JPS6334122B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an improved method for manufacturing enteric-coated capsules. Enteric-coated capsules enclose pharmaceutical products and are either ingested or administered rectally as suppositories.
As such capsules, methods are known in which capsules made of gelatin are treated with formalin as a base, coated with an enteric polymer material, or capsules are manufactured from the enteric polymer material itself. However, gelatin-based enteric-coated capsules do not dissolve in gastric fluid when treated with formalin, making it difficult to control the process to dissolve them in intestinal fluid, and when coated with enteric-coated polymeric substances, gelatin There are problems such as poor adhesion between the surface and the coating film. To manufacture capsules using the enteric polymer material itself, immerse a molding pin in an organic solvent solution of the enteric polymer material in the same manner as in the production of gelatin capsules, and then
The capsule is pulled up, dried, and extracted, but in conventional manufacturing methods, the molded capsule adheres to the pin, making it difficult to extract using normal methods. The inventors of the present invention investigated various methods for solving the above-mentioned drawbacks and making it easier to remove the capsules, and found that by applying carnaupal wax or beeswax as a release agent to the molding pin before immersion, the capsule can be easily removed from the pin. The present invention was completed based on the discovery that this can be done. That is, the present invention provides an enteric-coated capsule characterized by applying carnaupal wax or beeswax to the surface of the molding pin prior to dipping the molding pin in a solvent solution of an enteric-coated polymer substance to produce an enteric-coated capsule. The present invention relates to a method for manufacturing capsules. To explain this, carnaupal wax and beeswax exhibit excellent mold release properties even when they come into contact with organic solvents, and even when they are attached to capsules and taken together with pharmaceuticals, they have traditionally been used as lubricants or long-lasting tablets. As is clear from the fact that it is used as a disintegration prolonging agent, it has the advantage of being harmless to the human body. In the method of the present invention, a molded pin is coated with carnaupal wax or beeswax in advance. Methods for this application include immersing the molding pin in molten carnaupal wax or beeswax and pulling it up; Alternatively, there is a method of immersing it in beeswax, or a method of applying a solution of the coating agent in an organic solvent such as chloroform to the molding pin.
The application method is not particularly limited to these, and other application methods may be used. Enteric polymeric substances used in the method of the present invention include cellulose derivatives such as cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, cellulose acetate succinate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, methacrylic acid and methacrylic acid. Examples include vinyl polymers such as methyl ester copolymers and copolymers of styrene and maleic acid, and polyvinyl alcohol derivatives such as polyvinyl phthalate. In addition, the solvent used for preparing the immersion liquid is
Although it may differ depending on the type of enteric polymer substance, generally an organic solvent or a mixed solvent of organic solvent and water is used, and organic solvents include alcohols such as methyl alcohol, ethyl alcohol, and isopropyl alcohol, acetone, and methyl ethyl ketone. Examples include ketones such as dioxane, ethers such as methyl cellosolve and ethyl cellosolve, and chlorinated hydrocarbons such as methylene chloride. Note that these solvents are not limited to one type, and may be used as a mixed solvent of two or more types or as a mixed solvent with water. The concentration of the enteric polymer substance is determined taking into account the ease of molding operation using pins, etc., and is usually in the range of 5 to 40% by weight. When the purpose is to obtain thin-walled capsules, it is desirable to use a low-concentration immersion liquid, and when the purpose is to obtain thick-walled capsules, it is desirable to use a high-concentration and viscous immersion liquid. It should be noted that various additives such as coloring agents, flavoring agents, fragrances, plasticizers, fillers, etc. may be added to the dipping liquid as necessary, but these additives may It should be kept within a range that does not adversely affect the original function. Enteric-coated capsules are specifically manufactured by the following steps. First, carnaupal wax or beeswax is applied to a molding pin, which is dipped into a solvent solution of an enteric polymeric substance.Then, the pin is pulled up and the viscous film that has formed around the pin is dried. By pulling out the capsule from the pin and cutting off unnecessary parts, an enteric-coated capsule having the desired size and shape can be obtained. In some cases, post-drying may be performed to reduce the amount of solvent (organic solvent) remaining in the capsule. Next, a specific example will be given. Example A molding pin made of SUS-304 and having a shape corresponding to the body of gelatin capsule No. 1 coated with various mold release agents is immersed in a solution of an enteric polymer substance in an organic solvent or an organic solvent-water mixed solvent. After being pulled up, the pieces were air-dried for 1 hour, then 50°C for 1 hour, and then 70°C for 1 hour, and a manual sampling test was conducted to compare the mold releasability. The results are shown in the table below, and carnaupal wax and beeswax showed good mold release performance. The enteric polymer substances used here are as follows. Hydroxypropyl methylcellulose acetate succinate (abbreviated as HPMC-AS) Number of substitutions per anhydroglucose unit Hydroxypropoxyl group 0.26 Methoxyl group 1.82 Acetyl group 0.43 Succinoyl group 0.43 Hydroxypropyl methylcellulose phthalate (Shin-Etsu Chemical HP-55) Anhydrous glucose Number of substitutions per unit Hydroxypropoxyl group 0.25 Methoxyl group 1.85 Phthalyl group 0.72 Carboxymethylethyl cellulose (abbreviated as CMEC) Number of substitutions per anhydroglucose unit Carboxymethyl group 0.55 Ethoxyl group 2.14 Methacrylic acid - methacrylic acid methyl ester co Polymer (abbreviated as PMA-MMA) Methacrylic acid; Methyl methacrylate = 55:45 (mole ratio) In addition, the abbreviations used in the solvent section in the following table are as follows. DCM: dichloromethane, EtOH: ethyl alcohol, MeOH: methyl alcohol, IPA:
Isopropyl alcohol.

[Table] ○: Good releasability, △: Difficult to release, ×: Unable to release.

Claims (1)

[Claims] 1. A method for manufacturing enteric-coated capsules, which comprises applying carnaupal wax or beeswax to the molding pin prior to dipping the molding pin in a solvent solution of an enteric polymeric substance.