EP2464344A2 - Comprimé pharmaceutique comprenant de la rosuvastatine calcique - Google Patents

Comprimé pharmaceutique comprenant de la rosuvastatine calcique

Info

Publication number
EP2464344A2
EP2464344A2 EP10739873A EP10739873A EP2464344A2 EP 2464344 A2 EP2464344 A2 EP 2464344A2 EP 10739873 A EP10739873 A EP 10739873A EP 10739873 A EP10739873 A EP 10739873A EP 2464344 A2 EP2464344 A2 EP 2464344A2
Authority
EP
European Patent Office
Prior art keywords
tablet
core
rosuvastatin
barrier layer
calcium phosphate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP10739873A
Other languages
German (de)
English (en)
Inventor
Marta Vivancos
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Synthon BV
Original Assignee
Synthon BV
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Synthon BV filed Critical Synthon BV
Publication of EP2464344A2 publication Critical patent/EP2464344A2/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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
    • A61K31/495—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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to pharmaceutical tablets comprising the active agent rosuvastatin calcium.
  • Rosuvastatin is a pharmaceutically active compound that acts as a competitive inhibitor of 3-hydroxy- 3-methylglutarylcoenzyme A reductase (HMG CoA reductase).
  • HMG CoA reductase 3-hydroxy- 3-methylglutarylcoenzyme A reductase
  • Rosuvastatin was disclosed in EP 521471 and US 5,260,440 (reissued as RE37,314) by Shionogi Seiyaku Kabushiki Kaisha. Rosuvastatin is marketed as a calcium salt by AstraZeneca under the brand name CRESTOR®.
  • EP 1223918 and US 6,316,460 indicate that rosuvastatin undergoes degradation under certain conditions, which can make formulating a stable pharmaceutical composition difficult.
  • EP 1223918/US 6,316,460 teach that the major degradation products are the corresponding (3R, 5S) lactone and an oxidation product, in which the hydroxy group adjacent to the carbon-carbon double bond is oxidized to a ketone.
  • These patents purport to reduce these degradation products by the use of tribasic phosphate salts; e.g., tribasic calcium phosphate, tribasic magnesium phosphate or tribasic aluminium phosphate.
  • Example 1 reports that a 2.5 mg direct compression tablet containing tribasic calcium phosphate developed only 0.50% lactone after 1 week at 7O 0 C under 80% humidity whereas replacement of the tribasic with dibasic calcium phosphate resulted in 15.61% lactone.
  • Example 4 where tablets are compressed after wet granulation and fluid bed drying, replacement of the tribasic with dibasic calcium phosphate results in 28.15 % lactone after 1 week 7O 0 C at 80% humidity compared to 0.28 %. All of the tablets in these examples are uncoated.
  • a first aspect of the invention relates to a tablet comprising i) a compressed core, which comprises rosuvastatin calcium, a dibasic calcium phosphate, and at least one pharmaceutically acceptable excipient; and ii) moisture barrier layer around said core, which comprises a polyvinyl alcohol.
  • the polyvinyl alcohol can be partially hydrolyzed.
  • the barrier layer can contain other ingredients including pigments and dyes. Generally the barrier layer coating weight is from 2 to 7%, more typically 3 to 6% the weight of the compressed core.
  • the compressed core contains a dibasic calcium phosphate, preferred tablets of the invention have stability that is similar or superior to the commercial CRESTOR® coated tablets.
  • Another aspect of the invention relates to a process for making a stable pharmaceutical tablet comprising rosuvastatin calcium which comprises:
  • Another aspect of the invention relates to the use acts as a competitive inhibitor of 3-hydroxy-3-methylglutarylcoenzyme A reductase (HMG CoA reductase) in medicine, such as in the treatment of hypercholesterolemia, hyperlipidemia, mixed dyslipidaemia and atherosclerosis
  • HMG CoA reductase 3-hydroxy-3-methylglutarylcoenzyme A reductase
  • the present invention is based on the discovery that a sufficient moisture barrier layer around a rosuvastatin tablet can minimize degradation, especially the formation of the lactone degradation product.
  • This moisture barrier layer can permit the use of dibasic calcium phosphate in forming a tablet with good storage stability, despite the admonition to avoid dibasic calcium phosphate shown in EP 1223918/US 6,316,460.
  • the moisture barrier layer used in the present invention generally contains a polyvinyl alcohol.
  • a polyvinyl alcohol includes hydrolyzed, such as partially hydrolyzed polyvinyl alcohol, as well as unhydrolyzed forms.
  • the moisture barrier layer can contain, and typically does contain, additional excipients as is conventional in the art. Typically such excipients may include a plasticizer, a lubricant, a filler, and/or a colorant. Examples of such excipients include talc, lecithin, triacetin, xanthan gum, lactose monohydrate, titanium dioxide, and iron oxide.
  • the polyvinyl alcohol generally accounts for at least 15% and more typically at least 20% of the moisture barrier layer, by weight.
  • the moisture barrier layer contains a colorant.
  • a colorant can be useful in protecting the rosuvastatin from photodegradation.
  • Colorant is used in a broad sense to embrace coloring materials as well as opacifiers and includes pigments and/or dyes.
  • the dye can be in free form or associated with a substrate, i.e., in "lake" form.
  • one or more pigments e.g., metal oxides such titanium dioxide and/or iron oxide(s) are contained in the moisture barrier layer, optionally with one or more dyes.
  • the moisture barrier layer can be formed from commercially available products such as Colorcon's OPADRY® II 85-series (a PVA-based coating) or OP ADR Y® amb (Aqueous Moisture Barrier); the latter being a preferred barrier material.
  • the moisture barrier layer is generally applied to a weight of 2 to 7%, preferably 3 to 6%, of the weight of the compressed core, e.g., the uncoated tablet.
  • Such coatings include enteric coatings (e.g. coatings that contain enteroresistant polymers) and non-enteric coatings (e.g. enterosoluble coatings); the latter being preferred.
  • Suitable polymers may include polymethacrylates and copolymers thereof, and polyvinylacetates including esters thereof such as
  • polyvinylacetate phthalates Such polymers may be used instead of, or in addition to, polyvinyl alcohol in the moisture barrier layer.
  • polyvinyl alcohol in the moisture barrier layer.
  • hydroxypropyl in this regard, hydroxypropyl
  • methylcellulose-based coatings generally provide insufficient moisture barrier resistance for purposes of the present invention and thus are not a suitable replacement for polyvinyl alcohol. Any of the above-mentioned polymers can be used in combination with polyvinyl alcohol.
  • the moisture barrier layer is coated on a compressed core that contains rosuvastatin calcium, a dibasic calcium phosphate, and at least one pharmaceutically acceptable excipient.
  • the compressed core tablet typically contains from 1 to 100 mg of rosuvastatin calcium (expressed in terms of the weight of rosuvastatin base), particularly 5, 10, 15, 20, or 40 mg of rosuvastatin calcium.
  • the conventional pharmaceutically acceptable dibasic calcium phosphate is either an anhydrate or a dihydrate. Either or both forms may be used in making the compositions of the present invention.
  • the dibasic calcium phosphate is an anhydrous form, i.e. with a water content of 2 weight % or less.
  • the rosuvastatin calcium is present in an amount from 3 to 15 weight per cent and the dibasic calcium phosphate is present in an amount from 6 to 10 weight per cent, based on the total weight of the compressed core. More particularly, the ratio between the rosuvastatin calcium and the dibasic calcium phosphate is typically between 0.5:1 and 1.5: 1 by weight.
  • the remaining excipients in the compressed core typically total from 75 to 89 weight per cent.
  • Pharmaceutically acceptable excipients typically include binders, diluents or fillers, lubricants, and/or disintegrants. A particular excipient may act both as a binder and a diluent, or both as a binder and a disintegrant, etc.
  • binders include polyvinylpyrrolidone, lactose, starch, modified starch, waxes, cellulose, and modified cellulose (methyl cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, or hydroxypropylmethyl cellulose).
  • diluents include calcium phosphates, lactose, mannitol, sorbitol, xylitol, starch, a modified starch, cellulose, a modified cellulose, etc.
  • Suitable lubricants include, for example, magnesium stearate, stearic acid, talc, calcium stearate, hydrogenated castor oil, sodium stearyl fumarate.
  • Typical disintegrants include sodium starch glycolate and crosspovidone.
  • excipients include preservatives, colorants, flow conditioners, etc.
  • inert excipients The list of inert excipients presented above is not exhaustive; other suitable excipients may be found, e.g., in Handbook of Pharmaceutical Excipients edited by Arthur H. Kibbe, 3rd Edition, American Pharmaceutical Association.
  • the compressed core comprises rosuvastatin calcium; a dibasic calcium phosphate; a binder such as microcrystalline cellulose; a water-soluble diluent such as lactose (including lactose monohydrate), mannitol, sorbitol, or xylitol; a disintegrant such as crosspovidone; and a lubricant such as magnesium stearate.
  • the total amount of water present in the compressed core prior to applying the moisture barrier layer is less than 6.0%, measured as the loss on drying or by K. Fischer method.
  • a pH- adjustor i.e. an acid, a base and/or a salt thereof
  • such an excipient is not required and is preferably omitted from the composition.
  • the tablets of the present invention can be made by conventional techniques known in the art.
  • the active substance and the excipients are formed into a tablet blend which is then compressed to form a tablet.
  • This tablet serves as the compressed core of the present invention.
  • the tablet blend can be made by any convenient method.
  • the active substance and at least one pharmaceutically acceptable excipient are, after optional sieving, blended together in one or more steps.
  • the blend is optionally screened.
  • a lubricant such as magnesium stearate is added in the last blending step, as is common in the art, to form the final tablet blend; i.e., a powder blend that contains all the ingredients of the compressed core in a homogeneous mixture.
  • the tablet blend is then compressed into a tablet which is then used as the compressed core of the present invention.
  • a wet granulation technique may be used in making the tablet blend.
  • the active substance and at least one excipient are, after optional sieving, blended together in a granulator and then granulated with a small volume of purified water.
  • the granulate includes a dibasic calcium phosphate as well as a diluent and/or binder.
  • the granulate is dried and typically passed through a mill and/or sieved.
  • Lubricant and, optionally, all or part of a disintegrant are blended with the granulate, and the obtained homogeneous mixture is compressed into tablets.
  • the tablets are subsequently coated with a polyvinyl alcohol-containing composition to form the moisture barrier layer.
  • a sub-coat may be applied before forming the moisture barrier layer, but such a sub-coat is generally avoided in tablets of the invention.
  • the coating of the tablet cores can be performed by any suitable technique including the conventional techniques of spray coating and pan coating.
  • the coating step involves applying an aqueous or non-aqueous solution or suspension of polyvinyl alcohol and auxilliary excipients onto the tablets and drying to form a moisture barrier layer around a compressed core.
  • the tablets may be packed in a suitable package material, preferably in a blister package, to provide the final dosage form for administration of rosuvastatin by patients in need thereof.
  • the invention is further illustrated by some non-limiting examples.
  • Opadry® AMB is a combination of Polyvinyl alcohol - part, hydrolyzed, Titanium dioxide, Talc, Lecithin (soya), Xanthan gum, iron oxide yellow
  • a pre-mixture of rosuvastatin calcium and microcrystalline cellulose was made in a tumbling blender.
  • the pre-mixture was sieved through 0.5 mm mesh and also a part of the lactose (approx. half of the lactose) was sieved to drag the remainder of the drug substance.
  • the rest of the excipients were added to the blend, except Mg stearate, and mixed for 30 min in a free fall blender. Finally, Mg stearate was added and mixed for 5 min.
  • the lubricated blend was compressed in a tablet press.
  • a 15 % ( w/w) suspension of Opadry® AMB Yellow in purified water was prepared. Tablet cores were transferred into t a standard perforated pan system and coated with the suspension of Opadry® AMB Yellow to a theoretical weight gain of 4%.
  • Opadry® AMB is a combination of Polyvinyl alcohol - part, hydrolyzed, Titanium dioxide, Talc, Lecithin (soya), Xanthan gum, iron oxide red, FD&C yellow #6/Sunset yellow FCF, Aluminium lake, iron oxide yellow.
  • a pre-mixture of rosuvastatin calcium and microcrystalline cellulose was made in a tumbling blender.
  • the pre-mixture was sieved through 0.5 mm mesh and also a part of the lactose (approx. half of the lactose) was sieved to drag the remainder of the drug substance.
  • the rest of the excipients were added to the blend, except Mg stearate, and mixed for 30 min in a free fall blender. Finally, Mg stearate was added and mixed for 5 min.
  • the lubricated blend was compressed in a tablet press.
  • a 15 % (w/w) suspension of Opadry® AMB Pink in purified water was prepared. Tablet cores were transferred into a standard perforated pan system and coated with the suspension of Opadry® AMB Pink to a theoretical weight gain of 4%.
  • Rosuvastatin tablets were prepared containing dibasic calcium phosphate dihydrate and coated with various coatings; namely Opadry II 31 K32626 (HPMC-based coating same composition as CRESTOR®), Opadry AMB (moisture barrier coating system, based on PVA) and Opadry ns-g (based on CMC Na). Each coating was applied to achieve 4% weight gain.
  • the tablet composition was as follows:
  • the coated tablets were put in stability at 70°C/80% RH for two weeks, in open dish.
  • the lactone content both initially and at the conclusion of two weeks, is shown below as percentage of the active.
  • PVA polyvinyl alcohol
  • hydroxypropyl methylcellulose HPMC
  • CMC- Na sodium carboxymethyl cellulose

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L’invention concerne un comprimé comprenant : i) un noyau compressé, qui comprend de la rosuvastatine calcique, un phosphate de calcium dibasique, et au moins un excipient pharmaceutiquement acceptable; et ii) une couche barrière contre l’humidité autour dudit noyau, qui comprend un poly(alcool vinylique), un procédé pour fabriquer le comprimé et son utilisation en médecine.
EP10739873A 2009-08-13 2010-07-29 Comprimé pharmaceutique comprenant de la rosuvastatine calcique Withdrawn EP2464344A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US23354209P 2009-08-13 2009-08-13
PCT/EP2010/004796 WO2011018185A2 (fr) 2009-08-13 2010-07-29 Comprimé pharmaceutique comprenant de la rosuvastatine calcique

Publications (1)

Publication Number Publication Date
EP2464344A2 true EP2464344A2 (fr) 2012-06-20

Family

ID=43334705

Family Applications (1)

Application Number Title Priority Date Filing Date
EP10739873A Withdrawn EP2464344A2 (fr) 2009-08-13 2010-07-29 Comprimé pharmaceutique comprenant de la rosuvastatine calcique

Country Status (4)

Country Link
EP (1) EP2464344A2 (fr)
AU (1) AU2010281913A1 (fr)
EA (1) EA201270269A1 (fr)
WO (1) WO2011018185A2 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2805714A1 (fr) 2013-04-25 2014-11-26 Antibiotice S.A. Composition pharmaceutique stable comprenant de la rosuvastatine calcique amorphe

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104473899B (zh) * 2014-12-19 2017-10-03 河南润弘制药股份有限公司 一种瑞舒伐他汀钙片剂及其制备方法
WO2018093144A1 (fr) * 2016-11-15 2018-05-24 주식회사 엘지화학 Complexe médicinal destiné au traitement du diabète de type 2 et de la dyslipidémie diabétique
GB2622822A (en) 2022-09-28 2024-04-03 Novumgen Ltd A rapidly disintegrating tablet of rosuvastatin and its process of preparation

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008075320A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques antilipidémiques et leur procédé de préparation

Family Cites Families (4)

* 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
GB0001621D0 (en) 2000-01-26 2000-03-15 Astrazeneca Ab Pharmaceutical compositions
AU2003283769A1 (en) * 2002-12-20 2004-07-14 Pfizer Products Inc. Dosage forms comprising a cetp inhibitor and an hmg-coa reductase inhibitor
JP2008528542A (ja) * 2005-01-31 2008-07-31 チバ ホールディング インコーポレーテッド ロスバスタチンカルシウム塩の結晶形

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008075320A2 (fr) * 2006-12-21 2008-06-26 Ranbaxy Laboratories Limited Compositions pharmaceutiques antilipidémiques et leur procédé de préparation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2011018185A2 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2805714A1 (fr) 2013-04-25 2014-11-26 Antibiotice S.A. Composition pharmaceutique stable comprenant de la rosuvastatine calcique amorphe

Also Published As

Publication number Publication date
WO2011018185A2 (fr) 2011-02-17
AU2010281913A1 (en) 2012-04-05
WO2011018185A3 (fr) 2011-11-24
EA201270269A1 (ru) 2012-09-28

Similar Documents

Publication Publication Date Title
FI111806B (fi) Farmaseuttisia koostumuksia
US9463164B2 (en) Tablet having improved elution properties
JP5235676B2 (ja) （ｅ）−７−〔４−（４−フルオロフェニル）−６−イソプロピル−２−〔メチル（メチルスルホニル）アミノ〕ピリミジン−５−イル〕−（３ｒ，５ｓ）−３，５−ジヒドロキシヘプタ−６−エン酸を含む医薬組成物
JP7094944B2 (ja) ロスバスタチン及びエゼチミブを含む医薬組成物並びにその調製方法
EP2464344A2 (fr) Comprimé pharmaceutique comprenant de la rosuvastatine calcique
EP2323634B1 (fr) Composition à base de ropinirole
WO2018041281A1 (fr) Composition pharmaceutique comprenant de la rosuvastatine et de l'ézétimibe et son procédé de préparation
WO2010030201A2 (fr) Composition pharmaceutique orale stable contenant un sel pharmaceutiquement acceptable de l'acide [(e)-7-[4-(4-fluorophényl)-6-isopropyl-2-[méthyl(méthylsulfonyl)amino]pyrimidin-5-yl]-(3r,5s)-3,5-dihydroxyhept-6-énoïque
EP2805714B1 (fr) Composition pharmaceutique stable comprenant de la rosuvastatine calcique amorphe
WO2010140992A1 (fr) Compositions pharmaceutiques stables contenant du calcium rosuvastatine
EA040745B1 (ru) Фармацевтическая композиция, содержащая два различных активных ингредиента, и способ ее получения

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

AK Designated contracting states

Kind code of ref document: A2

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

AX Request for extension of the european patent

Extension state: BA ME RS

17P Request for examination filed

Effective date: 20120524

RBV Designated contracting states (corrected)

Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO SE SI SK SM TR

DAX Request for extension of the european patent (deleted)
17Q First examination report despatched

Effective date: 20140205

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 20140617