JPH08229103A - Fluidizing method of low replaceability hydroxy propylcellulose and manufacture of solid preparation - Google Patents

Abstract

PURPOSE: To achieve a larger pelletizing speed in the extrusion production by repeating an operation of dispersing specified low replaceability hydroxy proplycellulose, applying an impact thereto and circulating it again to disperse to improve disintegration property by a reduction in the weight deviation of solid preparation. CONSTITUTION: In a fluidizing method of low replaceability hydroxy propylcellulose, a low replaceability hydroxy propylcellulose with the content of a hydroxy propoxyl group of 5-16wt.% is dispersed, and an impact force is applied thereto by a rotor 1 and the material is circulated again to be dispersed. This operation is repeated and under this impact force, fibrous particles are vanished or little eliminated from the low replaceability hydroxy propylcellulose to make surface of the hydroxy propylcellulose very smooth with a smaller angle of repose, eventually increasing fluidity with a larger bulk density. In this case, if the content of the hydroxy propoxyl group is lower than 5wt.% or more than 16wt.%, the swelling of the hydroxy propylcellulose after the dosing of the solid preparation lowers to make a disintegration property poor.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for fluidizing low-substituted hydroxypropylcellulose, which is incorporated as a disintegrating agent and a binder into a solid preparation such as a pharmaceutical product, and a method for producing the solid preparation.

[0002]

2. Description of the Related Art Solid preparations such as pharmaceuticals contain a disintegrating agent and a binder so that they swell and disintegrate after administration.
Examples of the disintegrants and binders include low-substituted hydroxypropyl cellulose, carboxymethyl cellulose and salts thereof, starch and derivatives thereof, and microcrystalline cellulose. Among these, low-substituted hydroxypropyl cellulose is a nonionic disintegrant / binder that has little interaction with drugs. JP-B-46-42792 and JP-B-57-53100 disclose that low-substituted hydroxypropyl cellulose is used as a disintegrant and binder.

The main drug component is uniformly dispersed in the solid preparation,
It is necessary that the weight deviation is small. To this end, it has been desired that the disintegrant and binder additives have excellent fluidity. In addition, among the solid preparations, extrusion granulation is generally performed when producing granules, and it has been desired to increase the granulation speed in order to improve productivity.

In the method for producing low-substituted hydroxypropylcellulose, the pulp is caused to undergo a substitution reaction with propylene oxide by using alkali hydroxide as a catalyst. After the substituted pulp is neutralized with an acid such as acetic acid and hydrochloric acid, low-substituted hydroxypropylcellulose powder is obtained through processes such as purification, drying and pulverization.

[0005]

As described above, the low-substituted hydroxypropyl cellulose contains a large amount of fibrous particles because the raw material is pulp, has a low bulk density, a large angle of repose, and a fluidity. Was sometimes not enough. For this reason, when low-substituted hydroxypropylcellulose is compounded in a tableting composition, the fluidity of the powder of the active ingredient and other compounding ingredients becomes low, the weight deviation of the manufactured solid preparation becomes large, and the extrusion granulation becomes difficult. In the case of production, the granulation speed may decrease.

The present invention has been made to solve the above-mentioned problems, and when it is added to a tableting composition and tableted to produce a solid preparation, the weight deviation is small, the disintegration is good, and the extrusion is excellent. It is an object of the present invention to provide a method for fluidizing low-substituted hydroxypropylcellulose and a method for producing a solid preparation, which can increase the granulation rate in the case of producing by granulation.

[0007]

The method for fluidizing low-substituted hydroxypropyl cellulose of the present invention, which was made to achieve the above object, comprises a low-substituted hydroxypropyloxy group having a hydroxypropoxyl group content of 5 to 16% by weight. Propyl cellulose is dispersed, impact force is applied with rotor 1 (see FIG. 1), and circulation is carried out again to disperse the propyl cellulose.

The method for producing a solid preparation of the present invention, which has been made to achieve the above-mentioned object, comprises dispersing a low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 5 to 16% by weight, and impacting with a rotor. A method for producing a solid preparation by tableting a composition containing 2 to 50% by weight of a high-fluidity low-substituted hydroxypropylcellulose, which is obtained by recirculating and re-dispersing it. Degree of substitution Hydroxypropyl cellulose has an average particle size of 5
１５０150 μm.

The method for producing a solid preparation of the present invention, which has been made to achieve the above-mentioned object, comprises dispersing a low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 5 to 16% by weight, and applying a shock force with a rotor. A method for producing a solid preparation by extrusion-granulating a composition containing 3 to 50% by weight of a high-fluidity low-substituted hydroxypropylcellulose, which is obtained by recirculating and dispersing again. The low-substituted hydroxypropyl cellulose has an average particle size of 5 to 150 μm.

When the hydroxypropoxyl group content of the high-fluidity, low-substituted hydroxypropylcellulose is less than 5% by weight or more than 16% by weight, the swelling amount of hydroxypropylcellulose after taking a solid preparation is low,
The disintegration becomes insufficient. The hydroxypropoxyl group content is particularly preferably 7 to 13% by weight.

When the average particle size of the high-fluidity, low-substituted hydroxypropylcellulose is 5 μm or less, the fluidity of hydroxypropylcellulose is low, and when it is 150 μm or more, the mixture of the hydroxypropylcellulose and the drug becomes non-uniform, and the binding occurs. And the hardness of the solid preparation becomes low. The average particle diameter is particularly preferably 40 to 100 μm.

When the content of the high-fluidity and low-substituted hydroxypropylcellulose of the composition for tableting is less than 2% by weight, the binding and disintegrating properties are insufficient. If the content of the high-fluidity, low-substituted hydroxypropylcellulose of the composition for extrusion granulation is less than 3% by weight, a stable granulation rate cannot be obtained. The solid preparation produced by tableting or extrusion granulation contains, for example, an excipient, a lubricant, a colorant, and a flavoring agent as components other than the high-fluidity and low-substituted hydroxypropylcellulose.

[0013]

In the method for fluidizing low-substituted hydroxypropyl cellulose of the present invention, the low-substituted hydroxypropyl cellulose is dispersed and the rotor 1 (see FIG. 1) is used to apply an impact force. Due to this impact force, the low-substituted hydroxypropyl cellulose loses or almost disappears fibrous particles, and at the same time the surface becomes very smooth, the angle of repose is small, the bulk density is large, and the fluidity is high.

[0014]

EFFECTS OF THE INVENTION When a low-substituted hydroxypropyl cellulose is treated by the fluidizing method of the present invention, a high-fluidity low-substituted hydroxypropyl cellulose is obtained, which is added to a composition for tableting and produced by tableting. The solid preparation has small weight deviation, high hardness, and good disintegration. In the case of manufacturing by extrusion granulation, the granulation speed can be increased.

[0015]

EXAMPLES Examples of the present invention will be described in detail below.

FIG. 1 is a sectional view showing a hybridizer 9 which is a main part of a hybridization system for carrying out the method for fluidizing low-substituted hydroxypropylcellulose of the present invention.

At the center of the hybridizer main body, a rotary rotor 1 having a large number of blades 2 is arranged.
The body is cooled by the jacket 8. The circulation device 3 is
The space 10 between the inner wall of the body and the rotor 1 and the central portion 7
And is connected at its central part 7 to a tube leading to the low-substituted hydroxypropylcellulose feed port 5. A pipe having a discharge port 6 and a discharge valve 4 are arranged above the hybridizer main body.

Using this hybridization system, the fluidization method is carried out as follows. When low-substituted hydroxypropylcellulose is put into the supply port 5, it is dispersed in the central portion 7 as indicated by the chain line arrow.
Then, the blades 2 of the rotating rotor 1 collide with each other and an impact force is applied. After that, it is sucked into the circulation device 3 and dispersed again in the central portion 7 is repeated. When the treatment is completed, the valve 4 is opened and the low-substituted hydroxypropylcellulose is discharged from the discharge port 6 toward a collector (not shown).

Example 1 Specifically, the hybridization stem NHS-1
(Nara Machinery Co., Ltd.), 120 g of low-substituted hydroxypropyl cellulose LH-21 (manufactured by Shin-Etsu Chemical Co., Ltd.) was put, and the rotor 1 was rotated at 8000 rpm for 5 minutes and 10 minutes.
Fluidization treatment for 20 minutes
o. It was set to 1, 2, and 3.

The angle of repose of these samples was measured by the cone deposition method using a powder tester PT-D type (manufactured by Hosokawa Micron), and then the average particle diameter and bulk density were measured.
The results are shown in Table 1.

[0021]

[Table 1]

As shown in the table, the fluidized low-substituted hydroxypropyl cellulose had a large bulk density, a small angle of repose and a high fluidity.

Next, using the aspirin granulated powder (aspirin / corn starch = 95/5) as a base, sample No. 1
To 10 parts by weight, aspirin granulated powder was 90 parts by weight, and magnesium stearate was 0.5 parts by weight to prepare a tableting composition. Sample No. 2 and sample No. Three
A tableting composition was prepared in the same manner as above.

Each tableting composition was tabletted using RT-S15K-T35 (manufactured by Kikusui Seisakusho) as a tableting machine at a rotation speed of 30 rpm and a tableting pressure of 0.6 ton to give a diameter of 9 m.
A tablet with m and a weight of 300 mg was obtained. The weight deviation, hardness, and disintegration time of these tablets were measured, and the results are shown in Table 1. As shown in the table, the obtained tablets had small weight deviation, high hardness, and short disintegration time.

Example 2 Sample No. 1 of Example 1 Sample No. 1 using phenacetin as a base. 1 is 10 parts by weight and phenacetin powder is 90 parts by weight, and the mixture is put in a 10 liter Henschel mixer and mixed for 1 minute, then 52 parts by weight of water is added and then kneaded for 3 minutes to obtain a composition for extrusion granulation. Was prepared.
The composition was subjected to extrusion granulation using a 5-inch cylindrical extrusion granulator (manufactured by Kikusui Seisakusho) equipped with a screen having a diameter of 0.6 mm, and the granulation speed was measured. Sample No. Two
In the same manner, the granulation speed was measured. as a result,
Sample No. Granulation speed of 350g / min when 1 was used,
Sample No. When 2 was used, it was as good as 400 g / min.

Comparative Example 1 The low-substituted hydroxypropylcellulose LH-21 (manufactured by Shin-Etsu Chemical Co., Ltd.) was subjected to the repose angle, the average particle size and the bulk density in the same manner as in Example 1 without fluidization treatment. The results are shown in Table 1. As shown in the table, Example 1
The low-substituted hydroxypropyl cellulose of which the fluidization treatment was carried out had a low bulk density, a large angle of repose and a low fluidity.

Next, a tableting composition was prepared and tabletted in the same manner as in Example 1 except that low-substituted hydroxypropylcellulose LH-21 which had not been fluidized was used as a sample. Got The weight deviation, hardness, and disintegration time of the obtained tablets were measured, and the results are shown in Table 1. As shown in the table, the obtained tablets had larger weight deviation, lower hardness and longer disintegration time than the tablets using the fluidized low-substituted hydroxypropylcellulose LH-21 of Example 1. .

COMPARATIVE EXAMPLE 2 Except that a non-fluidized low-substituted hydroxypropylcellulose LH-21 was used as a sample.
A composition for extrusion granulation was prepared in the same manner as in Example 2, and the granulation speed was measured while performing extrusion granulation. As a result, the granulation rate was 300 g / min, and it was slower than when the fluidized low-substituted hydroxypropylcellulose LH-21 was used.

[Brief description of drawings]

FIG. 1 is a cross-sectional view showing a main part of an apparatus for carrying out a method for fluidizing low-substituted hydroxypropylcellulose to which the present invention is applied.

[Explanation of symbols]

1 is a rotor, 2 is a blade, 3 is a circulation device, 4 is a discharge valve, 5 is a supply port, 6 is a discharge port, 7 is a central portion, 8 is a jacket, 9 is a hybridizer, and 10 is a space.

Claims (3)

[Claims] 1. Hydroxypropoxyl group content 5 to 1
A method for fluidizing low-substituted hydroxypropyl cellulose, which comprises repeatedly dispersing 6% by weight of low-substituted hydroxypropyl cellulose, imparting an impact force with a rotor, and circulating the dispersion again. 2. Hydroxypropoxyl group content 5 to 1
A composition containing 2 to 50% by weight of a high-fluidity low-substituted hydroxypropylcellulose obtained by dispersing 6% by weight of a low-substituted hydroxypropylcellulose, giving an impact force with a rotor, and recirculating and dispersing. A method for producing a solid preparation by tableting, wherein the high-fluidity and low-substituted hydroxypropyl cellulose has an average particle diameter of 5 to 150 μm.
A method for producing a solid preparation, comprising: 3. Hydroxypropoxyl group content 5 to 1
A composition containing 3 to 50% by weight of a high-fluidity low-substituted hydroxypropylcellulose obtained by dispersing 6% by weight of a low-substituted hydroxypropylcellulose, imparting an impact force with a rotor, and recirculating and dispersing. A method for producing a solid preparation by extrusion granulation, wherein the high-fluidity and low-substituted hydroxypropyl cellulose has an average particle diameter of 5 to 150.
The method for producing a solid preparation is characterized in that it is μm.