JPH0466204B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a gelatin capsule coating with improved solubility using a natural calcium phosphate compound, a synthetic calcium phosphate compound, or a protein-containing natural or synthetic calcium phosphate compound as an opacifying agent. For gelatin capsules, excellent solubility after oral administration is an essential quality characteristic for improving the absorption and quick-acting properties of pharmaceuticals. Particularly for soft capsules, since it is necessary to use glycerin, titanium oxide, etc., a decrease in solubility and deterioration over time are often problems. Traditionally, gelatin was used as a plasticizer in soft capsules.
20 to 40 parts by weight of glycerin is used per 100 parts by weight, but when added in an appropriate amount that does not soften the film, gelatin becomes insolubilized over time due to crosslinking reactions caused by its decomposed products. Capsule solubility decreases. Furthermore, if the contents have poor stability against light, an opacifying agent such as titanium oxide or calcium carbonate is used, but this also reduces solubility. Addition of low-molecular substances such as organic acids and amino acids, and enzymes are known as methods for improving _{solubility .} =3.0~
By using a calcium phosphate compound with a rating of 3.4, it has excellent solubility and does not cool down over time.
It has been found that a good opaque gelatin capsule film can be formed. The present invention provides a molar ratio of calcium and phosphorus, CaO/
Natural calcium phosphate compounds, such as calcined bone meal, hexite, phosphate rock, containing in a ratio of P ₂ O ₅ = 3.0 to 3.4; and synthetic calcium phosphate compounds, such as tricalcium phosphate, hydroxyapatite; or natural or protein-containing calcium phosphate compounds; Concerning a gelatin capsule film obtained by adding 0.5 to 70 parts by weight of a synthetic calcium phosphate compound, such as cow, pig, and chicken bone meal and deflated bone meal, in the form of a fine powder of not more than 60 Tyler meshes, to 100 parts by weight of gelatin. It is. The amount of calcium phosphate added is preferably between 0.5 and 70 parts by weight per 100 parts by weight of gelatin; if it is less than 0.5 parts by weight, the opacity will decrease, and if it is more than 70 parts by weight, the formation of a film will be poor. A more practically preferred range is 1 to 20 parts by weight. Furthermore, the powder
It is best to pass through a Tyler 60 mesh sieve; if it is coarser than this, the surface of the film will lose its flat bones, and the solubility of the compound itself will be poor. In the present invention, to produce the film, a conventional method for producing a film for soft capsules or hard capsules can be used, and for encapsulation, all conventional methods can be applied. For example, for soft capsules, gelatin is used as a base, and if necessary, plasticizers such as glycerin and sorbitol, colorants and fragrances are added.
Preservatives such as paraoxybenzoic acid ester and sorbic acid ester may be used, and titanium oxide,
Concomitant use of other opacifying agents such as calcium monohydrogen phosphate is also possible. The contents of the coated gelatin capsule according to the present invention are not limited to any form, such as liquid, powder, or granule, and can also be other orally acceptable substances in addition to pharmaceuticals. The film according to the present invention improves the solubility and light-shielding properties of gelatin capsules, is a chemically stable film, has little interaction with the contents, and has no problem with its stability to the human body when administered orally. It can also be expected to have nutritional value as a calcium source. The present invention will be explained in more detail below based on Examples and Comparative Examples, but these are not intended to limit the present invention. Example 1 4 w/v % phosphoric acid solution 1 was added to 100 w/v % calcium chloride (dihydrate) solution 1 at room temperature with strong stirring, and stirring was continued for 30 minutes. 10% of reaction solution
After boiling for several minutes, it was filtered, and the resulting filter cake was thoroughly washed with water, dried at 100°C for 3 hours, calcined at 800°C, crushed, and passed through a Tyler 200 mesh sieve to obtain 60g of powder. Regarding the obtained powder, phosphorus and calcium were determined by phosphovanadomolybdic acid absorption spectrophotometry and EDTA titration, respectively, and the molar ratio of CaO/P ₂ O ₅ was 3.33. Furthermore, a hydroxyapatite peak was detected by X-ray analysis and infrared absorption.

[Table] First, add gelatin to the recipe shown in Table 1.
Swell 100g with 150g of water and 30g of glycerin for 1 hour, dissolve at 65℃, and add 2g of apatite to the solution for 50g.
Disperse the liquid in 50g of water and homogenize it with a 50ml homogenizer for 10 minutes. After stirring and dissolving, heat at 65°C.
Defoaming was performed for 30 minutes using a vacuum pump. This liquid was poured onto a stainless steel plate to form a film with a thickness of 2 mm, and dried with hot air at 35°C for 10 hours to obtain a capsule film. The dissolution time of the resulting film was measured using a pharmacopoeial disintegration test method. As a control, a test was also conducted on a film obtained by the same manufacturing method using the same weight of titanium oxide. Table 2 shows the results for 30 samples.

[Table] The results of the contingency table test were significant at 1%, indicating that the film of the present invention had superior solubility compared to the control. Regarding the film obtained in Example 1, the temperature was 45°C and the humidity was 60°C.
Table 3 shows the average values of 10 samples that were stored for 3 months in an atmosphere of 10% and tested for deterioration of dissolution time over time.

[Table] The results of the analysis of variance test were significant at 1%, indicating that the film of the present invention showed less change over time than the control. Example 2 Slaughtered beef bones were ground into pieces with a diameter of about 1 cm, 500 g of which was placed in a homogenizer, and washed with running water for 30 minutes.
It was placed in a basket and rinsed in boiling water for 1 to 2 minutes to degrease it. The defatted bones were placed on a wire mesh and dried at 40°C for 5 hours, then placed in a gas furnace, baked at 800°C, cooled, and crushed.
The calcined bone meal was obtained through a Tyler 200 mesh sieve. A film was formed using the same manufacturing method as in Example 1 except that calcined bone powder was used in place of the apatite in Example 1, and the change in dissolution time depending on the amount added was examined. Table 4 shows the average value of 10 samples using titanium oxide as a control.

[Table] The result of the analysis of variance test was 5% significant, and the film of the present invention was superior in dissolution time compared to the control at each addition amount.

Claims (1)

[Claims] 1 Calcium and phosphorus as CaO/P ₂ O ₅ 3.0
natural calcium phosphate compounds, synthetic calcium phosphate compounds, in a molar ratio of ~3.4;
Or a gelatin capsule film containing 0.5 to 70 parts by weight of a natural or synthetic calcium phosphate compound containing protein in the form of a fine powder after passing through a 60-mesh sieve, based on 100 parts by weight of gelatin.