JPS59193816A - Preparation of enteric soft capsule - Google Patents

Abstract

PURPOSE:To obtain the titled soft capsule resistant to the change of the enteric dissolution property with time, the degradation of the content, etc., by dissolving gelatin in an alkaline aqueous solution of a film-forming substance soluble in alkali and insoluble in acidic state, encapsulating a drug component with said solution, and treating the capsule with an acid after drying. CONSTITUTION:Gelatin is dissolved in an alkaline aqueous solution of a film- forming substance soluble in alkaline state and insoluble at <=5 pH (e.g., alpha,beta- ethylenic unsaturated carboxylic acid copolymer, a polycarboxylic acid-modified cellulose derivative, etc.), a drug component is encapsulated with the aqueous solution of the encapsulation agent, the obtained soft capsule is dried and immersed in a solution of an acid of preferably 5-15wt% concentration at <=10 deg.C for about 3min, and the product is washed with water and dried to obtain the objective soft capsule. The amounts of gelatin and the film-forming substance are preferably 60-70% and 10-20%, based on the encapsulation agent, respectively. Preferably, the capsule is incorporated with 10-20% of a polyol such as sorbit, glycerol, etc. as a plasticizer.

Description

[Detailed description of the invention] The present invention relates to a method for manufacturing enteric-coated soft capsules.

Conventionally, enteric-coated soft capsules include gelatin-based soft capsules treated with formalin, gelatin-based soft capsules coated with enteric polymeric substances, and enteric-coated polymeric substances. There are known base materials, but each has its advantages and disadvantages, and the one that should be satisfied is i.
Not qed.

For example, formalin-treated capsules do not disintegrate with gastric juices, but it is difficult to prepare capsules that disintegrate with intestinal fluids;
Excessive formalin treatment has the disadvantage that it does not disintegrate even in intestinal fluid, making it difficult to adjust. In addition, capsules made of soft gelatin capsules coated with enteric polymer substances tend to have poor adhesion between the gelatin surface and the coating film, and the polymer coating film is denatured due to the influence of water in the gelatin. It has the serious drawback that its enteric properties deteriorate over time, and it eventually loses its enteric properties. Soft capsules using enteric polymer materials require a large amount of plasticizer to impart flexibility, and this may leach onto the capsule surface over time and adversely affect the contents11. teeth,
The present invention provides a method for easily producing enteric-coated soft capsules that eliminate the drawbacks of the conventional capsules described above. That is, according to the present invention, gelatin is dissolved in an alkaline aqueous solution of a film-forming substance that dissolves with noflukalinity, but does not dissolve below H5, and after converting the encapsulated component into a capsule, it is dried, and then This invention relates to a method for producing enteric-coated Kabuhiru, which is characterized by treatment with an acid.

In the present invention, a film-forming substance J3 that dissolves in alkali but does not dissolve at temperatures below 1-15F is, for example, a film-forming polymeric substance having a reverse carboxyl group in its molecule, such as polycarboxylic acid. Examples thereof include modified hill[]-su derivatives, copolymers of carboxylic acids having α,β-unsaturated ethylene bonds, and the like. Examples of polycarboxylic modified cellulose derivatives include cellulose partially esterified with phthalic acid, maleic acid, etc., hirulose ester, cellulose ether derivatives, etc., and typically hydroxypropyl methylcellulose phthalate, phthalate acetate, etc. acid cellulose, etc. Examples of carboxylic acids containing α,β-ethylenically unsaturated bonds include acrylic acid, methacrylic acid, itaconic acid, Nisdel or amides of chloro-1-chloric acid, etc. Typical examples are It is a methacrylic acid-alkyl methacrylate Nisder copolymer. These carboxyl group-containing IlQ-forming polymer substances are soluble in alkali, but p
Those containing carboxyl groups in a range that does not dissolve at H5 or lower are used. The amount of the film-forming substance used is 1
1) 5-30% by weight of the total weight, preferably 10-20%
0-20 weight.

The alkaline aqueous solution that dissolves and coats the film-forming substance is an aqueous solution of a suitable alkali, such as ammonia, caustic soda, carbonate sorter, caustic f1 potash, etc., and its tl +-1 depends on the type of film-forming substance and the treatment process. 1], 1, although it varies depending on the temperature etc. l) H is preferably about 8 to 9;
In particular, when the film-forming substance is dissolved, it may be 1) 1" or more than 7.5, preferably I) 87.5 to 8.5. The concentration when dissolving the film-forming substance in an alkaline aqueous solution is not particularly limited;
It is preferably in the range of 30% by weight. Dissolution can be carried out at any temperature, but to promote dissolution
Preferably, the reaction is carried out at a temperature of 0.degree. C. or higher. Gelatin is added to the alkaline solution of the film-forming substance.

You can add gelatin to the alkaline solution first, but
Since gelatin may be hydrolyzed by an alkaline solution depending on the humidity and dissolution time, it is preferable to dissolve the film-forming substance first. The gelatin is preferably one with high bloom, but is not particularly limited. The appropriate amount of gelatin to be used is 50 to 80%, particularly 60 to 70%, of the total amount of the capsule forming agent. It is preferable to further add polyols such as polyols such as glycerin and the like as plasticizers to the above-mentioned mixture.
0% by weight is preferred. The plasticizer may be added in advance to the Al 7J aqueous solution, or may be added before, at the same time, or in one pot when adding gelatin. Preferably, it is added before adding gelatin. The capsule-forming agent of the present invention may further contain a masking agent such as titanium liquefied or a dye.

Although the order of addition is not particularly limited, they are usually added before or after adding gelatin. The resulting aqueous solution of the capsule forming agent is used to soft capsule the encapsulated component. This soft encapsulation method is used, for example, in Japanese Patent Application Laid-Open No.
The method described in No. 8875 may be used. The soft capsules obtained are dried and then acid treated. Acid treatment is usually carried out by immersion in an aqueous solution.

The acid used is an organic or non-alcoholic acid such as hydrochloric acid, phosphoric acid, acetic acid, lactic acid, etc., and the acid solution is usually 1 to 20% by weight, preferably 5 to 15% by weight, preferably at 15°C or lower. Treat the pox for 1 to 10 minutes, especially 2 to 5 minutes, especially at a temperature below 10°C. A particularly preferred acid is hydrochloric acid. 1! Rinse the drip-resistant soft capsules with water and dry them. Washing temperature is 10℃
It is preferable to carry out the following, with n and 1 being 2 to 10 minutes;
In particular, around 3 minutes is appropriate. It goes without saying that the conditions in E below are not necessarily limited and can be arbitrarily selected depending on the film-forming substance used, its blending amount, etc.

The enteric-coated soft capsules obtained by the present invention have not only passed the enteric-coated soft capsule disintegration test specified in A3 of the 10th edition of the Japanese Pharmacopoeia, but also the enteric-coated soft capsule lji of the 9th edition of the Japanese Pharmacopoeia.
It also passes the destructive test method. Also, the manufacturing method is very simple,
Moreover, it is possible to obtain a uniform product.

The present invention will be explained below with reference to Examples.

Example 1 1.3 parts by weight of 28% ammonia water to 73.7 parts by weight of water (a)
To this was added 1.5 parts of methacrylic acid-methacrylic acid alkyl ester copolymer (manufactured by Palmer Co., Ltd.: A Itrakit 1 to 1-100), and 50 parts.
'C Stir until uniformly dissolved.

To this, Tsurupi 1-2.5 M part d5 Yohigi Latin 18
A weight part of the mixture is added and uniformly dissolved to prepare a turnip-forming agent composition. Separately, prepare a component to be converted into a curd, which is dispersed in 10 parts by weight of bizacodyl and 90 parts by weight of vegetable oil.

Next to one soft cabrel, 100 m of the above-mentioned component to be converted into cabrel
50m of a composition that turns g into a cabzel! II (in terms of solid content) to produce soft capsules with a diameter of 6.4 mm 3. The soft capsules were dried at 20°C under air blowing, and the obtained dry soft capsules were mixed with a 10% HCffi aqueous solution (10'
C) for 3 minutes, then soaked in tap water (10'C)
After washing for 3 minutes, it was dried at 20°C. The obtained soft caprels were subjected to a soft capsule disintegration test according to the 9th and 10th edition Japanese Pharmacopoeia. The results are shown in Table-1.

Example 2 Methacrylic acid of Example '1 as the +1Q-forming bamboo material
Other than using 7.5 parts by weight of methacrylic acid argyl ester copolymer (instead, phthalic acid 1 to pyrumethyllerulose (manufactured by Shin-Etsu Chemical Co., Ltd., l-IPMCP)) Soft capsules were obtained in the same manner as in Example 1.

The results of this disintegration test are also shown in Table-1.

Example 3 The same procedure as Example 1 was used except that 7.0 parts by weight of the methacrylic acid-methacrylic acid alkyl ester copolymer (Koyari, cellulose acetate phthalate (manufactured by Wako Pure Chemical Industries, Ltd., CAP) of Example 1 was used. Soft capsules were obtained in the same manner.The results of the disintegration test of the obtained soft capsules are shown in Table-1.

Claims (1)

[Claims] 1. Gelatin is dissolved in an alkaline aqueous solution of a film-forming substance that dissolves in alkalinity but does not dissolve in pt-15 or less, and the encapsulated component is 7J encapsulated with this solution, and then dried. 1. A method for producing enteric-coated soft capsules, which is then treated with an acid. 2. The method according to item 1, 8, wherein the film-forming substance is a copolymer of α,β-ethylenically unsaturated carboxylic acid. 3. The method according to item 2, which is a copolymer having α,β-ethylenically unsaturated carboxylic acid and acrylic acid or methacrylic acid as at least its component. 4. The method according to item 1, wherein the film-forming substance is a polycarboxylic acid-modified cellulose derivative. 5. The method described in Section 1, 8e, in which the acid treatment is performed with a 1-(9λ aqueous solution).