JP2001019635A - Microcapsule containing sparingly water-soluble granule with bitterness as core substance and its production, and solid preparation containing such microcapsule - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain microcapsules so designed that a powdery bulk drug intended for a core substance can be directly put to microencapsulation without the need of granulation, and as the sparingly water-soluble granules having bitterness when put to internal use, is not released from the microcapsules, thereby enabling such bitterness to be suppressed, and furthermore, smooth in tongue touch in the form of tablets (in particular, chewable ones), and to obtain a solid preparation containing such microcapsules. SOLUTION: The microcapsules each <=150 μm in granular size are obtained by coating sparingly water-soluble granules having bitterness with a water- insoluble polymeric compound; wherein the above sparingly water-soluble granules preferably consist of a composition comprising caffeine, caffeine anhydride, or isopropylantipyrine or a mixture thereof.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a microcapsule containing a hardly water-soluble powder having a bitter taste as a core substance, a method for producing the same, and a solid preparation containing the microcapsule. The poorly water-soluble powder having a bitter taste is not released from the inside of the microcapsule, the bitterness can be suppressed, and the microcapsule having a good texture when formed into a tablet (especially a chewable tablet) and a method for producing the same And so on.

[0002]

2. Description of the Related Art Conventionally, in order to reduce the bitterness of poorly water-soluble powders having strong bitterness, such as caffeine, isopropylantipyrine and ibuprofen, microencapsulation using an appropriate coating agent has been carried out. Bitterness has been reduced. As a technique for such microencapsulation, a spray coating method of spraying a core material with a coating agent using a fluidized bed granulation coating apparatus, a swirling type fluidized bed granulation coating apparatus, a centrifugal flow type coating apparatus, and the like is often performed. Have been done.

[0003] However, in the spray coating method, in many cases, it is necessary to use granules which have been artificially granulated in advance as the core material, so that the particle size of the core material becomes large, and during the spray coating, Because the particle size of the granular material becomes considerably large due to the coating agent,
The particle size of the obtained microcapsules is about 150 μm (about 1 μm).
(00 mesh). And when taking such a large particle size microcapsule, not only a rough feeling occurs in the oral cavity,
Due to the large particle size of the core substance, the microcapsules themselves are destroyed by mastication, and a hardly water-soluble powdery substance having a strong bitterness, which is a core substance, may be released, which may cause a noticeable bitter taste. .

[0004] When a tablet is prepared using microcapsules having a large particle size, the microcapsules are mixed with an appropriate excipient and tableted. Therefore, it is not only difficult to mix with other active ingredients and excipients, granulation, tableting, etc., but also the microcapsules themselves may be destroyed during tableting, which also causes There may be noticeable bitterness within. Therefore, microcapsules having the smallest possible particle size are desired.

[0005] On the other hand, chewable tablets, which are particularly large in dosage form among tablets, are often taken not only directly without water but also by chewing in the mouth. For this reason, the above-mentioned microcapsules are required to suppress bitterness particularly when the active ingredient has a bitter taste in chewable tablets prepared using the microcapsules. Is desired.

[0006]

DISCLOSURE OF THE INVENTION The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a method of converting a powdered drug substance into a microparticle as it is without granulating the drug to obtain a nuclear substance. It can be provided for encapsulation, and when taken, the poorly water-soluble powder having a bitter taste is not released from the inside of the microcapsule, the bitterness can be suppressed, and the tablet is formed into a tablet (particularly a chewable tablet). It is an object of the present invention to provide a microcapsule having a good texture, a method for producing the same, and a solid preparation containing the microcapsule.

[0007]

Means for Solving the Problems A microcapsule which solves the above-mentioned problems is a microcapsule obtained by coating a hardly water-soluble powdery substance having a bitter taste with a water-insoluble polymer compound and has a particle diameter of 150 μm or less. There is a feature.

[0008] The microcapsules as described above are:
It is produced by microencapsulation of a poorly water-soluble powder dispersion in which a poorly water-soluble powder having a bitter taste and a water-insoluble polymer compound are dispersed in water by spray drying. The hardly water-soluble powder dispersion is preferably prepared by adding a hardly water-soluble powder having bitterness to an aqueous dispersion in which a water-insoluble polymer compound is dispersed, and dispersing the same. In addition, it is preferable that at least one plasticizer selected from the group consisting of triethyl citrate, acetylated monoglyceride, and triacetin is blended into the poorly water-soluble powder dispersion.

The poorly water-soluble powdery substance having a bitter taste is preferably caffeine, anhydrous caffeine, or isopropylantipyrine, or a poorly water-soluble powdery-particle-containing composition containing these. Further, the glass transition temperature of the water-insoluble polymer compound is preferably 20 ° C. or more,
Ethyl cellulose is mentioned as such a water-insoluble polymer compound.

[0010] Further, a solid preparation according to the present invention, which is another means for solving the above problems, contains the above microcapsules. The solid preparation is preferably a chewable tablet having a hardness of 5 kg to 10 kg and a dosage form of 500 mg or more.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will be described below in detail focusing on its manufacturing method. As used herein, the term "bitterness" refers to causing an unpleasant taste to be felt, and in addition to the so-called normal "bite," a crisp sensation on the tongue, throat, and mucous membranes in the oral cavity. It also includes the stimulus that causes it.

In the present invention, first, a hardly water-soluble powder dispersion in which a hardly water-soluble powder having a bitter taste and a water-insoluble polymer compound are dispersed in water is prepared. It may be prepared by adding and dispersing a poorly water-soluble powder having a bitter taste to purified water and a water-insoluble polymer compound, or a commercially available water-insoluble polymer compound dispersed in water. A slightly water-soluble powder having a bitter taste may be added to the dispersion to prepare a poorly water-soluble powder dispersion. In addition, a dispersing agent is preferably added to the poorly water-soluble powder dispersion to promote the dispersion of the poorly water-soluble powder and the water-insoluble polymer compound.
As the dispersant, any suitable surfactant can be used, and cetanol and metal lauryl sulfate are particularly preferable.

[0013] Since the powdery substance as the core material of the microcapsule according to the present invention eventually becomes the core material of the microcapsule, it should not be dissolved in the poorly water-soluble powdery particle dispersion. That is, the powder should not be readily soluble in water. Examples of such poorly water-soluble powdery particles having bitterness used in the present invention include caffeine, anhydrous caffeine, isopropylantipyrine, ibuprofen, biferamine hydrochloride and the like. Among them, particularly from the viewpoint that the bitter taste is remarkably suppressed by the present invention, the microcapsules according to the present invention contain caffeine and anhydrous caffeine as hardly water-soluble powders having a bitter taste as a core substance. Or isopropylantipyrine.

The particle size of the poorly water-soluble powder may be any size as long as it is suitable for being a core material in the microcapsules. The particle size of the granules is preferably from about 20 μm to about 100 μm, and from about 30 μm to about 70 μm
The following is more preferred.

In the present invention, as long as the particle size is within the above range, it is not necessary to produce the core material by granulation. That is, in many cases, unlike the spray coating method in which it is necessary to use granules previously granulated as the core substance, in the production method according to the present invention, as a poorly water-soluble powder having a bitter taste, powder Drug substance can be used as is. Therefore, since it is not necessary to manufacture the core material by granulation in advance, it is possible to reduce the particle size of the obtained microcapsules. In addition, as long as the particle diameter of the microcapsules falls within the above-described range, the drug-containing poorly water-soluble composition obtained by mixing the core substance and a suitable excipient may be used as the poorly water-soluble powder. . In the present specification, unless otherwise specified, the term "poorly water-soluble powder" includes the drug-containing poorly water-soluble composition as described above.

As the water-insoluble polymer compound, for example,
Ethylcellulose derivatives such as ethylcellulose and carboxymethylethylcellulose, and polyacrylic acids such as ethyl methacrylate acrylate copolymer, dimethylaminoethyl methacrylate methyl methacrylate copolymer, aminoalkyl methacrylate copolymer, ethyl acrylate methyl methacrylate methyl copolymer Derivatives, as well as polyvinyl acetal diethylaminoacetate, hydroxypropylmethylcellulose acetate succinate, hydroxypropylmethylcellulose phthalate, cellulose acetate phthalate and the like. Among them, the bitterness of the poorly water-soluble powder as a core substance is more strongly suppressed, and particularly when caffeine, anhydrous caffeine, or isopropylantipyrine is used as the poorly water-soluble powder, the effect is remarkable. From the viewpoint that bitterness can be suppressed, it is preferable to use ethyl cellulose. When ethyl cellulose is used, the substitution degree is preferably 2 or more. Ethyl cellulose having a degree of substitution of less than 2 may exhibit water solubility.

The particle size of the water-insoluble polymer compound is not particularly limited as long as the film can form a film on the surface of the hardly water-soluble powdery material serving as a nucleus material when microencapsulation and the bitterness can be suppressed. However, specifically, it is preferably about 0.01 μm or more and about 1 μm or less, and more preferably about 0.1 μm or more and about 0.3 μm
The following is preferred.

Lower alcohols (eg, methanol, ethanol, etc.), halogenated alkanes (eg, dichloromethane, chloroform, chloroethane, trichloroethane, carbon tetrachloride), ethyl acetate, ethyl ether, cyclohexane, benzene, n-hexane, toluene, etc. If a liquid organic compound is used as a dispersion medium, the poorly water-soluble powder will be dissolved and not only cannot be used as a nuclear substance, but also this liquid organic compound may cause an adverse effect on the human body. It is necessary to remove the liquid organic compound remaining in the obtained microcapsules. In addition, since the boiling point of such a liquid organic compound is lower than that of water, and the liquid organic compound concerned may explode when heated in the manufacturing process, the manufacturing apparatus requires an explosion-proof structure. There is a disadvantage that the management of the liquid organic compound becomes complicated in the process. From the above, in the present invention, by using the aqueous dispersion as described above, the poorly water-soluble powder does not dissolve,
Microcapsules that have little adverse effect on the human body can be easily obtained. Furthermore, since the manufacturing apparatus can be simplified, the microcapsules according to the present invention can be manufactured safely.

An aqueous dispersion in which the water-insoluble polymer compound is dispersed is commercially available. Examples of the aqueous dispersion of ethyl cellulose include Aquacoat (available from Asahi Kasei Kogyo Co., Ltd.) and Sure Lease (available from Nippon Colorcon Co., Ltd.). Available). The aqueous dispersion of the polyacrylic acid polymer / copolymer includes Eudragit series available from Higuchi Shokai Co., Ltd. Further, purified water may be added to an aqueous dispersion in which such a water-insoluble polymer compound is dispersed, and diluted to use.

The ratio of the hardly water-soluble powder to the water-insoluble polymer compound is determined so long as the hardly water-soluble powder is sufficiently dispersed in the hardly water-soluble powder dispersion and does not adversely affect microencapsulation. Although not particularly limited, it is preferable to use about 20 parts by weight or more and about 720 parts by weight or less of a water-insoluble polymer compound with respect to 100 parts by weight of the hardly water-soluble powder, and about 30 parts by weight or more and about 220 parts by weight or less. It is more preferable to use a water-insoluble polymer compound.

The ratio between the poorly water-soluble powder and water is not particularly limited as long as the water-insoluble polymer compound is sufficiently dispersed in the poorly water-soluble powder dispersion and does not adversely affect microencapsulation. Preferably, about 90 parts by weight or more and about 2000 parts by weight or less of water is used, more preferably about 140 parts by weight or more and about 200 parts by weight or less of water with respect to 100 parts by weight of the poorly water-soluble powder.

About 2 parts per 100 parts by weight of the poorly water-soluble powder
When less than 0 parts by weight of the water-insoluble polymer compound is used, the amount of the water-insoluble polymer compound is too large while the amount of the water-insoluble polymer compound is too small in the hardly water-soluble powder dispersion. Therefore, in the obtained microcapsules, the coating of the water-insoluble polymer compound on the surface of the poorly water-soluble powder, which is the core substance, by the film formation becomes insufficient, and the bitter taste of the poorly water-soluble powder becomes high. In some cases, the compound is not sufficiently shielded by the molecular compound and bitterness is not reduced.

On the other hand, when more than about 720 parts by weight of the water-insoluble polymer compound is used per 100 parts by weight of the poorly water-soluble powder, the water-insoluble polymer in the dispersion of the poorly water-soluble powder is used. Since the amount of the compound is too large, there may be a case where a useless water-insoluble polymer compound which is not coated on the poorly water-soluble powdery material serving as a core substance increases, which is uneconomical.

About 2 parts per 100 parts by weight of the poorly water-soluble powder
When water in excess of 000 parts by weight is used, the amount of water in the poorly water-soluble powdery particle dispersion is remarkably large, which makes it insufficient to evaporate water during microencapsulation. In some cases, a film of the water-insoluble polymer compound is not formed.

For proper microencapsulation, especially when using ethylcellulose or aminoalkyl methacrylate copolymer as a water-insoluble polymer compound, a plasticizer may be added to the poorly water-soluble powdery particle dispersion. preferable. The plasticizer uniformly spreads a large number of water-insoluble polymer compounds attached to the surface of the poorly water-soluble powder, which is a core substance, on the surface.The water-insoluble polymer compound uniformly spreads the poorly water-soluble powder. In addition to coating, to impart flexibility to the film formed of the water-insoluble polymer compound, that is, to form a film in which the water-insoluble polymer compound forms a uniform, soft, and strong film on the surface of the poorly water-soluble granular material. Formulated for If the film formed by coating in the microcapsule is not flexible, the coating may be broken when the microcapsule is subjected to tableting due to its fragility, but as described above, the water-insoluble polymer When the film formed of the compound is given flexibility, the coating is prevented from being destroyed during tableting, which makes it possible to more effectively release the bitterly poorly water-soluble powder from the microcapsules. Can be prevented.

[0026] Such plasticizers include, for example, triethyl citrate, acetylated monoglycerides, and triacetin.

In order to form a more uniform film of the water-insoluble polymer on the surface of the poorly water-soluble powder, it is preferable to use a water-insoluble polymer having a glass transition temperature of 20 ° C. or higher. When a water-insoluble polymer compound having a glass transition temperature of less than 20 ° C. is used, a state in which the water-insoluble polymer compound related to the hardly water-soluble powder that becomes a core material is sticky when microencapsulated. Since the uniform water-insoluble polymer film is not formed, the bitterness of the poorly water-soluble powder cannot be reduced. The diameter may be significantly increased. For this reason, since the microcapsules adhere inside the spray-drying granulation device (spray dryer), not only must the device be cleaned frequently, but also when manufacturing the tablets using the microcapsules, the microcapsules are removed. It may not be possible to mix uniformly.

When a plasticizer is used, the glass transition point of the water-insoluble polymer compound tends to decrease.
In this case, the glass transition point of the water-insoluble polymer compound after adding the plasticizer is preferably 20 ° C. or more. After preparing the poorly water-soluble powder dispersion, the poorly water-soluble powder dispersion is sufficiently stirred to uniformly mix the poorly water-soluble powder and the water-insoluble polymer compound. preferable.

Next, the poorly water-soluble powdery particle dispersion thus prepared is microencapsulated by spray drying. Unlike the spray coating method in which a coating material is sprayed directly on a core material, in the present invention, a core material (that is, a poorly water-soluble powder) and a coating agent (that is, a water-insoluble polymer compound) are previously dissolved in water. Dispersed,
This aqueous dispersion is spray-dried to form microcapsules.

For spray drying, a spray drying granulator (spray dryer) used for producing granules and powders can be used. Spray dryers include a liquid nozzle type, a pressure nozzle type, and a rotating disk type, depending on the shape of the nozzle to which the raw material is sprayed. Among them, the rotating disk type spray is preferred from the viewpoint of easy and reliable spraying. It is preferable to use a dryer.

Various conditions, such as the amount of the hardly water-soluble powder dispersion to be supplied to the spray dryer, depend on the hardly water-soluble powder, the water-insoluble polymer compound, the ratio thereof, and the specifications of the spray dryer. A person skilled in the art can appropriately select, for example, a rotating disk type spray drier (Okawara Kakoki Co., Ltd.) using caffeine as a poorly water-soluble powder and ethyl cellulose as a water-insoluble polymer compound. Made, pilot series L
-8 type), the amount of the hardly water-soluble particulate dispersion to be supplied to the spray dryer is about 1 kg / hour or more and about 3 k.
g / hour or less. The poorly water-soluble powder dispersion is sprayed into the spray dryer, and the water is evaporated inside the spray dryer by hot air, so that a uniform film of the water-insoluble polymer compound is formed on the surface of the poorly water-soluble powder dispersion. Are formed and microencapsulated.

In the present invention, since the poorly water-soluble powder and the water-insoluble polymer compound are once dispersed in an aqueous dispersion and spray-dried, the granular material is compared with the core material produced by granulation. Since the powdered drug substance having a very small diameter can be directly subjected to microencapsulation and the aggregation of coated particles can be prevented, the particle diameter of the obtained microcapsules can be reduced. The particle size of the microcapsules obtained by the production method according to the present invention depends on the particle size of the poorly water-soluble powder which is a core material,
Usually, it is about 20 μm or more and about 150 μm or less, and in many cases, about 25 μm or more and about 100 μm or less.

As described above, the particle diameter of the microcapsules obtained by the method for producing microcapsules according to the present invention described above is compared with that of the microcapsules obtained by the conventional spray coating method, the particle diameter of which exceeds about 150 μm. The water-insoluble polymer compound forms a uniform film and has a uniform coating of the poorly water-soluble powder having a bitter taste. The granules are less likely to be released in the oral cavity, and therefore, even if the microcapsules according to the present invention are taken directly, the bitter taste is hardly felt by the tongue. Furthermore, since the particle size is very small, there is no feeling of roughness in the oral cavity. Further, since the polymer compound forming such a film is insoluble in water, it is not dissolved by saliva in the oral cavity, and therefore, the bitter taste of the poorly water-soluble powder is more effectively suppressed.

Needless to say, the obtained microcapsules may be further coated in order to further reduce bitterness.

The above-mentioned microcapsules according to the present invention may be taken as they are, but are mixed with appropriate excipients from the viewpoint of enhancing compliance by further reducing bitterness and increasing ease of handling. Thereafter, a solid preparation may be prepared by an ordinary method. Examples of the solid preparation include powders, granules, and tablets. The tablet weight per tablet is about 500 mg to about 3000 mg (preferably, about 800 mg to about 1500 mg), and the tableting pressure is about 700 kg. / Cm ² or more about 10
It is preferable that the tablet is a chewable tablet having a hardness of about 5 kg or more and about 10 kg or less by tableting at a rate of 00 kg / cm ² or less. That is, a chewable tablet satisfying the above-mentioned conditions has a very good texture, and even when the tablet is fragmented by mastication, it has a good texture (Japanese Patent Application No.
-113935). Chewable tablets are used by chewing or dissolving in the oral cavity, and are often taken directly without water.Therefore, suppression of bitterness is particularly required, but the microcapsules according to the present invention are poorly water-soluble. It is very useful when used in chewable tablets to prevent the bitterness of the powder from being released in the oral cavity.

Further, since the microcapsules according to the present invention have a very small particle size, when the microcapsules are mixed with excipients and tableted to prepare a solid preparation,
The microcapsules can be uniformly mixed in the composition to be subjected to such tableting, so that the active ingredient (that is, the poorly water-soluble powder) as the core substance in the microcapsules can be uniformed. .

The term "hardness" used in the present specification refers to the pressure at the moment when the tablet disintegrates when the pressure is gradually applied while sandwiching the tablet from the side. Of course, other active ingredients may be added to the tablet. In particular,
Even with the addition of a poorly water-soluble powder and an agent that causes a change in formulation,
Since the poorly water-soluble powder is microencapsulated,
Such a change in the composition can be suppressed.

[0038]

The present invention will now be described in more detail with reference to the following examples, which are used for illustrative purposes only and should not be used for limiting purposes. Example 1 Ethyl cellulose aqueous dispersion containing 87% by weight of ethyl cellulose, 9% by weight of cetanol, and 4% by weight of sodium lauryl sulfate (obtained from Asahi Kasei Corporation, trade name: Aquacoat, glass transition temperature: about 89 ° C.) ) After adding 480 g of water to 840 g and diluting, 600 g of powdered caffeine (obtained from Yatsushiro Pharmaceutical Co., Ltd.) and 80 g of triethyl citrate (obtained from Chugai Trading Co., Ltd., trade name: (Citroflex No. 2 SC-60) was added, and the mixture was sufficiently stirred, and caffeine powder and ethyl cellulose were uniformly dispersed to prepare a caffeine dispersion as a poorly water-soluble powdery particle dispersion.

Next, this caffeine dispersion is charged into a rotating disk type spray dryer (Pilot Series L-8, manufactured by Okawara Kakoki Co., Ltd.) at a rate of 2.26 kg / hour, and then into the spray dryer. While heating the caffeine dispersion liquid by setting the inlet temperature immediately before to 150 ° C., it was spray-dried at a disk rotation speed of 18,000 rpm to obtain fine-grained microcapsules. In addition, the temperature of the outlet from which the obtained microcapsules are discharged is set to 80 ° C.
, And the temperature inside the spray dryer was kept high. The average particle size of the obtained microcapsules is about 30μ.
m to about 40 μm, and the shape of the particles was almost spherical. Ethyl cellulose was uniformly coated as a film on the surface of caffeine grains.

When the obtained fine-grained microcapsules were taken, bitterness was hardly felt, and the bitterness of powdered caffeine was greatly reduced. Before taking the microcapsules, a very small amount of powdered caffeine was licked and found to be extremely bitter.

Example 2 Instead of triethyl citrate,
Microcapsules were prepared in the same manner as in Example 1 except that 40 g of triacetin (obtained from Organic Synthetic Chemicals Co., Ltd., trade name: YUXOL) was used. The particle size of the obtained microcapsules was about 40 μm to about 50 μm, and the shape of the particles was almost spherical. Ethyl cellulose was uniformly coated as a film on the surface of caffeine grains.

When this microcapsule was licked, bitterness was not so much felt, and the bitterness of powdered caffeine was reduced. Note that the microcapsules obtained in Example 2 felt slightly bitter compared to the microcapsules obtained in Example 1.

Comparative Example 1 An aqueous gelatin solution was prepared by adding 40 g of commercially available gelatin to 1360 g of water and sufficiently stirring, and 600 g of powdered caffeine (obtained from Yatsushiro Pharmaceutical Co., Ltd.) was added to the aqueous solution. The mixture was sufficiently stirred to prepare a caffeine dispersion as a poorly water-soluble powder dispersion in which caffeine powder was uniformly dispersed.

Next, this caffeine dispersion was supplied to a rotating disk type spray drier (Okawara Kakoki Co., Ltd., pilot series L-8 type) at 2.052 kg / kg.
Injection was carried out at a rate of time, and fine microcapsules were obtained in the same manner as in Example 1. When the obtained microcapsules were taken, the strong bitterness of caffeine was felt. This is considered to be because the gelatin coating the caffeine grains easily dissolves or swells in saliva in the oral cavity.

[0045]

[Table 1]

(Example of Preparation of Chewable Tablets) 167 g of the fine-grained microcapsules obtained in Example 1 and 603 g of lactose (excipient, obtained from Freund Corporation, trade name:
Dilactose R), 200 g of calcium hydrogen phosphate (excipient, obtained from Fuji Chemical Co., Ltd., trade name: Fujicalin SG), 10 g of aspartame (flavoring agent, obtained from Ajinomoto Co., trade name: PAL SWEET DIET) , 1
0 g of magnesium stearate (obtained from Taihei Chemical Industry Co., Ltd.) and 10 g of coffee micron H80
151 were mixed so as to be sufficiently uniform. Then 800
Compress at a tableting pressure of Kg / cm ² , and
0 mg of chewable tablets were obtained. The hardness of the chewable tablet was about 6.0 Kg, and when the chewable tablet was taken, the tongue was extremely good, and even when the chewable tablet was fragmented by chewing, the tongue was still good.

[0047]

According to the present invention, since the microcapsules are coated with a water-insoluble polymer, they are not dissolved by saliva. For this reason, when the microcapsules according to the present invention are taken, the poorly water-soluble drug having a strong bitterness, which is a core substance, is released from the microcapsules, and the bitterness in the oral cavity is suppressed.

Further, since the poorly water-soluble powder and the water-insoluble polymer compound are once dispersed in an aqueous dispersion and spray-dried, the particle size is extremely large as compared with the core material produced by granulation. In addition, a small powdered drug substance can be directly microencapsulated, and aggregation of coated particles can be prevented, so that the particle size of the obtained microcapsules can be reduced. For this reason, when the microcapsules according to the present invention are taken, a rough feeling is not generated in the oral cavity, and the microcapsules are less likely to be destroyed by mastication, so that the bitter taste is suppressed better. Further, the present invention has an advantage that if the particle size is within a predetermined range, it is not necessary to granulate the drug to make it a nuclear substance.

When the microcapsules according to the present invention are subjected to tableting, the particle diameter of the microcapsules according to the present invention is very small, so that the microcapsules are uniformly mixed in the composition subjected to tableting. Accordingly, the core active ingredient (ie, poorly water-soluble powder) in the microcapsules can be made uniform. In addition, even when it is prescribed together with the poorly water-soluble powder in the microcapsules and another drug that causes a change in the composition, such a change in the composition can be suppressed. Further, when the microcapsules are subjected to tableting for tableting, if the microcapsules are flexible, there is an advantage that the microcapsules are hardly broken at the time of tableting.

As described above, the bitterness of the microcapsules according to the present invention is remarkably suppressed, so that the microcapsules can sufficiently respond to the suppression of bitterness particularly required in chewable tablets.

When manufacturing such a microcapsule according to the present invention, water can be used as a dispersion medium, so that it is not necessary to remove the liquid organic compound remaining in the obtained microcapsule. The adverse effect on the human body can be suppressed. Further, the manufacturing apparatus does not require an explosion-proof structure, and the microcapsule according to the present invention can be manufactured safely.

Therefore, according to the present invention, a powdered drug substance can be directly subjected to microencapsulation without granulating the drug to make it into a core substance, and a poorly water-soluble drug having a bitter taste when taken. The powdery substance does not release from the inside of the microcapsule, the bitterness can be suppressed, and furthermore, a microcapsule having good tongue when formed into a tablet (particularly a chewable tablet), a method for producing the same, and the microcapsule are contained. A solid formulation is provided.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) C07D 473/12 C07D 473/12 (72) Inventor Ryokichi Yuri 35 3rd F-term in Higashi Yakuhin Kogyo Co., Ltd. (reference) 4C076 AA39 AA61 BB01 CC01 DD05 DD26 DD37 DD41 DD46 DD51 DD67 EE32 EE58 FF52 GG32 4C086 AA01 AA02 BC36 CB07 MA01 MA03 MA04 MA05 MA35 MA38 MA52 NA09 ZA02 ZA07 ZA08

Claims (14)

[Claims] 1. A microcapsule obtained by coating a poorly water-soluble powder having a bitter taste with a water-insoluble polymer compound, wherein the particle diameter of the microcapsule is 150 μm or less. 2. The microparticle according to claim 1, wherein the poorly water-soluble powdery substance having a bitter taste is caffeine, anhydrous caffeine, isopropylantipyrine, or a composition containing a poorly water-soluble powdery substance containing these. capsule. 3. The microcapsule according to claim 1, further comprising at least one plasticizer selected from the group consisting of triethyl citrate, acetylated monoglyceride, and triacetin. 4. The microcapsule according to claim 1, wherein the water-insoluble polymer compound is ethyl cellulose. 5. A solid preparation containing the microcapsule according to claim 1. 6. The solid preparation according to claim 5, which is a chewable tablet having a hardness of 5 kg or more and 10 kg or less and a dosage form having a weight of 500 mg or more. 7. A poorly water-soluble powder having a bitter taste, wherein a hardly water-soluble powder dispersion in which a water-insoluble powder having a bitter taste and a water-insoluble polymer compound are dispersed in water is microencapsulated by spray drying. A method for producing a microcapsule containing a powder as a core material. 8. A poorly water-soluble powder dispersion is prepared by adding and dispersing a poorly water-soluble powder having bitterness to an aqueous dispersion in which a water-insoluble polymer compound is dispersed.
The method according to claim 7. 9. The poorly water-soluble powdery substance having a bitter taste is caffeine, anhydrous caffeine, or isopropylantipyrine, or a composition containing a poorly water-soluble powdery substance containing them. The production method described in Crab. 10. The method according to claim 7, wherein at least one plasticizer selected from the group consisting of triethyl citrate, acetylated monoglyceride, and triacetin is blended in the hardly water-soluble powdery particle dispersion. The manufacturing method as described. 11. The production method according to claim 7, wherein the water-insoluble polymer compound is ethyl cellulose. 12. The microcapsule has a particle size of 150 μm.
The production method according to any one of claims 7 to 11, which is as follows. 13. A solid preparation containing microcapsules produced by the production method according to any one of claims 7 to 12. 14. The solid preparation according to claim 13, which is a chewable tablet having a hardness of 5 kg or more and 10 kg or less and a dosage form having a weight of 500 mg or more.