JPS58206535A - Preparation of pharmaceutical preparation of enteric coating - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing enteric coated preparations, and more particularly to a method for applying enteric coating to tablets having markings in a clear state.

When ingested solid drugs such as tablets, granules, pills, capsules, etc. do not change in the stomach and are desired to disintegrate only when they reach the intestines, it is not possible to apply an enteric coating to these solid drugs. It is publicly known. Enteric coating substrates used for this purpose are conventionally hydroxypropyl methylcellulose phthalate, cellulose acetate phthalate, or cellulose ethers such as hydroxypropyl methylcellulose acetate succinate, methylcellulose propionate succinate, and hydroxyethyl ethyl cellulose butyrate succinate. Acidic succinyl and aliphatic monoacyl mixed esters are known, and these have generally been used dissolved in organic solvents. However, this coating requires a large amount of organic solvent, which has the disadvantage of high cost. In addition, coating a solid drug with this material involves the volatilization of a large amount of organic solvent, so there is a risk of fire or explosion.

In view of these problems, the inventors of the present invention have earnestly studied the possibility of preparing a coating liquid in the form of an aqueous liquid, and have first prepared an aqueous coating liquid by dispersing fine powder of an enteric coating base material in water. proposed (Japanese Patent Application Laid-Open No. 55-98120
(see publication). This is a groundbreaking technological innovation in the pharmaceutical industry in that solid drugs can be coated without the involvement of troublesome organic solvents, but on the other hand, it is not necessarily the case in recent years. However, it is difficult to apply a coating to the i-marked area in a clear state).

In view of these technical issues, the present inventors have determined that (1) it is possible to coat tablets with markings clearly, and (2) that even if the tablet is not completely water-based, the water content in the water-based alcohol may be The higher the percentage, the lower the flash point and the lower the risk of fire or explosion, but especially when the water content exceeds 40% by volume, the advantage is that the Fire Service Act does not apply to government or ministerial ordinances regarding the regulation of dangerous substances. 2. It is possible to coat with such a solvent system.
We conducted repeated research from two perspectives. As a result, they discovered that this was possible for the first time by using an acidic succinyl and aliphatic monoacyl mixed ester of cellulose ether as an enteric coating base material, and completed the present invention.

That is, the present invention involves coating a solid drug using a solution or dispersion containing an acidic succinyl and aliphatic monoacyl mixed ester of cellulose ether in a water-alcohol mixed solvent with a water content of 40% by volume or more. The present invention relates to a method for producing an enteric coated preparation characterized by the following.

According to the method of the present invention, in fact, cellulose
(It dissolves or becomes a stable dispersion in a mixed solvent of acidic succinyl and aliphatic monoacyl, and by using the solution or dispersion, the coating operation on solid drugs can be carried out smoothly for practical purposes, resulting in a coating preparation. It also has the advantage of having very good properties.

Furthermore, alcohols generally have low toxicity and are unlikely to cause air pollution, and when 40% by volume or more of water is mixed with them, their flammability is significantly reduced, and the regulations regarding hazardous materials regulations under the Fire Service Act are not met. Organic solvents that have traditionally been mainly used because they are not subject to ministerial ordinances? subject and T
This is a significant improvement over conventional coating operations.

The acidic succinyl and aliphatic monoacyl mixed ester of cellulose ether used in the present invention comprises cellulose ether with succinic anhydride and aliphatic monocarboxylic acid,
It is obtained through an esterification reaction. Examples of this cellulose ether include alkylcelluloses such as methylcellulose, ethylcellulose, and propylcellulose; hydroxyalkylcelluloses such as hydroxyethylcellulose, hydroxypropylcellulose, and hydroxybutylcellulose; Examples include alkyl alkyl cellulose and hydroxyethyl hydroxypropyl methyl cellulose.

Examples of the aliphatic monocarboxylic acid anhydrides include anhydrides such as acetic acid, propionic acid, laconic acid, valeric acid, and lauric acid. Glucose unit 1 of the mixed ester
The average number of conversions per acidic succinyl group and aliphatic monoacyl group is preferably in the ranges of /' 0.1 to 1.5 and 0.05 to 2.0, respectively.

′ of this mixed ester in water-alcohol mixed solvent
Solubility varies depending on the type of alcohol used, temperature, and the type and amount of substituents in the hybrid ester, but
It dissolves in a water-alcohol mixed solvent containing 40% by volume or more of water, or becomes a stable dispersion state, which can be sufficiently used for coating.

The water content in the water-alcohol mixed solvent is set to 40% by volume or more for the reasons mentioned above, but,
As for the upper limit, even if it is desired to make it as large as possible, there is a limit from a practical point of view, and if it is too large, problems such as poor film forming ability during coating operations will occur. For this reason, it is desirable that the upper limit of the water content be no more than 70% by volume. ″″′ Examples of the alcohol used in the present invention include X-hydric alcohols such as methanol, ethanol, isopropanol, and mixtures of two or more thereof.

Note that a small amount of other organic solvents such as ethylene glycol, propylene glycol, ethylene glycol monoethyl ether, etc. may be added to the alcohol as appropriate.

In preparing the coating solution, the concentration of acidic succinyl and aliphatic monoacyl mixed esters of cellulose ethers is generally 3 to 20% by weight, particularly 5 to 20% by weight.
The content is preferably 15% by weight.

The coating solution may contain plasticizers such as polyethylene glycol, glycerin, triacetin, glycerin fatty acid ester, triethyl citrate, castor oil, sesame oil, olive oil, rapeseed oil, silicone oil, etc., as necessary.
Polyvinyl alcohol, water-soluble cellulose derivatives, hexalac, ethyl cellulose, etc., can be added to the film, as well as higher aliphatic alcohols, higher fatty acids, surfactants, titanium oxide, talc, pigments, and fragrances. Generally speaking, the coating solution is prepared by dispersing or dissolving the acidic satacinyl and aliphatic monoacyl mixed esters of cellulose ether in alcohol or hydrous alcohol, and adding a predetermined amount of water while stirring to form a solution. Alternatively, it may be prepared as a dispersion liquid, and then necessary additives may be added, but this order does not necessarily have to be followed.

The solid drug to which the method of the present invention is applied includes various types such as tablets, granules, pills, and capsules, and there are no restrictions on the type, and there are no restrictions on the medicinal ingredients in the solid drug. It can be any one.

The coating amount for these solid drugs is within a fixed range.

As the coating method, the same method as in the conventional case where an organic solvent is used as the main ingredient or when an aqueous coating liquid is used is applied. Namely.

Pan coating equipment, fluid coating equipment.

Alternatively, coating can be performed using a coating device in which dry air penetrates the inside of the pan, such as Hi-Coater (manufactured by Freund Sangyo Co., Ltd.) and Axela Coater (manufactured by Manestee Co., Ltd., UK). At this time, it is best to heat the coating liquid as necessary, at 20 to 60℃.
A range of is appropriate.

Next, examples of the present invention will be given.

Example 1 The following coating solution was prepared.

Acidic succinyl and acetyl mixed ester of hydroxypropyl methylcellulose (hydroxypropoxyl group MS 0.27, methoxyl group D 81.85, acedel group DS 0.46, acidic succiyl group D 80.41) 8 weight Part ethanol-water mixture (55:45 volume ratio)...
...92 parts by weight 24 inch Axela coater (manufactured by Maneste 1, UK)
Then, simulated tablets containing lactose and starch as main components and having a stamp on one side and having a diameter of 270 kg and a diameter of 9 kg were prepared with IQl[y, and a coating operation was performed using the above-mentioned coating liquid. However, the coating liquid should be heated to 40℃ before use.
Spraying was carried out at a rate of 60 mm per minute from an air spray gun with a nozzle diameter of 1.2 m.

The amount of coating per tablet was 22 capes when operated by J2F. The appearance was beautiful and the engraved parts were clear. A disintegration test was conducted on this tablet using the Japanese Pharmacopoeia's disintegration test method for enteric-coated preparations. As a result, there was no change in the test with the first liquid, and it disintegrated in 9 to 11 minutes in the test with the second liquid. However, the properties as an enteric-coated preparation were satisfied. .

On the other hand, for comparison, hydroxypropyl methylcellulose phthalate (Shin-Etsu Chemical Co., Ltd.
P-55) fine powder 400i triethyl citrate
Coating was performed using an aqueous dispersion consisting of P and 9 KP of water, and the coating amount was approximately 291'Jjl per tablet. There was no change in this product in the test with the first liquid,
In a test using the second liquid, it disintegrated in 10 to 12 minutes, which was satisfactory for an enteric-coated preparation, but the stamp was completely buried.

Example 2 Granules were coated using the same coating solution as in Example 1. For the granules, 12 to 32 mesh portions of spherical granules containing pancreatin as the main component are used.
19 of this was coated with a blood fluid coating system [WSG-1
(manufactured by Okawara Seisakusho) and coated with 24 particles of solid content per 100 iP of elementary granules.

When the thus obtained coated granules were subjected to a disintegration test for enteric-coated preparations according to the Japanese Pharmacopoeia, there was no change in the test with the first liquid, and they disintegrated in 7 to 8 minutes in the test with the second liquid. It was satisfactory as a soluble preparation.

Example 3 The various base materials shown in Table 1 were added to a mixed solution of water and ethanol at a volume ratio of 42:58 to a solid content of 7% by weight, and the resulting solution was thoroughly mixed and used as a coating solution. Using. Each football-shaped soft gelatin capsule I Ky containing 800 cm of soybean oil is placed in a small pan coating machine (FM-2 model, Freund Sangyo Department), and one capsule is coated by spraying and drying repeatedly. Approximately 50 μm of solids were coated per coat. However, the coating liquid was heated to 35°C before use.

Each of the obtained coated capsules had a beautiful appearance, and when tested using the Japanese Pharmacopoeia's disintegration test for enteric-coated preparations, the results shown in Table 2 were obtained. It was satisfying.

Table 2 [Experimental results] Patent applicant: Shin-Etsu Chemical Co., Ltd. 1嫡ha○;

Claims (1)

[Claims] 1. A solid drug is coated using a solution or dispersion containing acidic succinyl cellulose ether and fatty acid monoacyl mixed ester in a water-alcohol mixed solvent with a water content of 40% by volume or more. Method for producing enteric coated formulations