ES2643693T3 - Composición farmacéutica de rosuvastatina cálcica - Google Patents

Composición farmacéutica de rosuvastatina cálcica Download PDF

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ES2643693T3
ES2643693T3 ES12722820.3T ES12722820T ES2643693T3 ES 2643693 T3 ES2643693 T3 ES 2643693T3 ES 12722820 T ES12722820 T ES 12722820T ES 2643693 T3 ES2643693 T3 ES 2643693T3
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pharmaceutical composition
see example
coating
agent
calcium rosuvastatin
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ES12722820.3T
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Joseph Richard Creekmore
Sanjeev Hukmichand KOTHARI
Bradford J. MUELLER
Yingxu Peng
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AstraZeneca UK Ltd
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AstraZeneca UK Ltd
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/455—Nicotinic acids, e.g. niacin; Derivatives thereof, e.g. esters, amides
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    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
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    • A61K31/616—Salicylic acid; Derivatives thereof having the hydroxy group in position 2 esterified, e.g. salicylsulfuric acid by carboxylic acids, e.g. acetylsalicylic acid
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    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
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Description

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DESCRIPCIÓN
Composición farmacéutica de rosuvastatina cálcica
COMPOSICIÓN FARMACÉUTICA
La presente invención se refiere a composiciones farmacéuticas y más particularmente a una composición farmacéutica que contiene sal de calcio de ácido bis[(E)-7-[4-(4-fluorofenil)-6-isopropil-2[metil(metilsulfonil)amino]pirimidin-5-il]-(3R, 5S)-3,5-dihidroxihept-6-enoico] (de la fórmula I que figura más adelante, también conocida como rosuvastatina cálcica y a la que se hace referencia más adelante como “el Agente”) y procesos para su elaboración.
Fórmula I
El Agente se divulga como un inhibidor de 3-hidroxi-3-metilglutarilo CoA reductasa (HMG CoA reductasa) en la Solicitud de Patente Europea, Publicación No. 0521471 y en Bioorganic and Medicinal Chemistry, (1997), 5(2), 437-444, y es útil en el tratamiento de hipercolesterolemia, hiperlipoproteinemia y aterosclerosis.
Un problema asociado con el Agente es que, en ciertas condiciones, se degrada. Esto dificulta la formulación del producto y la posibilidad de proporcionar una composición farmacéutica con una vida útil adecuada. Los principales productos de degradación formados son la (3R, 5S) lactona (a la que se hace referencia en la presente más adelante como “la lactona”) correspondiente y un producto de oxidación (al que se hace referencia en la presente más adelante como “B2”) en los cuales el grupo hidroxi adyacente al doble enlace carbono-carbono se oxida para formar una funcionalidad de cetona.
Por lo tanto, es importante encontrar una composición farmacéutica del Agente que permanezca estable durante un período de tiempo prolongado. También es preferible que dicha composición tenga una buena tasa de flujo para facilitar el procesamiento en formas de dosificación unitarias para la administración oral, por ejemplo, en comprimidos, y características de buena desintegración y disolución cuando se procesa en comprimidos para administración oral, los cuales pueden presentarse con diferentes potencias de dosificación. Nuestra Solicitud Internacional WO01/54668 describió dicha formulación estable para comprimidos.
Los pacientes que requieren terapia con estatina también pueden requerir tratamiento simultáneo para otras afecciones cardiovasculares. Una alternativa conveniente para tomar múltiples comprimidos es proporcionar una terapia de combinación de una estatina con otra medicación cardiovascular comúnmente utilizada en un solo comprimido. Formular dicho comprimido de combinación puede ser problemático dado que, por ejemplo, los dos ingredientes activos pueden requerir permanecer separados para evitar la interacción entre sí, o pueden requerir diferentes condiciones (tales como pH o contenido de humedad) para que cada uno de ellos permanezca estable durante el período de vida útil del comprimido. Para proporcionar mayor flexibilidad en la elaboración de un rango de terapias de combinación posibles, sería ventajoso desarrollar un proceso en el cual la estatina pudiera recubrirse sobre un núcleo interno que contenga el otro ingrediente activo, por ejemplo, pulverizando una solución que contenga el Agente sobre un núcleo interno de forma tal que la evaporación del disolvente deje un recubrimiento que contenga el Agente en el núcleo (recubrimiento mediante pulverización). Sin embargo, para lograr una elaboración sólida y reproducible, la estatina, como el Agente, debe ser estable en la solución utilizada en el proceso de recubrimiento (solución de recubrimiento) durante un período prolongado. La inestabilidad del Agente descrito anteriormente sugiere que esto será muy difícil de lograr.
El documento WO2007/103557 describe un proceso para recubrir cápsulas mediante pulverización con un recubrimiento que contiene un ingrediente activo y se dirige principalmente a resolver las dificultades asociadas con el proceso de recubrir cápsulas mediante pulverización (tamaño, homogeneidad y solubilidad de la cubierta de la cápsula). Otros documentos importantes de la técnica anterior son WO2005/084666A1, WO2008/069546A1 y US2005/0096391A1.
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una temperatura de entrada de 67.0-68.5ºC. Después de que se completó el recubrimiento con el Agente, los comprimidos se recubrieron con un sistema de recubrimiento superior que consistía en Opadry 03B94523 y agua. La pulverización se llevó a cabo a una tasa de 15 g/min, durante 70 minutos, con una temperatura de entrada de 69.075.0ºC.
Valores de humedad después de recubrir y calentar a 50⁰C durante 24 h en % p/p
Ejemplo
Subrecubrimiento Recubrimiento con Agente Recubrimiento superior
1
1.00 N/D N/D
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1.46 N/D N/D
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Ver Ejemplo 1 2.17 1.74
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Ver Ejemplo 1 1.41 1.37
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Ver Ejemplo 1 2.34 1.89
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Ver Ejemplo 1 1.38 1.28
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Ver Ejemplo 2 3.25 3.11
8
Ver Ejemplo 2 2.07 1.96
9
Ver Ejemplo 2 3.60 2.92
10
Ver Ejemplo 2 1.98 1.98
11
0.79 1.26 Sin recubrimiento superior
12
0.95 1.20 Sin recubrimiento superior
13
Ver Ejemplo 1 0.78 0.81
14
Ver Ejemplo 1 0.76 0.89
15
Ver Ejemplo 1 0.94 0.90
16
Ver Ejemplo 1 0.86 0.83
17
Ver Ejemplo 1 0.79 0.76
18
Ver Ejemplo 1 0.81 0.97
19
Ver Ejemplo 1 1.34 1.26
Formación de lactona (%p/p)
La estabilidad de la formulaciones de la invención se ilustra mediante la siguiente información acerca de la estabilidad.
Ejemplo 3 (indicado como 10 a continuación)
Ejemplo 13 (indicado como 22 a continuación) Ejemplo 18 (indicado como 27 a continuación) Ejemplo 19 (indicado como 28 a continuación)
0 mes
0.273 0 mes 0.060 0 mes 0.041 0.055
1 mes
0.471 1 mes 0.120 1 mes 0.058 0.089
3 meses
0.848 8 meses 0.235 7 meses 0.071 0.198
18
imagen17
19

Claims (1)

  1. imagen1
    imagen2
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Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
MX358211B (es) * 2012-07-23 2018-08-10 Landsteiner Scient S A De C V Una composición farmacéutica de liberación comprendiendo hidroclorotiazida, losartán y basilato de amlodipino.
AR092439A1 (es) * 2012-09-06 2015-04-22 Bayer Healthcare Llc Composicion farmaceutica recubierta que contiene regorafenib
BR112017009521A2 (pt) * 2014-11-11 2017-12-19 Shionogi & Co comprimido de múltiplas camadas que contém um fármaco instável à luz
JP6095176B2 (ja) * 2015-04-24 2017-03-15 大原薬品工業株式会社 ロスバスタチンカルシウムの光安定性が向上したフィルムコーティング錠剤
US10413543B2 (en) 2015-09-01 2019-09-17 Sun Pharma Advanced Research Company Ltd. Stable multiparticulate pharmaceutical composition of rosuvastatin
EP3243506A1 (en) 2016-05-09 2017-11-15 Adamed sp. z o.o. Pharmaceutical composition
KR20190023938A (ko) 2017-08-30 2019-03-08 대원제약주식회사 안정성이 개선된 로수바스타틴을 포함하는 약학적 조성물
KR20190023940A (ko) 2017-08-30 2019-03-08 대원제약주식회사 안정성 및 용출율이 개선된 텔미사르탄, 암로디핀 및 로수바스타틴을 함유하는 복합제제 및 그 제조방법
TWI795462B (zh) * 2017-11-17 2023-03-11 日商鹽野義製藥股份有限公司 光安定性及溶出性優異的醫藥製劑
CN107823181A (zh) * 2017-12-13 2018-03-23 合肥凯石医药科技有限公司 一种稳定的瑞舒伐他汀钙肠溶微丸及其制备方法
CN110339365A (zh) * 2018-04-02 2019-10-18 强生化学制药厂股份有限公司 一种可提高口服他汀类药物生体可用率的医药组合物及其用途
CN108853029A (zh) * 2018-09-07 2018-11-23 南通雅本化学有限公司 一种罗苏伐他汀的制备方法

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2648897B2 (ja) 1991-07-01 1997-09-03 塩野義製薬株式会社 ピリミジン誘導体
DK0707475T3 (da) * 1993-06-14 1997-12-29 Janssen Pharmaceutica Nv Langsom frigørende, filmcoatet tablet af astemizol og pseudoephedrin
BR9815548A (pt) 1997-07-31 2000-11-07 Kos Pharma Inc Composição farmacêutica para administração em dose única diária para alteração de lipìdios num indivìduo sem causar hepatotoxicidade induzida por drogas, miopatia ou rabdomiólise, comprimido revestido para administração oral e método para administração de dita composição
GB0001621D0 (en) 2000-01-26 2000-03-15 Astrazeneca Ab Pharmaceutical compositions
US6858289B2 (en) * 2002-02-08 2005-02-22 The United States Of America As Represented By The Secretary Of The Navy Optical filters comprising solar blind dyes and UV-transparent substrates
HUP0500851A3 (en) * 2002-12-10 2008-02-28 Ranbaxy Lab Ltd Process for the preparation of rosuvastatin
DE10337697A1 (de) 2003-08-16 2005-03-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg Tablette enthaltend 3-[(2-{[4-(Hexyloxycarbonylamino-imino-methyl)-phenyl-amino]-methyl}-1-methyl-1H-benzimidazol-5-carbonyl)-pyridin-2-yl-amino]-propionsäure-ethylester oder dessen Salze
US20050096391A1 (en) * 2003-10-10 2005-05-05 Per Holm Compositions comprising fenofibrate and rosuvastatin
EP1734953A4 (en) * 2004-03-02 2008-08-20 Abeille Pharmaceuticals Inc CO-PR PARATIONS OF KITS OF BIOACTIVE AGENTS
DE102004038396A1 (de) 2004-08-06 2006-03-30 Lothar Sellin Vorrichtung zur Beschichtung von Medizinprodukten
WO2006037348A1 (en) 2004-10-01 2006-04-13 Lifecycle Pharma A/S Pharmaceutical compositions comprising fenofibrate and a statin
KR100582347B1 (ko) 2004-12-30 2006-05-22 한미약품 주식회사 3-하이드록시-3-메틸글루타릴 조효소 ａ 환원효소 억제제및 고혈압 치료제의 복합제제 및 그의 제조방법
KR100646576B1 (ko) 2005-02-15 2006-11-23 한국유나이티드제약 주식회사 고지혈증 환자의 동맥경화증 예방을 위한 에이치엠지이-씨오에이 환원효소 저해제 및 장용코팅된 아스피린을 함유하는 복합 펠렛
JP5628480B2 (ja) 2006-03-09 2014-11-19 グラクソスミスクライン エルエルシー 医薬成分を含有するコーティングカプセル
WO2008023958A1 (en) 2006-08-24 2008-02-28 Hanall Pharmaceutical Co., Ltd. Combined pharmaceutical formulation with controlled-release comprising dihydropyridine calcium channel blockers and hmg-coa reductase inhibitors
WO2008023869A1 (en) * 2006-08-24 2008-02-28 Hanall Pharmaceutical Co., Ltd. Combined pharmeceutical formulation with controlled-release comprising dihydropyridine calcium channel blockers and hmg-coa reductase inhibitors
HU227610B1 (en) * 2006-09-18 2011-09-28 Richter Gedeon Nyrt Pharmaceutical compositions containing rosuvastatin potassium
RU2453307C2 (ru) 2006-10-30 2012-06-20 Ханол Биофарма Ко.Лтд Комплексная фармацевтическая композиция с контролируемым высвобождением, содержащая блокаторы рецепторов ангиотензина-ii и ингибиторы гидроксиметилглутарил-кофермент а-редуктазы
KR100870396B1 (ko) * 2006-12-07 2008-11-25 보령제약 주식회사 심혈관계 질환 치료용 경구투여제제
WO2008124120A1 (en) * 2007-04-09 2008-10-16 Scidose, Llc Combinations of statins and anti-obesity agent
WO2008148798A2 (en) * 2007-06-04 2008-12-11 Egalet A/S Controlled release pharmaceutical compositions for prolonged effect
CN101385731B (zh) 2007-09-10 2010-12-15 鲁南制药集团股份有限公司 治疗高脂血症的渗透泵控释制剂组合物及其制备方法
MX344885B (es) * 2008-11-10 2017-01-10 Psicofarma S A De C V Proceso para la obtencion de una composicion de rosuvastatina calcica y producto obtenido.
WO2010066687A2 (en) 2008-12-11 2010-06-17 Dsm Ip Assets B.V. Stabalized statin-comprising compositions
EP2210595A1 (en) * 2009-01-14 2010-07-28 LEK Pharmaceuticals d.d. Active coating of pharmaceutical dosage forms
TR200902077A2 (tr) 2009-03-17 2010-01-21 Sanovel İlaç San.Veti̇c.A.Ş. Stabil rosuvastatin kompozisyonları
CN101574344A (zh) 2009-06-08 2009-11-11 山东新华制药股份有限公司 一种烟酸和他汀类药物组合物及其制备方法
JP5662475B2 (ja) * 2009-12-30 2015-01-28 ビーシーワールド ファーム． カンパニー リミテッド メトホルミン及びロスバスチンを含む医薬組成物
KR20110097168A (ko) 2010-02-24 2011-08-31 근화제약주식회사 고지혈증 치료용 약제학적 복합제제

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