JPH0419210B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to the improvement of a method for obtaining enteric coated preparations by coating solid drugs such as tablets, granules, and capsules with an enteric film base material. The object of the present invention is to obtain a formulation with excellent storage stability in terms of performance. Conventionally, it has been known to use hydroxypropyl methylcellulose phthalate (HPMCP), cellulose acetate phthalate (CAP), etc. as enteric film base materials for the purpose of obtaining enteric coated preparations, and enteric coated drugs are used for general solid drugs. Enteric-coated preparations have been obtained that are practically satisfactory in terms of storage stability and performance, although there are differences in degree. However, when the solid drug to be coated is particularly a soft gelatin capsule or a tablet or granule containing an alkaline substance, an enteric-coated preparation obtained by coating them with the above-mentioned enteric-coated film base material has the problem that its gastric juice resistance gradually decreases during storage and its enteric properties disappear. As a result of investigating the cause of the gradual decline in gastric juice resistance, we found that this is because when film layers such as HPMCP and CAP come into contact with soft gelatin capsules or alkaline substances, the carboxyl groups in the molecules of the film base material are released. It was presumed that this was due to separation, or some components in the solid drug migrated to the enteric film layer, thereby reducing the mechanical strength of the film layer. With this in mind, the present inventors have conducted extensive research into ways to solve this problem, and have found that it is possible to significantly reduce the They found that this can be improved and completed the present invention. That is, the present invention relates to a method for producing an enteric-coated preparation, which comprises providing an undercoating layer made of a film base material containing higher fatty acids on the surface of a solid drug, and then forming an enteric coating layer. . To explain this, examples of higher fatty acids used in the undercoating layer include stearic acid, palmitic acid, oleic acid, and linoleic acid. This undercoating layer formation is carried out by incorporating the higher fatty acid into the film layer, but there are no particular restrictions on the type of film base material for this purpose as long as it forms a uniform film layer. However, from a practical standpoint, cellulose ethers such as hydroxypropyl methylcellulose (HPMC) and hydroxypropylcellulose (HPC) are preferred, and enteric film base materials such as HPMCP and CAP may also be used. . The undercoating layer is formed using a coating liquid prepared by dissolving or dispersing a predetermined amount of a higher fatty acid in an organic solvent solution, aqueous solution, or mixed solvent solution of alcohol and water of the film base material. Incidentally, a plasticizer such as polyethylene glycol or propylene glycol, or a surfactant to improve the dispersibility of higher fatty acids may be added to this coating liquid, if necessary. The amount of higher fatty acids in the film layer formed by this undercoating is 5 to 200.
The amount of undercoating for a solid drug is preferably 10 to 100% by weight, and the amount of undercoating for a solid drug is 0.2 to 5% by weight for tablets or soft gelatin capsules. For granules, it is desirable to set the content to 1 to 10% by weight, which solves the disadvantage that enteric-coated preparations gradually become poor in gastric fluid resistance during storage and the disadvantage that enteric-coated properties begin to disappear. Ru. After undercoating, an enteric coating layer is formed, and the enteric film base material used here is HPMCP.
Alternatively, CAP is an example. The enteric coating layer may be provided by any conventionally known general method. That is, a coating liquid is prepared by dissolving the enteric film base material in a solvent such as an organic solvent or a hydrous alcohol, or by dispersing fine powder of the enteric film base material in water containing a plasticizer, which is known in the art. Coating can be carried out using the following coating equipment. As this coating device, a bun coating device, a fluid coating device, or a pan coating device in which dry air penetrates between the solid drugs to be coated in the pan is used. The amount of enteric coating is determined by the solids content relative to the weight of the solid drug;
For tablets or soft gelatin capsules it is preferably 2 to 20% by weight, and for granules it is preferably 5 to 50% by weight. The method of the present invention is particularly effective for soft gelatin capsules or tablets or granules containing alkaline substances. This soft gelatin capsule is generally in a commercially available form, and most of them have an oily substance encapsulated inside. In addition, alkaline substances contained in tablets or granules include salts such as lithium carbonate, sodium salicylate, sodium ascorbate, and sodium benzoate, various amino acids, and various amines, and when dissolved or dispersed in water, It is more alkaline than pH 6-7. The reason why the above effects are brought about by including higher fatty acids in the undercoating layer by the method of the present invention is not necessarily clear, but some components in soft gelatin capsules or alkaline components in tablets and granules are added to the coating layer. This is thought to be because, even if it migrates, it is first captured in the undercoating layer and is prevented from migrating to the outer enteric coating layer. Note that even if the undercoating layer contains a low molecular acid such as citric acid, the effects of the present invention cannot be obtained. Next, specific examples will be given. However, in the following description, "parts" or "%" simply indicate parts by weight or % by weight. Example 1 Each 1 kg of elongated soft gelatin capsules containing 800 mg of soybean oil per capsule was loaded into a small pan coating device (manufactured by Freund Sangyo), and undercoated using the coating liquid of each formulation shown in Table 1. And overcoating (enteric coating according to the present invention) was performed. However, the amount of coating relative to the weight of the soft gelatin capsule was as follows. Undercoating amount: 1.9 to 2.1% Overcoating amount: 5.8 to 6.2% In Experiment No. 1, only overcoating was performed without undercoating.

[Table] When each coating preparation obtained as above was sealed in a glass bottle and then left in a thermostat at 40℃ for 1 month, 2 months, or 4 months, and when such storage was not carried out. When each sample was subjected to the Japanese Pharmacopoeia's "disintegration test for enteric-coated preparations", the results were as shown in Table 2.

【table】

[Table] (Note) * Not tested because it did not meet the test with the first liquid Example 2 Weight 300 containing 150 mg of lithium carbonate per tablet
mg tablets (approximately 9.5 mm in diameter) were prepared. This tablet 1
Kg was loaded into a small pan coating device, and the following undercoating and overcoating were performed. However, in the comparative example, undercoating was not performed, and only overcoating was performed under the same conditions. Undercoating liquid formulation: Stearic acid 4 parts HPMCP (HP-55S) 6 parts Ethanol 80 parts Water 10 parts Overcoating liquid formulation: HPMCP (HP-55S) 6 parts Ethanol 80 parts Water 14 parts Coating amount per tablet weight is undercoating 1.1%, overcoating
The coating amount of the comparative example was 6.9%, and the coating amount of the comparative example was 7.0%. When the same tests as in Table 2 above were conducted on the coated preparations obtained as described above that were left as they were at 40°C and 75% RH for 3 months, and those that were not left as they were, it was found that The results shown in the table were obtained.

[Table] (Note) The test was not conducted because it did not comply with the test using the first liquid.
Example 3 20-30 mesh spherical granules containing 500 mg of sodium salicylate per gram of granules were prepared. 1 kg of the granules were loaded into a fluidized fluid coating system WSG-1 (manufactured by Okawara Seisakusho), and the following undercoating and overcoating were performed. However, in the comparative example, undercoating was not performed, and only overcoating was performed under the same conditions. Undercoating liquid formulation: Stearic acid 5 parts HPMC (TC-5R) 5 parts Isopropanol 80 parts Water 10 parts Overcoating liquid formulation: HPMCP (HP-55S) 5 parts Methylene chloride 50 parts Ethanol 45 parts However, coating per granule weight The amount is undercoating 3%, overcoating 16%
%, and the coating amount of the comparative example was also 16%. When the same tests as in Table 2 above were conducted on the coated preparations obtained as described above that were left as they were at 40°C and 75% RH for 3 months, and those that were not left as they were, it was found that The results shown in the table were obtained.

[Table] (Note) The test was not conducted because it did not comply with the test using the first liquid.

Claims (1)

[Claims] 1. An undercoating layer made of a film base material containing higher fatty acids is provided on the surface of a solid drug,
A method for producing an enteric coated preparation, which comprises subsequently forming an enteric coating layer. 2 The film base material used for forming the undercoating layer is hydroxypropyl methylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate,
or cellulose acetate phthalate, the method for producing an enteric coated preparation according to claim 1. 3. The method for producing an enteric coated preparation according to claim 1, wherein the enteric film base material of the enteric coating layer is hydroxypropyl methyl cellulose phthalate or cellulose acetate phthalate. 4. The method for producing an enteric coated preparation according to claim 1, wherein the solid drug is a soft gelatin capsule, or a tablet or granule containing an alkaline substance.