proposed in which a double salt of carbonate and Glauber's salt is prepared in advance, and an organic acid is added thereto.
Further, in JP-A-58-105910, the average molecular weight is 950-37.
Polyethylene glycol of 00 (hereinafter abbreviated as PEG) 30 to 7
After blending 0% by weight and 70 to 30% by weight of the other foaming component, PEG is melted by heating, and the foaming component is PEG.
A method of embedding therein is disclosed. In addition, JP-A-62-89
Japanese Patent No. 616 discloses a method in which these are further improved.

[0006]

Among the above publications, according to the methods described in JP-A-58-213714 and JP-A-58-105910, it is possible to obtain a bath agent composition having excellent storage stability. However, it is effective to mix a large amount of components to stabilize the product, not only to reduce the amount of carbon dioxide gas generated, which impairs the comfortable feeling of consumers, but also to express the purpose of the product. Since the blending amount of the components is reduced, the amount used per one time is also increased, resulting in an increase in cost. In particular, in the case of a bath agent that positively uses the generated carbon dioxide gas or a cleaning agent that uses the generated foam, the decrease in the amount of generated carbon dioxide gas is a fatal drawback.

On the other hand, from the viewpoint of productivity, it is indispensable to use a binder or a mold release agent, especially in tableting products, to obtain the mechanical strength of the tablet and to attach it to a die or a punch. However, these components also contribute to a decrease in the amount of carbon dioxide gas generated, and the fine powders of commonly used mold release agents such as metal soaps and talc are insoluble in water and are therefore insoluble in consumers. May give pleasure.

As a method for solving this problem, Japanese Patent Laid-Open No. 62-
89616 discloses that 100 parts by weight of an organic acid that is solid at room temperature is mixed with 1 to 20 parts by weight of PEG while heating with warm water or warm air using a rigid mixer with a jacket or a fluidized bed granulator. Among these methods, the method of vigorously mixing with a rigid stirrer and raising the temperature with the heat generated is said to be the most efficient in the shortest time.

PEG on the surface of organic acid by these methods
It was possible to obtain a pretreated product suitable for tableting, by uniformly spreading and receiving a sizing effect. However, in the case of producing a coating product of an organic acid by the above method, if the size of the mixer is increased, the PEG is not sufficiently spread under a condition that the stirring is insufficient, and the particles after the mixing and stirring are in an aggregated state,
It was found that a coating product having a desired particle size range could not be obtained in a high yield simply by cooling and powdering with a fluidized bed granulator equipped with a stirring blade in the next step. On the other hand, in order to maintain the tableting productivity and the quality of tablets, it is necessary to re-pulverize particles having a predetermined size or more. Therefore, the crushed surface of the coated particles newly generated by the operation is coated with PEG. Therefore, there is a problem that contact with alkaline powders such as sodium bicarbonate and sodium carbonate added in the blending process causes a reaction and adversely affects the stability of the tablet, so that a method for producing a tablet with superior stability can be established. Was wanted. Therefore, it is an object of the present invention to provide a manufacturing method capable of obtaining a tablet having more excellent stability by a simple method.

[0010]

Therefore, the present inventors have
As a result of diligent research to solve the above problems, it was found that when the organic acid was uniformly coated with PEG, the organic acid and PE were
It was found that it is important to pay attention to the centrifugal force due to the rotation of the rotary blades of the mixer during the heat-melt mixing with G, and the present invention has been completed.

That is, the present invention has an average particle size of 50 to 50 which does not substantially contain water or does not release water of crystallization at 50 ° C. or less.
A 300 μm organic acid and polyethylene glycol were rotated at a high speed in a mixer having a stirring blade at a high speed of 60 to 10 in a range where the Froude number (Fr) represented by the following formula (1) was 12 to 25.
After heating, melting and mixing at 0 ° C, cooling with stirring and pulverizing,
Coated particles having a particle size of 125 μm or less and 15% by weight or less and a particle size of 500 μm or more and 30% by weight or less are obtained.
The present invention provides a method for producing a tablet, which comprises adding an alkaline agent to the mixture and tableting.

Fr = V / (R × g) ^0.5 (1) (where Fr is the Froude number, V is the peripheral speed of the tip of the rotating blade (m
/ Sec), R is the radius of rotation of the rotating blade (m), g is the acceleration of gravity
According to the method of (m / sec ²⁾ shows a) the present invention, is applied by the rotation of the rotary blades of the mixer during the heating the melt-mixing of the organic acid and PEG by rotating the rotary blade in a range of the number of the above Froude The centrifugal force increases the degree of mixing and dispersion of the organic acid and PEG, and the heat generated by stirring shortens the temperature rise time.
During the melting process of EG, the ratio of aggregated particles forming coarse particles is reduced. By such an action, the uniformity of the PEG coating layer is increased, the adhesive force of the coated organic acids decreases due to the thinness of the PEG layer, or the agglomerates are crushed to give a predetermined particle size in the coated particles. The above particles are reduced. Therefore, the cause of poor stability due to the presence of the surface of uncoated organic acid when crushing coarse particles of a predetermined size or more and compressing and molding into tablets is eliminated.

Next, the characteristic part of the present invention will be described in detail. In the present invention, it is essential to apply a centrifugal force in a specific range to the mixture of the organic acid and PEG by rotating the rotary blades of the mixer when the organic acid and PEG are heated and melt mixed. Is a range in which the Froude number (Fr) represented by the above formula (1) is 12 to 25, more preferably 15 to
Heat melting and mixing are performed within a range of 22.

As can be seen from the above formula (1), as the radius of rotation of the rotary blade increases, that is, as the mixing device becomes larger, the centrifugal force decreases when the peripheral speed of the tip of the rotary blade is constant, As a result, stable driving cannot be performed. That is, the Fr number
If it is less than 12, the centrifugal force is insufficient, so even if the mixing speed in the circumferential direction is the same, the stirring force in the radial direction is insufficient and the organic acid and PEG are mixed.
Is not sufficiently mixed, that is, the binder PEG
Because the PEG melts and aggregates in a state where the powder is unevenly distributed unevenly, or reaches a predetermined temperature without forming a uniform PEG layer due to insufficient stirring force, the heating and mixing steps are completed. Even if the obtained agglomerate is cooled in the next step, particles in which the organic acid is uniformly coated with PEG cannot be obtained. Also, stirring heat is generated along with stirring to accelerate the melting of PEG, but if the stirring force is insufficient, not only the temperature rising time becomes longer, but also the heat used for melting PEG is mainly the mixer jacket. Since the heat is mainly transferred from the PEG, the PEG that comes into contact with the inner wall surface is melted and the rate of adhesion to the inner wall surface increases.
Therefore, it becomes difficult to form a uniform coating layer on the organic acid.

On the other hand, when the Froude number is higher than 25, the peripheral speed of the rotary blades is high, so that the frictional heat generated between the raw material and the rotary blades is excessively large, resulting in a local overheated state. It is also unfavorable in terms of quality, such as generation or decomposition of organic acid. Also in terms of operation management, since the temperature rising rate near the end of coating is fast,
It becomes overheated up to a predetermined temperature or higher, which makes control difficult.

From the above, in the present invention, the organic acid and PEG are heated and melt-mixed by selecting the mixing conditions such that the Froude number of the mixing blade is 12 to 25, more preferably 15 to 22. The temperature at this time is 60 to 100 ° C., and if it is less than 60 ° C., PEG may not be sufficiently melted, and it is difficult to form a uniform coating layer, which is not preferable. If the temperature exceeds 100 ° C, the viscosity of the melted PEG will be too low.
It is not preferable because a uniform coating layer is not formed on the organic acid.

In the present invention, as a mixing device used for heating and melting and mixing an organic acid and PEG, a stirrer shaft protruding from the bottom is provided inside a rigid type mixing tank, and a stirring blade is attached to this shaft. A device for mixing powders by mixing is preferable. The stirring blade has a plurality of blades and can be used by combining them in the vertical direction. In the heating and melting mixing of organic acid and PEG, a heating medium such as warm water is flown through the jacket of the mixing tank to raise the temperature and the stirring blade is rotated at a high speed to increase the temperature of the powder by using frictional heat due to friction between the powders. As it accelerates the melting of the thermoplastic binder, the organic acid P
The coating with EG can be completed in a short time. After raising the temperature of the system to a predetermined temperature, the lower discharge port is opened to discharge the molten mixture, and the mixture is conveyed to the next mixing / cooling step.

The apparatus used in the cooling step in the present invention is preferably a mixer having a stirring blade, a fluidized bed granulator, etc., and is agitated and cooled by such an apparatus so that the particle size of 125 μm or less is 15% by weight or less. It is possible to obtain coated particles having a particle size of 500 μm or more and 30% by weight or less. Therefore, in the method of the present invention, in order to obtain the mechanical strength of the tablet from the viewpoint of the productivity of the tablet, it is not necessary to grind the processed material having a large particle size to a predetermined particle size or less. This eliminates the cause of poor stability due to the collection of crushed products.

The organic acid used in the present invention is substantially free of water or does not liberate water of crystallization at 50 ° C. or lower, and is oxalic acid, citric acid, malic acid, which is solid at room temperature,
Examples thereof include one selected from succinic acid, fumaric acid, tartaric acid, and the like, or two or more thereof. However, succinic acid or fumaric acid is particularly desirable from the viewpoint of action on metal and stability. The organic acid used has an average particle size of 50 to 300 μm. When the average particle size of the organic acid is less than 50 μm, the surface area of the organic acid increases and the thickness of the coating layer decreases, so that the stabilizing effect of the coating decreases. Further, if it exceeds 300 μm, the dissolution rate of the organic acid in water becomes slow, which is not preferable.

The PEG used in the present invention preferably has an average molecular weight of 4000 to 20000. The mixing ratio of PEG to 100 parts by weight of organic acid is 1 to 20 parts by weight, preferably 2 parts by weight.
-10 parts by weight is preferable, and 4-10 parts by weight is particularly preferable. PE
When the mixing ratio of G is less than 1 part by weight, the stabilizing effect is poor and the tableting property is poor. On the other hand, when the mixing ratio of PEG is more than 20 parts by weight, not only the stabilization with a small amount of the component which is the object of the present invention is lost, but also a large amount of energy is wasted for heating and cooling, and further aggregation is caused. It is easy to form a product, and thus it becomes difficult to obtain a powdery processed product.

By mixing an organic acid pretreated with PEG with an alkali agent and other components and molding into tablets,
The tablets of the invention can be obtained. As the alkaline agent used in the present invention, sodium carbonate, potassium carbonate,
One or more selected from sodium bicarbonate and the like can be mentioned. Further, as other components, fragrances, pigments, surfactants, mirabilite, sodium sesquicarbonate, various condensed phosphates, inorganic salts such as sodium chloride, hydrogen peroxide adducts such as sodium perborate and sodium percarbonate, and If necessary, a bactericidal agent, an anti-inflammatory agent, a crude drug extract, etc. can be used. It is desirable that these substances are essentially anhydrous, but any substance that does not liberate water of crystallization at 50 ° C. or lower can be used.

[0022]

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

Example 1 6.5 kg of fumaric acid having an average particle size of 130 μm and 0.55 kg of PEG (average molecular weight of 6000) were mixed with a Henschel mixer (FM20B type).
Mix until 70 ° C. The rotation speed of the stirring blade at this time is
1464 rpm, blade tip peripheral speed 23 m / sec, Froude number 13.4
Met. This was transferred to a fluidized bed granulator having an inner diameter of 25 cm equipped with a propeller-shaped stirring blade having a diameter of 24.5 cm, and cooled with air at 20 ° C. At this time, when the treatment was carried out at a tip speed of the stirring blade of 10 m / sec and a superficial velocity of air of 0.3 m / sec, it was cooled to 40 ° C. in 6 minutes. This treatment was used as a sample for repeated tests. This pre-treated product 425kg, sodium bicarbonate 300kg, sodium carbonate 200kg, Glauber's salt 72kg, fragrance 2kg, pigment 1kg
(Total 1000 kg) was mixed with a Nauter mixer (made by Hosokawa Micron, capacity 2.5 m ³ ) and coarse particles were removed with a 10-mesh sieve, and then a tableting machine (DC-WD type manufactured by Masina Co., Ltd.)
Each tablet was compressed to 50 g. The tableted product was placed in a bag made of a film obtained by laminating a polymer film on an aluminum foil, heat-sealed and hermetically sealed.

Example 2 Instead of fumaric acid in Example 1, the average particle size was 200 μm.
When the raw material is heated and melted using the succinic acid of, the rotation speed of the stirring blade is 1910 rpm, the peripheral speed of the blade tip is 30 m / sec, and the fluid number is 17.5.
I rotated it. The pretreatment product was cooled under the same conditions as in Example 1, and a tableting product was obtained from the obtained pretreatment product in the same manner as in Example 1.

Example 3 When heating and melting the raw material in Example 1, the stirring blade was rotated at a rotation speed of 2420 rpm, a blade tip peripheral speed of 38 m / sec and a Froude number of 21.4. The pretreatment product was cooled under the same conditions as in Example 1, and a tableting product was obtained from the obtained pretreatment product in the same manner as in Example 1.

Example 4 368 kg of fumaric acid having an average particle diameter of 130 μm and 32 kg of PEG (average molecular weight 6000) were mixed with a Henschel mixer (FM1000EP type) until the temperature reached 70 ° C. At this time, the rotation speed of the stirring blade was 950 rpm, the peripheral speed of the blade tip was 50 m / sec, and the Froude number was 16. This is the inner diameter with a paddle type stirring blade with a diameter of 1.3 m
Transferred to a fluid bed granulator to 1.4 m and cooled with air at 20 ° C. At this time, the peripheral speed of the stirring blade tip is 5 m / sec, and the superficial velocity of air is 1.0 m.
When treated with / sec, it was cooled to 35 ° C in 15 minutes. A tableting product was obtained from this pretreated product in the same manner as in Example 1.

Comparative Example 1 In Example 1, when the raw material was heated and melted, the operation was carried out at a rotation speed of a Henschel mixer of 1090 rpm, a blade tip peripheral speed of 17 m / sec, and a Froude number of 10. The cooling conditions for the pretreated product are as in Example 1.
In the same manner as described above, a tableted product was obtained from the obtained pretreated product in the same manner as in Example 1. During the heating and mixing under these conditions, the processed product in the Henschel mixer did not move smoothly during the operation, and when the temperature reached a predetermined temperature, the processed product was raised to the side surface.

Comparative Example 2 In Example 1, when the raw material was heated and melted, the Henschel mixer was operated at a rotation speed of 3250 rpm, a blade tip peripheral speed of 51 m / sec, and a Froude number of 30. However, in the heating and mixing under these conditions, the treated material adhered from the bottom surface to the side surface of the Henschel mixer, and the scaling was severe and the coating was impossible.

Comparative Example 3 In Example 4, when the raw material was heated and melted, the stirring blade rotation speed of the Henschel mixer was 525 rpm, and the blade tip peripheral speed was 35 m / sec.
, Operated with Froude number 10. However, in the heating and mixing under these conditions, the processed material in the Henschel mixer adhered and grew on the side surface in the mixer during the operation, which made the operation impossible.

Test Example 1 The particle sizes of the pretreated products in Examples 1 to 4 and Comparative Example 1 were measured by the following method. Further, the obtained tableted product was subjected to a tableting test by the following test method to evaluate the quality of the tableted product. Table 1 summarizes the production conditions of Examples 1 to 4 and Comparative Examples 1 to 3, the particle size of the pretreated product, and the quality of the tableted product.

<Test Method> (1) Particle Size The particle size of the pretreatment product is measured from the weight fraction according to the size of the sieve mesh after vibrating for 5 minutes using a JIS Z 8801 standard sieve,
The proportions of particle sizes of 500 μm or more and 125 μm or less are shown by weight%. (2) Tablet hardness A Kiya type hardness meter (Kiya Seisakusho) was used to measure the force required to break the tablets. In order to make the conditions uniform, a comparison was made for tablets formed at a tableting pressure of 10 tons. The larger this value, the less the occurrence of cracks and chips in the product, which is desirable. (3) Tablet stability The test method for evaluating tablet stability is to measure 10 packages at 50 ° C.
The sample was left in the constant temperature bath for 24 hours, the volume change of each sample before and after that was measured, the average value was taken, and the smaller the volume change, the higher the stability. At this time, in order to accurately measure the volume change, a water tank (volume 3
Liter) was placed and the packed tablet was submerged in a water tank to measure the change in weight of water by the increased volume.

[0032]

[Table 1]

As can be seen from the results in Table 1, in Examples 1 to 4 of the present invention, there was no wall adhesion to the mixer at the time of coating and the operating condition was good, and the obtained coating-treated product also had a desired particle size. A range of products is obtained in good yield, and product quality such as tablet hardness and tablet stability is excellent.
On the other hand, in Comparative Examples 1 to 3, the production efficiency is remarkably inferior due to the adhesion to the vessel wall, and the desired product quality cannot be obtained. Therefore, the superiority of the present invention is clear.

Claims (3)

[Claims] 1. An organic acid having an average particle size of 50 to 300 μm, which is substantially free of water or does not liberate water of crystallization at 50 ° C. or less, and polyethylene glycol are mixed in a mixer having a stirring blade as follows. Froude number (Fr) shown in equation (1) is 12 ~
Rotate at high speed in the range of 25, heat and melt mix at 60 to 100 ℃, cool with stirring and powderize. A method for producing a tablet, characterized in that coated particles having a particle size of (1) are obtained, and an alkaline agent is added to the particles to form tablets. Fr ＝ V / (R × g) ^0.5 (1) (In the formula, Fr is the Froude number, V is the peripheral speed of the tip of the rotating blade (m
/ Sec), R is the radius of rotation of the rotating blade (m), g is the acceleration of gravity
(m / sec ² ) 2. The method according to claim 1, wherein the organic acid is succinic acid or fumaric acid. 3. The method according to claim 1, wherein the alkaline agent is one or more selected from sodium carbonate, potassium carbonate and sodium bicarbonate.