JPH09208458A - Offensive taste-masked preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a preparation good in elution of medicine and capable of masking offensive taste such as bitterness effectively, by wet granulation of a composition made by formulating the medicinal with a specified or more amount of a water-swellable substance with water or a hydrous alcohol. SOLUTION: This preparation is obtained by wet granulation of a composition comprising (A) a medicinal and (B) >=30wt.% of a water-swellable substance with (C) water or a hydrous alcohol. The component A may be any medicinal provided that it has offensive odor such as bitterness. The component B is esp. pref. a low-substitution degree hydroxypropyl cellulose, carmellose calcium or crosscarmellose sodium. The amount of the component A to be formulated is pref. <=70 (more pref. <=50)wt.% in the composition. It is preferable that the amount of the component C to be used is 2-5wt.% times that of the component B.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a pleasant-feeling preparation in which an unpleasant drug taste is masked.

[0002]

2. Description of the Related Art When a pharmaceutical product has an unpleasant taste such as bitterness,
It is extremely difficult for the patient to take as a powder or granules. Then, in order to mask the unpleasant taste in the mouth at the time of taking, (1) a method of adding a sweetener such as aspartame or a flavoring agent (JP-A-2-56416), (2) a method of adding an inclusion compound (JP-A-3-236316) and (3) a method of coating with a gastric-soluble polymer, an enteric polymer, a water-insoluble polymer, waxes and the like (JP-A-57-57).
No. 5,8631, JP-A-3-130214) have already been proposed.

However, in the method (1) or (2) described above, masking is impossible when the unpleasant taste such as bitterness is strong, and in the method (3) of coating, depending on the strength of the bitterness or the like. Although it is possible to mask by increasing the amount of the coating agent, a feeling of roughness when taking it peculiar to the coating agent occurs,
Further, the elution of the drug may be reduced by the coating agent.

[0004]

SUMMARY OF THE INVENTION Therefore, an object of the present invention is to provide a preparation having a good drug dissolution property and effectively masking any drug having an unpleasant taste such as bitterness.

[0005]

In view of such circumstances, the inventors of the present invention have conducted diligent research and, as a result, conducted a wet preparation of a composition prepared by mixing a drug with a certain amount or more of a water-swelling substance with water or hydrous alcohol. The inventors have found that if granulated, unpleasant taste is masked without reducing drug elution, and the present invention has been completed.

That is, the present invention relates to a drug and a composition
The present invention provides an oral preparation obtained by wet granulation of a composition containing water-swellable substance in an amount of at least wt% with water or hydrous alcohol.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The water-swellable substance used in the present invention is not particularly limited as long as it absorbs water and swells. For example, low-substituted hydroxypropylcellulose, carmellose or a salt thereof, croscarmellose. Sodium, sodium carboxymethyl starch, cros polyvinylpyrrolidone and the like can be mentioned. Of these, particularly preferred are low-substituted hydroxypropyl cellulose, carmellose calcium and croscarmellose sodium.

The water-swellable substance may be used alone or in admixture of two or more, and the amount used is 30% by weight or more, particularly 50 to 95, in the composition containing the drug and the water-swellable substance.
It is preferable to set the weight%.

The drug applied to the present invention is not particularly limited as long as it has a bitter taste and the like, and examples thereof include antipyretic analgesic and anti-inflammatory agents such as ibuprofen, diclofenac sodium, flufenamic acid, sulpiline, aspirin and ketoprofen;
Diuretics such as caffeine; Bronchodilators such as theophylline; Antihistamines such as chlorpheniramine maleate, diphenhydramine hydrochloride, promethazine hydrochloride; noscapine hydrochloride, carbetapentane citrate, dextromethorphan hydrobromide, isoaminyl citrate, phosphorus Antitussive expectorants such as dimemorphan acid; various antibiotics such as tarampicillin hydrochloride, bacampicillin hydrochloride, cefachlor, erythromycin; antiulcer agents such as cimetidine and pirenzepine hydrochloride; sympathomimetics such as dihydrocodeine phosphate and dl-methylephedrine hydrochloride; hydrochloric acid Cardiovascular agents such as delapril, meclofenoxate hydrochloride, diltiazem hydrochloride; cerebral circulation improving agents such as vinpocetine; anxiolytic agents such as chlordiazepoxide, diazepam; fursultiamine, thiamine hydrochloride, pantothete Vitamin preparations such as calcium acidate, ascorbic acid, tranexamic acid; antimalarial preparations such as quinine hydrochloride; cardiotonic preparations such as etilefrine hydrochloride and digitoxin; antiarrhythmic preparations such as propranolol hydrochloride and alprenolol hydrochloride; antidiarrheals such as loperamide hydrochloride; chlorpromazine And the like.

The compounding amount of the drug may be appropriately determined according to the purpose, but from the relationship of the compounding amount of the water-swelling substance, 70% by weight or less in the composition containing the drug and the water-swelling substance, 5
The content is preferably 0% by weight or less.

The alcohol in the hydrous alcohol used in the present invention includes ethyl alcohol, methyl alcohol,
Examples include pharmaceuticals such as isopropyl alcohol and alcohols that can be used in the production thereof. As the hydrous alcohol, alcohol having an alcohol content of 50% by weight or less, particularly 3
It is preferably 0% by weight or less. Water or hydrous alcohol is used as a kneading solvent for wet granulation to bring the water-swellable substance into a swollen state, and the amount used is 2 to 5 times the weight of the water-swellable substance. Is preferred. The kneading solvent of water or hydrous alcohol, depending on the purpose, a sweetener,
Additives that can be usually used in pharmaceuticals such as sugars such as purified sucrose, sugar alcohols such as D-mannitol, and polymers dissolved or dispersed in water may be added.

The "composition containing a drug and a water-swellable substance" in the present invention means a powder formulation containing the drug and a water-swellable substance, and may be only the drug and the water-swellable substance. However, in general, these are referred to as an additive. The additive used here is not particularly limited as long as it can be added as a medicine, and examples thereof include an excipient (diluent), a binder, a disintegrating agent, a sweetener, a flavoring agent, a dye and the like. Here, examples of the excipient (diluent) include sugars (lactose, purified sucrose, glucose, etc.), sugar alcohols (D-mannitol, sorbitol, xylitol, erythritol, etc.). Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, methylcellulose, polyvinylpyrrolidone, dextrin, pregelatinized starch and the like. Examples of the disintegrant include starches such as corn starch. Examples of the sweetener include saccharin sodium and aspartame. Examples of the flavor include citrus flavors such as orange and lemon, menthol and peppermint oil. Examples of the pigment include natural pigments and synthetic pigments.

The method used for wet granulation in the present invention is not particularly limited as long as it is a wet granulation method used for ordinary medicines such as stirring granulation, fluidized bed granulation and extrusion granulation. The extrusion granulation method is preferred.

The oral preparation of the present invention can be produced, for example, as follows. First, a drug, a water-swelling substance, and other additives as necessary are added, and the mixture is stirred, for example, a vertical granulator (Pawrec Co., Ltd.).
Manufactured) or the like, and then mixed with purified water or 10 to 30% by weight.
Hydrous alcohol is added to the water-swelling substance in an amount of about 2 to 5 times and kneaded to bring the water-swelling substance into a swollen state. This kneaded product is granulated by an extrusion granulator, for example, a Fine Luzer (manufactured by Fuji Paudal Co., Ltd.) extrusion granulator, and dried by a box dryer or a fluid bed granulator dryer. It is considered that when the water-swellable substance contracts due to this drying, a drug having an unpleasant taste is taken in and masked. Finally, a sieve is used to obtain granules having a target particle size. On the other hand, after extrusion granulation, sphere treatment was performed with Marumerizer (Fuji Paudal Co., Ltd.), followed by drying with a box dryer or fluidized bed dryer, and finally using a sieve to obtain the desired particle size. It is also possible to produce spherical granules of Further, the kneaded product can be immediately dried in a box dryer or a fluidized bed granulation dryer, and finally a sieve can be used to obtain granules having a desired particle size. The particle size of the target granules is adjusted by adjusting the amount of water or hydrous alcohol, or the screen diameter during extrusion granulation is 0.3 to 1.2 mm.
It is possible to obtain powders, fine granules and granules by changing within the range. The obtained granules may be further coated with saccharides or polymers in consideration of the feeling of ingestion and the stability of drugs. Further, excipients (diluents), disintegrating agents, lubricants, etc. may be added to the obtained granules to give tablets.

[0015]

INDUSTRIAL APPLICABILITY The preparation of the present invention masks the unpleasant taste of a drug, has a good feeling on ingestion, and has a good drug elution.

[0016]

The present invention will be described below in detail with reference to examples.

Example 1 100 g of ibuprofen and 900 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 2900 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a 30 and 42 mesh sieve to 30-
A 42 mesh fine granule was produced.

Example 2 300 g of ibuprofen and 700 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 2200 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a 30 and 42 mesh sieve to 30-
A 42 mesh fine granule was produced.

Example 3 500 g of ibuprofen and 500 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 1600 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a 30 and 42 mesh sieve to 30-
A 42 mesh fine granule was produced.

Example 4 700 g of ibuprofen and 300 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 950 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-60 (0.6 mm diameter screen,
Granmerizer Q4 granulated with Fuji Paudal Co., Ltd.
After sphering with 00 (Fuji Paudal Co., Ltd.), fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.)
Manufactured) and sized with a 30 and 42 mesh sieve to 30-
A 42 mesh fine granule was produced.

Comparative Example 1 900 g of ibuprofen and 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 250 g of 10% aqueous ethanol solution was added and kneaded, and the mixture was granulated with FineLuzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji Paudal Co., Ltd.). Spheroidizing treatment with a fluidized bed dryer WSG-5 (Okawara Seisakusho Co., Ltd.)
Manufactured) and sized with a 30 and 42 mesh sieve to 30-
A 42 mesh fine granule was produced.

Comparative Example 2 100 g of ibuprofen, 100 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were added to Vertical Granulator FM-VG-25 (manufactured by Paulec Co., Ltd.).
And mixed. To this, 120 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-60 (0.4
Granulate with a 5 mm screen, Fuji Paudal Co., Ltd.,
After spheroidizing with Marumerizer Q400 (Fuji Paudal Co., Ltd.), it was dried with a fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.) and sized with a 30 and 42 mesh sieve. Then, 30-42 mesh fine granules were produced.

Test Example 1 The bitterness test and the dissolution test were carried out on the fine granules obtained in Examples 1 to 4 and Comparative Examples 1 and 2 by the following test methods. The results are shown in Table 1. Test method Bitterness test: A time period in which a stimulating bitter taste of ibuprofen was felt by measuring the amount equivalent to 150 mg of ibuprofen was measured. Dissolution test: Paddle method 100 rpm Test liquid: JP 2nd liquid (pH 6.8)

[0024]

[Table 1]

From Table 1, it can be seen from the results of the bitterness test that Examples 1 to 4 of the present invention were more clearly suppressed in the stimulating bitterness of ibuprofen than Comparative Examples 1 and 2 (the time when the bitterness was felt). It was evaluated as masked for 30 seconds or more). When the dissolution property was examined, the elution of ibuprofen at 2 minutes was lower in the Example than in the Comparative Example, but 10 to 10
It can be seen from the results of the dissolution test that the drug is well dissolved in 20 minutes and there is no problem in the dissolution property (in the case of 50% or more at 10 minutes and 80% or more at 20 minutes, the drug release was evaluated as fast-dissolving). ).

Example 5 100 g of anhydrous caffeine and 900 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 2800 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.8 mm diameter screen, made by Fuji Paudal Co., Ltd.), spheroidized by Marumerizer Q400 (made by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a sieve of 24 and 30 mesh to
A 30 mesh granule was produced.

Example 6 300 g of anhydrous caffeine and 700 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 2100 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.8 mm diameter screen, made by Fuji Paudal Co., Ltd.), spheroidized by Marumerizer Q400 (made by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a sieve of 24 and 30 mesh to
A 30 mesh granule was produced.

Example 7 500 g of anhydrous caffeine and 500 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 1550 g of 10% aqueous ethanol solution was added and kneaded,
Granulated with FineLuzer EXR-60 (0.8 mm diameter screen, made by Fuji Paudal Co., Ltd.), spheroidized by Marumerizer Q400 (made by Fuji Paudal Co., Ltd.), and then dried in a fluidized bed. Machine WSG-5 type (Okawara Manufacturing Co., Ltd.)
Manufactured) and sized with a sieve of 24 and 30 mesh to
A 30 mesh granule was produced.

Example 8 700 g of anhydrous caffeine and 300 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 850 g of 10% ethanol aqueous solution was added and kneaded, and FineLuzer EXR-60 (0.8 mm diameter screen,
Granmerizer Q4 granulated with Fuji Paudal Co., Ltd.
After sphering with 00 (Fuji Paudal Co., Ltd.), fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.)
Manufactured) and sized with a sieve of 24 and 30 mesh to
A 30 mesh granule was produced.

Comparative Example 3 900 g of anhydrous caffeine and 100 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were added to a vertical granulator FM.
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 200 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-60 (0.6 mm diameter screen,
Granmerizer Q4 granulated with Fuji Paudal Co., Ltd.
After sphering with 00 (Fuji Paudal Co., Ltd.), fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.)
Manufactured) and sized with a sieve of 24 and 30 mesh to
A 30 mesh granule was produced.

Comparative Example 4 100 g of anhydrous caffeine, 100 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were added to Vertical Granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). )
And mixed. To this, 100 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-60 (0.6
mm screen, granulated with Fuji Paudal Co., Ltd., and spheroidized with Marumerizer Q400 (Fuji Paudal Co., Ltd.), and then fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.) and sized with a sieve of 24 and 30 mesh to produce granules of 24-30 mesh.

Test Example 2 With respect to the granules obtained in Examples 5 to 8 and Comparative Examples 3 to 4, a bitterness test and a dissolution test were carried out by the following test methods. The results are shown in Table 2. Test method Bitterness test: The time for feeling the bitterness of anhydrous caffeine was measured, including 80 mg of anhydrous caffeine in the mouth. Dissolution test: Paddle method 100 rpm Test liquid: Water

[0033]

[Table 2]

It can be seen from Table 2 that in the case of anhydrous caffeine, the bitterness of anhydrous caffeine is suppressed more in Examples 5 to 8 than in Comparative Examples 3 to 4 as in the case of ibuprofen.

Example 9 100 g of chlorpheniramine maleate and 900 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were used as a vertical granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). Mixed in. To this, 2900 g of 10% ethanol aqueous solution was added and kneaded, and granulated with FineLuzer EXR-60 (1.0 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji Paudal Co., Ltd.). Spheroidizing treatment with a fluidized bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.) and sized with a 20 and 24 mesh sieve to produce 20-24 mesh granules. did.

Example 10 Diclofenac sodium (100 g) and low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) (900 g) were mixed with a vertical granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). . To this, 2900 g of 10% aqueous ethanol solution was added and kneaded, and granulated with FineLuzer EXR-60 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji Paudal Co., Ltd.). Spheroidizing treatment was performed, and then dried with a fluidized bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.) and sized with a sieve of 24 and 30 mesh to produce granules of 24-30 mesh. did.

Example 11 100 g of ibuprofen and carmellose calcium (E
900 g of CG-505 and Gotoku Yakuhin Co., Ltd. were mixed with a vertical granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). To this, 2900 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-
60 (0.6 mm screen, Fuji Paudal Co., Ltd.)
After granulating with a spheroidizer and spheroidizing with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), fluidized bed dryer WS
Dried with G-5 type (Okawara Seisakusho Co., Ltd.), 30 and 4
The particles were sized with a 2-mesh sieve to produce 30-42 mesh fine granules.

Example 12 100 g of ibuprofen and croscarmellose sodium (Ac-di-sol, manufactured by Asahi Kasei Kogyo Co., Ltd.) 900
g was mixed with a vertical granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). 3000 g of 10% ethanol aqueous solution was added to this and kneaded, and granulated with FineLuzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji Paudal Co., Ltd.). Spheroidizing treatment with a fluidized bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.).
The particles were sized with a sieve of 0 and 42 mesh to produce a 30-42 mesh rod-shaped fine granule.

Comparative Example 5 100 g of chlorpheniramine maleate, 100 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were added to a vertical granulator FM-VG-25 (Paurec (stock). )) Was mixed. To this, 300 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-6
0 (0.8 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.) and granulated, and Marumerizer Q400 (Fuji Paudal Co., Ltd.)
Spheroidizing treatment with a fluidized bed dryer WSG-5
It was dried in a mold (manufactured by Okawara Seisakusho Co., Ltd.) and sized with a sieve of 20 and 24 mesh to produce granules of 20-24 mesh.

Comparative Example 6 100 g of diclofenac sodium, 100 g of low-substituted hydroxypropyl cellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) and 800 g of lactose were added to Vertical Granulator FM-VG-25 (manufactured by Paulec Co., Ltd.). Mixed in. To this, 300 g of 10% aqueous ethanol solution was added and kneaded, and FineLuzer EXR-6
0 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.) and granulated with Marumerizer Q400 (Fuji Paudal Co., Ltd.)
Spheroidizing treatment with a fluidized bed dryer WSG-5
It was dried in a mold (manufactured by Okawara Seisakusho Co., Ltd.) and sized with a sieve of 24 and 30 mesh to produce granules of 24-30 mesh.

Comparative Example 7 100 g of ibuprofen and carmellose calcium (E
CG-505, manufactured by Gotoku Yakuhin Co., Ltd., 100 g and lactose 8
00g to Vertical Granulator FM-VG-25
(Manufactured by Paulec Co., Ltd.). To this, 250 g of 10% aqueous ethanol solution was added and kneaded, and the mixture was granulated with FineLuzer EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji Paudal Co., Ltd.). Spheroidizing treatment with a fluidized bed dryer WSG-5 (manufactured by Okawara Seisakusho Co., Ltd.),
A 30-42 mesh sieve was used to prepare a 30-42 mesh fine granule.

Comparative Example 8 100 g of ibuprofen and 100 croscarmellose sodium (Ac-di-sol, manufactured by Asahi Chemical Industry Co., Ltd.)
g and lactose 800g vertical granulator FM
-VG-25 (manufactured by Paulec Co., Ltd.) was mixed. To this, 320 g of 10% aqueous ethanol solution was added and kneaded, and granulated with a Fine Luther EXR-60 (0.45 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and then a fluidized bed dryer W
It was dried with SG-5 type (manufactured by Okawara Seisakusho Co., Ltd.) and sized with a sieve of 30 and 42 mesh to produce a 30-42 mesh rod-shaped fine granule.

Test Example 3 A bitterness test and a dissolution test were carried out on the fine granules and granules obtained in Examples 9 to 12 and Comparative Examples 5 to 8 by the following test methods. Table 3 shows the results.

Test method Bitterness test: chlorpheniramine maleate 20 mg, diclofenac sodium 25 mg, ibuprofen 150 mg
A considerable amount was contained in the mouth, and the time for feeling the bitterness of each drug was measured. Dissolution test: Paddle method 100 rpm Test solution: Water (chlorpheniramine maleate, diclofenac sodium), JP 2nd solution pH 6.8 (ibuprofen)

[0045]

[Table 3]

From Table 3, in Examples 9 to 12, drugs such as chlorpheniramine maleate, diclofenac sodium and ibuprofen were ECG-505, Ac-di.
It can be seen that even if a water-swellable substance such as -sol is used, the bitterness of the drug is suppressed more than in the comparative example.

Example 13 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 997 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) are used as a vertical granulator FM-VG-25. (Manufactured by Paulec Co., Ltd.). To this, 2900 g of a 10% ethanol aqueous solution containing 13 g of aspartame was added and kneaded, and granulated with a FineLuzer EXR-60 (0.6 mm diameter screen, manufactured by Fuji Paudal Co., Ltd.), and Marumerizer Q400 (Fuji). After spheroidizing with Paudal Co., Ltd., it was dried with a fluidized bed dryer WSG-5 type (Okawara Seisakusho Co., Ltd.), and dried.
The granules were sieved with a sieve of 0 and 42 mesh to produce 30-42 mesh fine granules.

Example 14 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 650 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), erythritol (Niken Chemical Co., Ltd.) 347 g of vertical granulator F
It mixed with M-VG-25 (made by Paulec Co., Ltd.). To this, 2100 g of 10% ethanol aqueous solution containing 13 g of aspartame was added and kneaded, and FineLuzer EXR
-60 (0.6 mm screen, Fuji Paudal Co., Ltd.)
Granulated with a sol.), Spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then fluidized bed dryer WS
Dried with G-5 type (Okawara Seisakusho Co., Ltd.), 30 and 4
The particles were sized with a 2-mesh sieve to produce 30-42 mesh fine granules.

Example 15 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 390 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), erythritol (Niken Chemical Co., Ltd.) 607 g of vertical granulator F
It mixed with M-VG-25 (made by Paulec Co., Ltd.). To this, 1100 g of 10% aqueous ethanol solution containing 13 g of aspartame was added and kneaded, and FineLuzer EXR
-60 (0.6 mm screen, Fuji Paudal Co., Ltd.)
Granulated with a sol.), Spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then fluidized bed dryer WS
Dried with G-5 type (Okawara Seisakusho Co., Ltd.), 30 and 4
The particles were sized with a 2-mesh sieve to produce 30-42 mesh fine granules.

Example 16 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 997 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.) were used as a vertical granulator FM-VG-25. (Manufactured by Paulec Co., Ltd.). To this, 2100 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added and kneaded, and then fluidized bed dryer WS
Dried with G-5 type (Okawara Seisakusho Co., Ltd.), 30 and 1
The granules were sized with a 50-mesh sieve to produce 30-150 mesh fine granules.

Comparative Example 9 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 260 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), erythritol (Niken Chemical Co., Ltd.) Made) 737 g of vertical granulator F
It mixed with M-VG-25 (made by Paulec Co., Ltd.). To this, 700 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added and kneaded, and FineLuzer EXR-
60 (0.45mm diameter screen, Fuji Paudal Co., Ltd.)
Granulated with a sol.), Spheronized with Marumerizer Q400 (manufactured by Fuji Paudal Co., Ltd.), and then fluidized bed dryer WS
Dried with G-5 type (Okawara Seisakusho Co., Ltd.), 30 and 4
The particles were sized with a 2-mesh sieve to produce 30-42 mesh fine granules.

Comparative Example 10 150 g of ibuprofen, 60 g of allylisopropylacetylurea, 80 g of anhydrous caffeine and 260 g of low-substituted hydroxypropylcellulose (L-HPC LH31, manufactured by Shin-Etsu Chemical Co., Ltd.), erythritol (Niken Chemical Co., Ltd.) Made) 737 g of vertical granulator F
It mixed with M-VG-25 (made by Paulec Co., Ltd.). To this, 500 g of a 10% aqueous ethanol solution containing 13 g of aspartame was added and kneaded, dried with a fluidized bed dryer WSG-5 type (manufactured by Okawara Seisakusho Co., Ltd.), and sized with a sieve of 30 and 150 mesh to 30-. A 150 mesh fine granule was produced.

Test Example 4 With respect to the fine granules and granules obtained in Examples 13 to 16 and Comparative Examples 9 to 10, a bitterness test and a dissolution test were carried out on ibuprofen by the following test methods. The results are shown in Table 4.

Test method Bitterness test: The amount of ibuprofen equivalent to 150 mg was contained in the mouth, and the time for feeling the stimulating bitterness of ibuprofen was measured. Dissolution test: Paddle method 100 rpm Test liquid: JP 2 liquid (p
H6.8)

[0055]

[Table 4]

From Table 4, Examples 13 to 16 of the present invention are
It can be seen that the unpleasant taste of ibuprofen is obviously suppressed more than in Comparative Examples 9 to 10.

Claims (1)

[Claims] 1. An oral preparation obtained by wet granulation of a composition containing a drug and 30% by weight or more of a water-swellable substance in the composition with water or hydrous alcohol.