[go: up one dir, main page]

WO2016038532A1 - Tréprostinil diéthanolamine amorphe - Google Patents

Tréprostinil diéthanolamine amorphe Download PDF

Info

Publication number
WO2016038532A1
WO2016038532A1 PCT/IB2015/056859 IB2015056859W WO2016038532A1 WO 2016038532 A1 WO2016038532 A1 WO 2016038532A1 IB 2015056859 W IB2015056859 W IB 2015056859W WO 2016038532 A1 WO2016038532 A1 WO 2016038532A1
Authority
WO
WIPO (PCT)
Prior art keywords
treprostinil diethanolamine
pharmaceutically acceptable
solvent
amorphous solid
solid dispersion
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.)
Ceased
Application number
PCT/IB2015/056859
Other languages
English (en)
Inventor
Vinayak G Gore
Bindu Manojkumar
Chandrakant CHAUDHARI
Mahesh Patel
Rajesh Joshi
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.)
Mylan Laboratories Ltd
Original Assignee
Mylan Laboratories Ltd
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 Mylan Laboratories Ltd filed Critical Mylan Laboratories Ltd
Publication of WO2016038532A1 publication Critical patent/WO2016038532A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
    • 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
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic compounds

Definitions

  • the present disclosure relates to amorphous solid dispersion of treprostinil diethanolamine and its preparation thereof.
  • Treprostinil diethanolamine is a prostacyclin vasodilator indicated for treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity.
  • PAH pulmonary arterial hypertension
  • ORENITRAM ® tablets contain treprostinil diethanolamine, a tricyclic benzindene analogue of prostacyclin and the chemical name is acetic acid, 2-[[(lR,2R,3aS,9aS)- 2,3,3a,4,9,9a-hexahydro-2-hydroxy-l-[(3S)-3-hydroxyoctyl]-lH-benz[f]inden-5-yl] oxy]-, complexed with 2,2'-iminobis[ethanol] (1: 1). Its structural formula is:
  • Treprostinil diethanolamine is currently available as an active pharmaceutical ingredient in an extended-release formulation.
  • Non-immediate release formulations such as controlled-release and extended-release formulations often utilize drug carriers to modify and/or improve the delivery of the drugs from the dosage form.
  • Treprostinil diethanolamine is difficult to work with during formulation, thus limiting the pharmaceutical approaches that may be employed.
  • the present invention addresses these shortcomings of the prior art by providing amorphous solid dispersion of treprostinil diethanolamine and one or more pharmaceutically acceptable carriers that can be readily processed into a final dosage form.
  • the present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof.
  • Yet another aspect of the present invention is to provide a process for formulating different pharmaceutical compositions of amorphous solid dispersions of treprostinil diethanolamine.
  • Figure 1 is an X-ray powder diffractogram of amorphous solid dispersion of treprostinil diethanolamine.
  • the present invention provides amorphous solid dispersion of treprostinil diethanolamine and a process for the preparation thereof.
  • One aspect of the present invention provides treprostinil diethanolamine in solid dispersion with one or more pharmaceutically acceptable carriers useful for the formulation of solid dosage forms.
  • Another aspect of the present invention provides a process for the preparation of amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers, which may include the following steps: a) combining treprostinil diethanolamine with pharmaceutically acceptable carriers in a solvent;
  • treprostinil diethanolamine and pharmaceutically acceptable carriers are dissolved in a suitable solvent or mixture of solvents.
  • the treprostinil diethanolamine to be dissolved may be prepared by any prior-art process and may exist in crystalline or amorphous form.
  • the treprostinil diethanolamine may be dissolved in the solvent while one or more pharmaceutically acceptable carriers may be dissolved or suspended in a solvent or mixture of solvents
  • the solvent may be an alcoholic solvent, for example, methanol, ethanol, isopropanol, 1-butanol, 2-butanol, isoamyl alcohol, isobutyl alcohol, 1-pentanol, 1- propanol, 2-propanol, or mixtures thereof.
  • the solvent may be hydrocarbon solvent, for example n-hexane, n-heptane, cyclohexane or mixture thereof.
  • the solvent may be dimethyl formamide or dimethylsulfoxide.
  • the pharmaceutically acceptable carriers may be soluble in the solvent. In other embodiments, the pharmaceutically acceptable carriers may be soluble or suspendable in the solvent.
  • the specific pharmaceutically acceptable carriers that may be employed within the context of the present invention may be specified by the desired composition of the solid dispersion or the desired composition of the final pharmaceutical dosage form. Accordingly, the specific percentage of each pharmaceutically acceptable carrier may vary widely from about 0.1% to about 99.9%, depending on the particular composition desired. Examples of suitable pharmaceutically acceptable carriers include, as examples, povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate.
  • the amount of solvent and the temperature at which the solvent is held will vary based on the various components of the composition. Such parameters may be selected by one of ordinary skill in the art by routine experimentation.
  • the solvent may then be removed. This may be carried out by methods well known in the art. For example, the solvent may be removed by distillation, evaporation, freeze drying, spray drying or agitated thin film drier. One of skill in the art will additionally recognize other methods by which solvent may be removed from the mixture. Next, amorphous solid dispersion of treprostinil diethanolamine with pharmaceutically acceptable carriers may be isolated.
  • the solid dispersions of the present invention may be evaluated by performing a measurement of the X-ray powder diffraction pattern of the solid dispersion.
  • the X-ray diffraction pattern of an exemplary solid dispersion of the disclosure was measured on a BRUKER D-8 Discover powder diffractometer equipped with goniometer of ⁇ /2 ⁇ configuration and Lynx Eye detector.
  • the Cu-anode X-ray tube was operated at 40 kV and 30 mA. The experiments were conducted over the 2 ⁇ range of 2.0°-50.0°, 0.030° step size, and 0.4 seconds step time.
  • a representative solid dispersion of treprostinil diethanolamine of the present invention with povidone, silica gel, cellulose acetate, polyethylene glycol (for example, PEG-4000), and magnesium stearate included as the pharmaceutically acceptable carriers has an x-ray powder diffraction pattern as shown in FIG. 1.
  • reaction conditions e.g., reaction time or temperature
  • amorphous solid dispersions of treprostinil diethanolamine of the present invention may be used in the formulation of tablets for oral administration.
  • xylitol maltodextrin
  • sodium lauryl sulfate magnesium stearate
  • cellulose acetate triethyl citrate
  • polyvinyl alcohol titanium dioxide
  • polyethylene glycol polyethylene glycol
  • talc a wide variety of pharmaceutically acceptable excipients that may be included in such a tablet formulation, including xylitol, maltodextrin, sodium lauryl sulfate, magnesium stearate, cellulose acetate, triethyl citrate, polyvinyl alcohol, titanium dioxide, polyethylene glycol, and talc.
  • the tablets may also contain artificial flavorings and colorings.
  • the tablets formulated using the amorphous solid dispersions of the present invention may have an extended-release profile.
  • the extended-release profile may be accomplished by a variety of methods and formulations well known to those of skill in the art.
  • amorphous solid dispersions of treprostinil diethanolamine disclosed herein may be included in formulations administered to patients for the treatment of pulmonary arterial hypertension to improve exercise capacity.
  • An individual solid dosage form, such as tablets, may contain from about 0.125 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof) to about 2.5 mg treprostinil (or a pharmaceutically equivalent amount of a salt thereof).
  • PEG-4000 (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.
  • Magnesium stearate (0.5 g) was added to a stirred solution of treprostinil diethanolamine (0.5 g) in methanol (5 mL). This solution was then stirred for 1 hour at room temperature. The reaction mixture was concentrated to dryness under vacuum at temperature below 40°C to obtain amorphous solid dispersion of treprostinil diethanolamine.

Landscapes

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

Abstract

La présente invention concerne une dispersion solide amorphe de tréprostinil diéthanolamine avec des supports pharmaceutiquement acceptables et leur procédé de préparation. Les dispersions solides amorphes de tréprostinil diéthanolamine de l'invention sont utiles pour la préparation de formes posologiques pharmaceutiques solides.
PCT/IB2015/056859 2014-09-09 2015-09-08 Tréprostinil diéthanolamine amorphe Ceased WO2016038532A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN4417CH2014 2014-09-09
IN4417/CHE/2014 2014-09-09

Publications (1)

Publication Number Publication Date
WO2016038532A1 true WO2016038532A1 (fr) 2016-03-17

Family

ID=54249544

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2015/056859 Ceased WO2016038532A1 (fr) 2014-09-09 2015-09-08 Tréprostinil diéthanolamine amorphe

Country Status (1)

Country Link
WO (1) WO2016038532A1 (fr)

Cited By (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018058124A1 (fr) 2016-09-26 2018-03-29 United Therapeutics Corporation Promédicaments de tréprostinil
CN111801313A (zh) * 2018-03-09 2020-10-20 奇诺因药物和化学工厂私人有限公司 用于制备曲前列环素二乙醇胺盐的多晶型b的方法
JP2021502384A (ja) * 2017-11-10 2021-01-28 ディスパーソル テクノロジーズ リミテッド ライアビリティ カンパニー 改善された薬物製剤
WO2021041320A1 (fr) 2019-08-23 2021-03-04 United Therapeutics Corporation Promédicaments de tréprostinil
EP3838884A1 (fr) 2019-12-19 2021-06-23 Chirogate International Inc. Procédé de cristallisation efficace pour préparer du tréprostinil ultra-pur et cristal préparé à partir de celui-ci
WO2021211916A1 (fr) 2020-04-17 2021-10-21 United Therapeutics Corporation Tréprostinil destiné à être utilisé dans le traitement d'une pneumopathie interstitielle
WO2021252446A1 (fr) 2020-06-09 2021-12-16 United Therapeutics Corporation Promédicaments à base de fumaryle dicétopipéridine de tréprostinil
WO2022132655A1 (fr) 2020-12-14 2022-06-23 United Therapeutics Corporation Méthodes de traitement d'une maladie à l'aide de promédicaments tréprostinil
WO2022136545A1 (fr) * 2020-12-22 2022-06-30 Radiometer Medical Aps Échantillonneur de sang contenant un agent antiplaquettaire et un matériau matriciel soluble dans l'eau
WO2022187352A1 (fr) 2021-03-03 2022-09-09 United Therapeutics Corporation Composition de poudre sèche de treprostinil et son promédicament et comprenant en outre de l'(e)-3,6-bis[4-(n-carbonyl-2-propényl)amidobutyl]-2,5-dicétopipérazine (fdkp)
WO2023154705A1 (fr) 2022-02-08 2023-08-17 United Therapeutics Corporation Polythérapie à base de tréprostinil iloprost
WO2023206444A1 (fr) 2022-04-29 2023-11-02 兆科药业（广州）有限公司 Brume douce de tréprostinil à inhaler
WO2024155752A1 (fr) 2023-01-19 2024-07-25 United Therapeutics Corporation Analogues de tréprostinil
WO2025101824A1 (fr) 2023-11-09 2025-05-15 United Therapeutics Corporation Synthèses de composés utiles pour produire du tréprostinil

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070254032A1 (en) * 2006-04-27 2007-11-01 Argaw Kidane Osmotic drug delivery system
US7417070B2 (en) 2003-05-22 2008-08-26 United Therapeutics Corporation Compounds and methods for delivery of prostacyclin analogs
US8350079B2 (en) * 2008-05-08 2013-01-08 United Therapeutics Corporation Treprostinil formulation

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7417070B2 (en) 2003-05-22 2008-08-26 United Therapeutics Corporation Compounds and methods for delivery of prostacyclin analogs
US20070254032A1 (en) * 2006-04-27 2007-11-01 Argaw Kidane Osmotic drug delivery system
US8350079B2 (en) * 2008-05-08 2013-01-08 United Therapeutics Corporation Treprostinil formulation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GHASTE R ET AL: "Solid dispersions: An overview", vol. 7, no. 5, 11 February 2009 (2009-02-11), pages 12pp, XP009137552, ISSN: 1918-5561, Retrieved from the Internet <URL:http://www.pharmainfo.net/reviews/solid-dispersions-overview> [retrieved on 20090211] *
SANDRIEN JANSSENS ET AL: "Review: physical chemistry of solid dispersions", JOURNAL OF PHARMACY AND PHARMACOLOGY, vol. 61, no. 12, 1 December 2009 (2009-12-01), pages 1571 - 1586, XP055023760, ISSN: 0022-3573, DOI: 10.1211/jpp/61.12.0001 *

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018058124A1 (fr) 2016-09-26 2018-03-29 United Therapeutics Corporation Promédicaments de tréprostinil
US11672775B2 (en) 2016-09-26 2023-06-13 United Therapeutics Corporation Treprostinil prodrugs
JP7378393B2 (ja) 2017-11-10 2023-11-13 オースティンピーエックス リミテッド ライアビリティ カンパニー 改善された薬物製剤
EP3706731A4 (fr) * 2017-11-10 2021-08-18 Dispersol Technologies, LLC Formulations améliorées de médicaments
JP2021502384A (ja) * 2017-11-10 2021-01-28 ディスパーソル テクノロジーズ リミテッド ライアビリティ カンパニー 改善された薬物製剤
JP2021517138A (ja) * 2018-03-09 2021-07-15 キノイン・ジヨージセル・エーシユ・ベジエーセテイ・テルメーケク・ジヤーラ・ゼー・エル・テー トレプロスチニルジエタノールアミン塩の多形形態ｂを製造するための方法
JP7340534B2 (ja) 2018-03-09 2023-09-07 キノイン・ジヨージセル・エーシユ・ベジエーセテイ・テルメーケク・ジヤーラ・ゼー・エル・テー トレプロスチニルジエタノールアミン塩の多形形態ｂを製造するための方法
CN111801313B (zh) * 2018-03-09 2023-08-29 奇诺因药物和化学工厂私人有限公司 用于制备曲前列环素二乙醇胺盐的多晶型b的方法
CN111801313A (zh) * 2018-03-09 2020-10-20 奇诺因药物和化学工厂私人有限公司 用于制备曲前列环素二乙醇胺盐的多晶型b的方法
WO2021041320A1 (fr) 2019-08-23 2021-03-04 United Therapeutics Corporation Promédicaments de tréprostinil
US12173021B2 (en) 2019-08-23 2024-12-24 United Therapeutics Corporation Treprostinil prodrugs
US11634443B2 (en) 2019-08-23 2023-04-25 United Therapeutics Corporation Treprostinil prodrugs
EP3838884A1 (fr) 2019-12-19 2021-06-23 Chirogate International Inc. Procédé de cristallisation efficace pour préparer du tréprostinil ultra-pur et cristal préparé à partir de celui-ci
WO2021211916A1 (fr) 2020-04-17 2021-10-21 United Therapeutics Corporation Tréprostinil destiné à être utilisé dans le traitement d'une pneumopathie interstitielle
US20210330621A1 (en) 2020-04-17 2021-10-28 United Therapeutics Corporation Treatment for interstitial lung disease
US11826327B2 (en) 2020-04-17 2023-11-28 United Therapeutics Corporation Treatment for interstitial lung disease
WO2021252446A1 (fr) 2020-06-09 2021-12-16 United Therapeutics Corporation Promédicaments à base de fumaryle dicétopipéridine de tréprostinil
US12357599B2 (en) 2020-06-09 2025-07-15 United Therapeutics Corporation Prodrugs of treprostinil
US11793780B2 (en) 2020-06-09 2023-10-24 United Therapeutics Corporation Prodrugs of treprosiinil
WO2022132655A1 (fr) 2020-12-14 2022-06-23 United Therapeutics Corporation Méthodes de traitement d'une maladie à l'aide de promédicaments tréprostinil
US11826328B2 (en) 2020-12-14 2023-11-28 United Therapeutics Corporation Stable treprostinil prodrugs
WO2022136545A1 (fr) * 2020-12-22 2022-06-30 Radiometer Medical Aps Échantillonneur de sang contenant un agent antiplaquettaire et un matériau matriciel soluble dans l'eau
AU2021405712B2 (en) * 2020-12-22 2025-02-06 Radiometer Medical Aps Blood sampler containing anti-platelet agent and water-soluble matrix material
WO2022187352A1 (fr) 2021-03-03 2022-09-09 United Therapeutics Corporation Composition de poudre sèche de treprostinil et son promédicament et comprenant en outre de l'(e)-3,6-bis[4-(n-carbonyl-2-propényl)amidobutyl]-2,5-dicétopipérazine (fdkp)
US12168071B2 (en) 2021-03-03 2024-12-17 United Therapeutics Corporation Treprostinil derivatives and their use in pharmaceutical compositions
WO2023154705A1 (fr) 2022-02-08 2023-08-17 United Therapeutics Corporation Polythérapie à base de tréprostinil iloprost
WO2023206444A1 (fr) 2022-04-29 2023-11-02 兆科药业（广州）有限公司 Brume douce de tréprostinil à inhaler
WO2024155752A1 (fr) 2023-01-19 2024-07-25 United Therapeutics Corporation Analogues de tréprostinil
WO2025101824A1 (fr) 2023-11-09 2025-05-15 United Therapeutics Corporation Synthèses de composés utiles pour produire du tréprostinil

Similar Documents

Publication Publication Date Title
WO2016038532A1 (fr) Tréprostinil diéthanolamine amorphe
ES2562843T3 (es) Forma IV de clorhidrato de ivabradina
WO2015176602A1 (fr) Complexe de ténofovir alafénamide, son procédé de préparation et utilisation
CN105646584A (zh) 替诺福韦艾拉酚胺富马酸盐新晶型及其制备方法和用途
US20170129869A1 (en) Amorphous form of eliglustat hemitartarate
CN105121409B (zh) 德罗格韦钠盐的晶型及其制备方法
US20100297241A1 (en) Amorphous Fesoterodine Fumarate
WO2018073839A1 (fr) Mésylate d&#39;osimertinib amorphe, procédés pour sa préparation et dispersions amorphes solides de celui-ci
EP3102582A1 (fr) Formes cristallines de sodium de dolutegravir
US10660963B2 (en) Pharmaceutical composition containing tacrolimus and preparation methods thereof
WO2016135755A1 (fr) Aprémilast amorphe, pré-mélanges correspondant et nouvelles formes cristallines d&#39;aprémilast
WO2017163190A1 (fr) Citrate d&#39;ixazomib amorphe et dispersion solide de celui-ci
KR102276281B1 (ko) 의약으로 사용하기 위한 펄린돌 광학이성질체의 약학적으로 허용가능한 염
CN105218500B (zh) 黄芩素咖啡因共晶、其制备方法、药物组合物及其应用
US11466031B2 (en) Polymorphic forms of bictegravir and its sodium salt
CN116983429A (zh) 金属氢氧化物或金属氧化物复合体、包含其的药物组合物以及它们的制备方法
JP5809367B2 (ja) レボノルゲストレルの結晶多形α及びその製造方法
KR102697985B1 (ko) 약학 조성물 및 이를 제조하기 위한 방법
WO2018078383A1 (fr) Composition pharmaceutique comprenant du selexipag amorphe
CN104093400A (zh) 稳定的无定形雷特格韦钾盐预混料及其制备方法
TW201900646A (zh) 5型磷酸二酯酶抑制劑的甲磺酸鹽多晶物及其製備方法和應用
US20180030038A1 (en) Polymorphic Forms of Afatinib Dimaleate
WO2021233434A1 (fr) Nouvelle forme cristalline de bictégravir sodique et son procédé de préparation
ES2769581T3 (es) Polimorfos de clorhidrato de 4-metilbenzoato de 4-[2-dimetilamino-1-(1-hidroxiciclohexil)etil]fenilo, métodos para la preparación de los mismos y uso de los mismos
WO2017130219A1 (fr) Dispersion solide amorphe de palbociclib

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 15774717

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 15774717

Country of ref document: EP

Kind code of ref document: A1