JPS6366538B2 - - Google Patents
Info
- Publication number
- JPS6366538B2 JPS6366538B2 JP6993979A JP6993979A JPS6366538B2 JP S6366538 B2 JPS6366538 B2 JP S6366538B2 JP 6993979 A JP6993979 A JP 6993979A JP 6993979 A JP6993979 A JP 6993979A JP S6366538 B2 JPS6366538 B2 JP S6366538B2
- Authority
- JP
- Japan
- Prior art keywords
- capsule
- liquid
- soft capsules
- capsules
- groups
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 239000002775 capsule Substances 0.000 claims description 21
- 239000007901 soft capsule Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 11
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000000110 cooling liquid Substances 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 238000000034 method Methods 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 125000006219 1-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229940057995 liquid paraffin Drugs 0.000 description 8
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 238000000576 coating method Methods 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- 238000004140 cleaning Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000005469 granulation Methods 0.000 description 2
- 230000003179 granulation Effects 0.000 description 2
- 230000005484 gravity Effects 0.000 description 2
- 231100000053 low toxicity Toxicity 0.000 description 2
- 239000002075 main ingredient Substances 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- -1 ethylpentyl group Chemical group 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229940127557 pharmaceutical product Drugs 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229940069338 potassium sorbate Drugs 0.000 description 1
- 235000010241 potassium sorbate Nutrition 0.000 description 1
- 239000004302 potassium sorbate Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000009967 tasteless effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- QYSXJUFSXHHAJI-YRZJJWOYSA-N vitamin D3 Chemical compound C1(/[C@@H]2CC[C@@H]([C@]2(CCC1)C)[C@H](C)CCCC(C)C)=C\C=C1\C[C@@H](O)CCC1=C QYSXJUFSXHHAJI-YRZJJWOYSA-N 0.000 description 1
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
Description
本発明は軟カプセルの製法に関する。
従来軟カプセルの製法としては、液状のカプセ
ル化物質、例えばゼラチン液を環状孔から押出す
と同時に上記環状口の内側に同心円状に設けられ
た内孔口よりカプセル充填剤を押出し、この複合
ジエツトを冷却液中にて所望の粒径に造粒する、
いわゆる、例えば特公昭36−3700号公報に記載の
装置を用いた液中硬化被覆法によるシームレス軟
カプセル製造法が知られている。
この方法においてはカプセル造粒用冷却液とし
ては流動パラフインが常用されている。流動パラ
フインはその比重、粘度等の特性値が軟カプセル
の製造に好適に利用されているのであるが、反面
他溶媒との相溶性の悪さから、製造したカプセル
に付着した流動パラフインの洗滌にはトリクロロ
エタンの使用が余儀ない。トリクロロエタンの使
用が流動パラフインの洗滌に不可欠とはいうもの
の、その毒性は作業者にとつて好ましいものと言
い難いばかりでなく、本発明者らの研究によれ
ば、トリクロロエタンはゼラチン被膜を侵透し、
カプセル充填剤を汚染し、服用者に対する危険性
を有し又医薬品の安定性を害するものであること
が判明している。
本発明者らはこれらの点に鑑み鋭意研究の結
果、従来用いられてきた流動パラフインに替えて
次の一般式
（式中R1およびR2はアルキル基を、R3および
R4は水素原子または低級アルキル基を意味す
る。）で表わされる化合物を用いることにより極
めて安全で効率よく軟カプセルを製造し得ること
を見出し、更に検討を加えて本発明を完成した。
一般式（）で表わされる化合物は公知物質で
化粧品製造原料として用いられる極めて低毒性の
常温で液体の物質である。
例えば一般式（）におけるR1およびR2が１
―エチルペンチル基、R3およびR4がメチル基で
ある化合物（コスモール525なる商品名で市販さ
れている）は比重：約0.91、凝固点：−30℃以下
の無味・無臭の透明液体で25℃における粘度：10
〜13cpsという物理的性質を有する他、化学的に
も安定で酸・アルカリによる加水分解をほとんど
起すことなく空気中の酸素による影響も無視し得
る程度である。
このような化合物類を液中硬化被覆法による冷
却溶媒として用いることによりカプセルの造粒調
整が容易となり、従つて高速で製造されたカプセ
ルの重量偏差は驚くほど小さい。
更にカプセルの洗滌には危険なトリクロロエタ
ンを用いる必要がなく、低毒性のアルコール類で
簡単に処理でき、乾燥時間も極度に短縮すること
ができ、軟カプセルの量産に最適である。
また、このように優れた特性は、ロータリー式
軟カプセルの付着防止剤として全く同様に有利に
用いられ、同様の効果を上げることができ軟カプ
セルの製造に寄与するところ大である。
実施例 １
グローベツクス社（オランダ）製シームレス軟
カプセル製造機MarkによりビタミンD3のゼラ
チン被膜軟カプセルを次の処方により製造した。
＜ゼラチン液処方＞
ゼラチン 100 部
グリセリン 30 〃
ソルビン酸カリウム 0.4〃
＜充填物処方＞（１カプセル中）
VD3 1μｇ
エタノール 0.8mg
MCT 全量60mgとする
＜剤皮重量＞40mg（１カプセル）
冷却溶媒として流動パラフインを用いた場合
（対照）と本発明（冷却溶媒として前記コスモー
ル525使用）の場合とを比較すると第１表のとお
りである。
The present invention relates to a method for manufacturing soft capsules. Conventionally, soft capsules are manufactured by extruding a liquid encapsulating material, such as a gelatin solution, through an annular hole, and at the same time extruding a capsule filler through an inner hole provided concentrically inside the annular opening. granulate to the desired particle size in a cooling liquid,
A so-called seamless soft capsule manufacturing method is known, for example, by a submerged curing coating method using an apparatus described in Japanese Patent Publication No. 36-3700. In this method, liquid paraffin is commonly used as the cooling liquid for capsule granulation. Liquid paraffin is suitable for use in the production of soft capsules due to its specific gravity, viscosity, and other properties, but on the other hand, due to its poor compatibility with other solvents, it is not suitable for cleaning liquid paraffin adhering to produced capsules. Trichloroethane must be used. Although the use of trichloroethane is indispensable for cleaning liquid paraffin, its toxicity is not only not favorable for workers, but also, according to research by the present inventors, trichloroethane can penetrate gelatin coatings. ,
It has been found that it contaminates capsule fillers, poses a risk to users, and impairs the stability of pharmaceutical products. In view of these points, the inventors of the present invention have conducted extensive research, and have developed the following general formula in place of the conventionally used liquid paraffin. (In the formula, R 1 and R 2 are alkyl groups, R 3 and
R 4 means a hydrogen atom or a lower alkyl group. ) It was discovered that soft capsules could be produced extremely safely and efficiently by using the compound represented by the following formula, and after further investigation, the present invention was completed. The compound represented by the general formula () is a known substance that is liquid at room temperature and has extremely low toxicity and is used as a raw material for manufacturing cosmetics. For example, R 1 and R 2 in the general formula () are 1
- A compound in which ethylpentyl group and R 3 and R 4 are methyl groups (commercially available under the trade name Cosmol 525) has a specific gravity of approximately 0.91 and a freezing point of -30°C or lower, a tasteless and odorless transparent liquid at 25°C. Viscosity at: 10
In addition to its physical properties of ~13 cps, it is also chemically stable, hardly being hydrolyzed by acids or alkalis, and the effect of oxygen in the air can be ignored. By using such compounds as a cooling solvent in the submerged curing coating method, it becomes easy to control the granulation of capsules, and therefore the weight deviation of capsules produced at high speed is surprisingly small. Furthermore, there is no need to use dangerous trichloroethane to wash the capsules, they can be easily treated with low-toxicity alcohols, and the drying time can be extremely shortened, making it ideal for mass production of soft capsules. Moreover, such excellent properties can be advantageously used as an anti-adhesion agent for rotary type soft capsules, and the same effect can be achieved, greatly contributing to the production of soft capsules. Example 1 Gelatin-coated soft capsules of vitamin D 3 were manufactured using a seamless soft capsule manufacturing machine Mark manufactured by Globex (Netherlands) according to the following formulation. <Gelatin liquid formulation> Gelatin 100 parts Glycerin 30〃 Potassium sorbate 0.4〃 <Filling formula> (in 1 capsule) VD 3 1μg Ethanol 0.8mg MCT Total amount 60mg <Coat weight> 40mg (1 capsule) As cooling solvent Table 1 shows a comparison between the case using liquid paraffin (control) and the case of the present invention (using Cosmol 525 as the cooling solvent).
【表】
表に示したように対照の重量偏差は４％以上と
大きく、これが本製法の大きな欠点でもある。又
カプセル破壊強度はバラツキが大きく商品価値上
大きな問題である。特に冷却液を流動パラフイン
で製したカプセルは流動パラフインの粘度が高い
ので圧力伝達が悪く、カプセルの一部に切り口が
残る。この切り口は必らずでき、その部分の被膜
の厚さは局部的に薄くなり、その結果カプセル破
壊強度は低下する。
一方、本発明の場合コスモール525は低粘度で
あるから圧力伝達も高くなりカプセルがシヤープ
に切れる。よつてカプセルの切り口は全く残らな
いのでカプセル破壊強度は高まり重量偏差も著し
く改善される。
更にトリクロロエタンの残留性を比較すると対
照は１カプセル当り40ppm以上混入し、その結果
主剤の安定性はきわめて悪くなる。
然し、本発明の場合安定性で問題となるトリク
ロロエタンは製造工程から完全に除去できるので
主剤の安定性は著しく安定化できる。
実施例 ２
充填物処方を１カプセル中
リピドトロンボプラスチン 150mg
MCT 210mg
とし、剤皮重量160mg／１カプセルとした他は実
施例１と同様にし第２表の結果を得た。[Table] As shown in the table, the weight deviation of the control was as large as 4% or more, which is also a major drawback of the present manufacturing method. Furthermore, the capsule breaking strength varies widely, which is a big problem in terms of commercial value. In particular, capsules made of liquid paraffin as a cooling liquid have poor pressure transmission due to the high viscosity of liquid paraffin, leaving a cut in a portion of the capsule. This cut inevitably occurs, and the thickness of the coating in that area becomes locally thinner, resulting in a decrease in capsule rupture strength. On the other hand, in the case of the present invention, since Cosmol 525 has a low viscosity, pressure transmission is also high and the capsule can be cut sharply. Therefore, no cut ends of the capsule remain, so the capsule breaking strength is increased and the weight deviation is significantly improved. Furthermore, when comparing the residual strength of trichloroethane, the control contained more than 40 ppm per capsule, and as a result, the stability of the main ingredient was extremely poor. However, in the case of the present invention, trichloroethane, which poses a stability problem, can be completely removed from the production process, so the stability of the main ingredient can be significantly stabilized. Example 2 The filling formulation was the same as in Example 1, except that 1 capsule contained 150 mg of lipidothromboplastin and 210 mg of MCT, and the shell weight was 160 mg/capsule, and the results shown in Table 2 were obtained.
【表】
上記の通り、ほぼ実施例１と同様に本発明の軟
カプセルが対照に較べて著しく優れていることが
示された。[Table] As shown above, almost the same as in Example 1, the soft capsules of the present invention were shown to be significantly superior to the control.
Claims (1)
アルキル基を、R3およびR4は水素原子または低
級アルキル基を意味する。） で表される化合物をシームレス軟カプセル製造の
際のカプセル形成用冷却液またはロータリー式軟
カプセル製造機のローターに設けられたカプセル
形成用凹部とカプセル形成物質との付着防止液と
して使用することを特徴とする軟カプセルの製
法。 ２ R1およびR2が１―エチルペンチル基、R3お
よびR4がメチル基である特許請求の範囲第１項
記載の方法。[Claims] 1. General formula (In the formula, R 1 and R 2 are alkyl groups that may be the same or different, and R 3 and R 4 are hydrogen atoms or lower alkyl groups.) A method for producing soft capsules, which is used as a cooling liquid for forming or as a liquid for preventing adhesion between a capsule forming substance and a capsule forming recess provided in a rotor of a rotary type soft capsule manufacturing machine. 2. The method according to claim 1, wherein R 1 and R 2 are 1-ethylpentyl groups, and R 3 and R 4 are methyl groups.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6993979A JPS55163049A (en) | 1979-06-06 | 1979-06-06 | Preparation of soft capsule |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP6993979A JPS55163049A (en) | 1979-06-06 | 1979-06-06 | Preparation of soft capsule |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS55163049A JPS55163049A (en) | 1980-12-18 |
| JPS6366538B2 true JPS6366538B2 (en) | 1988-12-21 |
Family
ID=13417127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP6993979A Granted JPS55163049A (en) | 1979-06-06 | 1979-06-06 | Preparation of soft capsule |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS55163049A (en) |
-
1979
- 1979-06-06 JP JP6993979A patent/JPS55163049A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS55163049A (en) | 1980-12-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20200138723A1 (en) | Hydroxypropyl methyl cellulose hard capsules and process of manufacture | |
| JP5666595B2 (en) | Aqueous composition for enteric hard capsule, method for producing enteric hard capsule, and enteric hard capsule | |
| JP3822810B2 (en) | Capsule sealing method | |
| US6887307B1 (en) | Pullulan film compositions | |
| US7045184B2 (en) | Polyvinyl alcohol compositions | |
| WO2001091721A2 (en) | Modified starch as a replacement for gelatin in soft gel films and capsules | |
| WO2000018835A1 (en) | Modified starch film compositions | |
| WO2008119943A2 (en) | Enteric pharmaceutical capsules | |
| EP1942878A2 (en) | Method for banding hard capsules using hydroxypropylmethyl cellulose (hpmc) as a base | |
| JP2004526664A (en) | Method of preparing a pharmaceutical composition for use with a soft gelatin formulation | |
| JP2552937B2 (en) | Pharmaceutical hard capsule and method for producing the same | |
| JP4652052B2 (en) | Film coating for tablets and caplets | |
| EP1072633A1 (en) | Pullulan film compositions | |
| JP2013503847A (en) | Flavored capsules | |
| JP6227646B2 (en) | Aqueous composition for producing hard capsule and method for producing the same, hard capsule, and method for reusing hard capsule scrap | |
| JPS6366538B2 (en) | ||
| JPH0561943B2 (en) | ||
| US9700518B1 (en) | Dip molding process for the manufacture of hard capsule shells | |
| JP7377782B2 (en) | Film forming composition and film | |
| JPH07550B2 (en) | Essential oil containing soft capsule | |
| JP2014532069A (en) | Injection molded dosage form | |
| JP2007001873A (en) | Coating composition and coated solid preparation | |
| JP2002167444A (en) | Rigid gelatin capsule having increased lubricity by decreasing static electricity of its coated film | |
| JP2004315466A (en) | Coating composition for capsule | |
| JPS6336259B2 (en) |