TWI314142B - d-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it - Google Patents
d-crystalline form of ivabradine hydrochloride, a process for its preparation and pharmaceutical compositions containing it Download PDFInfo
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- C07D223/14—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
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- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
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- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
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- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/13—Crystalline forms, e.g. polymorphs
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Description
1314142 九、發明說明: 【發明所屬之技術領域】 本發明係關於化學式之(I)依伐布雷定鹽酸鹽之新型丫心 結晶型、其製備方法及含彼之醫藥組合物。
.HCI, 【先前技術】 依伐布雷定及其與醫藥學上可接受之酸之加成鹽(且更 尤其為其鹽酸鹽)’具有極富價值之藥理及治療特性(尤其心 動減緩特性),從而使彼等化合物適用於治療或預防心肌缺 血之各種臨床表現,諸如心絞痛、心肌梗塞及相關之心律 不整,且亦適用於治療或預防涉及心律不整,尤其室上性 心律不整之各種病狀及心臟衰竭。
依伐布雷定及其與醫藥學上可接受之酸之加成鹽(且更 尤其為其鹽酸鹽)的製備及治療用途已描述於歐洲專利說 明書 ΕΡ 0 534 859 中。 宴於此化合物之醫藥價值,獲得具有極高純度之該化合 :已為最重要的。亦為重要的是,能夠藉助可容易地轉化 業見桓之方法合成(尤其)允許快速過渡及乾燥之形態 的該化合物。最後,噹报能 忒形態必須為極佳地可再現的,易於 調配且足夠穩定以使其 w ^ . 要'皿度、光線或氧含量之特殊 要求而長期儲存。 108742.doc 1314142 專利說明書EP 〇 534 85W;+、>、 田述依伐布雷定及其鹽酸鹽之 口成方法。然而,該文獻並未指 古彳 疋用於獲得形成以再現性 式展示該等特徵之形態之依伐布雷定的條件。 【發明内容】 ” 曰申》月者現已發現,依伐布雷^之特定鹽(鹽酸鹽)可以結 曰曰型獲得,該結晶型經良好界定且展示有價值之穩定性及 加工性能之特徵。
更具體言之’本發明係關於依伐布雷定鹽酸鹽之外結晶 聖”由如下之粉末χ-射線繞射圖表徵,該粉末χ_射線繞 射圖使用一PANa丨ytical x,Pert Pr〇繞射儀連同一 X^elerator偵測器一起量測且根據射線位置(布拉格(Bragg) 角2Θ,以度數表示)、射線高度(以計數表示)、射線面積(以 計數X度數表示)、半高射線寬度("FWHM”,以度數表示)及 晶面間距d(以A表示)表示: 射線序號 角 2Θ (度數) 高度 (計數) 面積 (計數X 度數) FWHM (度數) 晶面間 距(A) 1 4.3 1077 124 0.1171 20 633 2 3 6.9 132 70 0.5353 12.787 _8.4 269 35 0 1338 1 〇 482 4 10.6 322 26 0.0836 8 310 5 6 一 .... 7 -JJ.9 733 97 0.1338 7.414 —J_2.5 1406 278 0.2007 7 069 13.4 2975 442 0 1506 8 14.4 825 122 0.1506 U · U 1 -7 6 134 9 ~H)~~ -J5.8 16.3 —1〇36_ 540 205 ~~Ϊ07~ 0.2007 0 2007 5.598 5 450 11 -,16.9 1007 183 0 184 5 233 12 」7·8 499 58 0 1171 4 978 13 14 .^18,9 1062 140 0.1338 4.686 19.8 570 85 〇 1506 4 48 5 15 -^0.2 549 63 0.1171 1 · 1 mJ 4.399 108742.doc 1314142 射線序號 16 17 18 19 20 21 22 23 24 25 26 27 28 角 2Θ (度數) 20.9 21.6 22.3 23.4 24.1 24.4 24.8 25.4 26.2 26.8 27.2 27.9 29.1 高度 (計數) .2565 531 213 278 1404 1526 676 702 ,1737 258 182 —83 8 152 面積 (計數X 度數) 635 105 35 27 185 176 100 139 401 51 24 249 20 FWHM (度數) 0.2509 0.2007 0.1673 0.1004 0.1338 0.1171 0.1506 0.2007 0.2342 0.2007 0.1338 0.3011 0.1338 晶面間 距(A) 4.241 4.104 3.981 3.807 3.694 3.650 3.591 3.504 3.403 3.331 3,282 3.193 -3.071 ,本發明亦係關於一種製備依伐布雷定鹽酸鹽之結晶 型之方S,該方法之特徵在於將依伐冑雷定鹽酸鹽與:乙 氧基乙醇之混合物,依伐布雷定鹽酸鹽、2_乙氧基乙醇與 水之混合物或依伐布雷定鹽酸鹽、乙醇與水之混合物加轨 直至完全溶解且接著將其冷卻直至完全結晶,且藉由過減 收集所得晶體且使其脫水。 2據本發明之結晶方法中,可使用以任何方法獲得之 2伐布雷定鹽M ’例如藉由描述於專利㈣树 中之製備方法所獲得之依伐布雷定鹽酸鹽。 可有利地於冷卻步驟期間接種該溶液。 本發明亦係關於包含作為活性 …晶型連同一或多種適·、鹽酸鹽 藥組合物。在祀攄太恭 s “ 、無f之賦形劑的醫 在根據本發明之醫藥組合物中,更 適用於口服、非姆胳/# /、可長:及 藥丸、舌下錠劑、明膠F壺八 "劑或糖衣 月膠唇囊、口含劑、拴 108742.doc 1314142 皮用凝膠(dermal gels)、可、、主在ϋ S ; j左射製劑、可飲用懸浮液之彼等 醫藥組合物。 適用劑量可根據病症之性質及嚴重性、投藥途徑及患者 之年齡及體重而加以變化。該劑量在每天一或多次投予】至 5 00 mg之間變化。 【實施方式】 下列實例說明本發明。 X-射線粉末繞射光譜於下列實驗條件下量測: -PANalytiCal X,Pert 射儀、x,Cele_r偵測器、溫度 調節腔室, -電壓45 kV,強度40 mA, -座架Θ-Θ, -鎳(Κβ)濾光片, -入射光束及繞射光束索勒狹缝(s〇ller sli〇: 〇 〇4拉德(rad), -發散狹縫之定角:1/8。, ^ -遮罩:10 mm, -反散射狹縫:1/4°, -量測模式:自3°至30。連續,增量為〇 〇17。, -每步驟之量測時間:19.7 S, -總時間:4 min 32 s, -量測速度:0.108°/s, -罝測溫度:周圍溫度。 實例1 :依伐布雷定鹽酸鹽之yd-結晶型 將4 0 m 1 2 -乙氧基乙醇預熱至8 〇它,且接著伴隨攪拌將8 · * I08742.doc 1314142 g根據描述於專利說明書ΕΡ Ο 534 859中之方法所獲得之依 伐布雷定鹽酸鹽以分成若干部分之方式加入,且於80°C加 熱該混合物直至完全溶解。在使該溶液返回周圍溫度之 後,將其儲存8日,且接著藉由過濾收集所形成之晶體且用 環己烷沖洗其。 藉由以5°C/min之速率逐步加熱直至80 °C之溫度使藉此獲 得之產物脫水。 X-射線粉末繞射圖:
依伐布雷定鹽酸鹽之yd-型之X-射線粉末繞射分佈(繞射 角)由整理於下表中之有效射線給出: 射線序號 角2Θ (度數) 高度 (計數) 面積 (計數X度數) FWHM (度數) 晶面間距 (A) 1 4.3 1077 124 0.1171 20.633 2 6.9 132 70 0.5353 12.787 3 8.4 269 35 0.1338 10.482 4 10.6 322 26 0.0836 8.310 5 11.9 733 97 0.1338 7.414 6 12.5 1406 278 0.2007 7.069 7 13.4 2975 442 0.1506 6.619 8 14.4 825 122 0.1506 6.134 9 15.8 1036 205 0.2007 5.598 10 16.3 540 107 0.2007 5.450 11 16.9 1007 183 0.184 5.233 12 17.8 499 58 0.1171 4.978 13 18.9 1062 140 0.1338 4.686 14 19.8 570 85 0.1506 4.485 15 20.2 549 63 0.1171 4.399 16 20.9 2565 635 0.2509 4.241 17 21.6 531 105 0.2007 4.104 18 22.3 213 35 0.1673 3.981 19 23.4 278 27 0.1004 3.807 20 24.1 1404 185 0.1338 3.694 21 24.4 1526 176 0.1171 3.650 22 24.8 676 100 0.1506 3.591 108742.doc 10 1314142 射線序號 角2Θ (度數) 南度 (計數) 面積 (計數x度數) FWHM (度數) 晶面間距 (A) 23 25.4 702 139 0.2007 3.504 24 26.2 1737 401 0.2342 3.403 25 26.8 258 51 0.2007 3.331 26 27.2 182 24 0.1338 3.282 27 27.9 838 249 0.3011 3.193 28 29.1 152 20 0.1338 3.071 實例2 :醫藥組合物 用於製備1000錠各含5 mg依伐布雷定基礎物質之錠劑之 配方: 實例1之化合物.....................................5.39 g 玉米澱粉................................................20 g 無水碎膠...............................................0*2 g 甘露糠醇............................................63.91 g PVP.......................................................10 g 硬脂酸鎖..................‘............................〇 · 5 g
108742.doc -11 -
Claims (1)
1314142 T\ I. . ^ 十、申請專利範圍: 1. 一種化學式(I)之依伐布雷定(ivabradine)鹽酸鹽之γ<1-結 晶型·
其由如下之粉末X-射線繞射圖表徵,該粉末X-射線繞射 圖係使用一 PANalytical X’Pert Pro繞射儀連同一 X'Celerator彳貞測器一起量測且根據射線位置(布拉格 (Bragg)角2Θ,以度數表示)、射線高度(以計數表示)、射 線面積(以計數X度數表示)、半高射線寬度("FWHM”,以 度數表示)及晶面間距d(以A表示)表示:
射線序號 角2Θ (度數) 南度 (計數) 面積 (計數X度數) FWHM (度數) 晶面間距 (A) 1 4.3 1077 124 0.1171 20.633 2 6.9 132 70 0.5353 12.787 3 8.4 269 35 0.1338 10.482 4 10.6 322 26 0.0836 8.310 5 11.9 733 97 0.1338 7.414 6 12.5 1406 278 0.2007 7.069 7 13.4 2975 442 0.1506 6.619 8 14.4 825 122 0.1506 6.134 9 15.8 1036 205 0.2007 5.598 10 16.3 540 107 0.2007 5.450 11 16.9 1007 183 0.184 5.233 12 17.8 499 58 0.1171 4.978 13 18.9 1062 140 0.1338 4.686 14 19.8 570 85 0.1506 4.485 15 20.2 549 63 0.1171 4.399 16 20.9 2565 635 0.2509 4.241 17 21.6 531 105 0.2007 4.104 18 22.3 213 35 0.1673 3.981 108742.doc 1314142 射線序號 角2Θ (度數) 南度 (計數) 面積 (計數X度數) FWHM (度數) 晶面間距 (Α) 19 23.4 278 27 0.1004 3.807 20 24.1 1404 185 0.1338 3.694 21 24.4 1526 176 0.1171 3.650 22 24.8 676 100 0.1506 3.591 23 25.4 702 139 0.2007 3.504 24 26.2 1737 401 0.2342 3.403 25 26.8 258 51 0.2007 3.331 26 27.2 182 24 0.1338 3.282 27 27.9 838 249 0.3011 3.193 28 29.1 152 20 0.1338 3.071 2. —種製備如請求項1之依伐布雷定鹽酸鹽之γ(1-結晶型的 方法,其特徵在於將依伐布雷定鹽酸鹽與2-乙氧基乙醇之 混合物,依伐布雷定鹽酸鹽、2-乙氧基乙醇與水之混合物 或依伐布雷定鹽酸鹽、乙醇與水之混合物加熱直至完全 溶解,且接著將其冷卻直至完全結晶,且藉由過濾收集 該等所得之晶體且使其脫水。 3. 如請求項2之方法,其特徵在於於該冷卻步驟期間接種該 依伐布雷定鹽酸鹽之溶液。 4. 一種醫藥組合物,其包含作為活性成分之如請求項1之依 伐布雷定鹽酸鹽的γ(1-結晶型,其與一或多種醫藥學上可 接受、惰性、無毒之載劑組合。 5. 一種如請求項1之依伐布雷定鹽酸鹽之yd-結晶型於製造 醫藥品的用途,該等醫藥品係用作心動減緩劑。 6. 一種如請求項1之依伐布雷定鹽酸鹽之γ(1-結晶型於製造 醫藥品的用途,該等醫藥品係用於治療或預防心肌缺血 I08742.doc 1314142 之各種臨床表現,諸如心絞痛、心肌梗塞及相關之心律 不整,且亦係用於治療或預防涉及心律不整,尤其室上 性心律不整之各種病狀及心臟衰竭。
108742.doc
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FR0501990A FR2882556B1 (fr) | 2005-02-28 | 2005-02-28 | Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
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Publication number | Priority date | Publication date | Assignee | Title |
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FR2868777B1 (fr) * | 2004-04-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
FR2882555B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882554B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882556B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882553B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2891826B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
FR2891827B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2894825B1 (fr) * | 2005-12-21 | 2010-12-03 | Servier Lab | Nouvelle association d'un inhibiteur du courant if sinusal et d'un inhibiteur de l'enzyme de conversion et les compositions pharmaceutiques qui la contiennent |
EP2097383B1 (en) | 2006-11-30 | 2012-02-08 | Cadila Healthcare Limited | Process for preparation of ivabradine hydrochloride |
CN101353325B (zh) * | 2007-07-27 | 2011-11-09 | 上海优拓医药科技有限公司 | 稳定型盐酸伊伐布雷定结晶及其制备方法 |
PT2471780E (pt) | 2007-05-30 | 2015-02-24 | Ind Swift Lab Ltd | Sais oxalato de ivabradina cristalinos e seus polimorfos |
ES2402765T3 (es) | 2008-12-22 | 2013-05-08 | Krka, D.D., Novo Mesto | Procedimiento de preparación de ivabradina |
CN101774969B (zh) | 2009-01-13 | 2012-07-04 | 江苏恒瑞医药股份有限公司 | 硫酸伊伐布雷定及其i型结晶的制备方法 |
WO2011098582A2 (en) | 2010-02-12 | 2011-08-18 | Krka, D.D., Novo Mesto | Novel forms of ivabradine hydrochloride |
HUP1000245A2 (en) | 2010-05-07 | 2011-11-28 | Richter Gedeon Nyrt | Industrial process for the production ivabradin salts |
WO2012025940A1 (en) | 2010-08-25 | 2012-03-01 | Cadila Healthcare Limited | Polymorphic form of ivabradine hydrochloride and process for preparation thereof |
EP2726462B1 (en) * | 2011-08-02 | 2017-03-22 | Sandoz AG | Acetone solvate of ivabradine hydrochloride |
EP2589594A1 (en) * | 2011-11-04 | 2013-05-08 | Urquima S.A. | Ivabradine hydrochloride Form IV |
WO2013064427A1 (en) | 2011-11-04 | 2013-05-10 | Synthon Bv | A process for making crystalline delta-form of ivabradine hydrochloride |
EP2780327A1 (en) | 2011-11-14 | 2014-09-24 | Cadila Healthcare Limited | Polymorphic forms of ivabradine hydrochloride |
WO2014114341A1 (en) | 2013-01-24 | 2014-07-31 | Synthon Bv | Process for making ivabradine |
CZ305096B6 (cs) | 2013-10-02 | 2015-04-29 | Zentiva, K.S. | Pevná forma Ivabradin hydrochloridu a (S)-mandlové kyseliny a její farmaceutická kompozice |
WO2015001133A1 (en) | 2013-12-12 | 2015-01-08 | Synthon B.V. | Pharmaceutical composition comprising amorphous ivabradine |
EP2774606B1 (en) | 2014-02-14 | 2019-01-30 | Synthon B.V. | Pharmaceutical composition comprising ivabradine hydrochloride polymorph IV |
CZ305436B6 (cs) | 2014-07-10 | 2015-09-16 | Zentiva, K.S. | Pevná forma Ivabradin hydrochloridu a (R)-mandlové kyseliny a její farmaceutická kompozice |
TWI598360B (zh) * | 2016-12-19 | 2017-09-11 | 義守大學 | Fsbm重組蛋白及其用途 |
TR201703066A2 (tr) | 2017-02-28 | 2018-09-21 | Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi | İvabradi̇ni̇n kati oral farmasöti̇k kompozi̇syonlari |
EP3366282A1 (en) | 2017-02-28 | 2018-08-29 | Sanovel Ilac Sanayi ve Ticaret A.S. | Solid oral pharmaceutical compositions of ivabradine |
IT202000025312A1 (it) | 2020-10-26 | 2022-04-26 | Cambrex Profarmaco Milano S R L | Processi per la preparazione di polimorfi di ivabradina hcl |
Family Cites Families (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US534859A (en) * | 1895-02-26 | Condenser for ice-machines | ||
DE3119874A1 (de) * | 1981-05-19 | 1982-12-09 | Dr. Karl Thomae Gmbh, 7950 Biberach | "benzazepinderivate, ihre herstellung und ihre verwendung als arzneimittel" |
DE3418270A1 (de) * | 1984-05-17 | 1985-11-21 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neue aminotetralinderivate, diese verbindungen enthaltende arzneimittel und verfahren zu ihrer herstellung |
CA2090759A1 (en) | 1990-08-29 | 1992-03-01 | Henry A. Lardy | Treatment process for promoting weight loss employing a substituted 5-androstene |
FR2681862B1 (fr) * | 1991-09-27 | 1993-11-12 | Adir Cie | Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent. |
FR2818552B1 (fr) | 2000-12-26 | 2003-02-07 | Servier Lab | Compositions pharmaceutique solide thermoformable pour la liberation controlee d'ivabradine |
FR2868777B1 (fr) * | 2004-04-13 | 2006-05-26 | Servier Lab | Nouveau procede de synthese de l'ivabradine et de ses sels d'addition a un acide pharmaceutiquement acceptable |
FR2882553B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline beta du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882556B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882554B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme critalline beta d du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2882555B1 (fr) * | 2005-02-28 | 2007-05-04 | Servier Lab | Forme cristalline gamma du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2891827B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline deltad du chlorhydrate de l'ivabradine, son procede de preparation, et les compositions pharmaceutiques qui la contiennent |
FR2891826B1 (fr) * | 2005-10-11 | 2007-12-28 | Servier Lab | Forme cristalline 6 du chlorhydrate de l'ivabradine, son procede de preparation et les compositions pharmaceutiques qui la contiennent |
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