JP4016128B2 - Light-resistant epinastine hydrochloride film-coated tablets - Google Patents
Light-resistant epinastine hydrochloride film-coated tablets Download PDFInfo
- Publication number
- JP4016128B2 JP4016128B2 JP25567499A JP25567499A JP4016128B2 JP 4016128 B2 JP4016128 B2 JP 4016128B2 JP 25567499 A JP25567499 A JP 25567499A JP 25567499 A JP25567499 A JP 25567499A JP 4016128 B2 JP4016128 B2 JP 4016128B2
- Authority
- JP
- Japan
- Prior art keywords
- film
- epinastine hydrochloride
- light
- titanium oxide
- polymer
- 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.)
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
【０００１】
【本発明の背景及び課題】
本発明は、塩酸エピナスチンフィルムコ−ト錠、詳しくは主薬の変質を防止するため施されたフィルムが光へ暴露することによって変色しないそのようなフィルムコ−ト錠に関する。
【０００２】
塩酸エピナスチンは選択的Ｈ1 受容体拮抗作用を有する薬物であり、気管支喘息、アレルギ−性鼻炎、蕁麻疹等のアレルギ−疾患の治療に使用されている。
【０００３】
塩酸エピナスチンは湿気、光等により変質し易いため、その錠剤は通常主薬の変質を防止するためのフィルムコ−ティングが施されている。しかしながらそのようなフィルムが酸化チタン顔料を含んでいる時は光へ暴露することによってフィルムの一部または全体がピンクないし赤に変色する。その大きい隠蔽力および無毒性のためフィルムの不透明化および着色に酸化チタン顔料の使用は実際上不可避である。
【０００４】
そこで本発明の課題は、光への暴露によって変色することがない、酸化チタン顔料を含んでいるポリマーフィルムでコートされた塩酸エピナスチン錠を提供することである。
【０００５】
【本発明の開示】
上記課題は、主薬の変質を防止するため酸化チタン顔料で着色したポリマーフィルムでコートされている塩酸エピナスチン錠において、主薬を含んでいる裸錠と前記着色フィルム層の中間に、酸化チタン顔料を含まないポリマーフィルム層が設けられている塩酸エピナスチンフィルムコート錠を提供する本発明によって解決される。
【０００６】
【詳細な議論】
一般に、主薬の変質を防止するために施されるコーティングフィルムに用いるポリマーは、胃液や腸液のような消化液に可溶でなければならない。そのようなポリマ−の例は、ヒドロキシプロピルセルロ−ス（ＨＰＣ）、ヒドロキシプロピルメチルセルロ−ス（ＨＰＭＣ）、ポリビニルピロリドン（ＰＶＰ）、プルラン、オイドラギットＮＥ３０Ｄなどである。
【０００７】
実際の着色コ−ティングフィルムは、酸化チタン顔料に加え、任意の添加成分としてポリエチレングリコ−ルのような可塑剤、タルクまたは炭酸カルシウムのような体質顔料を含むことができる。
【０００８】
実際のコ−ティング作業は、これらの成分を水、エタノ−ル又は水エタノ−ル混液に溶解又は分散したコ−ティング液を裸錠に噴霧し、温風乾燥することによって行われる。
【０００９】
よく知られているように、酸化チタンは強力な光触媒である。本発明は特定の理論に拘束されるものではないが、本発明者らは、塩酸エピナスチンが水やエタノ−ルに非常に溶け易いため、酸化チタン顔料を含む上のコ−ティング液を裸錠に適用する際塩酸エピナスチンが僅かにコ−ティング液中に溶け出し、そのためフィルムへ移行した主薬が酸化チタンを触媒とする光化学反応によって変色するものと考えた。
【００１０】
そこで酸化チタン顔料を含む着色ポリマーコーティング層と、裸錠との中間に酸化チタン顔料を含まない中間ポリマーコーティング層を設けたところ、首尾良く着色ポリマーコーティング層の光への暴露による変色を防止することに成功した。
【００１１】
中間コ−ティング層のポリマ−成分は、着色コ−ティング層のポリマ−と同じでよい。コ−ティング液は酸化チタン顔料を含まないことを除いて着色コ−ティング液の成分と同じ成分を含むことができる。好ましくは中間コ−ティング液は前記ポリマ−と媒体のみからなる。
【００１２】
中間コ−ティング層は着色コ−ティング層と同様な作業によって形成することができる。本発明のフィルムコ−ティング錠は、裸錠に直接酸化チタン顔料を含む着色コ−ティング層を施す代わりに、その前に中間コ−ティング層を施すことを除いて、慣用のフィルムコ−ティング方法に従って製造することができる。
【００１３】
前に述べたように塩酸エピナスチンフィルムコート錠の変色は光へ暴露することによって発生するので、錠剤を遮光包装、例えばアルミホイルを使ってＰＴＰ包装とすることによってもこれを防止することが可能であろう。しかしながらこのような包装はそれを破る前に中味を肉眼によって観察されることはできず、また包装前のバルク錠の変色またはそのプレ現象を防止することはできない。これに対し本発明による解決方法は、包装を破る前に中味を肉眼によって確認することを可能にし、そしてすべての製造過程における変色を防止することが可能になる。
【００１４】
以下に限定を意図しない実施例によって本発明を例証する。
【００１５】
実施例
１錠中、塩酸エピナスチン２０ｍｇ、乳糖１００ｍｇ、バレイショデンプン２０ｍｇ、結晶セルロース２０ｍｇ、ポビドンＫ２５ ２ｍｇおよび軽質無水ケイ酸２ｍｇを含むように各成分を均一になるまで混合した後、混合物に１錠あたり３ｍｇに相当するステアリン酸マグネシウムを混合し、直接打錠法によって１錠中塩酸エピナスチン２０ｍｇを含む裸錠を打錠した。
【００１６】
この裸錠に、１錠あたりの被覆量がそれぞれ下表に示す量になるように中間コーティング液および最終コーティング液を逐次常法によりコーティングした。
【００１７】
中間コーティング液
ＨＰＭＣ ２．０ｍｇ
５０％エタノール（媒体） ３０．０ｍｇ
【００１８】
最終コーティング液
ＨＰＭＣ ２．０ｍｇ
ポリエチレングリコール６０００ ０．５ｍｇ
タルク １．０ｍｇ
酸化チタン顔料 １．５ｍｇ
５０％エタノール（媒体） ３０．０ｍｇ
【００１９】
比較例
実施例の裸錠に、中間コーティング液を被覆することなく１錠あたりの被覆量が下表に示す量になるようにコーティング液を常法によりコーティングした。
【００２０】
比較例コーティング液
ＨＰＭＣ ４．０ｍｇ
ポリエチレングリコール６０００ ０．５ｍｇ
タルク １．０ｍｇ
酸化チタン顔料 １．５ｍｇ
５０％エタノール（媒体） ６０．０ｍｇ
【００２１】
安定性試験
実施例および比較例のフィルムコート錠をそれぞれ以下の条件で安定性について試験し、以下の結果を得た。
【００２２】
【００２３】
上の試験結果が示すように、本発明のフィルムコーティング錠はいずれの保存条件においてもフィルムの着色は認められなかった。[0001]
[Background and problems of the present invention]
The present invention relates to epinastine hydrochloride film-coated tablets, and more particularly to such film-coated tablets which do not discolor when exposed to light when applied to prevent alteration of the active ingredient.
[0002]
Epinastine hydrochloride is a drug having selective H 1 receptor antagonism and is used for the treatment of allergic diseases such as bronchial asthma, allergic rhinitis, urticaria and the like.
[0003]
Since epinastine hydrochloride is easily altered by moisture, light, etc., the tablets are usually subjected to film coating to prevent alteration of the active ingredient. However, when such films contain titanium oxide pigments, part or all of the film turns pink or red upon exposure to light. Due to its great hiding power and non-toxicity, the use of titanium oxide pigments for film opacification and coloring is practically inevitable.
[0004]
Accordingly, an object of the present invention is to provide an epinastine hydrochloride tablet coated with a polymer film containing a titanium oxide pigment that does not change color upon exposure to light.
[0005]
[Disclosure of the present invention]
In the epinastine hydrochloride tablet coated with a polymer film colored with a titanium oxide pigment to prevent alteration of the active ingredient, the above-mentioned problem includes a titanium oxide pigment between the bare tablet containing the active ingredient and the colored film layer. The present invention provides an epinastine hydrochloride film-coated tablet provided with no polymer film layer.
[0006]
[Detailed discussion]
In general, the polymer used in the coating film applied to prevent alteration of the active ingredient must be soluble in digestive fluids such as gastric juice and intestinal fluid. Examples of such polymers are hydroxypropylcellulose (HPC), hydroxypropylmethylcellulose (HPMC), polyvinylpyrrolidone (PVP), pullulan, Eudragit NE30D, and the like.
[0007]
The actual colored coating film may contain, in addition to the titanium oxide pigment, a plasticizer such as polyethylene glycol, an extender pigment such as talc or calcium carbonate as an optional additive component.
[0008]
The actual coating operation is carried out by spraying a coating solution in which these components are dissolved or dispersed in water, ethanol or a mixture of water ethanol on a bare tablet and drying with hot air.
[0009]
As is well known, titanium oxide is a powerful photocatalyst. Although the present invention is not bound by any particular theory, the present inventors have shown that the coating solution containing the titanium oxide pigment is barely tableted because epinastine hydrochloride is very soluble in water and ethanol. It was considered that epinastine hydrochloride was slightly dissolved in the coating solution when applied to the film, and the main agent transferred to the film was discolored by a photochemical reaction using titanium oxide as a catalyst.
[0010]
Therefore, when a colored polymer coating layer containing a titanium oxide pigment and an intermediate polymer coating layer not containing a titanium oxide pigment are provided between the bare tablets, the colored polymer coating layer can be successfully prevented from being discolored by exposure to light. succeeded in.
[0011]
The polymer component of the intermediate coating layer may be the same as the polymer of the colored coating layer. The coating liquid may contain the same components as the components of the colored coating liquid except that it does not contain a titanium oxide pigment. Preferably, the intermediate coating liquid consists only of the polymer and the medium.
[0012]
The intermediate coating layer can be formed by the same operation as the colored coating layer. The film-coated tablet of the present invention is a conventional film-coated tablet, except that instead of directly applying a colored coating layer containing a titanium oxide pigment to a bare tablet, an intermediate coating layer is applied in advance. It can be manufactured according to the method.
[0013]
As described above, the discoloration of epinastine hydrochloride film-coated tablets is caused by exposure to light, so this can be prevented by making the tablets into light-shielding packaging, for example, PTP packaging using aluminum foil. I will. However, such packaging cannot be visually observed for its contents before breaking it, and it cannot prevent the discoloration of the bulk tablet before packaging or its pre-phenomenon. In contrast, the solution according to the invention makes it possible to visually check the contents before breaking the packaging and to prevent discoloration in all manufacturing processes.
[0014]
The invention is illustrated by the following non-limiting examples.
[0015]
Example 1 In each tablet, each ingredient was mixed until it became homogeneous so that 20 mg of epinastine hydrochloride, 100 mg of lactose, 20 mg of potato starch, 20 mg of crystalline cellulose, 2 mg of povidone K25 and 2 mg of light anhydrous silicic acid were mixed, and then per tablet in the mixture. Magnesium stearate equivalent to 3 mg was mixed, and a plain tablet containing 20 mg of epinastine hydrochloride in one tablet was tableted by a direct tableting method.
[0016]
This uncoated tablet was sequentially coated with an intermediate coating solution and a final coating solution by a conventional method so that the coating amount per tablet was as shown in the table below.
[0017]
Intermediate coating solution HPMC 2.0mg
50% ethanol (medium) 30.0 mg
[0018]
Final coating solution HPMC 2.0mg
Polyethylene glycol 6000 0.5mg
Talc 1.0mg
Titanium oxide pigment 1.5mg
50% ethanol (medium) 30.0 mg
[0019]
The coating solution was coated on the bare tablets of Comparative Examples by a conventional method so that the coating amount per tablet was the amount shown in the table below without coating the intermediate coating solution.
[0020]
Comparative coating liquid HPMC 4.0 mg
Polyethylene glycol 6000 0.5mg
Talc 1.0mg
Titanium oxide pigment 1.5mg
50% ethanol (medium) 60.0mg
[0021]
Stability test The film-coated tablets of Examples and Comparative Examples were tested for stability under the following conditions, and the following results were obtained.
[0022]
[0023]
As the above test results show, the film-coated tablets of the present invention did not show film coloring under any storage conditions.
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25567499A JP4016128B2 (en) | 1999-09-09 | 1999-09-09 | Light-resistant epinastine hydrochloride film-coated tablets |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP25567499A JP4016128B2 (en) | 1999-09-09 | 1999-09-09 | Light-resistant epinastine hydrochloride film-coated tablets |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2001081033A JP2001081033A (en) | 2001-03-27 |
| JP4016128B2 true JP4016128B2 (en) | 2007-12-05 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP25567499A Expired - Lifetime JP4016128B2 (en) | 1999-09-09 | 1999-09-09 | Light-resistant epinastine hydrochloride film-coated tablets |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4016128B2 (en) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2002087963A (en) * | 2000-09-08 | 2002-03-27 | Nippon Boehringer Ingelheim Co Ltd | Epinastine-containing tablet produced by direct compression |
| JPWO2003011296A1 (en) * | 2001-07-30 | 2004-11-18 | 三菱ウェルファーマ株式会社 | Pharmaceutical preparations containing aminobenzenesulfonic acid derivative as active ingredient |
| US20050118202A1 (en) * | 2001-12-19 | 2005-06-02 | Akio Yamashita | Solid compositions containing compounds unstable to oxygen and method for stabilization thereof |
| US20040247686A1 (en) * | 2003-04-04 | 2004-12-09 | Boehringer Ingelheim International Gmbh | Pharmaceutical compositions comprising epinastine for the treatment of skin diseases |
| EP1757271A1 (en) * | 2004-04-08 | 2007-02-28 | Kyowa Hakko Kogyo Co., Ltd. | Solid pharmaceutical preparation with improved stability and process for producing the same |
| JP6440294B2 (en) * | 2014-07-01 | 2018-12-19 | 大原薬品工業株式会社 | Telmisartan-containing film-coated tablets |
| JP6132858B2 (en) * | 2015-01-09 | 2017-05-24 | ダイト株式会社 | Telmisartan-containing film-coated tablets |
| JP2020094024A (en) * | 2018-12-14 | 2020-06-18 | エルメッド株式会社 | Levetiracetam-containing film-coated tablet and method for producing the same, as well as method for inhibiting discoloration of levetiracetam-containing film-coated tablet |
| JP7262005B2 (en) * | 2019-01-25 | 2023-04-21 | 日本ジェネリック株式会社 | Solid composition containing silodosin and method for producing the same |
-
1999
- 1999-09-09 JP JP25567499A patent/JP4016128B2/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP2001081033A (en) | 2001-03-27 |
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