JP2000191517A - Granular composition whose unpalatable taste is masked and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain the subject composition capable of effectively and easily masking an unpalatable taste such as bitter, acidic or astringent taste to correct the taste by adding a taste-remedial agent to a component having the unpalatable taste, applying shear forces to the mixture and then granulating the product in a dry state. SOLUTION: This granular composition whose unpalatable taste is masked is obtained by applying shear forces to a mixture of (A) a component having an unpalatable taste with (B) a taste remedial agent and then granulating the obtained particles (preferably in a dry state). The composition is preferably further mixed with (C) a wax component. The composition may be obtained by a method comprising adding the component C to the mixture of the components A and B, applying shear forces to the mixture and then granulating the product in a dry state or a method comprising applying shear forces to the mixture of the components A and B, granulating the product in a dry state, and then adding and mixing the component C with the granules. Thereby, the excellent masking effect is obtained, and the good control in the change of the corrected taste with the passage of time can be expected. Even when the amount of the wax component is reduced, the effect can sufficiently be exhibited.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention is excellent in the effect of suppressing the unpleasant taste felt in the mouth and its effect is continued, especially when the active ingredient such as pharmaceuticals has strong bitterness, acidity, astringency, etc. The present invention relates to a granulated composition whose unpleasant taste is effectively and continuously masked, and a method for producing the same.

[0002]

2. Description of the Related Art When a physiologically active ingredient is used as a solid preparation, the unpleasant taste peculiar to the physiologically active ingredient often deteriorates the ingestibility of the preparation.
Particularly for children, when a bioactive ingredient having an unpleasant taste such as bitterness, acidity, astringency, etc. is blended, there are problems such as refusal of dosing or taking with a large amount of water. .

[0003] Generally, a solid preparation for internal use is prepared as a granule after previously mixing or appropriately granulating a physiologically active ingredient and an excipient, and further comprising a binder, a disintegrant, a disintegration aid,
Excipients, lubricants and the like are added and the mixture is compression-molded to prepare tablets.

[0004] In these general-purpose preparations, it is desired to reduce the amount of various additives in view of miniaturization in portability and safety considerations. There is a demand for a formulation that not only exerts its effects, but also enhances usability and palatability.

[0005] In response to these requirements, a method of coating the surface of a physiologically active ingredient and suppressing the dissolution of the physiologically active ingredient in the mouth to reduce unpleasant taste is disclosed in JP-A-63-301815 and JP-A-63-301815. JP-A-61-152623, JP-B-64-5
No. 004, for example. However, in any of these methods, the release of the active ingredient in the living body may vary, so there is a problem in application to a preparation requiring precise dissolution performance, and a complicated process is required for the preparation of the active ingredient. And the necessity of using an organic solvent.

Further, a method of masking by adding magnesium sulfate has been proposed in Japanese Patent Application Laid-Open No. 25528/1990, but a small amount of the effect of adding magnesium sulfate cannot always be expected to provide a sufficient flavoring effect. . On the other hand, Japanese Patent Application Laid-Open No. 61-69729 proposes a method of enclosing a physiologically active component, but when the amount of the physiologically active component is large, a larger amount of the host component is added to the physiologically active component. Cyclodextrin is required. This leads to an increase in the total amount of the preparation, which leads to worsening of the ingestibility. Furthermore, there are still fundamental problems such as a delay in the elution rate of the encapsulated active ingredient, and there is a serious problem particularly for an active ingredient that requires quick action.

[0007] In recent years, it has been widely known that antipyretics, analgesics, cold medicines and the like are formulated into tablets and granules for use. Excipients such as lactose and mannitol, and disintegrating agents such as carboxymethyl cellulose and crystalline cellulose are added. In particular, for preparations such as chewable preparations that are rapidly disintegrating in the oral cavity, the taste of the active ingredient spreads directly in the mouth, and therefore, in many cases, a sweetener is added to reduce unpleasant tastes such as bitterness. In this case, sucrose is most commonly used as a sweetener, but saccharides such as mannitol and fructose, dipotassium glycyrrhizinate, and saccharin, saccharin sodium, aspartame and the like as synthetic sweeteners are also blended. However, sucrose, mannitol, fructose, xylitol, glucose, etc., are not sufficiently effective even if the amount is increased. The mere compounding of the above sweetener was not a satisfactory method.

The present invention has been made in view of the above circumstances, and provides a granulated composition which has an excellent effect of suppressing an unpleasant taste felt in the mouth and which can perform flavoring more easily, and a method for producing the same. Aim.

[0009]

Means for Solving the Problems and Embodiments of the Invention The present inventors have conducted intensive studies in order to achieve the above object, and as a result, after adding a flavoring agent to a component having an unpleasant taste, the shear force was reduced. In addition, by dry granulation, the unpleasant taste (bitterness, sourness, astringency, etc.) of the component having the unpleasant taste is effectively masked, and further, after applying a shearing force to the mixture. Further, a wax component is added, and a dry granulation is performed after applying a shearing force again, or a wax component is further mixed with a granulated product obtained by subjecting the mixture to shearing and then granulating. By adding a wax component, masking of unpleasant taste can be more effectively achieved.Especially, large amounts of additives, organic solvents, etc. can be used without requiring expensive equipment and complicated steps. Unpleasant in the mouth, even without It is possible to obtain a granulated composition which can easily and continuously improve the flavor by suppressing the dissolution property of the component having the same, and can maintain good flavor even when prepared as a solid preparation such as granules and tablets. It was found that it was possible.

That is, as apparent from the results of Examples and Comparative Examples described later, the present inventor simply mixes a flavoring agent and a wax component with a component having an unpleasant taste and granulates it. The effect of suppressing the unpleasant taste is not long-lasting, but a flavoring agent is mixed with the component having an unpleasant taste, and after applying a shearing force to the mixture, and granulating, the component having the unpleasant taste is simply added. A granulated product consisting of a granule such as a complex in which these are strongly bonded is obtained, compared with a granulated product obtained by mixing a flavoring agent, and further, the wax component is granulated before granulation. And after again shearing, granulating or mixing the wax component after granulation, the wax component adheres to the granules such as the composite or the granules composed of the granules, In a state of being surrounded, ingredients with unpleasant taste, correction A dense dispersion system containing an ingredient and a wax component is obtained, and as a result, the flavoring agent elutes simultaneously with the elution of the component having an unpleasant taste in the mouth, and the unpleasant taste can be satisfactorily suppressed, giving high palatability. In addition, they have found that a change in taste over time can be suppressed, and have accomplished the present invention.

Accordingly, the present invention provides (1) an unpleasant characteristic characterized by granulating a granule obtained by applying a shearing force to a mixture containing a component having an unpleasant taste and a flavoring agent. A granulated composition having a good taste masked, and (2) a component having an unpleasant taste and a flavoring agent are mixed, and a shear force is applied to the mixture, followed by dry granulation of the obtained granules. A method for producing a granulated composition masked with an unpleasant taste, characterized in that: Here, it is more preferable that the granulated composition according to the above (1) further contains a wax component, and in the production method according to the above (2), the wax is added to the powder or granule. It is more preferable to add and mix the components, apply a shearing force, and then dry-granulate, or dry-granulate the powder and then add and mix a wax component.

Hereinafter, the present invention will be described in more detail. The granulated composition of the present invention comprises a component having an unpleasant taste, a flavoring agent, and if necessary, a wax component. Examples of the ingredient having an unpleasant taste include drugs such as physiologically active ingredients, food additives, and the like, and these can be used alone or in an appropriate combination of two or more.

Examples of the physiologically active ingredient include fursultiamine, ranitidine hydrochloride, cimetidine, naproxen,
Diclofenac sodium, piroxicam, famotidine, azulene, indomethacin, salicylic acid, aspirin, ketoprofen, ibuprofen, isosorbide dinitrate, dihydrocodeine phosphate, ephedrine, ephedrine hydrochloride, phenylpropanolamine hydrochloride, chlorpheniramine maleate, acetaminophen, theophylline, caffeine , Anhydrous caffeine, cephalexin, ampicillin, sulfixazole, sucralfate, various vitamins such as riboflavin and ascorbic acid, minerals, amino acids, peptides and proteins (e.g., insulin, vasopressin, interferon, urokinase, serathiopeptidase, Somatostatin) and the like.

[0014] As the food additive, thiamine mononitrate, riboflavin, pyridoxine hydrochloride, ascorbic acid, vitamin B _12, folic acid, calcium pantothenate, potassium chloride,蠣殻end, niacinamide, biotin, seaweed powder, nicotinamide , Cyanocobalamin, precipitated calcium carbonate, anhydrous calcium hydrogen phosphate, magnesium carbonate, brewer's yeast, chrysanthemum, butterbur, shimeji,
Examples include spinach-derived plant fibers and compounding ingredients for supplements (tablets, jellies, bars, flakes, and granules).

The component having an unpleasant taste described above is not particularly limited in its shape, particle size, etc., but it is preferable to match the particle size with the particles of the flavoring agent described later. Varies depending on the shape of the particles of the component having
0 μm, especially 1 to 50 μm, preferably 1 to 30 μm
m, more preferably in the range of 1 to 20 μm.
In the case of the present invention, the particle size can be confirmed by sieving in accordance with the particle size test described in the Japanese Pharmacopoeia, and for example, the ratio of fine particles having a particle size of about 1 to 50 μm is large. In this case, it is preferable to perform the measurement by a particle size distribution measurement using a laser light scattering method.

When the particle size is less than 1 μm, the scattering property is high, the content is uniform during granulation, selective adsorption by static electricity,
Problems such as re-aggregation may occur. On the other hand, when the particle diameter is 3
If it exceeds 00 μm, it takes too much processing time to make it uniform in the formulation system, which may not be efficient. For fibrous materials such as crude drugs, for example, after pre-processing alone so that the particle size is in the above range, and mixed with a flavoring agent as described below, the efficiency of subsequent processing Can be achieved.

In the present invention, the flavoring agent includes a component having a sweet taste, a component having a weak acidity, a component having an umami taste, and a component acting on a taste receptor.
Listed products such as pharmaceuticals and food additives outside of the Japanese Pharmacopoeia can be suitably used. Specifically, examples of components having a sweet taste include sugars such as sucrose, fructose, glucose, lactose, reduced maltose, and saccharin. , Saccharin sodium, aspartame, and the like; natural sweeteners such as glycyrrhizic acid, dipotassium glycyrrhizinate, and thaumatin; and sugar alcohols such as lactitol, maltitol, sorbitol, and erythritol.

The component having a weak acidity includes, for example, a citrus sour agent (including a flavor), tartaric acid, malic acid,
Citric acid and the like can be mentioned. Examples of the component having a taste include inosinic acid, sodium glutamate and the like.
Examples of the component that acts on the taste receptor and masks it include enzymatically degraded lecithin.
These components can be used alone or in an appropriate combination of two or more.

In the present invention, the amount of the flavoring agent is as follows:
It is appropriately selected depending on the solubility of the component having an unpleasant taste in water and the degree of the taste. Usually, 0.1 to 150% (% by weight, hereinafter the same) with respect to the amount of the component having an unpleasant taste,
Preferably 0.5 to 100%, more preferably 1 to 10
A range of 0% is preferable, and if it is less than 0.1%, a sufficient masking effect may not be obtained.
When the amount exceeds the above range, a large amount of the composition is required in order to take an effective amount of the drug, and there is a concern that the preparation becomes large.

As the wax component of the present invention, higher fatty acids and higher fatty acid esters which are solid at about room temperature but soften by heating can be used. Products listed in the Japanese Pharmacopoeia, pharmaceuticals outside the Japanese Pharmacopoeia, food additives, etc. are suitable. Specific examples of such components include higher fatty acids such as stearic acid, myristic acid, palmitic acid and linoleic acid, and higher fatty acid esters such as cocoa butter and hard fat. These can be used alone or in an appropriate combination of two or more.

In the present invention, the wax component is blended as required. When the wax component is blended, the amount of the wax component depends on the solubility of the component having an unpleasant taste in water and the degree of taste. Although it is appropriately selected, it is usually 5 to 150%, preferably 15 to 100%, more preferably 35 to 80% based on the amount of the component having an unpleasant taste.
The following range is preferable. If the amount of the wax component is too small, the effect of the wax component may not be sufficiently obtained.If the amount is too large, the processability is reduced, and the dissolution of the drug is also deteriorated. In some cases. In addition, for the same reason, the total blending amount with the flavoring agent is 1 to 40% with respect to the whole composition,
The range is preferably from 3 to 20%, more preferably from 5 to 15%.
Flavoring agent: wax component (weight ratio) = 1: 1 to 1:15,
It is more preferable that the ratio is 1: 2 to 1: 6.

The granulated composition of the present invention can be prepared by blending the above-mentioned flavoring agent with the above-mentioned ingredient having an unpleasant taste, applying a shearing force, and then performing dry granulation. When blending, the method of blending is not particularly limited, and for example, it may be blended with the above-mentioned components together with a flavoring agent, and a shearing force may be applied.However, a shearing force is applied to a mixture containing the above-mentioned components and the flavoring agent. After the addition, add the wax component before granulation, mix and apply the shearing force again to the whole, then granulate or add the wax component after granulation, and use a usual method so that the whole becomes uniform. Mixing is more preferable, especially when the above-mentioned ingredient having an unpleasant taste and the above-mentioned flavoring agent are each not melted by shearing, they are mixed in advance, and after adding a shearing force, further mixing the above-mentioned wax component. do it When shear the whole, it is more effective.

In the present invention, in the shearing treatment, the powder particles are rotated and flown in a high-speed rotating blade, passed through a disk having a pendulum-shaped hammer mounted around the disk while being rotated at a high speed, or the powder particles are dispersed. It can be carried out by grinding or by a method in which suspended particles collide with each other in a gas circulating at a high speed.

The device used for the shearing treatment may be any device having the above-mentioned mechanism. Examples of commercially available devices include a stirring mixer (Fukae Kogyo), a turbo mill (Turbo Kogyo), A sample mill (manufactured by Fuji Paudal), a jet mill (manufactured by Freund Corporation), a mechanomill (manufactured by Okada Seiko), and the like can be given.

These devices can be appropriately selected depending on the type of the processing material and the like. For example, when performing a shearing treatment of a material that does not melt at the time of shearing, a sample mill or the like is suitable. When a shearing treatment is performed after adding a material to be melted, a stirrer-type mixer or the like is preferable. The device to be used can be appropriately selected.

In the present invention, the method of shearing treatment is not particularly limited, and the shearing treatment can be carried out by a method employing the usual setting conditions of the above-mentioned equipment. For example, when a sample mill is used, the shearing treatment is performed at 20,000 rpm at 5 to 5,000 rpm. When using a stirring type mixer for about 10 minutes, the shearing blade (chopper) 30
0 to 3,000 rpm, main blade (agitator) 100 to
Processing conditions of 800 rpm for about 1 to 15 minutes can be exemplified, but the shearing treatment of the present invention is not limited to such processing conditions.

In the case of the present invention, known methods such as melt extrusion granulation, tumbling granulation, fluidized bed granulation and roll compression granulation can be used as the granulation method. The method is preferable, and in particular, the dry roll compression granulation method is more preferable.

The granulated composition of the present invention may be prepared, for example, as granules or fine granules, or the granules or fine granules may be further tableted by a conventional method to give oral tablets, chewable tablets, troche tablets, It can be prepared as tablets such as buccal tablets and solid preparations such as capsules and sachets. Processing as food is also possible.

In the case of the present invention, when granulating or tableting, additives usually used as needed in the composition of the present invention, such as lubricants, binders, coating agents, excipients, disintegrants, It is possible to freely mix a disintegration assistant or the like alone or a plurality of types within a range that does not affect the disintegration aid. Specific examples of the optional additive include the following components. In addition,
These additives can be appropriately added as long as the effects of the present invention are not hindered.

Lubricants: gum arabic, cacao butter, carnauba wax, hydrous silicon dioxide, dried aluminum hydroxide gel, glycerin, magnesium silicate, liquid paraffin, crystalline cellulose, sucrose fatty acid ester, stearyl alcohol, stearic acid, gelatin, Lactose, white sugar,
Hydroxypropylcellulose, hydroxypropylmethylcellulose, fumaric acid, beeswax, etc. Binder: hydroxypropylcellulose (degree of substitution 53.
4-77.5%), methylcellulose, gelatin, polyvinylpyrrolidone, partially pregelatinized starch, etc. Coating agent: glycerin, liquid paraffin, silicone resin, stearic acid, gelatin, sorbitol, corn oil, lactose, polyvinyl alcohol, macrogol, methacryl Acid copolymer, calcium hydrogen phosphate, sodium hydrogen phosphate, etc. Excipients: gum arabic, ethyl cellulose, kaolin,
Cocoa butter, fructose, silicon dioxide, xylitol, citric acid or its salts, crystalline cellulose, stearic acid or its salts, dextran, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, macrogol, calcium hydrogen phosphate, sodium hydrogen phosphate Disintegrant: cellulose or a derivative thereof, starch or a derivative thereof, etc. Disintegration aid: cellulose or a derivative thereof, stearic acid,
Sodium hydrogen carbonate, hydroxypropyl cellulose, etc.

[0031]

The granulated composition of the present invention has an excellent effect of suppressing unpleasant taste felt in the mouth and has a good taste. Particularly, when a wax component is blended, a component having an unpleasant taste and a flavoring agent are added. Elution occurs simultaneously, so that an excellent masking effect can be obtained, and not only the temporal change of good flavor can be controlled, but also the effect of the wax component blending can be reduced even if the amount of the wax component used is reduced. It can be obtained satisfactorily and can be prepared with simple and inexpensive equipment and processes. It can be prepared as granules and fine granules, or these granules and fine granules can be further taken orally, Tablets such as tablets, troches and buccal tablets, solid preparations such as capsules and sachets, or can be widely prepared as foods.Especially even in the case of chewable preparations, a good masking effect can be obtained. A.

[0032]

EXAMPLES The present invention will be described below in detail with reference to Examples and Comparative Examples, but the present invention is not limited to the following Examples. In the following examples, the physiologically active substance used as a component having an unpleasant taste was coarsely pulverized with a suitable pulverizer as necessary, and then passed through a 300 μm sieve in advance.

Example 1, Comparative Example 1 Granules having the following composition were prepared by the following method.

[Composition] Example 1, Comparative Example 1 Acetaminophen 1000 g Aspartame 100 g Erythritol 730 g Lactose 570 g Hard fat 400 g Total 2800 g

First, 1,000 g of acetaminophen,
100 g of aspartame and 730 g of erythritol were weighed, and were weighed with a V-type mixer (V-5; manufactured by Tokushou Co., Ltd.).
After mixing for minutes, shearing was performed for 10 minutes at 20,000 rpm in a sample mill (KIIW1; manufactured by Fuji Paudal). This is mixed with a stirring mixer (FS-10).
J; Fukae Kogyo Co., Ltd.), lactose 570 g and hard fat (trade name “Pharmazol”; manufactured by NOF Corporation) 400
g, and a shearing blade (chopper) of 2,000 rpm,
The main blade (agitator) was mixed at 100 rpm for 5 minutes, and subjected to a shearing treatment again. Furthermore, a dry roll compression granulator (WP-50N type; ALEXANDERWERK)
And then granulated by roll compression at 50 Klbf / in ² using the above method, and then sized to conform to the particle size test of granules according to the Japanese Pharmacopoeia to obtain the granules of Example 1.

Further, with the same composition as in Example 1, 1,000 g of acetaminophen, 100 g of aspartame, 730 g of erythritol, 570 g of lactose and 400 g of hard fat (the same as above) were weighed, and a ribbon mixer (R-5) was used.
After mixing for 10 minutes, dry roll compression granulator (WP-50N type; ALEXANDE)
After granulation by roll compression at 50 Klbf / in ² using RWERK (product of RWERK), the granules were sized so as to conform to the granule size test of the Japanese Pharmacopoeia to obtain granules of Comparative Example 1.

Each of the obtained granules was dissolved in the mouth by six evaluators, and the taste over time was evaluated according to the following criteria. Table 1 shows the results. +: Bitter to very bitter ±: slightly bitter −: not bitter

[0038]

[Table 1]

From the results shown in Table 1, it was confirmed that the granules according to the present invention (Example 1) continue to suppress the bitterness of the physiologically active ingredient.

Example 2, Comparative Example 2 Granules having the following composition were prepared by the following method.

[Composition] Example 2, Comparative Example 2 Ethenzamide 1000 g Dipotassium glycyrrhizinate 100 g Xylitol 730 g Lactose 570 g Stearic acid monoglyceride 400 g Total 2800 g

First, 1,000 g of ethenzamide, 100 g of dipotassium glycyrrhizinate and 730 xylitol
g was weighed and mixed for 10 minutes by a V-type mixer (V-5; manufactured by Tokushou Kogyo Co., Ltd.), and then the sample mill (KIIW1; manufactured by Fuji Paudal Company) was used for 10 minutes at 20,000 rpm. Shearing was performed. This was mixed with a stirring mixer (FS-1).
0J; Fukae Kogyo Co., Ltd.), 570 g of lactose and 400 g of stearic acid monoglyceride were added, and the shearing blade (chopper) 2,500 rpm and the main blade (agitator) 1 were added.
The mixture was mixed at 50 rpm for 12 minutes and subjected to a shearing treatment again. Next, a dry roll compression granulator (WP-50N)
50 Kl using ALEXANDERWERK)
After granulation by roll compression at bf / in ² , the granules were sized to conform to the granule size test of the Japanese Pharmacopoeia to obtain the granules of Example 2.

The composition was the same as that of Example 2 except that 1,000 g of ethenzamide and 100 g of dipotassium glycyrrhizinate were used.
g, xylitol 730 g, lactose 570 g, and stearic acid monoglyceride 400 g were weighed and placed in a ribbon mixer (R-5; manufactured by Tokusui Seisakusho), mixed for 15 minutes, and then dried by a dry roll compression granulator (WP-50N). ; ALEX
50Klbf / in ²
Then, the mixture was roll-compressed and granulated, and then sized to conform to the test for the particle size of granules according to the Japanese Pharmacopoeia to obtain granules of Comparative Example 2.

The taste of the obtained granules was evaluated over time in the same manner as in Example 1 and Comparative Example 1. Table 2 shows the results.

[0045]

[Table 2]

From the results shown in Table 2, it was confirmed that the granules according to the present invention (Example 2) continue to have the effect of suppressing the bitter taste of the physiologically active ingredient.

Example 3, Comparative Example 3 Granules having the following composition were prepared by the following method.

[Composition] Example 3, Comparative Example 3 Ibuprofen 500 g Anhydrous caffeine 500 g Saccharin sodium 50 g Saccharin 50 g Crystalline cellulose 130 g Carboxymethyl cellulose 500 g Anhydrous lactose 470 g Hydroxypropyl methylcellulose 200 g Stearic acid 400 g Total 2800 g

First, ibuprofen was roughly crushed for 3 minutes using a stirring type mill (Henschel mixer 10 L; manufactured by Mitsui Miike Kakoki Co., Ltd.), and 500 g, 500 g of anhydrous caffeine, 50 g of saccharin sodium and 50 g of saccharin were weighed. , V-type mixer (V-5; manufactured by Tokushou Co., Ltd.) for 10 minutes, and then mixed with a sample mill (KIIW).
1; manufactured by Fuji Paudal Co., Ltd.) at 20,000 rpm for 10 minutes. This was taken in a stirring type mixer (FS-10J; manufactured by Fukae Kogyo KK), and 130 g of crystalline cellulose, 500 g of carboxymethyl cellulose, 470 g of anhydrous lactose, and 200 g of hydroxypropyl cellulose were added.
g and stearic acid (400 g) were added, and the shearing blade (chopper) was 2,800 rpm and the main blade (agitator) was 25.
The mixture was mixed at 0 rpm for 10 minutes and subjected to a shearing treatment again. Next, a dry roll compression granulator (WP-50N)
50 Kl using ALEXANDERWERK)
After granulation by roll compression at bf / in ² , the granules were sized to conform to the granule size test of the Japanese Pharmacopoeia to obtain the granules of Example 3.

Further, with the same composition as that of Example 3, ibuprofen was roughly crushed for 3 minutes by using a stirring-type mill (Henschel mixer 10 L; same as above), and 500 g thereof, 500 g of anhydrous caffeine, 50 g of sodium saccharin,
Saccharin 50 g, crystalline cellulose 130 g, carboxymethyl cellulose 500 g, anhydrous lactose 470 g, hydroxypropyl cellulose 200 g and stearic acid 4
After weighing 00g, taking it into a ribbon type mixer (R-5; manufactured by Tokusui Seisakusho) and mixing for 10 minutes, a dry roll compression granulator (WP-50N; ALEXANDERWERK).
Roll compression at 50 Klbf / in ² using
After granulation, the granules were sized to conform to the granule size test of the Japanese Pharmacopoeia to obtain granules of Comparative Example 3.

With respect to the obtained granules, the taste over time was evaluated in the same manner as in Example 1 and Comparative Example 1. Table 3 shows the results.

[0052]

[Table 3]

From the results shown in Table 3, it was confirmed that the granules according to the present invention (Example 3) continue to suppress the bitterness of the physiologically active ingredient.

Example 4, Comparative Example 4 Granules having the following composition were prepared by the following method.

[Composition] Example 4, Comparative Example 4 Acetaminophen 50 g Dihydrocodeine phosphate 0.1 g Thomatin 5 g Amalty 5 g Low-substituted hydroxypropylcellulose 13 g Carboxymethylcellulose 50 g Anhydrous lactose 47 g Hydroxypropyl Methylcellulose 20 g Cocoa butter 39.9 g Total 230 g

First, 50 g of acetaminophen, 0.1 g of dihydrocodeine phosphate, thaumatin (thaumatin)
5 g and amalty 5 g were weighed and preliminarily pulverized with a home coffee mill for 10 minutes, and then jet-milled (TJ6).
0; manufactured by Freund Corporation) under an air pressure of 8 kg / cm ² for 45 minutes. This was taken in a small stirring type mixer (Mechanomiru; manufactured by Okada Seiko), and 13 g of low-substituted hydroxypropylcellulose, 50 g of carboxymethylcellulose, 47 g of anhydrous lactose, 20 g of hydroxypropylcellulose and 39.9 g of cocoa butter were added.
The plate was treated at 00 rpm for 10 minutes and subjected to a shearing treatment again. Then, a dry roll compression granulator (WP-50N type;
50Klbf using ALEXANDERWERK)
Example 4 After roll-pressing at / in ² and granulating, the granules were sized to conform to the granule size test of the Japanese Pharmacopoeia.
Granules were obtained.

The same composition as in Example 4 was used except that 50 g of acetaminophen, 0.1 g of dihydrocodeine phosphate,
5 g of thaumatin and 5 g of amalti, 13 g of low-substituted hydroxypropylcellulose, 50 g of carboxymethylcellulose, 47 g of anhydrous lactose, 20 g of hydroxypropylcellulose and 39.9 g of cocoa butter were weighed, and a small mixer (V-5; manufactured by Tokuju Seisakusho) ) And mixed for 10 minutes, then dry roll compression granulator (WP-50N type; A
LEXANDERWEK) and 50Klbf /
The granules were roll-compressed in ² and granulated, and then sized to meet the granule size test of the Japanese Pharmacopoeia to obtain granules of Comparative Example 4.

The taste of the obtained granules over time was evaluated in the same manner as in Example 1 and Comparative Example 1. Table 4 shows the results.

[0059]

[Table 4]

From the results shown in Table 4, it was confirmed that the granules according to the present invention (Example 4) continue to suppress the bitterness of the physiologically active ingredient.

Example 5, Comparative Example 5 To each of 2,000 g of the granules obtained in Example 3 and Comparative Example 3, 28 g of magnesium stearate was added, and a V-type mixer (manufactured by Tokuju Kogyo Co., Ltd.) After mixing for 5 minutes with a rotary tableting machine (L-41; manufactured by Hata Iron Works), diameter 10 mm,
Tablets having an average weight of 150 mg were prepared.

[Composition] Example 5, Comparative Example 5 Ibuprofen 357 g Anhydrous caffeine 357 g Saccharin sodium 36 g Saccharin 36 g Crystalline cellulose 93 g Carboxymethyl cellulose 357 g Lactose anhydride 336 g Hydroxypropyl methylcellulose 143 g Stearic acid 285 g Stearic acid Magnesium 28 g Total 2028 g

Each of the obtained tablets was chewed in the mouth by six evaluators, and the taste over time was evaluated according to the following criteria. Table 5 shows the results. +: Bitter to very bitter ±: slightly bitter −: not bitter

[0064]

[Table 5]

From the results shown in Table 5, it was confirmed that even when the granules according to the present invention were incorporated into chewable tablets (Example 5), the effect of suppressing the bitterness of the physiologically active ingredient was continued.

Claims (5)

[Claims] An unpleasant taste-masked composition obtained by applying a shearing force to a mixture containing a component having an unpleasant taste and a flavoring agent to granulate the obtained granules. Grain composition. 2. The composition according to claim 1, further comprising a wax component.
A granulated composition wherein the unpleasant taste described is masked. 3. An unpleasant taste masking, comprising mixing a component having an unpleasant taste and a flavoring agent, applying a shearing force to the mixture, and subjecting the obtained granules to dry granulation. A method for producing a granulated composition. 4. The method for producing a granulated composition having an unpleasant taste masked according to claim 3, wherein a wax component is added to the granules, mixed, and further subjected to a shearing force, followed by dry granulation. 5. The method for producing a granulated composition having an unpleasant taste masked according to claim 3, wherein a wax component is added and mixed after dry granulation of the granules.