JPH04290817A - Enteric pharmaceutical preparation and production thereof - Google Patents

Abstract

PURPOSE:To obtain an enteric pharmaceutical preparation by a producing method being safe and applicable even to drug unstable to water because of disuse of water and solvent such as an organic solvent, having excellent resistance to gastric juice, appearance, strength, safety, etc., and having arbitrary drug content. CONSTITUTION:A two-layered type enteric pharmaceutical preparation obtained by coating a core substance containing drug compounds with a coating film of enteric substance containing heat-melted meltable substance as a binder or further providing a coating layer of water-insoluble substance containing a meltable substance as a binder around the enteric film and production thereof.

Description

[Detailed description of the invention]

0001

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an enteric-coated preparation in which a core material containing a medicinal compound is coated with a film of an enteric-coated material containing a heat-melted fusible material as a binder, and a method for producing the same.

0002

[Prior Art] Enteric-coated preparations coated with a film of enteric-coated substances in pharmaceuticals may be inactivated by gastric juices, or may reduce the effectiveness of the drug, irritate the stomach, or impair the digestive action of the stomach. It is a dosage form that is often used for the purpose of efficiently exerting the medicinal effects of drugs, drugs whose intestinal concentration is desired to be increased, or drugs whose dissolution amount needs to be controlled or sustained.

Conventional methods for coating the surface of granules containing a pharmaceutical compound with an enteric substance include dissolving the enteric substance in an organic solvent or dispersing it in water, spraying it on the surface of the granule, and then drying. Generally, a method of applying an enteric coating is used. However, although methods using organic solvents have the advantage of being easy to dry, they also pose problems such as residual organic solvents in the formulation, disaster prevention safety and health problems, etc.
There are also problems such as the installation of exhaust gas recovery equipment. For this reason, a method using an enteric substance dispersed in water together with a plasticizer has recently been widely used. However, this method also takes a long time to dry, is unsuitable for drugs that are unstable in water, and is easy to dissolve in the coating liquid for easily water-soluble drugs, which causes particles to stick to each other during coating. However, there are drawbacks such as poor coating formation.

[0004] As a method that does not use solvents such as organic solvents or water, Japanese Patent Application Laid-Open No. 153213/1982 discloses that a finely powdered enteric coated material is added to granules containing a drug granulated with a low melting point substance as a core. A method of depositing a base is disclosed. This method uses a granular low-melting-point substance as a core and sequentially attaches drug powder and finely powdered enteric substance to it under heating and flow, so the coating amount of drug powder and enteric substance is limited. The enteric-coated formulations thus obtained have the disadvantage that the drug content tends to be too low or the coating tends to lack gastric fluid resistance and uniformity.

[0005]

[Problems to be Solved by the Invention] The present invention has been made in view of the above circumstances, and is safe, can be applied in a short period of time, can be applied to water-unstable drugs, and can control the amount of coating. The purpose of the present invention is to provide an enteric-coated preparation that has excellent gastric juice resistance, appearance, strength, and stability, and can have any drug content, by a manufacturing method that allows the preparation of the drug.

[0006]

[Means for Solving the Problems] As a result of extensive research to achieve the above object, the present inventors added a mixture of a meltable substance and an enteric substance to a core substance containing a pharmaceutical compound, and heated the mixture. By rolling them down, you can safely and quickly remove them without using solvents such as water or organic solvents.
It was discovered that a film of an enteric material can be formed around a core material in an arbitrary coating amount using a meltable material as a binder, and the present invention was completed.

That is, the present invention provides a method in which a core material containing a pharmaceutical compound is coated with a film of an enteric material containing a heat-melted fusible material as a binder, or the core material containing a medicinal compound is further coated with a film of an enteric material containing a heat-melted fusible material as a binder, or the core material containing a medicinal compound is further coated with a film of an enteric material containing a heat-melted fusible material as a binder, or the core material containing a medicinal compound is It is an enteric-coated preparation comprising a coating layer of a water-insoluble substance with a binder made of a meltable substance.

[0008] The above formulation is prepared by rolling the core material containing the medicinal compound under temperature conditions where the meltable material melts.
A mixed powder of a meltable substance and an enteric substance is added, and a film of the enteric substance is formed around the core substance using the heated and melted meltable substance as a binder, or the meltable substance is melted onto this. Produced by adding a mixed powder of a meltable substance and a water-insoluble substance under temperature conditions to form a coating layer of a water-insoluble substance around the enteric coating, using the heated melted substance as a binder. Can be done.

[0009]

EXAMPLES The enteric-coated preparation of the present invention has a core material containing a pharmaceutical compound and a coating of enteric material containing a meltable material as a binder surrounding the core material.

[0010] In one form, the enteric coating may be surrounded by a coating layer of an insoluble substance using a meltable substance as a binder.

In the present invention, the pharmaceutical compound contained in the core substance is not particularly limited, and the enteric-coated preparation of the present invention can be applied to all pharmaceutical compounds.

The core material may contain various additives commonly used in this field, such as excipients, binders, lubricants, and anti-aggregation agents.

The form of the core material is not particularly limited, and various forms such as bare tablets, pills, granules, and fine granules can be suitably used.
Particles of 2,000 μm, especially about 100 to 1,500 μm are preferable, and granules close to spheres are preferable. Such core materials can be prepared by conventional methods.

The meltable substance used as a binder in the present invention is a powder at room temperature, and has a molecular weight of 30 to 100%.
Any substance may be used as long as it melts within the range of 100°C, and examples thereof include higher fatty acids, higher aliphatic alcohols, higher fatty acid esters, and hydroxy higher fatty acid esters. Furthermore, these meltable substances can be used in combination with polyethylene glycols, which are water-soluble meltable substances, if desired.

[0015] As higher fatty acids, for example, those having 10 carbon atoms
-32 saturated or unsaturated fatty acids, and higher aliphatic alcohols include, for example, aliphatic monohydric alcohols having 12 to 30 carbon atoms. In addition, higher fatty acid esters include esters of saturated or unsaturated fatty acids having 14 to 24 carbon atoms and aliphatic monohydric alcohols having 12 to 24 carbon atoms, and esters of saturated or unsaturated fatty acids having 12 to 18 carbon atoms and glycerin. or their hydrogenated products, or mixtures thereof; examples of hydroxy higher fatty acid esters include esters of hydroxy fatty acids with 12 to 22 carbon atoms and aliphatic monohydric alcohols with 12 to 22 carbon atoms; Examples include esters of fatty acids and glycerin, esters of hydroxy unsaturated fatty acids having 12 to 22 carbon atoms and glycerin, hydrogenated products thereof, and mixtures thereof.

Specific examples of higher fatty acids include capric acid, undecylic acid, lauric acid, tridecylic acid, myristic acid, pentadecylic acid, palmitic acid, heptadecylic acid, stearic acid, nonadecanoic acid, arachidic acid, behenic acid, lignoceric acid, Examples include cerotic acid, heptacosanoic acid, montanic acid, melisic acid, lactic acid, elaidic acid, and brassicic acid, among which myristic acid,
Palmitic acid, stearic acid, nonadecanoic acid or behenic acid are preferred, especially palmitic acid, stearic acid or behenic acid.

Specific examples of higher aliphatic alcohols include lauryl alcohol, tridecyl alcohol, myristyl alcohol, pentadecyl alcohol, cetyl alcohol, heptadecyl alcohol, stearyl alcohol, nonadecyl alcohol, eicosyl alcohol,
Examples include seryl alcohol and merisyl alcohol. Among these, cetyl alcohol, stearyl alcohol, or eicosyl alcohol is preferred, and cetyl alcohol or stearyl alcohol is particularly preferred.

Further, specific examples of higher fatty acid esters include fatty acid esters such as myristyl palmitate, stearyl stearate, myristyl myristate, ceryl lignocerate, laxeryl cerotate, and laxeryl lactate, lanolin, beeswax, spermaceti, Natural waxes derived from animals such as shellac wax, natural waxes derived from plants such as carnauba wax and candelilla wax, glyceryl monolaurylate, glyceryl monomyristyrate, glyceryl monostearate, glyceryl dilaurylate, glyceryl dimyristylate, Glyceryl distearate, glyceryl trilaurylate, glyceryl trimyristyrate,
In addition to glyceryl tristearate, beef tallow, pork fat,
Hydrogenated beef tallow, hydrogenated rapeseed oil, hydrogenated castor oil, hydrogenated coconut oil,
Examples include hydrogenated soybean oil. Specific examples of hydroxy higher fatty acid esters include hydroxystearic acid triglyceride. In the above, natural wax, beef tallow, lard, and various hardened oils contain various components, and any of them can be suitably used in the enteric-coated preparation of the present invention. For example, ceramic wax has ceryl lignocerate as its main component, and contains ceryl cerotate and laxeryl lactate as a mixture, as well as
Although it also contains components such as free alcohol, hydrocarbons, and resin components, they can be suitably used.

Specific examples of polyethylene glycols include polyethylene glycol 600, polyethylene glycol 1000, polyethylene glycol 1500, polyethylene glycol 1540, polyethylene glycol 4000, polyethylene glycol 6000, and polyethylene glycol 20000.

[0020] These meltable substances can be used alone to form a film, or two or more types can be appropriately mixed to form a film.

[0021] The meltable substance has an average particle size of about 1 to
Preference is given to using powders that are 500 μm, especially about 5 to 300 μm.

[0022] As an enteric substance, it is substantially insoluble in water with a pH of 4 or less, but in water with a pH of 4.5 or more, especially p.
Any substance that is soluble in water with an H5.5 to H7.5 may be used, such as cellulose derivatives, dibasic acid esters of cellulose or polyvinyl compounds, acrylic acid copolymers, maleic acid copolymers, etc. Those used for enteric-coated preparations can be used.

Examples of cellulose derivatives include carboxymethylethylcellulose.

Examples of dibasic acid esters of cellulose or polyvinyl compounds include cellulose acetate phthalate, cellulose acetate succinate, cellulose acetate maleate, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, and polyvinyl acetate. - Phthalate, polyvinyl propionate phthalate, polyvinyl butyrate phthalate, etc.

Examples of the acrylic acid copolymer include methyl acrylate/methacrylic acid copolymer, ethyl acrylate/methacrylic acid copolymer, and methyl methacrylate/methacrylic acid copolymer. It will be done.

Examples of the maleic acid copolymer include vinyl acetate/maleic anhydride copolymer, styrene/maleic acid copolymer, and the like.

[0027] The enteric substances mentioned above can be suitably used even if they are commercially available; for example, as hydroxypropyl methyl cellulose phthalate, HP-50 or HP-55 (both manufactured by Shin-Etsu Chemical Co., Ltd.) may be used. Can be used. Furthermore, as a methyl methacrylate/methacrylic acid copolymer, Eudragit L,
Eudragit S (both manufactured by Rehm Pharma (Germany)) or the like can be used.

[0028] The enteric material has an average particle size of about 1 to 500
Preference is given to using powders that are .mu.m, especially about 5 to 300 .mu.m.

One form of the enteric-coated preparation of the present invention is
In a two-layer enteric-coated preparation in which a coating layer of a water-insoluble substance with a meltable substance as a binder is provided around the enteric coating, the water-insoluble substances include magnesium stearate,
Water-insoluble substances that do not dissolve below 100°C, such as calcium stearate, talc, titanium oxide, light anhydrous silicic acid, synthetic magnesium silicate, dried aluminum hydroxide gel, precipitated calcium carbonate, and calcium sulfate, can be suitably used; As such, the above-mentioned meltable substances can be suitably used.

The enteric-coated preparation of the present invention is prepared by adding a mixed powder of a melting substance and an enteric substance while rolling a core material containing a pharmaceutical compound under temperature conditions where the meltable substance melts. It is manufactured by forming a film of an enteric material around a core material using a heat-melted fusible material as a binder.

[0031] The weight mixing ratio of the meltable substance and the enteric substance is:
Preferably, the ratio is from 5:95 to 5:5, especially from 1:9 to 4:6. If the amount of the meltable substance is greater than the enteric substance, the cohesiveness and adhesion of the granules during coating formation will increase, resulting in a decrease in recovery rate and good product rate. Furthermore, if the amount of the meltable substance is less than the above ratio, the scattering of particulates during coating formation increases, the coating does not adhere to the particles of the core material, and the effectiveness of the coating decreases.

The amount of the mixed powder used is 0.05 to 3.0 parts by weight, particularly 0.1 to 2 parts by weight, per 1 part by weight of the core material.
．． Preferably, 0 parts by weight are used.

[0033] Also, as a rolling means when coating,
Although there are no particular limitations, it can be carried out using, for example, a centrifugal fluid coating device, a fluidized bed granulator, or a coating pan. The rolling speed is generally 5 per minute.
0 to 400 rotations, the rolling time varies depending on the amount of mixed powder used and its addition rate, but is generally 5 to 180 minutes, and the temperature is higher than the melting temperature of the melting substance, for example, about 5 degrees Celsius or higher. Good, but preferably about 5-3
Temperatures as high as 0°C, particularly about 5-10°C, are preferred.

[0034] The mixed powder of the meltable substance and the enteric substance may contain additives that do not melt at temperatures below 100°C, such as excipients, binders, lubricants, and anti-agglomeration agents, which are commonly used in this technical field. Additives may also be added.

[0035] In addition, enteric-coated preparations in which a coating layer of a water-insoluble substance having a heat-melted fusible substance as a binder is provided around the enteric-coated coating are coated with the enteric-coated coating on the core material, and then further rolled. This can be carried out by gradually adding a mixed powder of a water-insoluble substance and a meltable substance under temperature conditions such that the meltable substance melts.

[0036] The weight mixing ratio of the meltable substance and the water-insoluble substance is preferably about 5:95 to 5:5, particularly 1:9 to 4:6, and the amount used in the core substance is in the form of a mixed powder. It is preferably 0.05 to 3.0 parts by weight, especially 0.1 to 2.0 parts by weight per part by weight of core material. Further, the coating conditions such as heating temperature and rolling speed may be the same as those for coating with the above-mentioned enteric coating, and coating can be easily performed.

Next, the present invention will be explained in more detail with reference to Examples, but the present invention is not limited thereto.

Example 1 Dilthiacem hydrochloride containing dilthiacem hydrochloride heated to 90° C. by rolling at 150 revolutions per minute using a centrifugal flow type granulation coating device (CF-360) with an average particle size of about 800
On top of 200 g of μm spherical core material, an average particle size of 5
200 g of a mixed powder (7:3) of enteric substance hydroxypropyl methylcellulose acetate succinate (HPMC-AS(M)) with a particle size of 25 μm and hydrogenated castor oil, a meltable substance with an average particle size of 25 μm, at a rate of 20 g per minute. added. After further rotating at 150 revolutions per minute for 5 minutes, the mixture was cooled to a temperature below the melting point of hydrogenated castor oil, yielding 395 g of an enteric-coated preparation. Furthermore, no scattering of powder or agglomeration of particulate matter was observed during coating.
The obtained preparation was close to a true sphere.

[0039] Regarding the preparation thus obtained, the Japanese
liquid (pH 1.2), second liquid (pH 6.8), pH 7
．． An elution test was conducted using 900 ml of each of the 5 buffer solutions as a solvent at 37°C and a paddle rotation speed of 100 rpm.
Figure 1). As is clear from FIG. 1, the elution was suppressed in the first solution, but the enteric function of relatively rapid elution was observed in the second solution, pH 7.5 buffer.

[0040] In addition, for the purpose of predicting dissolution in the gastrointestinal tract, a dissolution test was conducted with the first solution (pH 1.2) for the initial 2 hours, and then the preparation was transferred to the second solution (pH 6.8). A dissolution test was conducted (Figure 2). As is clear from Figure 2, diltiazem hydrochloride did not elute in the first liquid, but eluted relatively quickly after being transferred to the second liquid, so it is a formulation that has the function of dissolving quickly after being excreted from the stomach into the small intestine. I was able to confirm something.

Example 2 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing dilthiacem hydrochloride heated to 90° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
200 g of mixed powder (7:3) of enteric substance hydroxypropyl methylcellulose acetate succinate (HPMC-AS(L)) and hydrogenated castor oil, which is a meltable substance with an average particle size of 25 μm, was added to prepare enteric-coated preparation 394.
I got g.

Example 3 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing dilthiacem hydrochloride heated to 90° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
200 g of a mixed powder (7:3) of enteric substance hydroxypropyl methyl cellulose acetate succinate (HPMC-AS(H)) and hydrogenated castor oil, a meltable substance with an average particle size of 25 μm, were added to form an enteric-coated preparation 394.
I got g.

Example 4 200 g of the formulation shown in Example 1 above was heated to 90°C, and a mixture of talc, a non-melting substance with an average particle size of 10 μm, and hydrogenated castor oil, a melting substance with an average particle size of 25 μm, was heated to 90°C. 20, 60, and 80 g of the mixed powder (8:2) were added, respectively (i.e., the ratio of the coating layer of the water-insoluble substance to the core granules: 10, 30, 40% (W/W)), and Example 1 The same procedure as above was carried out to obtain a preparation coated with an enteric substance and further coated with talc and hydrogenated castor oil.

Regarding the above formulation, the second solution (pH 6.8)
900ml as solvent, 37℃, paddle rotation speed 100r
A dissolution test was conducted under conditions of pm (Figure 3). As is clear from FIG. 3, the elution of diltiacem hydrochloride was suppressed as the coating rate increased, confirming that this preparation was sustained-release and enteric-coated.

Example 5 200 g of the formulation shown in Example 2 above was heated to 90°C, and a mixture of talc, a non-melting substance with an average particle size of 10 μm, and hydrogenated castor oil, a melting substance with an average particle size of 25 μm, was heated to 90°C. Mixed powder (8:2) 20, 60, 80, 100 respectively
g was added thereto, and the same operation as in Example 1 was carried out to obtain a preparation coated with an enteric substance and further coated with talc and hydrogenated castor oil.

Example 6 200 g of the formulation shown in Example 3 above was heated to 90°C, and a mixture of talc, a non-melting substance with an average particle size of 10 μm, and hydrogenated castor oil, a melting substance with an average particle size of 25 μm, was heated to 90°C. 20, 40, and 60 g of mixed powder (8:2) were added, respectively, and the same operation as in Example 1 was carried out to obtain a preparation coated with an enteric substance and further coated with talc and hydrogenated castor oil.

Example 7 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing dilthiacem hydrochloride heated to 75° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
120 g of a mixed powder (7:3) of an enteric substance methacrylic acid copolymer (Eudragit S) and a meltable substance hydrogenated rapeseed oil (7:3) with an average particle size of 25 μm were added to obtain 315 g of an enteric preparation.

Example 8 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing nicotinic acid amide was heated to 75° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
A mixed powder (
2:6:2) and 296 g of enteric-coated preparation.
I got it.

Example 9 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing nicotinic acid amide was heated to 75° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
A mixed powder (
2:6:2) and 295 g of enteric-coated preparation.
I got it.

Example 10 The operation was carried out according to the conditions of Example 1, and an intestine having an average particle size of 5 μm was placed on 200 g of a spherical core material containing theophylline and having an average particle size of about 800 μm heated to 75°C. Soluble substance hydroxypropyl methyl cellulose acetate succinate (HPMC-AS(M)), non-melting substance talc with an average particle size of 10 μm and average particle size of 25 μm
A mixed powder of hardened rapeseed oil (2:6:
2) Added 60 g to obtain 258 g of enteric-coated preparation.

Example 11 The operation was carried out according to the conditions of Example 1, and the average particle diameter was about 800 μm containing dilthiacem hydrochloride heated to 80°C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
enteric-coated substance hydroxypropyl methylcellulose acetate succinate (HPMC-AS(M)), non-melting substance talc with an average particle size of 10 μm and particle size 2
Add 200 g of mixed powder (4:4:2) of stearic acid, which is a meltable substance with a diameter of 50 μm or less, to form an enteric-coated preparation 394.
I got g.

Example 12 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing nicotinic acid amide was heated to 70° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
Enteric-coated substance hydroxypropyl methyl cellulose acetate succinate (HPMC-AS(M)), non-melting substance talc with an average particle size of 10 μm and particle size 250
Add 200 g of mixed powder (4:4:2) of stearyl alcohol, which is a soluble substance below μm, and enteric-coated preparation 3.
I gained 90g.

Example 13 The operation was carried out according to the conditions of Example 1, and an average particle size of about 800 μm containing nicotinic acid amide was heated to 70° C.
On top of 200 g of spherical core material of m, an average particle size of 5 μm
Enteric-coated substance carboxymethylethylcellulose (CM
EC), 200 g of a mixed powder (4:3:3) of talc, a non-melting substance with an average particle size of 10 μm, and stearyl alcohol, a melting substance with a particle size of 250 μm or less, were added to obtain 392 g of an enteric-coated preparation.

Example 14 The operation was carried out according to the conditions of Example 1, and an enteric coated material having an average particle size of 30 μm was placed on 200 g of a spherical core material containing theophylline and having an average particle size of 800 μm heated to 65° C. A mixed powder of the substance hydroxypropyl methylcellulose phthalate (HP-55), the non-melting substance talc with an average particle size of 10 μm, the melting substance hydrogenated rapeseed oil with an average particle size of 25 μm, and the water-soluble melting substance polyethylene glycol 6000. (4:4:1.5:0.
5) 100 g was added to obtain 292 g of enteric-coated preparation.

Example 15 The operation was carried out according to the conditions of Example 1, and the average particle size of the particles containing diltiacem hydrochloride heated to 75° C. was about 200 μm.
On top of 1000 g of spherical core material of m, an average particle size of 5 μm
Add 2000 g of a mixed powder (7:3) of enteric-coated substance hydroxypropyl methylcellulose acetate succinate (HPMC-AS(M)) and hardened rapeseed oil, a meltable substance with an average particle size of 25 μm, to form an enteric-coated preparation 28
I got 50g.

[0056]

Effects of the Invention The enteric-coated preparation of the present invention is prepared by coating a core substance containing a pharmaceutical compound with an enteric substance using a meltable substance as a binder using a melt-coating method. It has the advantage that it does not require the use of a solvent, the amount of coating can be controlled, and the drug content can be arbitrary.

That is, since no organic solvent is used, there are problems in terms of disaster prevention, safety and health, and problems with organic solvents remaining in the formulation.
There are no problems such as installation of exhaust gas recovery equipment, etc.
It is extremely superior in terms of disaster prevention, health and safety, economics, and safety of the formulation.

Furthermore, since water is not used, it can be applied to drugs that are unstable in water, and coatings of readily water-soluble drugs can be formed very well without adhesion of particulates to each other.

Furthermore, since no solvent is used, there is no need to prepare a coating liquid, the time required for coating formation is shortened, and a drying step is not required, resulting in a significant reduction in the time required for production. In addition, it does not require complicated condition settings and can be produced with a high yield using a simple device, resulting in low cost and extremely high working efficiency.

In addition, since the amount of coating is not limited, it is possible to increase the drug content as desired, and it is also possible to reliably obtain enteric-coated preparations with excellent gastric juice resistance, appearance, strength, etc. has advantages.

[0061] In addition, enteric-coated preparations in which a coating layer of a water-insoluble substance with a meltable substance as a binder is provided around the enteric coated film have a sustained-release effect in addition to enteric properties, so that they can be used as sustained-release preparations. It is also useful as

[Brief explanation of the drawing]

FIG. 1 is a graph showing the results of a dissolution test of the enteric-coated preparation obtained in Example 1 in the 11th revised Japanese Pharmacopoeia liquid 1, liquid 2, and a pH 7.5 buffer.

FIG. 2 is a graph showing the dissolution test results when the enteric-coated preparation obtained in Example 1 was dissolved in the 11th revised Japanese Pharmacopoeia liquid 1 for 2 hours and then in the same liquid 2. It is.

FIG. 3 shows the dissolution test results when the enteric-coated preparations obtained in Example 4, in which a coating layer of water-insoluble substances was formed at various ratios, were dissolved in liquid 2 of the 11th revised Japanese Pharmacopoeia. This is a graph showing.

Claims (4)

[Claims] 1. An enteric-coated preparation, in which a core material containing a medicinal compound is coated with a film of an enteric-coated material whose binder is a meltable material heated and melted. 2. The enteric-coated preparation according to claim 1, wherein a coating layer of a water-insoluble substance whose binder is a meltable substance heated and melted is provided around the film of the enteric-coated substance. [Claim 3] Under temperature conditions where the meltable substance melts,
A mixed powder of a meltable substance and an enteric-coated substance is added while rolling a core material containing a pharmaceutical compound, and a film of an enteric-coated substance is formed around the core material using the heated and melted meltable substance as a binder. A method for producing an enteric-coated preparation, characterized by: 4. After obtaining granules in which a film of an enteric substance is formed around a core substance, the granules are rolled under temperature conditions where the meltable substance melts, and the meltable substance and the water-soluble substance are separated. 4. The method for producing an enteric-coated preparation according to claim 3, characterized in that a mixed powder of a water-insoluble substance is added to the granules, and a coating layer of a water-insoluble substance is formed around the granules using a heat-melted fusible substance as a binder.