JPH0710746A - Hard capsule agent improved in adhesivity on administration - Google Patents

Abstract

PURPOSE:To obtain the subject hard capsule agent coated with a water-repelling substance such as physiologically acceptable solid paraffin, carnauba wax or silicone oil, not adhered to throats or esophagi on administration, and improved in adhesivity. CONSTITUTION:Capsules comprising granule-containing gelatin and water are charged in a sugar-coating pan, rotated at 40rpm, simultaneously mixed with a coating solution, subjected to the development of the coating solution, and subsequently dried at a temperature of 40 deg.C to provide the objective hard capsule agent not adhered to throats and esophagi on administration and improved in the adhesivity on the administration. The water-repelling substance is desirably used in an amount of 0.1-10wt.% based on the capsule basic material. As the coating solution, that containing one or more kinds among solid paraffin, carnauba wax, silicone oil, white wax, stearic acid, stearyl alcohol, shellac, etc., dissolved in ethanol, n-hexane, etc., is used.

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a hard capsule having improved adhesion when the hard capsule is taken.

[0002]

Hard capsules are widely used as a dosage form of solid preparations, but when they are taken, they may adhere to the throat and esophagus, disintegrate, or develop ulcers due to drug elution. [Clin. Pharmac., 18, p. 250 (1984), Cl
in. Pharmacol Ther. , Jan. 72 (1985), Britis
h. Medical. Journal. Volume 1, p. 1673 (1979)]. Conventionally,
No attempt has been made to solve such problems. As a result of various investigations by the present inventors to solve the above problems, the adhesion phenomenon of hard capsules was found to be adhered to the throat and esophagus when ingested because gelatin, which is the main ingredient of the capsules, is easily soluble in water and has an adhesive property. In order to make it easier to pass through the throat and esophagus, by coating the surface of the hard capsule with a water-repellent substance to the extent that it does not impair the fast-disintegrating function that is characteristic of hard capsules. I found that I can improve the sex.

[0003]

That is, the present invention relates to a hard capsule having a surface coated with a physiologically acceptable water-repellent substance. In the present invention, the physiologically acceptable water-repellent substance has a solubility in water at 25 ° C. of not more than 0.03 g / l. Examples of this include paraffin (liquid paraffin, solid paraffin),
C15-55 aliphatic saturated hydrocarbons such as microcrystalline wax, such as carnauba wax, hardened oil, white beeswax, white wax, and other oils and fats having a melting point of 60 to 90 ° C, silicone oil, silicone resin, etc. 25 ° C
Having a viscosity of 95 to 1050 centistokes, fatty acids such as stearic acid, fatty acid esters such as sucrose fatty acid ester, glycerin fatty acid ester and polyglycerin fatty acid ester, such as stearyl alcohol and cetanol, melting point 4 to 65 ° C polyhydric alcohols and shellac,
Examples include polymers used as a film base such as ethyl cellulose. Among them, solid paraffin, carnauba wax, silicone oil, silicone resin, white wax, stearic acid, stearyl alcohol, shellac are preferable.

To coat a hard capsule, a physiologically acceptable water-repellent substance (hereinafter also referred to as a coating agent) is dissolved by heating or in an organic solvent to prepare a coating solution, which is coated according to a conventional method. It is carried out by coating a hard capsule with a device. The water-repellent substance is dissolved by heating by heating it to a temperature equal to or higher than the melting point of the water-repellent substance. Examples of the organic solvent that dissolves the water-repellent substance include normal hexane, methylene chloride, alcohol and the like. In this case, the concentration of the water-repellent substance is not particularly limited, but normally 5% by weight to the saturated concentration is preferable. Among them, those close to the saturated concentration are particularly preferable. If the concentration is too low, it takes time to dry, which is not preferable in practice. Any conventional coating device can be used, for example, High Coater (Freund Sangyo KK), Accela Coater (Manestie), Doria Coater (Pawreck), Sugar Coat Bread (Kikusui Seisakusho), VG Coater (Kikusui Seisakusho). ) Etc. are preferably used. The coating liquid has a coating amount of 0.1 to 10.0% by weight, preferably 0.5 to 1.5% by weight, based on the capsule base. The thickness of the coating agent layer formed on the surface of the hard capsule is preferably 0.1 to 100 µ, and particularly preferably 1 to 50 µ. If the coating layer is too thick, capsule disintegration will be delayed, which is not preferable. If the coating agent layer is too thin, the effect of the present invention will not be sufficiently exhibited.

In addition to the above-mentioned water-repellent substances, coating liquids include, for example, coating aids (eg polyethylene glycol, glycerol, polysorbate 80, etc.), flavoring agents (eg sucrose, lactose, mannitol, maltitol, etc.).
Sorbitol, xylit, aspartame, stevia, saccharin, etc.), flavoring agents (eg, menthol, peppermint oil, lemon oil, banana oil, etc.), coloring agents (eg, tar-based food dyes, aluminum lake, red iron oxide, titanium oxide, etc.) May be. These are usually 0.1-
It is compounded in the range of 10% by weight. The thus obtained hard capsule of the present invention is filled with pharmaceutical powders, granules, semi-solids, liquids and the like and used orally as in the conventional hard capsules.

[0006]

EXAMPLES The present invention will be described in more detail with reference to the following examples. The methods for evaluating the ingestability and disintegration of the capsules in each example are as follows. 1) Ingestibility (sensory evaluation) Take the prepared capsule without water, stick to the throat,
The presence or absence of residual feeling was evaluated. (5 panelists were used) 1: Easy to pass without sticking 2: Easy to pass without sticking but with a slight residual feeling 3: Slightly sticky or residual feeling 4: With sticky feeling or residual feeling 2) Disintegration (Japan Post Office 12) Time from the start to the end of the release of the contents granules after the capsules are disintegrated by the disintegration tester (water 37 °, with disc)

Example 1 500 g of No. 1 capsule filled with granules (about 1119c
p, 447 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. ) Sugar-coated bread (1
2 inch) was charged, various coating liquids were added while rotating (40 rpm), spread and dried (40 ° C) to obtain a sample. Comparative product Hard capsule after filling (gelatin 85 wt%, water 15 wt%) 447.00 mg (empty capsule 77.00 mg) Invention product 1 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight empty capsule Ratio to shellac 0.46 mg 0.60 W / W% castor oil 0.12 mg 0.16 W / W% carnauba wax 0.52 mg 0.68 W / W% (99% ethanol 4.2 μl) (n-hexane 3.1) μl) Total 1.44 W / W%

[Table 1] The product of the present invention has no change in disintegration, sticking during administration,
The residual feeling was eliminated and the drugability was improved. The comparison product is
It was sticky and had a residual feeling.

Example 2 500 g of No. 1 capsule filled with granules (about 1119c
p, 447 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. ) Was charged into a high coater (HCT-20), and various coating solutions were sprayed and dried (40 ° C.) while rotating (20 rpm) to obtain a sample. Inventive product 2 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight ratio to empty capsule Carnauba wax 0.38 mg 0.49 W / W% Shiro wax 0.04 mg 0.05 W / W% (n -Hexane 8.4 μl) Total 0.54 W / W%

[Table 2] The product of the present invention showed a tendency of improved ingestibility.

Example 3 No. 2 capsule filled with granules 500 g (about 2000 c)
p, 255 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. ) Is charged into a high coater (HCT-20), various coating liquids are added while rotating (20 rpm), and after spreading (40 ° C.).
It was used as a sample. Invention 3 Hard capsule after filling 255.00 mg (empty capsule 65.00 mg) Coating liquid composition Weight ratio to empty capsule Silicone oil 1.79 mg 2.75 W / W% (KS66)

[Table 3] The product of the present invention was found to have improved ingestibility.

Example 4 No. 1 capsule filled with granules 500 g (about 1119c)
p, 447 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. Was charged into a doria coater (DC2500), and various coatings were spray-dried (40 ° C) while rotating (40 rpm) to obtain samples. Invention 4 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight ratio to empty capsule Carnauba wax 0.20 mg 0.26 W / W% White wax 0.03 mg 0.04 W / W% Silicone oil 4.47 mg 5.81 W / W% (KS66) (n-hexane 4.4 μl) Total 6.11 W / W% Invention 5 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight Percentage of empty capsule Carnauba wax 0.20 mg 0.26 W / W% White wax 0.03 mg 0.04 W / W% Silicone oil 0.89 mg 1.15 W / W% (KS66) (n-hexane 4.4 μl) Total 1.45W / W%

Invention 6 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight ratio to empty capsule Carnauba wax 0.40 mg 0.52 W / W% White wax 0.06 mg 0.08 W / W % Silicone oil 1.79 mg 2.32 W / W% (KS66) (n-hexane 8.8 μl) Total 2.92 W / W%

[Table 4] The product of the present invention was found to have improved ingestibility. The comparative product had a sticky feeling after use and a residual feeling.

Example 5 No. 1 empty capsule 500 g (about 6500 cp, the composition of the empty capsule is 85% by weight of gelatin and 15% by weight of water) was charged into a VG coater, and the pressure was reduced (about 100 mm).
Hg) The coating solution was sprayed and dried (40 ° C) to obtain a sample. Invention 7 Empty capsule 77.00 mg Coating liquid composition Weight Ratio to empty capsule Solid paraffin 0.89 mg 1.16 W / W% (n-hexane 89.0 μl)

[Table 5] The product of the present invention did not impair the disintegration property and had improved ingestibility.

Example 6 500 g of No. 1 capsule filled with granules (about 1119c)
p, 447 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. ) Was put in a pan for sugar coating, various coatings were added while rotating (40 rpm), and after spreading (40 ° C.), a sample was obtained. Invention product 8 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating liquid composition Weight ratio to empty capsule Carnauba wax 0.20 mg 0.26 W / W% White wax 0.03 mg 0.04 W / W% Solid type Paraffin 0.45 mg 0.58 W / W% (n-hexane 49.4 μl) Total 0.88 W / W% Invention 9 Hard capsule after filling 447.00 mg (empty capsule 77.0 mg) Coating solution composition Weight empty capsule Ratio to Carnauba wax 0.20 mg 0.26 W / W% white wax 0.03 mg 0.04 W / W% solid paraffin 0.89 μl 1.16 W / W% (n-hexane 93.4 μl) total 1.46 W / W%

[Table 6] The product of the present invention did not impair the disintegration property and had improved ingestibility.
Each of the invention products has improved ingestibility, particularly invention product 7,
The doses of 8 and 9 were excellent. In the storage test, the capsules were also good at 60 ° -4 weeks without any sticking between the capsules.

Example 7 No. 1 capsule filled with granules 500 g (about 1119c)
p, 447 mg / cp, empty capsule composition is gelatin 8
It consists of 5% by weight and 15% by weight of water. ) Was charged into a high coater (HCT-20), and various coating solutions were sprayed and dried (40 ° C.) while rotating (20 rpm) to obtain a sample. Inventive product 2 Hard capsule after filling 447.00 mg (empty capsule 77.00 mg) Coating solution composition Weight ratio to empty capsule Carnauba wax 0.42 mg 0.54 W / W% (n-hexane 8.4 μl) Total 0.54 W / W%

[Table 7] The product of the present invention showed a tendency of improved ingestibility.

[0015]

EFFECTS OF THE INVENTION According to the present invention, sticking to the throat and esophagus can be eliminated when taking a hard capsule, and the adhesiveness when taking can be improved.

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Claims (7)

[Claims] 1. A hard capsule which has a surface coated with a physiologically acceptable water-repellent substance. 2. The hard capsule according to claim 1, wherein the amount of the physiologically acceptable water-repellent substance used is 0.1 to 10% by weight based on the capsule base. 3. The hard capsule according to claim 1, wherein the surface coating layer made of a physiologically acceptable water-repellent substance has a thickness of 0.1 to 100 μm. 4. The solubility in water at 25 ° C. is 0.0.
The hard capsule preparation according to claim 1, wherein a physiologically acceptable water-repellent substance of 3 g / l or less is used. 5. A water-repellent substance is a saturated aliphatic hydrocarbon having 15 to 55 carbon atoms, an oil or fat having a melting point of 60 to 90 ° C., a silicone having a viscosity of 95 to 1050 centistokes at 25 ° C., a fatty acid or a fatty acid ester. The hard capsule according to claim 1, which is one or more selected from the group of polyhydric alcohols having a melting point of 4 to 65 ° C. 6. The hard capsule according to claim 1, wherein the water-repellent substance is one or more selected from the group consisting of solid paraffin, carnauba wax, silicone oil, silicone resin, white wax, stearic acid, stearyl alcohol and shellac. . 7. The hard capsule according to claim 1, wherein the water-repellent substance is one or more selected from the group consisting of solid paraffin, carnauba wax, silicone oil, white wax and shellac.