JP5414539B2 - 経口徐放性三層錠剤 - Google Patents
経口徐放性三層錠剤 Download PDFInfo
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- JP5414539B2 JP5414539B2 JP2009549005A JP2009549005A JP5414539B2 JP 5414539 B2 JP5414539 B2 JP 5414539B2 JP 2009549005 A JP2009549005 A JP 2009549005A JP 2009549005 A JP2009549005 A JP 2009549005A JP 5414539 B2 JP5414539 B2 JP 5414539B2
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
- A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
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- Bioinformatics & Cheminformatics (AREA)
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- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Medicinal Preparation (AREA)
Description
薬剤と医薬的に許容される添加剤を混合し且つ必要に応じ造粒して、徐放性三層錠剤の即放性内部層用の混合物を調製することと、
膨潤性ポリマーと、医薬的に許容される添加剤と、任意に薬剤とを混合し且つ必要に応じ造粒して外層二層用の混合物をそれぞれ調製することと、
各混合物を順次錠剤化することと、を含む調製方法も提供する。
表1に従って、水性顔料(イエローNo.5)、コポヴィドン、デキストラートを50メッシュの篩を通してから混合して内層用の混合物とした。また、ポリエチレンオキシド(商品名:ポリオクスWSR凝集剤、ダウケミカル)の膨潤性ポリマーとステアリン酸マグネシウムを30メッシュの篩を通してから混合して外層二層用の混合物とした。各混合物をそれぞれプレス(水圧プレス、最終圧6MPa)することにより錠径9.0mmの三層錠剤とした。
表2に従って、塩酸テラゾシン2水和物、コポヴィドン及びデキストラート又はラクトースを50メッシュの篩を通してから混合して内層用の混合物とした。また、ポリエチレンオキシド(商品名:ポリオクスWSR凝集剤、ダウケミカル)とステアリン酸マグネシウムを30メッシュの篩を通してから混合して外層二層用の混合物とした。各混合物をそれぞれプレス(水圧プレス、最終圧6MPa)することにより錠径9.0mmの三層錠剤とした。
表3に従って、塩酸タムスロシン及びポヴィドンK30を1錠当たり4mgの精製水に溶解し、その溶液をラクトースに添加した。混合物を混練、乾燥、造粒した。続いてコポヴィドン及びデキストラートを50メッシュの篩を通してから混合して内層用の混合物とした。また、ポリエチレンオキシド(商品名:ポリオクスWSR凝集剤、ダウケミカル)とステアリン酸マグネシウムを30メッシュの篩を通してから混合して外層二層用の混合物とした。各混合物をそれぞれプレス(水圧プレス、最終圧6MPa)することにより錠径9.0mmの三層錠剤とした。
表4に従って、塩酸テラゾシン2水和物、コポヴィドン及びデキストラート又はラクトースを50メッシュの篩を通してから混合して錠剤用組成物とした。混合物をプレス(水圧プレス、最終圧6MPa)することにより錠径9.0mmの錠剤とした。
表5に従って、塩酸タムスロシン及びポヴィドンK30を1錠当たり4mgの精製水に溶解し、その溶液をラクトースに添加した。混合物を混練、乾燥、造粒した。続いてコポヴィドンと更に混合し、得られた混合物をプレス(水圧プレス、最終圧6MPa)することにより錠径9.0mmの錠剤とした。
実施例1について攪拌ゲル化試験を行って、水性媒体に曝された際に三層錠剤が内層を覆うゲル化層を形成するかどうか、また、各層が分離するかどうかを確認した。攪拌試験はpH6.8のリン酸バッファー(韓国薬局方、崩壊性試験第二溶液)(900mL)中、マグネティックスターラーを用いて行った。図2に結果を示す。
比較例1及び2、実施例4〜7について溶解試験を行った。試験はpH6.8のリン酸バッファー(韓国薬局方、崩壊性試験第二溶液)(900mL)においてパドル法(100rpm)により実施した。図3、4に結果を示す。
Claims (7)
- 1)医薬活性成分を含む中間層と、2)膨潤性ポリマーを含む外層二層とからなる経口徐放性三層錠剤において、
上記中間層は、上記外層がない場合、水性媒質との接触時に1時間以内に上記医薬活性成分が80%以上放出される即放性内部層であり、
上記外層のうち少なくとも一つの層は上記膨潤性ポリマーとしてポリエチレンオキシドを含み、
上記中間層は上記外層によって覆われずに露出された側面を含み、上記三層錠剤が水性媒質との接触時、上記外層が膨潤されて上記中間層の上記露出された側面を覆うことを特徴とする経口徐放性三層錠剤。 - 上記医薬活性成分は、ドキサゾシン、テラゾシン、タムスロシン、シムバスタチン、ロバスタチン、フルバスタチン、アセトアミノフェン、ザルトプロフェン及びトラマドールからなる群から選択される、請求項1に記載の経口徐放性三層錠剤。
- 上記膨潤性ポリマーを含む上記外層二層は、医薬的に許容される賦形剤、結合剤、崩壊剤又は滑沢剤を含む、請求項1に記載の経口徐放性三層錠剤。
- 上記膨潤性ポリマーを含む上記外層二層は、医薬活性成分を含む、請求項1に記載の経口徐放性三層錠剤。
- 上記即放性内部層は錠剤の総重量に対して5〜60重量%を占める、請求項1に記載の経口徐放性三層錠剤。
- 上記膨潤性ポリマーを含む上記外層二層は錠剤の総重量に対して40〜95重量%を占める、請求項1に記載の経口徐放性三層錠剤。
- 前記ポリエチレンオキシドは粘度400cps(2%水溶液)以上を有する、請求項1に記載の経口徐放性三層錠剤。
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