JP2017523164A - コハク酸メトプロロールのカプセル剤形 - Google Patents
コハク酸メトプロロールのカプセル剤形 Download PDFInfo
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- JP2017523164A JP2017523164A JP2017501201A JP2017501201A JP2017523164A JP 2017523164 A JP2017523164 A JP 2017523164A JP 2017501201 A JP2017501201 A JP 2017501201A JP 2017501201 A JP2017501201 A JP 2017501201A JP 2017523164 A JP2017523164 A JP 2017523164A
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- Prior art keywords
- sustained release
- dosage form
- capsule dosage
- release capsule
- coated
- Prior art date
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- 239000002775 capsule Substances 0.000 title claims abstract description 47
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- 229960000939 metoprolol succinate Drugs 0.000 title claims abstract description 22
- 238000013268 sustained release Methods 0.000 claims abstract description 56
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- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 13
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- 208000019270 symptomatic heart failure Diseases 0.000 description 1
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- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
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Abstract
Description
a)不活性コア、
b)コハク酸メトプロロールを含み、不活性コアを覆う薬剤層、及び
c)薬剤層を覆う徐放性層
を含む。
a)コハク酸メトプロロールの溶液又は分散体を用いて不活性コアを被覆して、薬剤層被覆コアを得る工程、
b)徐放性ポリマーの溶液又は分散体を用いて、工程a)の薬剤層被覆コアを被覆する工程、及び
c)工程b)の徐放性コアを、適切なサイズのカプセル内に充填する工程、
を含む。
1)コハク酸メトプロロール及びオパドライ(登録商標)クリアを精製水に添加して、分散体を形成させた。
2)工程1)の分散体を糖球の上に噴霧して、薬剤被覆コアを形成した。
3)エチルセルロースをイソプロピルアルコール及び精製水中に分散させた。
4)ヒドロキシプロピルメチルセルロース、タルク、及びクエン酸トリエチルを、工程3)の分散体中へ添加した。
5)工程4)の分散体を工程2)の薬剤被覆コアの上に噴霧して、徐放性の分散単位を形成した。
6)工程5)の単位を、タルクで潤滑した。
7)工程6)の潤滑した徐放性の分散単位を、サイズ4のカプセル殻内に充填した。
実施例1で調製したカプセル及びToprol−XL(登録商標)錠剤を使用して、溶解試験を実施した。
ソフトウェアPhoenix WinNonlin(登録商標)6.4及びPhoenix IVIVC Toolkit2.2を使用して、実施例1の薬物動態プロファイル(Cmax及びAUC)を予測した。予測された実施例1の薬物動態値を、摂食条件下及び絶食条件下で、Toprol−XL(登録商標)錠剤の薬物動態値と比較した。表2は、シミュレーションによる実施例1の生物学的同等性のデータを示す。
Claims (15)
- 被覆された分散単位の形態である、コハク酸メトプロロールの徐放性カプセル剤形であって、前記カプセル剤形は、前記剤形の総重量の約30%から約70%の量でコハク酸メトプロロールを含み、市販のToprol−XL(登録商標)錠剤と生物学的同等性を有する、徐放性カプセル剤形。
- 前記カプセルが、スプリンクルカプセルの形態である、請求項1記載の徐放性カプセル剤形。
- 前記被覆された分散単位が、約0.2mmから約2.5mmまでの粒子サイズを有する、請求項1記載の徐放性カプセル剤形。
- 前記被覆された分散単位が、複数のペレット、顆粒、極小の錠剤、又はビーズの形態の、被覆された不活性コアである、請求項1記載の徐放性カプセル剤形。
- 前記被覆された分散単位が、
a)不活性コア、
b)コハク酸メトプロロールを含み、不活性コアを覆う薬剤層、及び
c)前記薬剤層被覆コアを覆う徐放性層
を含む、請求項1記載の徐放性カプセル剤形。 - 前記不活性コアが、水溶性又は水膨潤性である、請求項5記載の徐放性カプセル剤形。
- 前記水溶性又は水膨潤性の不活性コアが、糖、微結晶セルロース、セルロース、デンプン、加工デンプン、又はそれらの混合物で構成される、請求項6記載の徐放性カプセル剤形。
- 前記糖が、グルコース、マンニトール、ラクトース、キシリトール、デキストロ―ス、及びスクロースからなる群から選択される、請求項7記載の徐放性カプセル剤形。
- 前記徐放性層が、薬剤層被覆コアの重量に基づき、5%から20%の量で徐放性ポリマーを含む、請求項5記載の徐放性カプセル剤形。
- 前記徐放性ポリマーが、水溶性/膨潤性ポリマー、水不溶性ポリマー、及びそれらの混合物からなる群から選択される、請求項9記載の徐放性カプセル剤形。
- 前記水溶性のポリマーが、ヒドロキシプロピルメチルセルロース、ヒドロキシエチルセルロース、ポリエチレングリコール、ポリ(エチレンオキシド)、ヒドロキシプロピルセルロース、カルボキシメチルセルロース、キサンタンガム、デンプン、及びそれらの混合物からなる群から選択される、請求項10記載の徐放性カプセル剤形。
- 前記水不溶性ポリマーが、セルロースエーテル、セルロースエステル、ポリメタクリル酸エステル共重合体、アミノアルキルメタクリレート共重合体、ポリ酢酸ビニルとポリビニルピロリドンとの共重合体、及びそれらの混合物からなる群から選択される、請求項11記載の徐放性カプセル剤形。
- 前記セルロースエーテルがエチルセルロースである、請求項12記載の徐放性カプセル剤形。
- 前記水不溶性のポリマーが細孔形成剤を更に含む、請求項12記載の徐放性カプセル投剤形。
- 前記細孔形成剤が、低粘度等級のヒドロキシプロピルメチルセルロース、アルギン酸ナトリウム、糖及び糖アルコール、低分子量ポリエチレングリコール、ポリビニルアルコール、並びにそれらの混合物からなる群から選択される、請求項14記載の徐放性カプセル剤形。
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US201462022316P | 2014-07-09 | 2014-07-09 | |
US62/022,316 | 2014-07-09 | ||
PCT/IB2015/055195 WO2016005934A1 (en) | 2014-07-09 | 2015-07-09 | Capsule dosage form of metoprolol succinate |
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US20070009589A1 (en) * | 2005-07-07 | 2007-01-11 | Kandarapu Raghupathi | Extended release compositions |
US20090311319A1 (en) * | 2005-12-16 | 2009-12-17 | Add Advanced Drug Delivery Technologies Ltd. | Oral Preparation With Controlled Release |
JP2013505724A (ja) * | 2009-09-25 | 2013-02-21 | カッパーアールエヌエー,インコーポレイテッド | フィラグリン(flg)の発現および活性の調整によるflg関連疾患の処置 |
WO2014018570A1 (en) * | 2012-07-25 | 2014-01-30 | Sova Pharmaceuticals, Inc. | Cystathionine-υ-lyase (cse) inhibitors |
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US5246714A (en) | 1985-10-11 | 1993-09-21 | Aktiebolaget Hassle | Drug preparation |
US6156342A (en) * | 1998-05-26 | 2000-12-05 | Andex Pharmaceuticals, Inc. | Controlled release oral dosage form |
SI1355633T1 (en) * | 2001-12-19 | 2005-06-30 | Astrazeneca Ab | NEW FILM COATING containing an ethyl acrylate/methyl methacrylate copolymer and polyvinyl acetate |
SE0201110D0 (sv) * | 2002-04-12 | 2002-04-12 | Astrazeneca Ab | New film coating |
US7314640B2 (en) * | 2003-07-11 | 2008-01-01 | Mongkol Sriwongjanya | Formulation and process for drug loaded cores |
CA2581775A1 (en) * | 2004-09-27 | 2006-04-06 | Sigmoid Biotechnologies Limited | Dihydropyrimidine microcapsule - formulations |
WO2009087663A2 (en) * | 2007-11-30 | 2009-07-16 | Sun Pharmaceutical Industries Ltd. | Oral controlled release coated tablet |
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US20070009589A1 (en) * | 2005-07-07 | 2007-01-11 | Kandarapu Raghupathi | Extended release compositions |
US20090311319A1 (en) * | 2005-12-16 | 2009-12-17 | Add Advanced Drug Delivery Technologies Ltd. | Oral Preparation With Controlled Release |
JP2013505724A (ja) * | 2009-09-25 | 2013-02-21 | カッパーアールエヌエー,インコーポレイテッド | フィラグリン(flg)の発現および活性の調整によるflg関連疾患の処置 |
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US20160143856A1 (en) | 2016-05-26 |
JP6626492B2 (ja) | 2019-12-25 |
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EP3166599A4 (en) | 2017-12-20 |
CA2954474C (en) | 2023-09-05 |
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