RS50599B - KRISTALNI OBLIK BETA-d IVABRADIN HLORHIDRATA, POSTUPAK NJEGOVE IZRADE I FARMACEUTSKE SMEŠE KOJE GA SADRŽE - Google Patents

KRISTALNI OBLIK BETA-d IVABRADIN HLORHIDRATA, POSTUPAK NJEGOVE IZRADE I FARMACEUTSKE SMEŠE KOJE GA SADRŽE

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Publication number
RS50599B
RS50599B RSP-2008/0366A RSP20080366A RS50599B RS 50599 B RS50599 B RS 50599B RS P20080366 A RSP20080366 A RS P20080366A RS 50599 B RS50599 B RS 50599B
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Serbia
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expressed
ivabradine
degrees
ivabradine hydrochloride
crystalline form
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RSP-2008/0366A
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Stéphane Horvath
Marie-Noelle Auguste
Gérard Damien
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Les Laboratoires Servier
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Publication of RS50599B publication Critical patent/RS50599B/sr

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Abstract

βd kristalni oblik ivabradin hlorhidrata formule (I): naznačen time što je dijagram difrakcije X zraka na prašku, u nastavku, izmeren na difraktometru PANalytical X'Pert Pro sa detektorom X'Celerator i, izražen je u vidu položaja linije (ugao Bragg 2 teta, izražen u stepenima), visinom linije (izražena u brojevima), površinom linije (izražena kao brojevi x stepeni), širinom linija u sredini visine ("FWHM", izražena u stepenima) i inter-retikularnom udaljenošću d (izražena u A):Linija n° Ugao 2 teta (stepeni) Visina (brojevi) Površina (brojevi x stepeni) FWHM (stepeni) Inter-retikularna udaljenost (A)1 4,0 244 80 0,3346 22,1392 5,9 377 56 0,1506 14,8293 6,9 94 50 0,5353 12,8354 9,2 1975 293 0,1506 9,6235 11,8 136 27 0,2007 7,4736 12,5 1826 241 0,1338 7,0837 13,6 1834 303 0,1673 6,4918 14,5 51 20 0,4015 6,1199 16,0 1441 214 0,1506 5,52510 17,3 4472 738 0,1673 5,13411 18,4 546 108 0,2007 4,80812 19,6 1025 169 0,1673 4,52413 20,0 688 91 0,1338 4,44814 20,4 1027 186 0,184 4,36215 21,4 102 24 0,2342 4,14316 22,3 1903 283 0,1506 3,99017 22,8 674 89 0,1338 3,89718 23,0 623 62 0,1004 3,86619 24,4 845 56 0,0669 3,64720 25,0 3749 557 0,1506 3,55421 25,5 512 84 0,1673 3,49722 26,6 289 76 0,2676 3,34623 28,3 275 91 0,3346 3,15124 29,1 126 21 0,1673 3,066Prijava sadrži još 5 patentnih zahteva.

Description

KRISTALNI OBLIK BETA-d
IVABRADIN HLORHEDRATA,
POSTUPAK NJEGOVE IZRADE I
FARMACEUTSKE SMEŠE KOJE GA
SADRŽE
Ovaj pronalazak se odnosi na nove kristalne oblike pd ivabradin hlorhidrata formule (I), njegov postupak izrade, kao i farmaceutske smeše koje ga sadrže.
Ivabradin, kao i njegove adicione soli sa farmaceutski prihvatljivom kiselinom i, posebno, njegov hlorhidrat, poseduju veoma korisna farmakološka i terapeutska svojstva, između ostalih, bradikardijalna svojstva, koja omogućavaju ovim jedinjenjima da se upotrebljavaju za lečenje ili prevenciju različitih kliničkih situacija ishemije miokarda, kao što su angina pektoris, infarkt miokarda i udruženi poremećaji ritma, kao i u različitim patologijama ponašanja poremećaja ritma, između ostalog, supra-ventrikularnim i u srčanoj insuficijenciji.
Izrada i korišćenje u terapiji ivabradina i njegovih adicionih soli sa farmaceutski prihvatljivom kiselinom i, posebno, njegovog hlorhidrata, opisani su u evropskom patentu EP 0534 859.
Uzimajući u obzir farmaceutsku isplativost jedinjenja, bilo je glavno da se ono dobije u odličnoj čistoći. Isto tako, bilo je važno omogućiti sintezu u skladu sa postupkom koji je lako prevodiv na industrijski proces i, posebno, u jednom obliku koji će omogućiti filtraciju i brzo sušenje. Konačno, taj oblik derivata je bio savršeno reproducibilan, lako je formulisan i zadovoljavajuće stabilan kako bi se odobrilo njegovo produženo skladištenje bez posebnih uslova temperature, svetla ili protoka kiseonika.
Patent EP 0534 859 opisuje postupak sinteze ivabradina i njegovog hlorhidrata. Međutim, ovaj dokument ne precizira uslove dobijanja ivabradina u nekom obliku koji ispoljva svoje karakteristike na reproducibilan način.
Zahtevalac sada nalazi da se jedna posebna so ivabradina, hlorhidrat, može dobiti u jednom kristalnom obliku koji je dobro definisan i koji ispoljava korisne osobine stabilnosti i mogućnosti za postavljanje u postupak.
Preciznije, ovaj pronalazak se odnosi na |3d kristalni oblik ivabradin hlorhidrata, koji se karakteriše sledećim dijagramom difrakcije X zraka na prašku, koji je izmeren na difraktometru PANalvtical X'Pert Pro sa X'Celerator detektorom i izražen je u vidu položaja linija (ugao Bragga 2 teta, izražen u stepenima), visinom linije (izražene brojevima), površinom linije (izražene kao broj x stepeni), širinom linija po sredini visine ("FWHM", izraženih u stepenima) i inter-retikularnom d udaljenošću (izraženo u A) :
Pronalazak se, isto tako, odnosi na jedan postupak izrade pd kristalnog oblika ivabradin hlorhidrata, koji se karakteriše time da se zagreva smeša ivabradin hlorihdrata i vode ili smeša ivabradin hlorihdrata, izopropanola i vode do potpunog rastvaranja zatim, progresivno hladi dok se ne završi kristalizacija, sakupljaju se tako obrazovani kristali, a zatim se deshidratišu. • U postupku kristalizacije, koji je u skladu sa pronalaskom, može se koristiti ivabradin hlorhidrat, koji je dobijen bilo kojim postupkom, na primer, ivabradin hlorhidrat dobijen postupkom izrade, koji je opisan u Patentu EP 0534 859.
• Rastvor, korisno, može biti zasejan tokom etape hlađenja.
Pronalazak se, takođe, odnosi na farmaceutske smeše koje, kao aktivni princip, sadrže (3d kristalni oblik ivabradin hlorhidrata sa jednim ili više inertnih ekscipijenata, koji su odgovarajući i nisu otrovni. Među farmaceutskim smešama koje su u skladu sa pronalaskom mogu se navesti naročito one koje su pogodne za oralnu, parenteralnu (intravensku ili subkutanu) ili nazalnu primenu, jednostavne pilule ili dražeje, sublingvalne pilule, želatinske kapsule, tablete, supozitorije, kremovi, masti, dermo-gelovi, injektabilni preparati, suspenzije koje se piju.
Doziranje koje se koristi, prilagodi se prema prirodi i ozbiljnosti bolesti, načinu primenjivanja, kao i starosti i težini pacijenta. Takvo doziranje varira od 1 do 500 mg dnevno, jednom ili više puta.
Primeri koji slede ilustruju pronalazak.
Spektar difrakcije X zrakova na prašku izmeren je pod sledećim eksperimentalnim uslovima: - Difraktometar PANalvtical X'Pert Pro, detektor X'Celerator, odeljak regulisane temperature,
- Pritisak 45 KV, intenzitet 40 mA,
- Sklapanje 9-9,
- Niklovani filter (K0),
- Sollerov prorez na umetnutom zračenju i na prelomljenom zračenju : 0,04 rad,
- Prorezi fiksne divergencije : ugao 1/8°,
- Zaklon : 10 mm,
- Anti-difuzioni prorez : 1/4°,
- Način merenja : neprekidno od 3° do 30°, sa jednim porastom od 0,017°,
- Vreme merenja po koraku : 19,7 s,
- Ukupno vreme : 4 min 32 s,
- Brzina merenja : 0,108°/s,
- Temperatura merenja : temperatura sredine.
PRIMER 1: 0d kristalni oblikivabradinhlorhidrata
720 ml prečišćene vode je prethodno zagrejano na 50°C, a zatim je, deo po deo, uz mešanje, dodato 250 g ivabradin hlorhidrata, koji je dobijen u skladu sa postupkom, koji je opisan u Patentu EP 0534 859 i, reakciona sredina je grejana na 74°C do potpunog rastvaranja. Dobijeni bistar rastvor je grejan dodatnih 2h na 74°C, zatim je progresivno ohlađen do 40°C, a zatim, na temperaturu sredine. Rastvor je onda čuvan na temperaturi sredine tokom 2 dana, a zatim je čvrsta suspenzija izložena kao fini sloj za kristalizaciju. Višak vode je istisnut pod slabim prilivom azota. Tako dobijeni proizvod je deshidratizovan progresivnim grejanjem pri brzini od 5°C/min sve do temperature od 80°C.
Dijagram difrakcije X zraka na prašku :
Profil difrakcije X zraka na prašku (difrakcioni uglovi) pd oblika ivabradin hlorhidrata je prikazan značajnim linijama, koje su zajedno date u sledećoj tabeli.
PRIMER 2 :Farmaceutska smeša
Formula za izradu 1000 pilula doze od 5 mg ivabradin baze:

Claims (6)

1. pd kristalni oblik ivabradin hlorhidrata formule (I): naznačentime što je dijagram difrakcije X zraka na prašku, u nastavku, izmeren na difraktometru PANalvtical X'Pert Pro sa detektorom X'Celerator i, izražen je u vidu položaja linije (ugao Bragg 2 teta, izražen u stepenima), visinom linije (izražena u brojevima), površinom linije (izražena kao brojevi x stepeni), širinom linija u sredini visine ("FVVHM", izražena u stepenima) i inter-retikularnom udaljenošću d (izražena u A):
2. Postupak izrade |3d kristalnog oblika ivabradin hlorhidrata, kao u Patentnom zahtevu 1, naznačen time što se zagreva smeša ivabradin hlorihdrata i vode ili smeša ivabradin hlorihdrata, izopropanola i vode do potpunog rastvaranja zatim, progresivno hladi dok se ne završi kristalizacija, sakupljaju se tako obrazovani kristali, a zatim se deshidratišu.
3. Postupak, kao u Patentnom zahtevu 2, n az n ač e n time što se rastvor ivabradin hlorhidrata zasejava u toku etape hlađenja.
4. Farmaceutska smešanaznačena timešto kao aktivni princip sadrži pd kristalni oblik ivabradin hlorhidrata, kao u Patentnom zahtevu 1, zajedno sa jednim ili više inertnih vehikuluma, koji nisu otrovni i farmaceutski su prihvatljivi.
5. Korišćenje |3d kristalnog oblika ivabradin hlorhidrata, kao u Patentnom zahtevu1,naznačeno timešto je za proizvodnju lekova, koji se koriste kao bradikardiačni lekovi.
6. Korišćenje pd kristalnog oblika ivabradin hlorhidrata, kao u Patentnom zahtevu1, naznačeno timešto je za proizvodnju lekova, koji se koriste u lečenju ili prevenciji različitih kliničkih situacija ishemije miokarda, kao što su angina pektoris, infarkt miokarda i udruženi poremećaji ritma, kao i u različitim patologijama ponašanja poremećaja ritma, između ostalog, supra-ventrikularnim i u srčanoj insuficijenciji.
RSP-2008/0366A 2005-02-28 2006-02-28 KRISTALNI OBLIK BETA-d IVABRADIN HLORHIDRATA, POSTUPAK NJEGOVE IZRADE I FARMACEUTSKE SMEŠE KOJE GA SADRŽE RS50599B (sr)

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Families Citing this family (33)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005053405A1 (de) * 2003-12-04 2005-06-16 Bayer Cropscience Aktiengesellschaft Wirkstoffkombinationen mit insektiziden und akariziden eigenschaften
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
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
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
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
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
KR101478855B1 (ko) 2007-05-30 2015-01-02 인드-스위프트 래버러토리즈 리미티드 이바브라딘 히드로클로라이드 및 그의 다형태의 제조방법
FR2920773B1 (fr) 2007-09-11 2009-10-23 Servier Lab Derives de 1,2,4,5-tetrahydro-3h-benzazepines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
EP2367782B1 (en) 2008-12-22 2013-02-13 KRKA, D.D., Novo Mesto Process for preparation of ivabradine
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
SI23290A (sl) 2010-02-12 2011-08-31 Krka D.D., Novo Mesto Nove oblike ivabradin hidroklorida
HUP1000245A2 (en) 2010-05-07 2011-11-28 Richter Gedeon Nyrt Industrial process for the production ivabradin salts
US20130116239A1 (en) 2010-06-14 2013-05-09 ratiopharm GnbH Ivabradine-containing pharmaceutical composition with modified release
WO2012025940A1 (en) 2010-08-25 2012-03-01 Cadila Healthcare Limited Polymorphic form of ivabradine hydrochloride and process for preparation thereof
US9440924B2 (en) 2011-08-02 2016-09-13 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
EP2948432B1 (en) 2013-01-24 2018-09-19 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
ES2672472T3 (es) 2013-12-12 2018-06-14 Synthon Bv Composición farmacéutica que comprende ivabradina amorfa
SI2774606T1 (sl) 2014-02-14 2019-05-31 Synthon B.V. Farmacevtski sestavek, ki obsega polimorf IV ivabradin hidroklorida
CZ2014478A3 (cs) 2014-07-10 2015-09-16 Zentiva, K.S. Pevná forma Ivabradin hydrochloridu a (R)-mandlové kyseliny a její farmaceutická kompozice
CN107056706B (zh) * 2015-12-21 2020-05-05 江苏恒瑞医药股份有限公司 一种用于制备盐酸伊伐布雷定α晶型的方法
EP3366282B1 (en) 2017-02-28 2025-10-01 Sanovel Ilac Sanayi ve Ticaret A.S. Solid oral pharmaceutical compositions of ivabradine
TR201703066A2 (tr) 2017-02-28 2018-09-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi İvabradi̇ni̇n kati oral farmasöti̇k kompozi̇syonlari
IT202000025312A1 (it) 2020-10-26 2022-04-26 Cambrex Profarmaco Milano S R L Processi per la preparazione di polimorfi di ivabradina hcl
IT202100019967A1 (it) 2021-07-27 2023-01-27 Campagnolo Srl Dispositivo manuale di comando per bicicletta
IT202100019988A1 (it) 2021-07-27 2023-01-27 Campagnolo Srl Dispositivo manuale di comando per bicicletta

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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
FR2681862B1 (fr) * 1991-09-27 1993-11-12 Adir Cie Nouvelles (benzocycloalkyl)alkylamines, leur procede de preparation, et les compositions pharmaceutiques qui les contiennent.
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
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
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

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SA06270039B1 (ar) 2010-03-30
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UY29404A1 (es) 2006-07-31
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US7361652B2 (en) 2008-04-22
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