JP2808231B2 - Soft coated capsule - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a soft capsule which prevents the soft capsules from adhering to each other and the soft capsules from adhering to a container or the like, and maintains the transparency of the film.

[0002]

2. Description of the Related Art In a soft capsule, gelatin is mixed with a plasticizer such as glycerin or sorbitol, and the strength of the soft capsule is improved by these plasticizers.

[0003] However, soft capsules to which a plasticizer is added have the disadvantage that they tend to absorb moisture and tend to adhere to each other and to containers and the like. For this reason, soft capsules stored under hot and humid conditions are
There has been a problem that the work efficiency is lowered during manufacturing and it is difficult to take it out of a container or the like during taking. Conventionally, as a means for solving such a drawback, a method of adding an anti-adhesion agent to the film of a soft capsule (JP-A-2-180815, JP-A-3-988638).
JP-A-5-4914) and a method of adhering fats and oils to the surface of a soft capsule film (JP-A-56-15).
No. 6212, JP-A-1-42419, JP-A-1-79
No. 110, JP-A-4-288011, JP-A-6-40
No. 891).

However, in the method of adding an anti-adhesion agent, the resulting capsule preparation film has poor transparency, the surface becomes uneven, and the feeling of taking is reduced. However, there are drawbacks such as a problem that the dissolution of a medicinal component is lowered and a problem that the excipient exceeds the maximum precedent of approved use of a pharmaceutical additive.

On the other hand, in the method of adhering fats and oils, the effect of preventing adhesion of capsules is insufficient, the effect of preventing adhesion is lost at high temperature and high humidity, and the transparency of the film is further impaired, resulting in poor commercial value. There was a problem such as falling.

[0006]

Accordingly, an object of the present invention is to provide a soft capsule which does not adhere to other capsules or containers even under conditions of high temperature and high humidity, maintains the transparency of the film, and is stable even at room temperature. To provide a soft capsule which can be stored for a long period of time.

[0007]

In this situation, the present inventors have conducted intensive studies. As a result, if the hydroxyalkyl-substituted cellulose or / and polyvinyl acetal-based polymer is transparently coated on the film of the soft capsule, the above-mentioned adhesion is obtained. The present inventors have found that a soft capsule which has improved properties, maintains transparency, and does not decrease in commercial value can be obtained, and has completed the present invention.

That is, the present invention provides a soft capsule whose coating surface is transparently coated with a hydroxyalkyl-substituted cellulose and / or a polyvinyl acetal polymer.

In the present invention, the soft capsule means a film mainly made of gelatin, and glycerin, D-sorbitol, etc. added as a plasticizer to form a film, and an oily liquid, suspension, A soft gelatin capsule filled with powder, granules, tablets and the like.

The hydroxyalkyl-substituted cellulose used in the present invention includes hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose and the like.

[0011] Examples of the polyvinyl acetal polymer include polyvinyl acetal diethylaminoacetate.

The hydroxyalkyl-substituted cellulose and the polyvinyl acetal-based polymer may be used alone or as a mixture. The coating amount is 0.01 to 10 parts by weight per 100 parts by weight of the soft capsule film. In particular, it is preferably 0.05 to 1 part by weight. Further, the soft capsule of the present invention, in addition to the above essential components, if necessary,
Macrogol, glycerin fatty acid ester and the like as a plasticizer, dimethylpolysiloxane, shellac, hydrogenated oil, carnauba wax, beeswax and the like as a lubricant, and / or crystalline cellulose, carmellose, water-insoluble cellulose such as carmellose calcium and The derivative may be added as a fluidizing agent and coated, or may be further coated on an essential component-containing layer.

In order to produce the soft capsule of the present invention,
If a normal coating method such as that applied to tablets and granules is used for soft capsules, the surface becomes white and opaque due to friction due to rolling, and the transparency and smoothness of the soft capsules are lost, and commercial value Goes down.

Therefore, as a method for producing the soft capsule of the present invention, for example, the soft capsule is tumbled by a pan-type or centrifugal-flow type coating machine, and the solution of the above-mentioned coating agent is applied to this. After spraying, it is preferable to repeat the operation of drying while performing intermittent rolling.

The method is not limited to this method, and any method may be used as long as the soft capsule is coated with the coating agent transparently.

[0016]

The soft capsule of the present invention thus obtained maintains good transparency even under high temperature and high humidity conditions,
Since the capsules do not adhere to each other or the capsule and the container, they can be stored very stably at room temperature. Further, the soft capsule of the present invention has good disintegration properties.

[0017]

Next, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples.

Example 1 10000 Oval No. 4 soft capsules (total weight of capsule film: 1500 g) containing 100 mg of d-α-tocopherol per capsule were coated with a coating machine (Hicoater HT-48 type: Freund Sangyo Co., Ltd.). The soft capsule was rolled by rotating the pan at 10 revolutions per minute. 90 to 6 g of hydroxypropyl methylcellulose
About 20 g of the coating solution dissolved by adding 114 g of a weight% ethanol solution was added to the rolling soft capsule and coated. Immediately after coating, air was blown, and the coated soft capsule was dried by intermittent rolling in which the rotation of the pan was stopped for 30 seconds and the rotation was repeated for 5 seconds. After drying, reapply about 20
g, and the same operation was repeated to complete the coating of a predetermined amount. The coated amount of hydroxypropylmethylcellulose in the obtained soft capsule was 0.4% by weight based on the weight of the film.

Example 2 Isopropanol / ethanol mixed solution (8: 2) 150 g in 3 g of polyvinyl acetal diethylaminoacetate
The operation was performed in the same manner as in Example 1 except that a coating solution dissolved by adding was used. The coating amount of polyvinyl acetal diethylaminoacetate in the obtained soft capsule was 0.2% by weight based on the weight of the film.

Example 3 90% by weight in 6 g of hydroxypropyl methylcellulose
The same operation as in Example 1 was carried out except that 114 g of an ethanol solution was added and dissolved, and further, 0.3 g of dimethylpolysiloxane was added and a coating solution sufficiently dispersed was used.
The coating amount of the obtained soft capsule was 0.1% based on the film weight.
It was 42% by weight.

Example 4 90% by weight in 6 g of hydroxypropylmethylcellulose
The same operation as in Example 1 was performed, except that 114 g of an ethanol solution was added and dissolved, and 0.3 g of crystalline cellulose was further added, and a coating solution sufficiently dispersed was used. The coating amount of the obtained soft capsule was 0.42% by weight based on the weight of the film.

Example 5 Example 2 was carried out using a solution prepared by dissolving 0.075 g of shellac in 30 g of ethanol in 5000 capsules (total weight of capsule film: 751.5 g) of the coated soft capsule obtained in Example 2. In the same manner as in Example 1, shellac was coated on the surface of the coated soft capsule. The shellac coating amount of the obtained soft capsule was 0.01% by weight based on the film weight.
Met.

Comparative Example 1 An Oval No. 4 soft capsule without film coating containing 100 mg of d-α-tocopherol per capsule was prepared.

Comparative Example 2 A coating machine (2-P-) equipped with 3000 Oval No. 4 soft capsules (total weight of capsule coating: 450 g) containing 100 mg of d-α-tocopherol per capsule and a cloth pan having an inner diameter of 30 cm was attached. (S type: manufactured by Freund Corporation), and the bread was rotated to roll the soft capsule. 45 mg of Carnauba wax passed through an 80-mesh sieve was sprayed little by little on this and covered. The coating amount of the obtained soft capsule was 0.01% by weight based on the weight of the film.
Met.

Comparative Example 3 The same operation as in Example 1 was carried out except that a coating solution prepared by dissolving 114 g of ethanol in 6 g of the aminoalkyl methacrylate copolymer E was used. Aminoalkyl methacrylate copolymer E of the obtained soft capsule
The coating amount was 0.4% by weight based on the film weight.

Comparative Example 4 The procedure of Example 1 was repeated except that a coating solution prepared by dissolving 114 g of ethanol in 6 g of ethyl cellulose was used. The amount of ethyl cellulose coated on the obtained soft capsule was 0.4% by weight based on the weight of the film.

Test Example 1 The soft capsules obtained in Examples 1 to 5 and Comparative Examples 1 to 4
0 capsules each were put in a No. 4 standard bottle, and kept in a thermo-hygrostat at 40 ° C. and 75% RH for 24 hours with the bottle opening, and after returning the soft capsule to room temperature, the diameter was 5 cm.
The inverted sample was vertically dropped on a desk using a transparent tube having a height of 7 cm. The falling height was 1 cm, 3 cm and 5 cm, and the adhesion preventing effect was evaluated by the cumulative number of soft capsules that fell without sticking between the soft capsules. Table 1 shows the results.
Shown in

[0028]

[Table 1]

Test Example 2 Disintegration tests according to the Japanese Pharmacopoeia were carried out for Examples 1 to 5 and Comparative Examples 1 to 4 using water as a test solution. In addition, the transparency of the coating was evaluated on the following three levels. A: transparent, B: slightly cloudy, C: cloudy These results are shown in Table 2.

[0030]

[Table 2]

From the above results, it can be seen that the product of the present invention is excellent in anti-adhesion effect and transparency even under high temperature and high humidity conditions, has no problem in disintegration, and is a good soft capsule.

──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor You Iwasa 886-16 Shiwatari, Yotsukaido-shi, Chiba (58) Field surveyed (Int.Cl. ⁶ , DB name) A61K 9 / 48,47 / 32,47 / 38 A61J 3/07

Claims (2)

(57) [Claims] 1. A soft capsule whose coating surface is transparently coated with a hydroxyalkyl-substituted cellulose and / or a polyvinyl acetal polymer. 2. The soft capsule according to claim 1, wherein the coating amount of the hydroxyalkyl-substituted cellulose and / or polyvinyl acetal polymer is 0.01 to 10 parts by weight based on 100 parts by weight of the film of the soft capsule.