JP2016145242A - カルシウムブロッカーを含有する固形医薬組成物 - Google Patents
カルシウムブロッカーを含有する固形医薬組成物 Download PDFInfo
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- JP2016145242A JP2016145242A JP2016076802A JP2016076802A JP2016145242A JP 2016145242 A JP2016145242 A JP 2016145242A JP 2016076802 A JP2016076802 A JP 2016076802A JP 2016076802 A JP2016076802 A JP 2016076802A JP 2016145242 A JP2016145242 A JP 2016145242A
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- solid pharmaceutical
- pharmaceutical composition
- meglumine
- calcium blocker
- calcium
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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Abstract
Description
アゼルニジピンを含有する錠剤を以下の表1に記載の処方により製造した。アゼルニジピン((±)-3-(1-dipheylmethylazetidin-3-yl)5-isopropyl 2-amino-1,4-dihydro-6-methyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate;特許文献2)、D−マンニトール(花王株式会社製)、ポリソルベート80(日光ケミカルズ株式会社製)、メグルミン(メルク社製)、軽質無水ケイ酸(フロイント産業株式会社製アドソリダー(登録商標)−101)、ヒドロキシプロピルセルロース−L(日本曹達株式会社製)、カルメロースカルシウム(ニチリン化学工業株式会社製)、L−ヒドロキシプロピルセルロース(信越化学工業株式会社製)、ステアリン酸マグネシウム(太平化学産業株式会社製)、エタノール、水を混合・造粒し、錠径8.0mmに打錠して、錠剤を製造した。
メグルミンを用いなかったことおよびD−マンニトールの量を増やしたこと以外は、実施例1と同様にして、錠剤を製造した。
実施例1および比較例1で製造した錠剤、ならびに市販の「カルブロック(登録商標)錠8mg」(第一三共株式会社製:比較例2)について、アゼルニジピンの保存安定性を過酷試験にて評価した。すなわち、各製剤を過酷な条件下で保存した後に、アゼルニジピンの分解産物である類縁物質をUPLC(Ultra Performance Liquid Chromatography)にて定量した。
カラム温度:40℃
移動相:リン酸二水素カリウム0.9gを水300mLに溶解させた液300mLとアセトニトリル700mLとを混合し、0.1mol/L水酸化ナトリウム液でpH6.0に調整した溶液
検出器:紫外吸収光度計(測定波長:254nm)
分析時間:10分間
試料注入量:3μL
アゼルニジピンを含有する錠剤を以下の表3に記載の処方により製造した。アゼルニジピン、D−マンニトール、ポリソルベート80、メグルミン、ヒドロキシプロピルセルロース−L、L−ヒドロキシプロピルセルロース、ステアリン酸マグネシウム、エタノールを混合・造粒し、錠径8.0mmに打錠して、錠剤を製造した。
メグルミンに代えてアルギニンを用いたこと以外は、実施例2と同様にして、錠剤を製造した。
メグルミンに代えて炭酸水素ナトリウムを用いたこと以外は、実施例2と同様にして、錠剤を製造した。
メグルミンに代えて炭酸カルシウムを用いたこと以外は、実施例2と同様にして、錠剤を製造した。
実施例2および3ならびに比較例3および4で製造した錠剤、ならびに市販の「カルブロック(登録商標)錠8mg」(第一三共株式会社製:比較例2)について、アゼルニジピンの保存安定性を過酷試験にて評価した。保存条件として、80℃にて3日間保存の条件であって、錠剤を包装しなかった場合(無包装で蓋なしのシャーレに放置)についてのみ試験した以外は、上記と同様にして試験した。結果を以下の表4に示す。
Claims (5)
- 固形医薬組成物であって、
ジヒドロピリジン誘導体からなるカルシウムブロッカーと、アミノ基を有する化合物とを含有し、かつPTP包装、ガラス瓶封入、またはポリエチレン瓶封入されており、
該アミノ基を有する化合物が、メグルミンおよびアルギニンからなる群から選択される少なくとも1つの化合物である、
固形医薬組成物。 - 前記PTP包装を、さらにシリカゲルとともにもしくはシリカゲルなしでアルミ包装した、請求項1に記載の固形医薬組成物。
- 前記ガラス瓶またはポリエチレン瓶がさらにシリカゲルを含有する、請求項1に記載の固形医薬組成物。
- 前記カルシウムブロッカーが、アゼルニジピンまたはその薬理上許容される塩である、請求項1から3のいずれかに記載の固形医薬組成物。
- 前記固形医薬組成物が錠剤である、請求項1から4のいずれかに記載の固形医薬組成物。
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