JPH0624570B2 - Bromhexine hydrochloride content reduction prevention method - Google Patents
Bromhexine hydrochloride content reduction prevention methodInfo
- Publication number
- JPH0624570B2 JPH0624570B2 JP61213433A JP21343386A JPH0624570B2 JP H0624570 B2 JPH0624570 B2 JP H0624570B2 JP 61213433 A JP61213433 A JP 61213433A JP 21343386 A JP21343386 A JP 21343386A JP H0624570 B2 JPH0624570 B2 JP H0624570B2
- Authority
- JP
- Japan
- Prior art keywords
- bromhexine hydrochloride
- packaging material
- plastic
- prevention method
- content reduction
- 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 - Lifetime
Links
Landscapes
- Medical Preparation Storing Or Oral Administration Devices (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Description
【発明の詳細な説明】 ［産業上の利用分野］ 本発明は固形製剤中の塩酸ブロムヘキシン含有量が減少
することを防止する方法に関する。DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for preventing a decrease in bromhexine hydrochloride content in a solid preparation.
［従来の技術］ 従来、塩酸ブロムヘキシンとデンプン、結晶セルロース
等の賦形剤、ヒドロキシプロピルセルロース、ポリビニ
ルピロリドン等の結合剤からなる塩酸ブロムヘキシン組
成物を常法により散剤、細粒剤または顆粒剤等の固形製
剤とし、これをガラスビンまたはステンレス製容器で包
装し、用時秤量し小分けしていた。[Prior Art] Conventionally, a bromhexine hydrochloride composition comprising an excipient such as bromhexine hydrochloride and starch, crystalline cellulose, etc., and a binder such as hydroxypropylcellulose, polyvinylpyrrolidone etc. is prepared by a conventional method into powder, fine granules or granules. The solid preparation was packaged in a glass bottle or a stainless steel container, weighed before use, and subdivided.
［発明が解決しようとする問題点］ しかしながら、使用の都度これを秤量し小分けするのは
多忙時には煩瑣であるので、予めプラスチック包材また
はプラスチック積層アルミニウム包材に分包して保存し
ておくのが便利である。[Problems to be Solved by the Invention] However, it is troublesome to weigh and subdivide each time each time it is used, so it is necessary to package and store in advance in a plastic packaging material or a plastic laminated aluminum packaging material. Is convenient.
ところが、本発明者らの研究の結果、塩酸ブロムヘキシ
ン固形製剤を通常用いられているプラスチック包材また
はプラスチック積層アルミニウム包材に分包したとこ
ろ、製剤中の塩酸ブロムヘキシンが前記包材に吸着し、
分包中の塩酸ブロムヘキシンの含有量が減少するという
問題が生じた。However, as a result of the research conducted by the present inventors, when the bromhexine hydrochloride solid preparation was packaged in a commonly used plastic packaging material or a plastic laminated aluminum packaging material, bromhexine hydrochloride in the formulation was adsorbed to the packaging material,
The problem arises that the content of bromhexine hydrochloride in the package is reduced.
塩酸ブロムヘキシンは、優れた去痰薬として広く利用さ
れている薬物であるが、その投与量は１回に４mg程度の
少量にすぎない。従って、保存の間に製剤中の塩酸ブロ
ムヘキシンがプラスチック包材またはプラスチック積層
アルミニウム包材に吸着して、微量といえどもその含有
量を減ずることは、薬効に重大な影響を与える。Bromhexine hydrochloride is a drug widely used as an excellent expectorant, but the dose is only 4 mg at a time. Therefore, when bromhexine hydrochloride in the preparation is adsorbed to the plastic packaging material or the plastic laminated aluminum packaging material during storage and the content thereof is reduced even if it is a very small amount, it has a significant effect on the drug efficacy.
本発明の目的は、プラスチック包材またはプラスチック
積層アルミニウム包材により分包した固形製剤中の塩酸
ブロムヘキシンが包材のプラスチックに吸着して製剤中
の含有量を減ずるのを防止する方法を提供することにあ
る。An object of the present invention is to provide a method for preventing bromhexine hydrochloride in a solid preparation packaged by a plastic packaging material or a plastic laminated aluminum packaging material from adsorbing to the plastic of the packaging material and reducing the content in the preparation. It is in.
［問題点を解決するための手段］ 本発明の方法は、酸素透過度20cc/m2・24hr・1atm(23℃、
30μｍ)以下で、かつ水蒸気透過度60g／m2・24hr.1atm
（30μｍ)以上であるプラスチック包材またはプラスチ
ック積層アルミニウム包材を用いて固形製剤を包装して
保存することにより、前記製剤中の塩酸ブロムヘキシン
含有量が減少することを防止するものである。[Means for Solving Problems] The method of the present invention has an oxygen permeability of 20 cc / m 2 , 24 hr, 1 atm (23 ° C.,
30 μm) or less, and water vapor permeability 60 g / m 2 · 24 hr.1 atm
By packaging and storing a solid preparation using a plastic packaging material or a plastic laminated aluminum packaging material having a size of (30 μm) or more, it is possible to prevent the content of bromhexine hydrochloride in the preparation from decreasing.
上における酸素透過度の値は酸素透過率計(OX-TRAN100
型、MODERN-CONTROLS社製)により温度23℃、厚さ30μｍ
の条件で測定したものであり、水蒸気透過度の値は透湿
カップ法（JIS-Z0208）により厚さ30μｍの条件で測定
したものである。The oxygen permeability value above is based on the oxygen permeability meter (OX-TRAN100
Type, manufactured by MODERN-CONTROLS), temperature 23 ℃, thickness 30μm
The value of the water vapor permeability is measured by the moisture permeable cup method (JIS-Z0208) at a thickness of 30 μm.
前記酸素透過度、水蒸気透過度の基準に適合するプラス
チック類として、例えば特公昭46-25005号公報に記載の
アクリロニトリル系樹脂、エチレン−ビニルアルコール
共重合体、ポリビニルアルコール等が挙げられる。Examples of the plastics that meet the oxygen permeability and water vapor permeability standards include acrylonitrile-based resins, ethylene-vinyl alcohol copolymers, and polyvinyl alcohol described in JP-B-46-25005.
前記塩酸ブロムヘキシン固形製剤には、散剤、細粒剤、
顆粒剤があり、これらは、塩酸ブロムヘキシンを通常の
賦形剤(例えばデンプン、結晶セルロース等)および結合
剤(例えばヒドロキシプロピルセルロース、ポリビニル
ピロリドン等)を用いて常法により製造される。The bromhexine hydrochloride solid preparation, powder, fine granules,
There are granules, which are produced by a conventional method using bromhexine hydrochloride using a usual excipient (eg starch, crystalline cellulose etc.) and a binder (eg hydroxypropyl cellulose, polyvinylpyrrolidone etc.).
［発明の効果］ 本発明の、酸素透過度20cc/m2・24hr・1atm(23℃、30μ
ｍ)以下で、かつ水蒸気透過度60g／m2・24hr・1atm(30μ
ｍ)以上であるプラスチック類またはこれをアルミニウ
ム包材に積層した包材を用い、塩酸ブロムヘキシン固形
製剤を包装する方法では、製剤中の塩酸ブロムヘキシン
が前記包材に吸着することなく、製剤中の塩酸ブロムヘ
キシン含有量を長期にわたって保持することができる。[Effect of the invention] Oxygen permeability of the present invention 20cc / m 2 · 24hr · 1atm (23 ℃, 30μ
m) or less and a water vapor permeability of 60 g / m 2 , 24 hr, 1 atm (30 μ
m) In the method of packaging a solid preparation of bromhexine hydrochloride using a plastic or a packaging material obtained by laminating it with an aluminum packaging material, bromhexine hydrochloride in the preparation does not adsorb to the packaging material and hydrochloric acid in the preparation does not adsorb. The bromhexine content can be retained for a long time.
［実施例］ （実施例） 塩酸ブロムヘキシン４ｇ、結晶セルロース700gを混合し
て乳鉢に入れ、これにヒドロキシプロピルセルロース14
gをエタノール90gに溶解したものを結合剤として加え、
乳鉢中で練合した。練合後、12号のふるいを通し、循環
式乾燥器により60℃で２時間乾燥した。乾燥品をふるい
にかけ、12号のふるいを通り、42号のふるいに残ったも
のを集め、顆粒剤680gを得た。これを製剤１とした。[Example] (Example) 4 g of bromhexine hydrochloride and 700 g of crystalline cellulose were mixed and placed in a mortar, and hydroxypropyl cellulose 14
g dissolved in 90 g of ethanol was added as a binder,
Kneaded in a mortar. After kneading, it was passed through a No. 12 sieve and dried at 60 ° C. for 2 hours by a circulation type dryer. The dried product was sieved, passed through a No. 12 sieve, and the remaining residue on the No. 42 sieve was collected to obtain 680 g of granules. This was designated as Formulation 1.
（試験例） 製剤１を、塩酸ブロムヘキシン４mg相当量ずつに分け
て、内側にそれぞれバレックス210[アクリロニトリル系
樹脂の商品名、三井東圧化学(株)製]、エバール[エチレ
ン−ビニルアルコール共重合体の商品名、(株)クラレ
製]およびポバール[ポリビニルアルコールの商品名、
(株)クラレ製]を積層したアルミニウム包材に包装し、
加温条件下(50℃)で保存し、１週間後、２週間後、３週
間後および４週間後における包材中の塩酸ブロムヘキシ
ン含有量を、下記の条件により、高速液体クロマトグラ
フ法を用いて定量した。包材中の塩酸ブロムヘキシンに
ついては、包材をクロロホルム中で50℃、30分間還流し
た抽出液について定量した。なお、比較として、製剤１
を内側にポリエチレンを積層したアルミニウム包材に包
装し、同様に定量試験を行なった。(Test Example) Formulation 1 was divided into 4 mg equivalents of bromhexine hydrochloride, and inside each of them, Barex 210 [trade name of acrylonitrile resin, manufactured by Mitsui Toatsu Chemicals, Inc.], EVAL [ethylene-vinyl alcohol copolymer] Brand name of Kuraray Co., Ltd. and Poval [brand name of polyvinyl alcohol,
Made by Kuraray Co., Ltd.]
Store under warming conditions (50 ° C), and measure the content of bromhexine hydrochloride in the packaging material after 1 week, 2 weeks, 3 weeks, and 4 weeks by high performance liquid chromatography under the following conditions. Was quantified. Regarding the bromhexine hydrochloride in the packaging material, the packaging material was quantified in an extract that was refluxed in chloroform at 50 ° C for 30 minutes. As a comparison, Formulation 1
Was packaged in an aluminum packaging material having polyethylene laminated inside, and a quantitative test was conducted in the same manner.
定量条件 １）ポンプ ；HITACHI 655A-12 ［(株)日立製作所製］ ２）検出器 ；HITACHI 655A ［(株)日立製作所製］ ３）操作条件； 検出器 ：紫外吸光光度計 測定波長 ：210nm 検出器感度：0.04AUFS カラム ：内径４mm、長さ150mmのステンレス
管に、充填剤としてオクタデシルシリル化した５μｍの
シリカゲルを充填する。Quantitative conditions 1) Pump; HITACHI 655A-12 [manufactured by Hitachi, Ltd.] 2) Detector; HITACHI 655A [manufactured by Hitachi, Ltd.] 3) Operating conditions; Detector: UV absorptiometer Measurement wavelength: 210nm Detection Sensitivity: 0.04AUFS column: A stainless steel tube with an inner diameter of 4 mm and a length of 150 mm is packed with octadecylsilylated 5 μm silica gel as a packing material.
カラム温度：50℃付近の一定温度 移動相 ：アセトニトリルと、ラウリル硫酸ナ
トリウムの1/15Ｍリン酸二水素カリウム溶液の混液(混
合比520：480) 流量 ：毎分約１mlの一定流量 ４）注入量 ；塩酸ブロムヘキシン濃度20μｇ／ml程度
のものと10μｌ注入 この結果を、製造直後の製剤中の塩酸ブロムヘキシン含
有量を100として百分率表示し、第１表にまとめた。Column temperature: Constant temperature around 50 ° C Mobile phase: Mixture of acetonitrile and 1/15 M potassium dihydrogen phosphate solution of sodium lauryl sulfate (mixing ratio 520: 480) Flow rate: Constant flow rate of about 1 ml per minute 4) Injection rate Bromhexine hydrochloride having a concentration of about 20 μg / ml and 10 μl were injected. The results are shown in percentages with the content of bromhexine hydrochloride in the preparation immediately after production being 100, and summarized in Table 1.
Claims (1)
μｍ)以下で、かつ水蒸気透過度が60g/m2・24hr.1atm(30
μｍ)以上であるプラスチック類またはこれをアルミニ
ウムに積層した包材を用いて固形製剤を包装することに
より、前記製剤中の塩酸ブロムヘキシン含有量が減少す
ることを防止する方法。1. Oxygen permeability of 20cc / m 2 · 24hr · 1atm (23 ℃, 30
μm) and water vapor permeability of 60 g / m 2 · 24 hr. 1 atm (30
A method for preventing a decrease in the content of bromhexine hydrochloride in the above-mentioned preparation by packaging the solid preparation with a plastic having a thickness of at least μm or a packaging material obtained by laminating the plastic with aluminum.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61213433A JPH0624570B2 (en) | 1986-09-10 | 1986-09-10 | Bromhexine hydrochloride content reduction prevention method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP61213433A JPH0624570B2 (en) | 1986-09-10 | 1986-09-10 | Bromhexine hydrochloride content reduction prevention method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6368167A JPS6368167A (en) | 1988-03-28 |
| JPH0624570B2 true JPH0624570B2 (en) | 1994-04-06 |
Family
ID=16639147
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP61213433A Expired - Lifetime JPH0624570B2 (en) | 1986-09-10 | 1986-09-10 | Bromhexine hydrochloride content reduction prevention method |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH0624570B2 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0928533A (en) * | 1995-07-18 | 1997-02-04 | Takekoshi Seisakusho:Kk | Flower vase and manufacture thereof |
-
1986
- 1986-09-10 JP JP61213433A patent/JPH0624570B2/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0928533A (en) * | 1995-07-18 | 1997-02-04 | Takekoshi Seisakusho:Kk | Flower vase and manufacture thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6368167A (en) | 1988-03-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EXPY | Cancellation because of completion of term |