JPS59110628A - Preparation of drug coated with coating soluble in stomach - Google Patents

Abstract

PURPOSE:To provide the titled drug by coating a solid preparation with a solution prepared by dissolving a water-insoluble and gastric juice-soluble polymeric film-forming agent in an aqueous solution containing an acid. CONSTITUTION:A water-insoluble and gastric juice-soluble polymeric film-forming agent is dissolved in an aqueous solution (adjusted to 1-5pH, preferably 2- 4pH) containing an acid (e.g. organic acid such as citric acid, tartaric acid, succinic acid, etc. and inorganic acid such as hydrochloric acid, sulfuric acid, etc.), and a solid preparation is coated with the obtained solution to afford the objective coated drug soluble in the stomach. A coating solution having practically sufficient concentration of the coating agent can be prepared by dissolving the coating agent using a stirrer (e.g. propeller stirrer, paddle stirrer, etc.). The coating liquid may contain, if necessary, an additive such as lactose, sucrose, etc. or a coating agent such as talc, bentonite, food dye, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing gastrosoluble coated drugs by aqueous coating.

Conventionally, methods for masking young plants of drugs that have a bitter taste generally include polyvinyl acetal diethylamino acetate (AEA), methyl vinyl pyridine methyl acrylate methacrylic acid copolymer (MPM), and cellulose acetate dibutylamino hydroxypropyl ether (CARP). ), dimethylaminoethyl methacrylate-
Coating methods have been taken with water-insoluble coating agents (gastric soluble coating agents) such as methyl methacrylate copolymer (Eudragit PE), but since these coating agents do not dissolve in water, they are generally coated with highly volatile organic In reality, spray coating is performed by dissolving it in a solvent.

However, in recent years, the coating of pharmaceutical products using organic solvents has come with various restrictions, such as work environment issues in terms of occupational safety and health, pollution regulations such as air pollution, and regulations regarding solvents remaining in pharmaceuticals. There is now a demand for switching to aqueous solvents, which are the safest and do not harm the environment.

The above problems can be solved by using an aqueous solvent as a coating solvent, but so far there have been no effective aqueous coatings with film agents that are insoluble in water and soluble in acids. I haven't found a way.

Recently, it has become difficult to work with acrylic resin-water dispersant as an aqueous coating agent for water-insoluble film agents aimed at masking effects of chemicals, and in coating products, emulsifying and dispersing agents in coating liquids (
It had drawbacks such as the development of an unpleasant taste when taken, which was thought to be caused by folysorbate 80), and was not necessarily a fully satisfactory coating agent.

Therefore, the present inventors conducted extensive studies on the possibility of water-based coating with polymer coating agents such as AEA, MPM, CAHP, Eudragit%, etc., which are insoluble in water and soluble in gastric fluid. They focused on the fact that they have the property of dissolving in an acidic region, and discovered that these coating agents could be dissolved by using water in which an acid was dissolved, thereby completing the present invention.

Examples of the acid used in the present invention include organic acids such as citric acid, tartaric acid, succinic acid, gluconic acid, malic acid, fumaric acid, lactic acid, and acetic acid, and inorganic acids such as hydrochloric acid and sulfuric acid. , it is preferable to use organic acids.

Here, when preparing an aqueous solution containing an acid, the amount of acid added varies depending on the acid used, but P)1 of the aqueous acid solution
It may be adjusted so that the number is 1 to 5, preferably 2 to 4.

The method for dissolving the coating agent is usually a commonly used stirrer (e.g. propeller type, food type, turbine type stirrer).
By using this method, it is possible to prepare a coating solution with a sufficiently practical film-forming agent concentration.

In addition, to this coating liquid, if necessary, formulation additives such as lactose, sucrose, and dextrose, or coating agents such as talc, benthite, and food coloring may be added. The coated drug according to the present invention can be produced by coating tablets or granules with the coating liquid thus prepared by a conventional coach ink method (pan coating, fluidized bed coating, etc.).

The coated drug prepared in this way showed sufficient drug masking effect when taken, and also rapidly disintegrated in acidic liquid, showing the same coating effect as in the conventional case using an organic solvent.

In addition, since this coating condition uses water as the coating solvent, unlike conventional coating conditions that use organic solvents, there is no coating failure due to static electricity during coating, and the coating efficiency is increased. It was found that it also has

Hereinafter, the present invention will be specifically explained with reference to Examples, but the present invention is not limited thereto.

In addition, the disintegration test in the examples shown in F below was conducted according to the 10th revised Japanese Pharmacopoeia General Test Method No. 33, disintegration test, and the first solution was used as the test solution.

Example 1 (Preparation of coating solution) Purified water 9゛5.5 parts Citric acid 0.5 part AEA 4.0 parts Dissolve citric acid in the purified water so that the above composition ratio is achieved, (PH2,5) Subsequently, AEA was dissolved to prepare a coating solution.

(Coating) Lactose-starch granules containing 1004/l of sulpiride as the main ingredient were wet-granulated in a conventional manner using a cylindrical granulation iron having a 0.8 mm 11 screen to produce sulpiride-containing granules. Thereafter, using a portion of 12 to 48 meshes, a coating operation was performed using the above-mentioned coating solution under the conditions shown to obtain gastric soluble coated granules.

Covering conditions: □□ 2. Reveal, 7 o -: l-9"" F L 20 type spray gun: Air spray type liquid feed pump with nozzle diameter Q, gytm: Gear pump Coating liquid temperature = 23°C Granule charge amount: 1 kg Coating liquid Supply rate: 15+++7/min Spray air amount: 6017 min Supply air temperature: 80°C Coating operation time: 70 min Coating liquid usage: 1 kg Coating in this way: approx.
Gastric soluble coated granules coated with W were obtained.

These coated granules do not taste like sulpiride when taken, and have a good feeling when taken.

In addition, the disintegration test results showed a disintegration time of 5 to 7 minutes, indicating that the product disintegrated quickly.

Example 2 (Preparation of coating solution) Purified water 96.7 parts Tartaric acid 0.3 parts AEA 8.0 parts Tartaric acid was dissolved in purified water (P
H8, 7) Subsequently, AEA was dissolved to prepare a coating liquid.

(Coating) Under the same conditions as in Example 1, gastric soluble coated granules with a coating of about 20 μm/g were obtained by coating with the above coating solution.

When taking these coated granules, they do not taste like sulpiride and have a good feeling when taken. In addition, the disintegration test results show that the disintegration time is 4~
It showed 6 minutes and immediately collapsed.

Example 3 (Preparation of coating liquid) Purified water 95.7 parts Citric acid 0.3 parts Eudragit ρ hard 4.0 parts Citric acid was dissolved in purified water to the above-mentioned compaction ratio (PH 2.8
) Continue to dissolve the Eudragit bonito and prepare a liquid solution.

(Coating) Gastric soluble coated granules were obtained by coating with the above coating liquid under the same conditions as in Example 1, with a coating of about 5 otty per gram.

The coated granules did not taste the bitter taste of sulpiride when taken, and had a good feeling when taken. In addition, the disintegration test results show that the disintegration time is 4 to 6.
minutes and promptly collapsed.

Example 4 (Preparation of coating liquid) Purified water 95.7 parts Citric acid 0.3 parts A E A 4.0 parts Citric acid was dissolved in purified water so that the above composition ratio was obtained (
PH2, 8) Continue to dissolve AEA to prepare a coating solution.

(Coating) Tablets with a diameter of 9M and a weight of 240~ per 11 tablets containing 200# of sulpiride in one tablet were coated under the following conditions to obtain gastric soluble coated tablets.

Coating conditions: Coating equipment: ・・Manufactured by RM Industry Co., Ltd.・・・−3−”f(
CT-60 type spray gun: Nozzle diameter 1.2 NM Air spray type liquid feed pump: Gil type pump Coating liquid temperature = 28°C Tablet loading amount: 18 kg Coating liquid supply rate: 90 m 11 minutes Spray air flow Wind: 2201 / Temperature of supplied air = 70°C Tablet temperature during coating operation: 88 to 41°C Coating operation time: 140 minutes Amount of coating liquid used: 121 By coating in this manner, approximately 4 coats per tablet were coated. Gastric soluble coated tablets were obtained.

It took 4 to 8 minutes and rapidly disintegrated.

Example 5 (Preparation of coating liquid) Purified water 85.7 parts Citric acid 0.8 parts AEA 4.0 parts Lactose 10.0 parts Citric acid was dissolved in purified water to have the above composition ( P
H2, 8) Subsequently, AEA and lactose were dissolved to prepare a coating solution.

(Coating) By coating with the above coating liquid under the same conditions as in Example 4, 81q of AEA was obtained per tablet.
Gastric soluble coated tablets were obtained.

The coated tablets did not taste like sulpiride and had a good feeling when taken.

Moreover, the disintegration test results showed that the disintegration time was 4 to 7 minutes, and the product disintegrated quickly.

Claims (1)

[Scope of Claims] (1) A coating agent characterized in that a solid preparation is coated with a solution obtained by dissolving a water-insoluble, gastric juice-soluble polymer coating agent in an acid-containing aqueous solution. manufacturing method. (2) The method for producing a coated chemical according to claim 1, wherein the acid is an organic acid. (8) The method for producing a coated chemical according to claim 1 or 2, wherein the pH of the acid-containing aqueous solution is in the range of 1 to 5.