[go: up one dir, main page]

WO2017042731A1 - Forme amorphe du sélexipag et dispersion solide associée - Google Patents

Forme amorphe du sélexipag et dispersion solide associée Download PDF

Info

Publication number
WO2017042731A1
WO2017042731A1 PCT/IB2016/055386 IB2016055386W WO2017042731A1 WO 2017042731 A1 WO2017042731 A1 WO 2017042731A1 IB 2016055386 W IB2016055386 W IB 2016055386W WO 2017042731 A1 WO2017042731 A1 WO 2017042731A1
Authority
WO
WIPO (PCT)
Prior art keywords
selexipag
sodium
potassium
amorphous
cellulose
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/IB2016/055386
Other languages
English (en)
Inventor
Purna Chandra Ray
Dattatray Bajirao RASHINKAR
Ashok Sopan YADAV
Gaurav Kumar
Surinder Kumar Arora
Girij Pal Singh
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.)
Lupin Ltd
Original Assignee
Lupin 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 Lupin Ltd filed Critical Lupin Ltd
Publication of WO2017042731A1 publication Critical patent/WO2017042731A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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
    • C07D241/20—Nitrogen atoms
    • 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
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1611—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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/08—Bronchodilators
    • 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
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/08—Vasodilators for multiple indications

Definitions

  • the present invention relates to a novel amorphous form of selexipag sodium (lb) and selexipag potassium (Ic) and methods for preparing the same.
  • the present invention also relates to a process for the preparation of amorphous form of selexipag (la).
  • the present invention further relates to a solid dispersion of amorphous selexipag, amorphous selexipag sodium and amorphous selexipag potassium and method for its preparation.
  • the present invention comprises of selexipag (la) which has an PGI2 agonistic effect and shows a platelet aggregation inhibitory effect, a vasodilative effect, a bronchodilative effect, a lipid deposition inhibitory effect, a leukocyte activation inhibitory effect etc.
  • the chemical name for selexipag is (2- ⁇ 4-[(5,6-diphenylpyrazin-2-yl) (propan-2- yl)amino]butoxy ⁇ -N-(methanesulfonyl)acetamide, and is represented by the following structure.
  • Selexipag (la) is disclosed in the PCT application WO 2002/088084.
  • the patent US 8,791 , 122 discloses crystalline form I, form II, form III and amorphous forms of selexipag, while PCT application WO 2011024874 discloses base addition salts like t- butylamine, potassium, sodium and dimethylaminoethanol of selexipag in crystalline form.
  • amorphous forms in a number of drugs exhibit different dissolution characteristics and in some cases different bioavailability patterns compared to crystalline forms. For some therapeutic indications one bioavailability pattern may be favored over another.
  • An amorphous form of Cefuroxime axetil is a good example for exhibiting higher bioavailability than the crystalline form. Therefore, there is a need to develop an amorphous form of selexipag or its salt which has improved characteristics.
  • the patent as well as publication literature lack in providing information on an amorphous form of selexipag sodium and potassium. The inventors of the present invention provide here efficient and simple processes to obtain amorphous selexipag sodium and potassium.
  • the present invention provides amorphous form of selexipag sodium (lb) and selexipag potassium (Ic) and methods for their preparation.
  • the present invention also provides a process for the preparation of amorphous form of selexipag (la).
  • the present invention further provides a solid dispersion of amorphous selexipag, amorphous selexipag sodium and amorphous selexipag potassium.
  • the present invention further describes process for the preparation of solid dispersion of amorphous selexipag, amorphous selexipag sodium and amorphous selexipag potassium.
  • Figure 1 X-ray powder diffractogram (XRPD) for amorphous selexipag (la).
  • Figure 2 X-ray powder diffractogram (XRPD) for amorphous selexipag sodium (lb).
  • Figure 3 X-ray powder diffractogram (XRPD) for amorphous selexipag potassium (Ic).
  • Figure 4 X-ray powder diffractogram (XRPD) for amorphous selexipag solid dispersion with syloid.
  • Figure 5 X-ray powder diffractogram (XRPD) for amorphous selexipag sodium solid dispersion with syloid.
  • Figure 6 X-ray powder diffractogram (XRPD) for amorphous selexipag potassium solid dispersion with syloid.
  • An embodiment of the present invention provides a process for the preparation of amorphous selexipag (la) comprising: a) dissolving the selexipag free base in suitable solvent;
  • suitable solvent in the above method includes water; alcohol such as methanol, ethanol, n-propanol, isopropanol; ketone such as acetone, 2-butanone, methyl isobutyl ketone; ester such as ethyl acetate, isopropyl acetate; ether such as ethyl ether, methyl t-butyl ether, di-isopropyl ether, tetrahydrofuran; nitrile such as acetonitrile, propionitrile, butyronitrile; chlorinated hydrocarbon such as dichloromethane, ethylene dichloride, chloroform; amide such as dimethylformamide & mixtures thereof.
  • Preferred solvent being mixture of acetonitrile and water or mixture of acetonitrile and hexane.
  • Removing solvent and isolating amorphous form of selexipag can be achieved by various methods such as concentration on rotavapor, removal of solvent by evaporation, distillation, crash cooling, flash evaporation, rotational drying, spray drying, agitated thin film drying (ATFD), lyophilization (freeze drying); more preferably lyophilization and concentration on rotavapor.
  • the process of lyophilization is carried out at -70 to -80 °C with 10-15 mm Hg of vacuum.
  • amorphous form of selexipag (la) obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) pattern as shown in figure 1.
  • Another embodiment of the present invention provides a novel amorphous form of selexipag sodium (lb).
  • Another embodiment of the present invention is process for the preparation of amorphous selexipag sodium (lb) comprising following steps: a) dissolving selexipag free base in suitable solvent;
  • suitable solvent in the above method includes water; alcohol such as methanol, ethanol, n-propanol, isopropanol; ketone such as acetone, 2-butanone, methyl isobutyl ketone; ester such as ethyl acetate, isopropyl acetate; ether such as ethyl ether, methyl t-butyl ether, di-isopropyl ether, tetrahydrofuran; nitrile such as acetonitrile, propionitrile, butyronitrile; chlorinated hydrocarbon such as dichloromethane, ethylene dichloride, chloroform; amide such as dimethylformamide & mixtures thereof. Preferred solvent being acetone.
  • the sodium ion source used in step b includes bases like sodium carbonate, sodium bicarbonate, sodium hydroxide, sodium acetate, sodium methoxide or mixtures thereof; the most preferred source is sodium hydroxide.
  • the sodium ion source is added directly to the reaction mass or used in the form of solution of sodium ion source in solvent selected from water, methanol, ethanol, isopropyl alcohol, propanol, n-butanol, acetonitrile, tetrahydrofuran, acetone, methyl ethyl ketone or mixtures thereof.
  • the amorphous form of selexipag sodium (lb) obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) pattern as shown in figure 2.
  • Another embodiment of the present invention provides a novel amorphous form of selexipag potassium (Ic).
  • Yet another embodiment of the present invention is process for the preparation of amorphous selexipag potassium (Ic) comprising following steps: a) dissolving selexipag free base in suitable solvent;
  • suitable solvent in the above method includes water; alcohol such as methanol, ethanol, n-propanol, isopropanol; ketone such as acetone, 2-butanone, methyl isobutyl ketone; ester such as ethyl acetate, isopropyl acetate; ether such as ethyl ether, methyl t-butyl ether, di-isopropyl ether, tetrahydrofuran; nitrile such as acetonitrile, propionitrile, butyronitrile; chlorinated hydrocarbon such as dichloromethane, ethylene dichloride, chloroform; amide such as dimethylformamide & mixtures thereof. Preferred solvent being tetrahydrofuran.
  • the potassium ion source used in step b includes bases like potassium carbonate, potassium bicarbonate, potassium hydroxide, potassium acetate, potassium methoxide or mixtures thereof; the most preferred source is potassium hydroxide.
  • the potassium ion source is added directly to the reaction mass or used in the form of solution of potassium ion source in solvent selected from water, methanol, ethanol, isopropyl alcohol, propanol, n-butanol, acetonitrile, tetrahydrofuran, acetone, methyl ethyl ketone or mixtures thereof.
  • the amorphous form of selexipag potassium (Ic) obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) pattern as shown in figure 3.
  • Removing solvent and isolating amorphous form of selexipag sodium or selexipag potassium can be achieved by various methods such as concentration on rotavapor, removal of solvent by evaporation, distillation, crash cooling, flash evaporation, rotational drying, spray drying, agitated thin film drying (ATFD) and lyophilization (freeze drying).
  • Another embodiment of the present invention provides a process for the preparation of an amorphous solid dispersion of selexipag or selexipag sodium or selexipag potassium and one or more pharmaceutically acceptable carrier comprising the steps of: a) dissolving selexipag or selexipag sodium or selexipag potassium in suitable solvent ;
  • solid dispersion defines a system in a solid state wherein one component is dispersed more or less evenly throughout the other component or components.
  • any physical form of selexipag, selexipag sodium or selexipag potassium such as crystalline, amorphous or their mixtures can be utilized in step a.
  • suitable solvent includes water; alcohols such as methanol, ethanol, n-propanol, isopropanol; ketones such as acetone, 2-butanone, 2- Pentanone, methyl isobutyl ketone; esters such as ethyl acetate, isopropyl acetate; ethers such as ethyl ether, methyl t-butyl ether, di-isopropyl ether, tetrahydrofuran; nitriles such as acetonitrile, propionitrile, butyronitrile; chlorinated hydrocarbons such as chloroform, ethylene dichloride, chloroform; and mixtures thereof; the most preferred solvent is mixture of water and acetonitrile.
  • the dissolving step comprises heating the mixture of selexipag or selexipag sodium or selexipag potassium in suitable solvent.
  • the heating is at a temperature of about 10 -100°C, until obtaining complete dissolution.
  • the pharmaceutically acceptable carriers include, but not limited to mannitol, lactose, fructose, sorbitol, xylitol, maltodextrin, dextrates, dextrins, lactitol, inositol, trehalose, , maltose, raffinose, .alpha.-, .beta.- and .gamma.-cyclodextrins, gum arabic, sodium alginate, propylene glycol alginate, agar, gelatin, tragacanth, xanthan gum, starch, lectins, urea, chitosan, chitosan glutamate, hydroxypropyl beta.-cyclodextrin chitosan, hydroxypropylmethylcellulose (HPMC), hydroxypropylcellulose (HPC), methylcellulose (MC), cellulose acetate phthalate (CAP), hydroxypropylmethylcellulose phthalate (HP
  • dextrin, pullulan, corn starch and potato starch pregelatinized starches lactose, sucrose, glucose, reduced maltose, mannitol, sorbitol, xylitol, trehalose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, crystalline cellulose/carmellose sodium, hydroxypropyl cellulose, magnesium aluminometasilicate, silica excipients like silicon dioxide, syloid, light anhydrous silicic acid or the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methylcelluloses, pregelatinized starches or the like; disintegrants such as hydroxypropyl cellulose, low- substituted hydroxypropyl cellulose, croscarmellose sodium, a starch, methylcellulose, sodium alg
  • compositions that can be used include, but are not limited to, film formers, plasticizers, colorants, viscosity enhancers, preservatives, antioxidants, or the like.
  • pharmaceutically acceptable carrier includes silica excipients like silicon dioxide, syloid, colloidal silica.
  • Isolation of amorphous solid dispersion of selexipag or selexipag sodium or selexipag potassium can be achieved by various methods such as concentration, removal of solvent by evaporation, distillation, crash cooling, flash evaporation, rotational drying, spray drying, agitated thin film drying (ATFD), and lyophilization (freeze drying).
  • the amorphous solid dispersion of selexipag with syloid obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) as shown in figure 4.
  • the amorphous solid dispersion of selexipag sodium with syloid obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) as shown in figure 5.
  • the amorphous solid dispersion of selexipag potassium with syloid obtained by the process of the present invention is characterized by XRPD (X-ray powder diffraction pattern) as shown in figure 6.
  • the selexipag used as starting material for the present invention can be prepared by any of the methods known in the art. For example as disclosed in the PCT application WO 2002/088084, which is herein incorporated as reference.
  • the amorphous solid dispersion of selexipag, selexipag sodium, selexipag potassium of the present invention may be formulated as solid oral dosage forms such as powders, granules, pellets, tablets and capsules, suppositories, sachets, troches or lozenges; liquid oral dosage forms such as syrups, suspensions, dispersions, emulsions; and injectables.
  • the powder X-ray diffraction spectrum is measured using Philips (PAN analytical X'pert pro) diffractogram (copper anti cathode) and expressed in terms of inter planar distance d, Bragg' s angle 2 theta, intensity (expressed as a percentage of the most intense peak).
  • the scanning parameters include: measurement range 3-40 degrees two theta; measurement temperature 25 °C; continuous scan.
  • the lyophilizer used for lyopilization is VERTIS New York- 12525.
  • Example 2 Preparation of amorphous selexipag solid dispersion with syloid:
  • Example 3 Preparation of amorphous selexipag solid dispersion with syloid:
  • Example 6 Preparation of amorphous selexipag sodium solid dispersion with syloid:
  • Example 7 Preparation of amorphous selexipag potassium solid dispersion with sylloid:

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pulmonology (AREA)
  • Inorganic Chemistry (AREA)
  • Cardiology (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un procédé de préparation de la forme amorphe du sélexipag (Ia). La présente invention concerne également une nouvelle forme amorphe du sélexipag de sodium (Ib) et du sélexipag de potassium (Ic), ainsi que des procédés pour la préparer. La présente invention concerne en outre une dispersion solide du sélexipag amorphe, du sélexipag de sodium amorphe et du sélexipag de potassium amorphe, et un procédé de préparation associé.
PCT/IB2016/055386 2015-09-10 2016-09-09 Forme amorphe du sélexipag et dispersion solide associée Ceased WO2017042731A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3481/MUM/2015 2015-09-10
IN3481MU2015 2015-09-10

Publications (1)

Publication Number Publication Date
WO2017042731A1 true WO2017042731A1 (fr) 2017-03-16

Family

ID=56990678

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/055386 Ceased WO2017042731A1 (fr) 2015-09-10 2016-09-09 Forme amorphe du sélexipag et dispersion solide associée

Country Status (1)

Country Link
WO (1) WO2017042731A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2018078383A1 (fr) * 2016-10-27 2018-05-03 Cipla Limited Composition pharmaceutique comprenant du selexipag amorphe
EP3335699A1 (fr) * 2016-12-15 2018-06-20 H e x a l Aktiengesellschaft Formulation de sélexipag dans un système liquisolide
WO2019098300A1 (fr) 2017-11-16 2019-05-23 日本新薬株式会社 Formulation à libération contrôlée
WO2020255157A1 (fr) * 2019-06-20 2020-12-24 Aizant Drug Research Solutions Private Limited Forme posologique solide stable de sélexipag et son procédé de préparation
CN112500499A (zh) * 2020-11-11 2021-03-16 万华化学集团股份有限公司 一种制备醋酸丁酸纤维素的方法
WO2021153716A1 (fr) * 2020-01-31 2021-08-05 Nippon Shinyaku Co., Ltd. Composition à libération contrôlée
US11434206B2 (en) * 2016-04-01 2022-09-06 Honour (R&D) Process for the preparation of diphenylpyrazine derivatives
US12427145B2 (en) 2019-02-03 2025-09-30 Innovate Therapeutics Llc Controlled release pharmaceutical composition of Selexipag or it's active metabolite

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002088084A1 (fr) 2001-04-26 2002-11-07 Nippon Shinyaku Co., Ltd. Derives de composes heterocycliques et medicaments
WO2011024874A1 (fr) 2009-08-26 2011-03-03 日本新薬株式会社 Sels d'addition avec une base
US8791122C1 (fr) 2009-06-26 2014-07-29

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002088084A1 (fr) 2001-04-26 2002-11-07 Nippon Shinyaku Co., Ltd. Derives de composes heterocycliques et medicaments
EP1400518A1 (fr) * 2001-04-26 2004-03-24 Nippon Shinyaku Co., Ltd. Derives de composes heterocycliques et medicaments
US8791122C1 (fr) 2009-06-26 2014-07-29
US8791122B2 (en) 2009-06-26 2014-07-29 Nippon Shinyaku Co., Ltd. Form-I crystal of 2-{4-[N-(5,6-diphenylpyrazin-2-yl)-N-isopropylamino]butyloxy}-N-(methylsulfonyl)acetamide and method for producing the same
WO2011024874A1 (fr) 2009-08-26 2011-03-03 日本新薬株式会社 Sels d'addition avec une base

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
GUY VAN DEN MOOTER: "The use of amorphous solid dispersions: A formulation strategy to overcome poor solubility and dissolution rate", DRUG DISCOVERY TODAY: TECHNOLOGIES, vol. 9, no. 2, 1 June 2012 (2012-06-01), AMSTERDAM, NL, pages e79 - e85, XP055317903, ISSN: 1740-6749, DOI: 10.1016/j.ddtec.2011.10.002 *
HANCOCK B C ET AL: "CHARACTERISTICS AND SIGNIFICANCE OF THE AMORPHOUS STATE IN PHARMACEUTICAL SYSTEMS", JOURNAL OF PHARMACEUTICAL SCIENCES, AMERICAN PHARMACEUTICAL ASSOCIATION, WASHINGTON, US, vol. 86, no. 1, 1 January 1997 (1997-01-01), pages 1 - 12, XP000929450, ISSN: 0022-3549, DOI: 10.1021/JS9601896 *

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US11434206B2 (en) * 2016-04-01 2022-09-06 Honour (R&D) Process for the preparation of diphenylpyrazine derivatives
WO2018078383A1 (fr) * 2016-10-27 2018-05-03 Cipla Limited Composition pharmaceutique comprenant du selexipag amorphe
EP3335699A1 (fr) * 2016-12-15 2018-06-20 H e x a l Aktiengesellschaft Formulation de sélexipag dans un système liquisolide
WO2018109158A1 (fr) 2016-12-15 2018-06-21 H E X A L Aktiengesellschaft Formulation de sélexipag dans un système liquisolide
WO2019098300A1 (fr) 2017-11-16 2019-05-23 日本新薬株式会社 Formulation à libération contrôlée
JPWO2019098300A1 (ja) * 2017-11-16 2020-11-19 日本新薬株式会社 放出制御製剤
US11382912B2 (en) 2017-11-16 2022-07-12 Nippon Shinyaku Co., Ltd. Controlled-release preparation
US12427145B2 (en) 2019-02-03 2025-09-30 Innovate Therapeutics Llc Controlled release pharmaceutical composition of Selexipag or it's active metabolite
WO2020255157A1 (fr) * 2019-06-20 2020-12-24 Aizant Drug Research Solutions Private Limited Forme posologique solide stable de sélexipag et son procédé de préparation
WO2021153716A1 (fr) * 2020-01-31 2021-08-05 Nippon Shinyaku Co., Ltd. Composition à libération contrôlée
CN112500499A (zh) * 2020-11-11 2021-03-16 万华化学集团股份有限公司 一种制备醋酸丁酸纤维素的方法

Similar Documents

Publication Publication Date Title
WO2017042731A1 (fr) Forme amorphe du sélexipag et dispersion solide associée
CN110636845A (zh) 卢美哌隆对甲苯磺酸盐的无定形形式和固体分散体
WO2014118808A2 (fr) Dispersion solide de ticagrelor
CN111405897A (zh) 辛波莫德、其盐及其固态形式的制备方法
WO2014170026A1 (fr) Ticagrelor amorphe stabilisé
WO2012135338A1 (fr) Procédés pour la préparation de sels de tofacitinib
ZA200407799B (en) Lansoprazole polymorphs and processes for preparation thereof
US20100081809A1 (en) Amorphous valganciclovir hydrochloride
US20170368031A1 (en) Solid dispersion formulations of antiviral compounds
JP2014526508A5 (fr)
WO2019102492A1 (fr) Polymorphes cristallins d'abémaciclib
US20180008624A1 (en) Pharmaceutical Compositions Comprising Ledipasvir And Sofosbuvir
US20190300483A1 (en) POLYMORPHS OF BETRlXABAN & ITS MALEATE SALT
US20170296570A1 (en) High Drug Load Tablets Comprising Sofosbuvir
JP6266006B2 (ja) 難溶性薬物の固体分散体およびその製造方法
CN105939715A (zh) 抗病毒化合物的固定剂量组合
WO2017137900A1 (fr) Lumacaftor amorphe et sa dispersion solide
CN105418614A (zh) 替格瑞洛的新结晶形式及其制备方法和用途
WO2013088384A2 (fr) Formes à l'état solide d'azilsartan et d'azilsartan médoxomil monopotassique et leur procédé de préparation
WO2014016842A1 (fr) Coprécipités amorphes du rivaroxaban
WO2023152773A1 (fr) Formes solides de sels de momélotinib et procédés améliorés pour la préparation de momélotinib
EP3784676A1 (fr) Formes polymorphes de bictégravir et son sel de sodium
WO2014115169A2 (fr) Dispersion solide de crizotinib
US20180228828A1 (en) Fixed-dose combinations of antiviral compounds
WO2014174529A2 (fr) Polymorphes d'avanafil

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: 16770560

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: 16770560

Country of ref document: EP

Kind code of ref document: A1