SI20425A - Priprava amorfnega atorvastatina - Google Patents
Priprava amorfnega atorvastatina Download PDFInfo
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- SI20425A SI20425A SI9900271A SI9900271A SI20425A SI 20425 A SI20425 A SI 20425A SI 9900271 A SI9900271 A SI 9900271A SI 9900271 A SI9900271 A SI 9900271A SI 20425 A SI20425 A SI 20425A
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- Prior art keywords
- atorvastatin
- amorphous
- solvent
- crystalline
- preparation
- Prior art date
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- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 title claims abstract description 55
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 title claims abstract description 55
- 229960005370 atorvastatin Drugs 0.000 title claims abstract description 55
- 238000002360 preparation method Methods 0.000 title abstract description 7
- 238000000034 method Methods 0.000 claims abstract description 17
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- 239000002904 solvent Substances 0.000 claims description 15
- 239000002244 precipitate Substances 0.000 claims description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 239000000203 mixture Substances 0.000 claims description 3
- 239000000155 melt Substances 0.000 claims 2
- 239000011877 solvent mixture Substances 0.000 claims 2
- 239000000126 substance Substances 0.000 abstract description 7
- 239000000843 powder Substances 0.000 abstract description 5
- 159000000007 calcium salts Chemical class 0.000 abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 3
- 230000000326 anti-hypercholesterolaemic effect Effects 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 abstract 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 abstract 1
- 239000003112 inhibitor Substances 0.000 abstract 1
- 239000006187 pill Substances 0.000 abstract 1
- 230000009466 transformation Effects 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000005286 illumination Methods 0.000 description 2
- 230000010354 integration Effects 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- WSRKLYQAZKDXKA-UHFFFAOYSA-N 7-pyrrol-1-ylheptanoic acid Chemical compound OC(=O)CCCCCCN1C=CC=C1 WSRKLYQAZKDXKA-UHFFFAOYSA-N 0.000 description 1
- 229940121710 HMGCoA reductase inhibitor Drugs 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002471 hydroxymethylglutaryl coenzyme A reductase inhibitor Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
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- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Diabetes (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Hematology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Pyrrole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
Atorvastatin, substanca s kemijskim imenom hemi kalcijeva sol (R-(R*,R*))-2-(4-fluorofenil)-beta,delta-dihidroksi-5-(1 metiletil)-3- fenil-4((enilamino)karbonil)-1H-pirol-1-heptanojske kisline, je poznana kot inhibitor HMG-CoA reduktaze in se uporablja kot antihiperholesterolemik. Atorvastatin se vedno pripravlja v obliki kalcijeve soli, s katero se da pripraviti primerne farmacevtske formulacije kot na primer tablete, kapsule, praške in druge za oralno administracijo primerne oblike. Obstaja lahko v amorfni ali pa v eni od štirih (Form I, II, III in IV) kristaliničnih oblik. Atorvastatin je substanca, ki je v vodi zelo slobo topna, ugotovljeno pa je bilo, da so kristalinične oblike slabše topne od amorfne, kar lahko vpliva tudi na biorazpoložljivosti atorvastatina v telesu. Predloženi izum se nanaša na nov postopek pretvorbe kristaliničnega atorvastatina v amorfnega.ŕ
Description
Priprava amorfnega atorvastatina
C07D 207/34
Področje tehnike
Atorvastatin, substanca s kemijskim imenom hemi kalcijeva sol (R(R*,R*))-2-(4-fluorofenil)-3,8-dihidroksi-5-(l-metiletil)-3-fenil-4((enilamino)karbonil)lH-pirol-l-heptanojske kisline, je poznana kot inhibitor HMG-CoA reduktaze in se uporablja kot antihiperholesterolemik. Postopki za pripravo atorvastatina in ključnih intermediatov so opisan v seriji ameriških patentov US 5.003.080, US 5.097.045, US 5.103.024, US 5.124.482, US 5.149.837, US 5.155.251, US
5.216.174, US 5.245.047, US 5.248.793, US 5.280.126, US 5.342.952, US
5.397.792. Atorvastatin se vedno pripravlja v obliki kalcijeve soli, s katero se da pripraviti primerne farmacevtske formulacije kot na primer tablete, kapsule, praške in druge za oralno administracijo primerne oblike.
Atorvastatin obstaja lahko v amorfni ali pa v eni od štirih (Form I, II, III in IV) kristaliničnih oblik, ki so opisane v patentnih prijavah WO 97/3958 in WO 97/3959. Znano je, da se amorfne oblike številnih farmacevtskih učinkovin razlikujejo od kristaliničnih oblik v disolucijskih in biorazpoložljivostnih lastnostih (Konno T., Chem. Pharm. Buli., 1990;38;2003-2007). Biorazpoložljivost je za nekatere terapevtske indikacije eden ključnih parametrov po katerih se odločamo, kakšno obliko substance bomo uporabili v farmacevtski formulaciji. Glede na to, da so postopki kristalizacije oziroma priprave amorfne snovi včasih težko vodljivi in kot produkt nastajajo amorfno-kristalinične mešanice oziroma kristalinična namesto amorfne oblike, obstaja stalna potreba po postopkih, ki bi omogočali pripravo amorfne oblike brez istočasne tvorbe kristaliničnih oblik, oziroma, ki bi omogočali pretvorbo kristaliničnih oblik v amorfno obliko.
Atorvastatin je substanca, ki je v vodi zelo slabo topna, ugotovljeno pa je bilo, da so kristalinične oblike slabše topne od amorfne, kar lahko povzroča probleme v biorazpoložljivosti atorvastatina v telesu. Za atorvastatin je bilo tudi ugotovljeno, da predhodno razkriti postopki za pripravo amorfnega atorvastatina niso konsistentno ponovljivi, zato je bil pripravljen postopek, ki je omogočal pretvorbo kristaliničnih oblik atorvastatina (ki so nastale pri sintezi atorvastatina) v amorfno obliko. Postopek je opisan v patentni prijavi WO 97/3960 in zaobsega raztapljanje kristaliničnega atorvastatina v ne-hidroksilnem topilu, ki ga nato odstranimo in dobimo amorfen atorvastatin. Kot prednostno uporabljeno ne-hidroksilno topilo je omenjen tetrahidrofuran in njegove mešanice s toluenom. Pomankljivost omenjenega postopka je predvsem uporaba okolju neprijaznih topil.
Predloženi izum se nanaša na nov postopek za pretvorbo atorvastatina v kristalinični obliki v njegovo amorfno obliko.
Po postopku, ki je predmet tega izuma, raztopimo kristalinični atorvastatin v topilu, kjer se dobro topi, nato pa vanj dodajamo topilo v katerem se atorvastatin ne otopi oziroma je v njem slabo topen. Druga možna izvedba tega postopka je, da kristalinični atorvastatin raztopimo v topilu, v katerem se dobro topi in to raztopino vlivamo v topilo, kjer se atorvastatin ne topi oziroma je slabo topen. V obeh primerih nastane oborina amorfnega atorvastatina, ki se jo v nadaljevanju odfiltrira in posuši. Po zgoraj opisanih postopkih dobimo amorfni atorvastatin, katerega rentgenski praškovni difraktogram je prikazan na Sliki 1. Referenčni rentgenski difraktogram kristaliničnega atorvastatina (kristali form I) je prikazan na Sliki 2.
Slika 1: Difraktogram amorfnega atorvastatina posnetega na rentgenskem praškovnem difraktometru Siemens D-5000 v območju od 2 do 37 °2θ s korakom 0.035 °20 in integracijskim časom 1 s na korak. Variabilne reže so bile nastavljene na 20 mm osvetlitve vzorca, sprejemna reža pa je bila 0.6 mm.
Slika 2: Difraktogram kristaliničnega atorvastatina (form I) posnetega na rentgenskem praškovnem difraktometru Siemens D-5000 v območju od 2 do 37 °2θ s korakom 0.035 °20 in integracijskim časom 1 s na korak. Variabilne reže so bile nastavljene na 20 mm osvetlitve vzorca, sprejemna reža pa je bila 0.6 mm.
Predloženi izum prikazujejo, vendar v ničemer ne omejujejo naslednji primeri.
PRIMERI
Primer 1
1.5 g atorvastatina (kristali Form I) smo raztopili v 37.5 ml metanola, skoncentrirali rotavaporju na 10 ml in v dobljeno raztopino vlili 100 ml etra. Nastalo oborino smo odfiltrirali in posušili na rotavaporju (50° C, 100 mbar, 24 ur). Dobili smo 1.3 g brezbarvne oborine amorfnega atorvastatina.
Primer 2
1.5 g atorvastatina (kristali Form I) smo raztopili v 300 ml etanola, skoncentrirali rotavaporju na 30 ml in v dobljeno raztopino vlili 300 ml etra. Nastalo oborino smo odfiltrirali in posušili na rotavaporju (50° C, 100 mbar, 24 ur). Dobili smo 1.3 g brezbarvne oborine amorfnega atorvastatina.
Primer 3
1.5 g atorvastatina (kristali Form I) smo raztopili v 136 ml acetona, skoncentrirali rotavaporju na 30 ml in v dobljeno raztopino vlili 300 ml etra. Nastalo oborino smo odfiltrirali in posušili na rotavaporju (50° C, 100 mbar, 24 ur). Dobili smo 1.3 g brezbarvne oborine amorfnega atorvastatina.
Primer 4 g atorvastatina (kristali Form I) smo raztopili v 130 ml metanola, skoncentrirali rotavaporju na 30 ml in v dobljeno raztopino dodali 300 ml etra. Dobljeno raztopino smo ob mešanju vlili v 1300 ml etra. Nastalo oborino smo odfiltrirali in posušili na rotavaporju (50°C, 100 mbar, 24 ur). Dobili smo 8.8 g brezbarvne oborine, vendar ba je imel dobljeni amorfni atorvastatin cca 110% višjo vsebnost kot vstopna kristalinična substanca.
Primer 5 g atorvastatina (kristali Form I) smo raztopili v 1 1 metanola, prefiltrirali in skoncentrirali rotavaporju na 300 ml. K dobljeni raztopini smo dodali 500 ml etra in jo ob mešanju vlili v 2.5 1 etra. Nastalo oborino smo odfiltrirali in posušili na rotavaporju (50° C, 100 mbar, 24 ur). Dobili smo 87 g brezbarvne oborine amorfnega atorvastatina.
Claims (6)
- Patentni zahtevki:1. Postopek za pretvorbo kristaliničnega atorvastatina v amorfni atorvastatin obliki, ki vključuje:a) raztapljanje kristaliničnega atorvastatina v topilu, v katerem se atorvastatin dobro topi;b) dodajanje topila, v katerem se atorvastatin ne topi oziroma slabo topi, v dobljeno raztopino atorvastatina;c) ločitev dobljene oborine od mešanice topil.
- 2. Postopek po Zahtevku 1, označen s tem, da je kot topilo, v katerem se atorvastatin topi uporabljen metanol, etanol oziroma aceton.
- 3. Postopek po Zahtevku 1, označen s tem, da je kot topilo, v katerem se atorvastatin ne topi uporabljen eter.
- 4. Postopek za pretvorbo kristaliničnega atorvastatina v amorfni atorvastatin obliki, ki vključuje:a) raztapljanje kristaliničnega atorvastatina v topilu, v katerem se atorvastatin dobro topi;b) dodajanje raztopine atorvastatina v topilo, v katerem se atorvastatin ne topi oziroma slabo topi;c) ločitev dobljene oborine od mešanice topil.
- 5. Postopek po Zahtevku 4, označen s tem, da je kot topilo, v katerem se atorvastatin topi uporabljen metanol, etanol, aceton, oziroma njihove mešanice z etrom, v katerih je atorvastatin še topen.
- 6. Postopek po Zahtevku 4, označen s tem, da je kot topilo, v katerem se atorvastatin ne topi uporabljen eter.
Priority Applications (24)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI9900271A SI20425A (sl) | 1999-12-10 | 1999-12-10 | Priprava amorfnega atorvastatina |
| UA2002054418A UA71041C2 (uk) | 1999-12-10 | 2000-05-12 | Спосіб одержання аморфного аторвастатину |
| SK783-2002A SK287032B6 (sk) | 1999-12-10 | 2000-12-05 | Spôsob prípravy atorvastatínu v amorfnej forme |
| PT00977807T PT1237864E (pt) | 1999-12-10 | 2000-12-05 | Processo de preparacao de atorvastatina amorfa |
| AU15438/01A AU776854B2 (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| PL356184A PL208226B1 (pl) | 1999-12-10 | 2000-12-05 | Sposób wytwarzania atorwastatyny w postaci amorficznej |
| PCT/IB2000/001797 WO2001042209A1 (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| SI200030470T SI1237864T1 (sl) | 1999-12-10 | 2000-12-05 | Postopek za pripravo amorfnega atorvastatina |
| EEP200200293A EE05328B1 (et) | 1999-12-10 | 2000-12-05 | Meetod amorfse atorvastatiini valmistamiseks |
| YUP-368/02A RS50307B (sr) | 1999-12-10 | 2000-12-05 | Postupak za dobijanje amorfnog atorvastatina |
| KR1020027007167A KR100729689B1 (ko) | 1999-12-10 | 2000-12-05 | 비결정형의 아토르바스타틴의 제조방법 |
| AT00977807T ATE270661T1 (de) | 1999-12-10 | 2000-12-05 | Verfahren zur herstellung von amorphem atorvastatin |
| CZ20021838A CZ301627B6 (cs) | 1999-12-10 | 2000-12-05 | Zpusob prípravy atorvastatinu v amorfní forme |
| CA002392025A CA2392025C (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| RU2002115272/04A RU2247113C2 (ru) | 1999-12-10 | 2000-12-05 | Способ получения аморфного аторвастатина |
| US10/149,348 US6613916B2 (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| HR20020482A HRP20020482B1 (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| JP2001543510A JP5087193B2 (ja) | 1999-12-10 | 2000-12-05 | 非晶質アトルバスタチンの調製方法 |
| DE60012045T DE60012045T2 (de) | 1999-12-10 | 2000-12-05 | Verfahren zur herstellung von amorphem atorvastatin |
| TR2004/02543T TR200402543T4 (tr) | 1999-12-10 | 2000-12-05 | Amorf atorvastatinin hazırlanması işlemi. |
| EP00977807A EP1237864B1 (en) | 1999-12-10 | 2000-12-05 | Process for the preparation of amorphous atorvastatin |
| ES00977807T ES2223615T3 (es) | 1999-12-10 | 2000-12-05 | Procedimiento para la preparacion de atorvastatina amorfa. |
| BG106786A BG65719B1 (bg) | 1999-12-10 | 2002-06-07 | Метод за получаване на аморфен аторвастатин |
| US10/614,534 US6891047B2 (en) | 1999-12-10 | 2003-07-07 | Process for the preparation of amorphous atorvastatin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SI9900271A SI20425A (sl) | 1999-12-10 | 1999-12-10 | Priprava amorfnega atorvastatina |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| SI20425A true SI20425A (sl) | 2001-06-30 |
Family
ID=20432564
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SI9900271A SI20425A (sl) | 1999-12-10 | 1999-12-10 | Priprava amorfnega atorvastatina |
Country Status (22)
| Country | Link |
|---|---|
| US (2) | US6613916B2 (sl) |
| EP (1) | EP1237864B1 (sl) |
| JP (1) | JP5087193B2 (sl) |
| KR (1) | KR100729689B1 (sl) |
| AT (1) | ATE270661T1 (sl) |
| AU (1) | AU776854B2 (sl) |
| BG (1) | BG65719B1 (sl) |
| CA (1) | CA2392025C (sl) |
| CZ (1) | CZ301627B6 (sl) |
| DE (1) | DE60012045T2 (sl) |
| EE (1) | EE05328B1 (sl) |
| ES (1) | ES2223615T3 (sl) |
| HR (1) | HRP20020482B1 (sl) |
| PL (1) | PL208226B1 (sl) |
| PT (1) | PT1237864E (sl) |
| RS (1) | RS50307B (sl) |
| RU (1) | RU2247113C2 (sl) |
| SI (1) | SI20425A (sl) |
| SK (1) | SK287032B6 (sl) |
| TR (1) | TR200402543T4 (sl) |
| UA (1) | UA71041C2 (sl) |
| WO (1) | WO2001042209A1 (sl) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ296967B6 (cs) * | 2002-02-01 | 2006-08-16 | Zentiva, A.S. | Zpusob výroby amorfní formy hemivápenaté soli (3R,5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorfenyl)-5-isopropylpyrrol-1-yl]-3,5-dihydroxyheptanové kyseliny (atorvastatinu) |
Families Citing this family (49)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IN191236B (sl) * | 1999-05-25 | 2003-10-11 | Ranbaxy Lab Ltd | |
| US7411075B1 (en) | 2000-11-16 | 2008-08-12 | Teva Pharmaceutical Industries Ltd. | Polymorphic form of atorvastatin calcium |
| SI20425A (sl) * | 1999-12-10 | 2001-06-30 | LEK tovarna farmacevtskih in kemi�nih izdelkov d.d. | Priprava amorfnega atorvastatina |
| IL156055A0 (en) | 2000-11-30 | 2003-12-23 | Teva Pharma | Novel crystal forms of atorvastatin hemi calcium and processes for their preparation as well as novel processes for preparing other forms |
| US7501450B2 (en) | 2000-11-30 | 2009-03-10 | Teva Pharaceutical Industries Ltd. | Crystal forms of atorvastatin hemi-calcium and processes for their preparation as well as novel processes for preparing other forms |
| WO2002057228A1 (en) * | 2001-01-17 | 2002-07-25 | Biocon India Limited | Atorvastatin calcium |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ296967B6 (cs) * | 2002-02-01 | 2006-08-16 | Zentiva, A.S. | Zpusob výroby amorfní formy hemivápenaté soli (3R,5R) 7-[3-fenyl-4-fenylkarbamoyl-2-(4-fluorfenyl)-5-isopropylpyrrol-1-yl]-3,5-dihydroxyheptanové kyseliny (atorvastatinu) |
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