JP3354172B2 - Heavy granulation of high drug content powder - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a particle processing operation such as granulation and coating for treating powders such as pharmaceuticals, and a granulation method suitable for heavy granulation of powders having a high drug content. I will provide a.

[0002]

2. Description of the Related Art Conventionally, as a granule for capsules and coatings, a method of coating and granulating a drug in a layer on the surface thereof using granulated sugar or the like as a nucleus (seed) has been widely used. High prescription (eg 80% drug
In the above), the granules are large, so the capsules must be large. Further, the granulated product obtained by fluidized bed granulation was bulky and was unsuitable for filling in capsules. Under such circumstances, the demand for techniques for preparing heavy granules without using seeds has increased.

[0003]

Among the properties of raw material powders to be granulated in pharmaceuticals, etc., the following wet granulation of fine powders having high adhesion and cohesion due to the properties due to static electricity and the properties of the powders themselves are as follows. There was a problem.

[0004] In the case of the fluidized-granulation method, due to its properties, poor flow such as adhesion to the apparatus wall and blow-through occurred, and a satisfactory granulation operation could not be performed. Therefore, in order to improve this, a large amount of a powder auxiliary agent for relaxing the property has been added.

In the case of extrusion granulation, the mixture is kneaded with a strong kneading device, extruded and granulated, and subjected to a drying process to form a granulated product.
Thus, multiple devices and operations were required. In addition, the formed granules are hard granules due to strong kneading, and have problems such as poor dissolution and disintegration. To improve this, it is necessary to add an auxiliary agent for relaxing the properties.

[0006] As described above, conventionally, an auxiliary agent is required for the granulation operation, so that the amount is increased by that amount and the size of the tablet is increased. However, it is difficult for elderly people and infants to take large tablets and capsules. Tablets may be disintegrated for easier administration. But,
In recent tablets and the like, a coating or the like for controlling drug release is provided on the tablet surface to impart enteric properties, sustained release properties, and the like. However, when the tablet is crushed, such a drug release control cannot be performed.

Accordingly, an object of the present invention is to provide a granulation method capable of minimizing the amount of an auxiliary agent added to powder having high adhesion and cohesion.

[0008]

SUMMARY OF THE INVENTION The present invention relates to a method for granulating a raw material powder comprising a fine powder having high adhesion and cohesion.
Adhesion and agglomeration of the raw material powder, etc., using a rolling fluidizing device equipped with a stirring member that rotates around a vertical rotation axis at the bottom of the vessel of the fluidized bed granulator that flows the raw material powder with the gas adjusted to an appropriate temperature A powder auxiliary for improving the properties is added to the raw material powder in an amount of 0 to 15%, and the powder is tumbled and fluidized in the apparatus. According to the wettability and solubility of the powder, the water content of the powder in the fluidized bed is previously determined. The binder is sprayed and granulated while controlling to the set value, and the obtained granulated material is sprayed with the binder, and the same powder or another powder is coated on the surface of the granulated material to perform heavy granulation. Is what you do.

[0009]

By using a tumbling fluidizing device equipped with a stirring member at the bottom of the fluidized bed device, poor flow of the powder is eliminated, and the flow of the raw material powder flowing according to the wettability and solubility of the raw material powder is improved. By adding the binder by spraying and granulating while controlling the moisture in the layer to be a value calculated or measured in advance, the fine powder attached to the wall also scrapes off the granulated material as the granulation progresses, Granulation is possible even with a small addition ratio of a powder auxiliary agent for improving properties such as adhesion and cohesion of the raw material powder within a range of about 0 to 15%.
Further, as a method for obtaining heavy granules, the granulated material (primary granules) obtained by the above operation is wetted by spraying a binder or the like, and the same substance is added thereto in a powder form to modify the granules (powder). ) To perform the operation of filling with powder in the valleys on the surface of the primary granulated particles, whereby a heavy, spherical, smooth granulated product having a spherical surface can be obtained.

[0010]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS First, a rolling fluidizing device used in the granulating method of the present invention illustrated in FIG. 1 (a) will be described. A rotatable disk (3) with stirring blades is provided rotatably, and from the lower center of the rotary disk (3) to the fluid chamber (2) through the outer periphery.
The gas adjusted to an appropriate temperature is vented. In this case, the rotating disk (3) with stirring blades constitutes a stirring member and gives the particles a strong rolling operation. In the structure of the stirring blade, for example, an inclined plane part and a horizontal plane part arranged so as to appear alternately in the circumferential direction are integrally formed on the upper surface of the rotating disk (3).
It should be noted that even a rotating disk having no such stirring blades can provide the powder particles with a stirring rotation operation,
The term "stirring member" includes a rotating disk having no stirring blade. As the ventilation structure, a slit is formed in the rotating disk (3 ') (FIG. 1 (b)), or a part of the rotating disk (3 ") is made of a permeable material such as a wire mesh or a perforated plate. It can also be used (FIG. 1 (c)).

The amount of powder auxiliary such as lactose or starch added to improve the properties such as adhesion and cohesion of the raw material powder is in the range of 0 to 15% based on the raw material powder.

The binder is sprayed while controlling the water content of the powder inside the fluidized bed to a predetermined value according to the wettability and solubility of the powder. Although the nozzle position is not shown, top spray, lower tangential spray,
Intermediate tangential spraying is possible. Top spray is suitable for granulation from powder, and there is no need for a large air volume because flow action does not occur due to the action of the rotating disk. For this reason, the ratio of the fine powder floating on the nozzle is small, and therefore, the ratio of contact with the spray mist and granulation is high. In addition, due to the rolling and dispersing action of the rotating disk, the generation of coarse particles is smaller than in the fluidized bed, and the particle size distribution becomes sharp. The tangential spray is a spray method suitable for modified granulation and coating, and the modified granulation has a structure capable of supplying powder coaxially with a spray nozzle. The sheathed nozzle is designed so that the sprayed mist comes into contact with the particles when it is dispersed. Even when inserted into the flowing particle layer, the particles do not enter the nozzle tip (the area where the mist does not become mist) The secondary air is ventilated to ensure a spray zone.
As a result, the nozzle is hardly stained (powdered powder).

Next, acetaminophen powder was charged into a multifunctional tumbling and fluidizing device (trade name “Multiplex”) having the structure shown in FIG. 1A, and tumbling was performed without adding any auxiliary agent. FIG. 2 shows the particle size distribution of the granulated product obtained by performing fluidized granulation (primary granulation), adding acetaminophen to the granulated product, and subjecting the granulated product to modified granulation. Table 1 shows the experimental conditions.
It is as follows.

[0014]

[Table 1]

As shown in FIG. 2, a heavy granulation having a sharp particle size distribution can be achieved by an easy operation without using a special seed.

In the formulation, acetaminophen was used as a poorly soluble drug which was difficult to granulate, but the surface state of the granulated material was slightly rough because it was a crystalline powder. A highly water-soluble drug tends to have a smooth surface state. In particular, acetaminophen has a large amount of wall adhesion in the fluidized-bed granulation method, and it is difficult to maintain a smooth fluidized state due to the blow-through phenomenon. ,
It is eliminated with the progress of granulation and shows good granulation properties.

The point of the operation is that the amount of air is not excessively large. In particular, the large amount of air in the modification granulation, that is, powdering, leads to a decrease in the adhesion efficiency due to the scattering of the added modification powder. The structure of the rotating disk, in which the powder for modification is adhered and compacted by the rolling operation, comes into contact with fluidized air, undergoes surface drying, is wetted again, and powder adhesion is repeated, is appropriate.

At the end of the granulation operation, tableting properties can be improved by adding a binder to the surface of the granulated product while suppressing the progress of granulation.

Further, since there is no strong kneading action, the granulated material has a moderate hardness and good tableting properties. The granulated material is nearly spherical and has a smooth surface, so that post-treatments such as coating for controlling drug release can be performed. Easy.

Depending on the nature of the powder to be added, similar results can be obtained by dispersing and suspending in a binder and spraying.

Further, depending on the condition of the granulated material, the modified granulation may be omitted.

[0022]

According to the present invention, the poor flow of the powder is eliminated, and the powder auxiliary agent for improving the properties such as the adhesion and cohesion of the raw material powder is added even at a small addition rate of about 0 to 15%. Granulation is possible. Therefore, as in the case of conventional fluidized bed granulation, the granulated material does not become large, and granulation with a sharp particle size distribution is possible, and the granulated material is modified and granulated with the same drug as a seed, or It is possible to perform operations such as multi-layer coating of multi-component powder and film coating. These granulated products are better as granules for capsule filling and coating than fluidized bed granulation, and can respond to diversified demands by multi-layer modified granulation.

[Brief description of the drawings]

FIG. 1 is a schematic longitudinal sectional view illustrating a tumbling flow device.

FIG. 2 is a particle size distribution diagram.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Fluid bed apparatus 2 Fluid chamber 3 Rotating disk

Claims (1)

(57) [Claims] When granulating a raw material powder comprising a fine powder having high adhesion and cohesion, a vertical rotation axis is centered on the bottom inside a vessel of a fluidized-bed granulator for flowing the raw material powder with a gas adjusted to an appropriate temperature. And a powder auxiliary agent for improving the properties such as adhesion and cohesion of the raw material powder is added to the raw material powder in an amount of from 0 to 15%.
%, And tumbled and fluidized in the apparatus. The binder was sprayed and granulated while controlling the water content of the powder in the fluidized bed to a preset value according to the wettability and solubility of the powder. A heavy granulation method for a high drug content powder, comprising spraying a binder onto the obtained granules, coating the surface of the granules with the same powder or another powder, and performing heavy granulation.