JPH0250885B2 - - Google Patents

Description

[Detailed description of the invention] The present invention relates to enteric coating compositions.

Conventionally, enteric coatings have often been applied to drugs in the form of tablets, pills, granules, fine granules, etc. in order to make them resistant to gastric juices and to quickly dissolve or disintegrate them in intestinal fluids. that time,
Known enteric film forming agents used include cellulose acetate phthalate (CAP), methylvinylpyridine/methyl acrylate/methacrylic acid copolymer (MPM), and the like. When using the above polymeric substances for coating, spray coating is generally performed after dissolving them in a volatile organic solvent. In this case, a device for washing the exhaust air with water is required to capture these organic solvents. Furthermore, in order to protect the environment in the coating workshop, a large amount of cost is required to make air conditioners and electrical appliances explosion-proof, and the cost of the solvents used cannot be ignored.

Enteric film-forming agents that can use water as a solvent are considered as a means to solve the above problems, and water-dispersible copolymers obtained by emulsion polymerization of ethyl acrylate and methacrylic acid have already been used. known to use. This enteric film forming agent requires the addition of a plasticizer, and it is known that polyethylene glycol 6000, sorbitan fatty acid ester, polysorbate 80, triacetin, etc. are good plasticizers.

However, when coating using the above-mentioned plasticizer, the objects to be coated stick to each other, which is inconvenient and problematic in terms of product quality and coating operation. As a result of intensive studies to solve the above-mentioned problems, the inventors of the present invention have discovered that the above-mentioned drawbacks can be effectively solved by adding sucrose fatty acid ester, and have completed the present invention.

That is, the present invention is an enteric film composition characterized by containing as main components a water-dispersible copolymer obtained by emulsion polymerization of ethyl acrylate and methacrylic acid, sucrose fatty acid ester, and water. Incidentally, a commonly known plasticizer can also be used in combination, if necessary.

Examples of water-dispersible copolymers obtained by emulsion polymerization of ethyl acrylate and methacrylic acid used in the present invention include Eudragit L30D-
55 (Rohm Pharma, aqueous dispersion with a solids content of 30% by weight). The emulsion polymerization referred to herein is a polymerization reaction that uses water as a medium to disperse polymerization heat and control the polymerization reaction to proceed appropriately. Although the amount used is not particularly limited, it is suitably 15.0 to 70.0 w/w%, particularly preferably 30.0 to 50.0 w/w% of the total amount of the suspension.

Sucrose fatty acid esters used in the present invention include esters of higher fatty acids such as lauric acid, myristic acid, palmitic acid, stearic acid, oleic acid, and linoleic acid, beef tallow, lard, lanolin, coconut oil, castor oil, Esters of mixed fatty acids such as safflower oil and their hydrogenated oils are available, and those with HLB 6 to 15 are preferred. The amount of sucrose fatty acid ester used in the method of the present invention is not particularly limited, but is 0.5 of Eudragit L30D-55.
~5.0w/w% is appropriate, particularly preferably 1.0~
It is 4.0w/w%.

The present composition can be prepared by dissolving or dispersing sucrose fatty acid ester in purified water, and adding and mixing thereto a water-dispersible copolymer obtained by emulsion polymerization of ethyl acrylate and methacrylic acid; There are methods such as dissolving or dispersing the sucrose fatty acid ester in the copolymer and diluting it with water, but the key is to evenly distribute the sucrose fatty acid ester, the copolymer, and water in a predetermined proportion of the total amount of the composition. The method is not limited to the above method as long as it is adjusted to form a cloudy liquid.

The enteric coating composition of the present invention as described above is applied according to a general particle coating process, but the enteric coating composition of the present invention has sufficient resistance to gastric juices and quickly disintegrates in intestinal fluids. However, it is possible to provide a coating with a smooth and good appearance. Furthermore, when coating particles with an aqueous solvent coating composition, as the amount of coating increases, the tackiness increases and the particles tend to stick together, making it difficult to form a smooth coating and coating, especially in large quantities. Although it may make production almost impossible, the present enteric coating composition avoids that defect. Furthermore, workability is much better and smoother than when polyethylene glycol, which is known as a plasticizer for water-dispersible copolymers obtained by emulsion polymerization of ethyl acrylate and methacrylic acid, is used. One of the features is that it is possible to obtain granules with a uniformly coated surface. Another feature is that since water is used as a solvent, it has become possible to solve various problems when using organic solvents, such as work environment problems in terms of occupational safety and health, air pollution problems, and regulations on solvents remaining in pharmaceuticals. It is one.

The present invention will be specifically described below with reference to Examples, but the present invention is not limited thereto.

Example 1 (Coating liquid preparation) Eudragit L30D-55 (manufactured by Rohm Pharma) 50 parts sucrose fatty acid ester (D ester F-160)
Daiichi Kogyo Seiyaku) 1.8 parts Purified water 48.2 parts After stirring and dispersing sucrose fatty acid ester in purified water according to the above composition ratio, Eudragit L30D
-55 was added and mixed with stirring to purify the coating liquid. The dispersion state of the obtained coating liquid was stable.

(Coating) Lactose/starch granules (weight ratio 8:1) were spray coated using the above coating liquid. No sticking of the granules was observed during the coating operation, and granules with a smooth coated surface were obtained.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties for the 1st and 2nd liquids 1st liquid (PH1.2)...does not disintegrate (1 hour) 2nd liquid (PH7.5)...10 minutes to 15 minutes Example 2 (Coating liquid preparation) Cane sugar Fatty acid ester (DK ester F-50
Daiichi Kogyo Seiyaku) (1.5 parts) was stirred and dispersed in 48.5 parts of purified water, and 50 parts of Eudragit L30-55 was added thereto to prepare a stirring-mixed coating solution.

(Coating) Coating was carried out under the same conditions as in Example 1 using the coating liquid having the above composition, and it was possible to obtain granules with a smooth coated surface without any granules being observed.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties for the 1st and 2nd liquids 1st liquid (PH1.2)...no disintegration (1 hour) 2nd liquid (PH7.5)...10-15 minutes Example 3 (Coating liquid preparation) Sucrose fatty acid Ester (DK Ester F-
110 (Daiichi Kogyo Seiyaku) was stirred and dispersed in 73.6 parts of purified water, 25 parts of Eudragit L30D-55 was added and mixed with stirring to prepare a coating liquid.

(Coating) Coating was carried out under the same conditions as in Example 1 using the coating liquid having the above composition, and it was possible to obtain granules with a smooth coated surface without any granules being observed.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties for the 1st and 2nd liquids 1st liquid (PH1.2)...does not disintegrate (1 hour) 2nd liquid (PH7.5)...10-15 minutes Example 4 (Coating liquid preparation) Sucrose fatty acid Ester (DK Ester F-
140 (Daiichi Kogyo Seiyaku) was stirred and dispersed in 30.8 parts of purified water, 66.5 parts of Eudragit L30D-55 was added thereto, and mixed with stirring to prepare a coating liquid.

(Coating) Coating was carried out under the same conditions as in Example 1 using a coating liquid having the above composition, and no granules were observed to be pebbled, and granules with a smooth coated surface could be obtained.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties for the 1st and 2nd liquids 1st liquid (PH1.2)...no disintegration (1 hour) 2nd liquid (PH7.5)...10-15 minutes Example 5 (Coating liquid preparation) Sucrose fatty acid Ester (DK Ester F-
160 (Daiichi Kogyo Seiyaku) was stirred and dispersed in 48.2 parts of purified water, 50 parts of Eudragit L30D-55 was added thereto, and mixed with stirring to prepare a coating liquid.

(Coating) Lactose/starch tablets (250 mg/tablet) were spray coated using the above coating solution. Tablets with a smooth coated surface were obtained, with no sticking between the tablets.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties against the 1st and 2nd liquids 1st liquid (PH1.2)...no disintegration (2 hours) 2nd liquid (PH7.5)...5 to 10 minutes Comparative Example 1 (Coating liquid preparation) Polyethylene glycol ( Stir and dissolve 1.8 parts of PEG1540) in 48.2 parts of purified water and add Eudragit to this.
50 parts of L30D-55 was added and mixed with stirring to prepare a coating liquid.

(Coating) Coating was carried out under the same conditions as in Example 1 using a coating liquid having the above composition, but the granules were noticeably scratched during coating and it was difficult to obtain granules with a smooth coated surface.

The results of the 33rd disintegration test method of the 9th revised Japanese Pharmacopoeia General Test Methods for the obtained preparation were as follows.

Disintegration properties for the 1st and 2nd liquids 1st liquid (PH1.2)...swells and slightly disintegrates (1 hour) 2nd liquid (PH7.5)...does not disintegrate (30 minutes)

Claims (1)

[Scope of Claims] 1. An enteric film composition characterized by containing as main components a water-dispersible copolymer obtained by emulsion polymerization of ethyl acrylate and methacrylic acid, a sucrose fatty acid ester, and water. 2. The enteric coating composition according to claim 1, wherein the HLB of the sucrose fatty acid ester is 6 to 15.