JP6335270B2 - 変性グアーガムを用いる医薬ソフトゼラチンカプセル剤形 - Google Patents
変性グアーガムを用いる医薬ソフトゼラチンカプセル剤形 Download PDFInfo
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- JP6335270B2 JP6335270B2 JP2016502347A JP2016502347A JP6335270B2 JP 6335270 B2 JP6335270 B2 JP 6335270B2 JP 2016502347 A JP2016502347 A JP 2016502347A JP 2016502347 A JP2016502347 A JP 2016502347A JP 6335270 B2 JP6335270 B2 JP 6335270B2
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- gelatin capsule
- soft gelatin
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Description
本出願は、2013年3月15日に出願された米国仮出願、出願番号61/794906号からの優先権を主張し、参照により本明細書にその全体が組み込まれている。
本発明は、医薬ソフトゼラチンカプセル剤形であって、粘膜付着性を高めたカプセルフィルにおける、医薬的に活性な成分の膣内投与に有利に使用できる剤形に関する。本発明のソフトゼラチンカプセル剤形は、シェルの一体性(硬度)及びフィル粘度を、保存期間に亘って維持する。
ソフトゼラチン医薬製剤は、飲みやすい点、いやな臭いや不快な味をマスキングする点、及び一旦飲み込まれると、内容物を迅速に放出する点等、いくつかの利点を有する。しかし、ソフトゼラチンカプセルについて、保存中の溶解の低下が知られ、それにより最終的に薬剤の放出が阻止される可能性又は放出が有害な影響を受ける可能性がある。溶解の低下は一般に、カプセルシェルにおいてゼラチンが架橋結合し、結果としてペリクルが形成されることに起因するとされている。ペリクルの形成は、例えば低グレード過酸化物及びアルデヒドに伴いカプセルフィルに賦形剤を使用すること、又は架橋剤の形成を最小化するためにペリクルを形成しにくいゼラチンのグレードを使用すること等、様々な方法で最小化できる。製造方法も、例えば窒素下でフィルを保存すること、製造環境の温度や湿度を制御すること、加熱工程の温度や熱暴露時間を最小化すること、賦形剤にホルムアルデヒドや低分子量アルデヒドの検査をすること、又は耐湿及び耐光包装を使用すること等で最適化できる。
[実施例]
Claims (22)
- 医薬ソフトゼラチンカプセル剤形であって、
ゼラチン及び塑性剤を含むシェルと、
少なくとも1つの医薬的に活性な成分、1つ以上のポリエチレングリコール、及びヒドロキシプロピルグアーガムを含むフィルとを含む、医薬ソフトゼラチンカプセル剤形。 - 前記医薬ソフトゼラチンカプセル剤形は、経口投与用又は膣内投与用である、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 前記医薬ソフトゼラチンカプセル剤形は、膣内投与用である、請求項2に記載の医薬ソフトゼラチンカプセル剤形。
- 前記少なくとも1つの医薬的に活性な成分は、ステロイド及び低用量非ステロイド性化合物並びにその医薬的に許容可能な塩、エステル、水和物、プロドラッグ、及び誘導体からなる群から選択される、請求項2に記載の医薬ソフトゼラチンカプセル剤形。
- 前記少なくとも1つの医薬的に活性な成分は、エストラジオール、エチニルエストラジオール、エステトロール、酢酸ノルエチンドロン、エトノゲストレル、ダリフェナシン、ウデナフィル、リセドロン酸、アレンドロン酸、エチドロン酸、イバンドロン酸、クロドロン酸、及びゾレドロン酸からなる群から選択される、請求項4に記載の医薬ソフトゼラチンカプセル剤形。
- 前記少なくとも1つの医薬的に活性な成分は、エストラジオール、及びその塩、エステル、水和物、プロドラッグ、及び誘導体からなる群から選択される、請求項4に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ヒドロキシプロピルグアーガムの量は、前記フィルの重量の約0.5%から約3.0%である、請求項6に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ポリエチレングリコールは、900より低い分子量を有する、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 少なくとも1つの900を超える分子量の追加のポリエチレングリコールをさらに含む、請求項8に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ポリエチレングリコールは、PEG400とPEG3350の組み合わせである、請求項9に記載の医薬ソフトゼラチンカプセル剤形。
- 前記PEG400とPEG3350は、90:10から95:5の範囲内の重量比率で含まれる、請求項10に記載の医薬ソフトゼラチンカプセル剤形。
- 前記フィルは、抗酸化剤をさらに含む、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 前記抗酸化剤は、トコフェロールである、請求項12に記載の医薬ソフトゼラチンカプセル剤形。
- 前記フィルは、溶剤をさらに含む、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 前記溶剤は、プロピレングリコールである、請求項14に記載の医薬ソフトゼラチンカプセル剤形。
- 前記プロピレングリコールは、前記フィルの総重量の約5%の量で含まれる、請求項15に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ヒドロキシプロピルグアーガムは、前記フィルの重量の約1.0%である、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 医薬ソフトゼラチンカプセル剤形であって、
ゼラチン及び塑性剤を含むシェルと、
少なくとも1つの医薬的に活性な成分、1つ以上のポリエチレングリコール、及びヒドロキシプロピルグアーガムを含むフィルとを含み、
前記フィルは、カプセル化後に、約−1.0から約1.0の対数せん断速度に亘って、カプセル化前のフィルの対数粘度よりも約1から約2倍大きい対数粘度を有する、医薬ソフトゼラチンカプセル剤形。 - 前記ヒドロキシプロピルグアーガムは、前記フィルの重量の約0.5%から約3.0%である、請求項1に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ヒドロキシプロピルグアーガムは、0.6超の置換レベルを有する、請求項19に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ヒドロキシプロピルグアーガムは、約1.0から約1.5の置換レベルを有する、請求項20に記載の医薬ソフトゼラチンカプセル剤形。
- 前記ヒドロキシプロピルグアーガムは、約1.2の置換レベルを有する、請求項21に記載の医薬ソフトゼラチンカプセル剤形。
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Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2014152269A1 (en) * | 2013-03-15 | 2014-09-25 | Warner Chilcott Company, Llc | Pharmaceutical soft gelatin capsule dosage form with modified guar gum |
ES2972665T3 (es) * | 2015-03-26 | 2024-06-13 | Patheon Softgels Inc | Cápsulas liquisoft |
JP2017214299A (ja) * | 2016-05-30 | 2017-12-07 | ライオン株式会社 | 半固形製剤及びその製造方法 |
CA3201467A1 (en) * | 2020-11-13 | 2022-05-19 | Pfizer Inc. | Talazoparib soft gelatin capsule dosage form |
CN116531444B (zh) * | 2023-07-06 | 2023-10-10 | 健码制药(广东)有限公司 | 镇咳清肺软胶囊及其制备工艺 |
Family Cites Families (38)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4708834A (en) | 1986-05-01 | 1987-11-24 | Pharmacaps, Inc. | Preparation of gelatin-encapsulated controlled release composition |
US5102666A (en) | 1990-09-11 | 1992-04-07 | Oramed, Inc. | Calcium polycarbophil controlled release composition and method |
FR2739558B1 (fr) | 1995-10-05 | 1997-11-28 | Innothera Lab Sa | Forme galenique unitaire pour hormonotherapie locale de la secheresse vaginale |
IT1275816B1 (it) * | 1995-10-27 | 1997-10-17 | Montefarmaco Spa | Composizioni farmaceutiche solide per uso vaginale |
AU1925697A (en) | 1996-03-12 | 1997-10-01 | Novartis Ag | Filled gelatin capsules having a reduced degree of cross-linking |
US6024980A (en) * | 1996-06-28 | 2000-02-15 | Mcneil-Ppc, Inc. | Multiphase soft gelatin dosage form |
US5919481A (en) * | 1996-06-28 | 1999-07-06 | Ncneil-Ppc, Inc. | Fill material for soft gelatin pharmaceutical dosage form |
US5989535A (en) | 1997-08-15 | 1999-11-23 | Soma Technologies | Polymeric bioadhesive emulsions and suspensions and methods of treatment |
IN188719B (ja) * | 1997-09-08 | 2002-11-02 | Panacea Biotec Ltd | |
US6187747B1 (en) * | 1997-09-08 | 2001-02-13 | Panacea Biotech Limited | Pharmaceutical composition comprising cyclosporin |
US7374779B2 (en) * | 1999-02-26 | 2008-05-20 | Lipocine, Inc. | Pharmaceutical formulations and systems for improved absorption and multistage release of active agents |
US6251426B1 (en) * | 1999-09-02 | 2001-06-26 | Banner Pharmacaps, Inc. | Ibuprofen-containing softgels |
US20040131670A1 (en) * | 2001-04-17 | 2004-07-08 | Ping Gao | Pellicle-resistant gelatin capsule |
FR2843304B1 (fr) * | 2002-08-07 | 2005-12-16 | Ricarimpex | Extraits de sangsues pour stents |
EP1599485A2 (en) | 2003-02-18 | 2005-11-30 | Ranbaxy Laboratories, Ltd. | Podophyllotoxin derivatives as antitumor agents |
KR100570450B1 (ko) * | 2003-09-25 | 2006-04-12 | 한국유나이티드제약 주식회사 | 가용성 로바스타틴의 연질캡슐제 조성물 및 그의 제조방법 |
US20050142185A1 (en) * | 2003-12-29 | 2005-06-30 | Beleno Alfredo B. | Softgel formulations of bisphosphonates bone resorption inhibitors |
EP1709061A1 (en) | 2004-01-15 | 2006-10-11 | Warner Chilcott Company Inc. | Di-steroidal prodrugs of ethinyl estradiol |
MXPA06007852A (es) | 2004-01-15 | 2007-01-31 | Warner Chilcott Co Inc | Profarmacos di-esteroidales de estradiol. |
US20060110415A1 (en) * | 2004-11-22 | 2006-05-25 | Bioderm Research | Topical Delivery System for Cosmetic and Pharmaceutical Agents |
US7485323B2 (en) | 2005-05-31 | 2009-02-03 | Gelita Ag | Process for making a low molecular weight gelatine hydrolysate and gelatine hydrolysate compositions |
US10016442B2 (en) | 2005-06-16 | 2018-07-10 | Allergan Pharmaceuticals International Limited | Estrogen compositions for vaginal administration |
US20070015741A1 (en) | 2005-07-12 | 2007-01-18 | James Keown | Novel prodrugs of estradiol |
EP2390260B1 (en) | 2005-07-12 | 2014-09-17 | Warner Chilcott Company, LLC | Ester derivative of ethinyl estradiol |
US7468970B2 (en) | 2005-10-24 | 2008-12-23 | Honeywell International Inc. | Routing of mobile agents in a network |
CN101360485B (zh) * | 2005-10-26 | 2013-04-17 | 班纳制药公司 | 作为胶囊填充物的基于亲水性载体的双重控释基质系统 |
US20070104778A1 (en) | 2005-11-07 | 2007-05-10 | Hongxia Zeng | Controlled-release emulsion compositions |
WO2007066837A1 (en) | 2005-12-06 | 2007-06-14 | Lg Household & Health Care Ltd. | Delivery system for tooth whitening component using in situ gelling |
EP1986591A1 (en) | 2006-02-10 | 2008-11-05 | LG Household & Health Care Ltd. | In-situ melting and gelling tablet composition for oral care |
US20080090569A1 (en) | 2006-10-13 | 2008-04-17 | At&T Knowledge Ventures, L.P. | Method and apparatus for performing signal processing in an ip multimedia subsystem network |
US20080122993A1 (en) | 2006-11-29 | 2008-05-29 | Sanyo Electric Co., Ltd. | Television image receiver |
MX2009007913A (es) | 2007-01-25 | 2009-07-31 | Panacea Biotec Ltd | Composicion farmaceutica de liberacion modificada y un procedimiento para elaborarla. |
WO2008122993A1 (en) | 2007-04-09 | 2008-10-16 | Panacea Biotec Limited | Controlled release formulation of coated microparticles |
CN101971130A (zh) | 2008-03-26 | 2011-02-09 | 十字科技股份有限公司 | 光学指向装置及具有该光学指向装置的便携式电子装置 |
CN101474167A (zh) * | 2009-01-23 | 2009-07-08 | 西安德天药业股份有限公司 | 雌二醇阴道用胶囊的制备方法 |
US20110003000A1 (en) | 2009-07-06 | 2011-01-06 | Femmepharma Holding Company, Inc. | Transvaginal Delivery of Drugs |
WO2011018800A2 (en) | 2009-08-13 | 2011-02-17 | Fdc Limited | A novel in-situ gel forming solution for ocular drug delivery |
WO2014152269A1 (en) * | 2013-03-15 | 2014-09-25 | Warner Chilcott Company, Llc | Pharmaceutical soft gelatin capsule dosage form with modified guar gum |
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