US20110313035A1 - Polymorphs of darunavir - Google Patents

Polymorphs of darunavir Download PDF

Info

Publication number
US20110313035A1
US20110313035A1 US13/128,157 US200913128157A US2011313035A1 US 20110313035 A1 US20110313035 A1 US 20110313035A1 US 200913128157 A US200913128157 A US 200913128157A US 2011313035 A1 US2011313035 A1 US 2011313035A1
Authority
US
United States
Prior art keywords
darunavir
solvent
solvate
alcohol
process according
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.)
Abandoned
Application number
US13/128,157
Other languages
English (en)
Inventor
Bandi Parthasaradhi Reddy
Kura Rathnakar Reddy
Dasari Muralidhara Reddy
Rapolu Raji Reddy
Kesireddy Subash Chander Reddy
Bandi Vamsi Krishna
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.)
Hetero Research Foundation
Original Assignee
Hetero Research Foundation
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 Hetero Research Foundation filed Critical Hetero Research Foundation
Assigned to HETERO RESEARCH FOUNDATION reassignment HETERO RESEARCH FOUNDATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: MURALIDHARA REDDY, DASARI, PARTHASARADHI REDDY, BANDI, RAJI REDDY, RAPOLU, RATHNAKAR REDDY, KURA, SUBASH CHANDER REDDY, KESIREDDY, VAMSI KRISHNA, BANDI
Publication of US20110313035A1 publication Critical patent/US20110313035A1/en
Abandoned legal-status Critical Current

Links

Images

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • 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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV

Definitions

  • the present invention provides novel solvated forms of darunavir and processes for there preparation.
  • the present invention also provides novel process for preparation of darunavir amorphous form and pharmaceutical composition comprising it.
  • Virus-encoded proteases which are essential for viral replication, are required for the processing of viral protein precursors. Interference with the processing of protein precursors inhibits the formation of infectious virions. Accordingly, inhibitors of viral proteases may be used to prevent or treat chronic and acute viral infections.
  • Darunavir has HIV protease inhibitory activity and is particularly well suited for inhibiting HIV-1 and HIV-2 viruses.
  • darunavir chemically (1S,2R,3′R,3′aS,6′ aR)-[3′-hexahydrofuro[2,3-b]furanyl-[3-(4-aminobenzenesulfonyl)isobutylamino]-1-benzyl-2-hydroxypropyl]carbamate.
  • Darunavir is represented by the following structure:
  • Polymorphism is defined as “the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice.
  • polymorphs are different crystalline forms of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules”.
  • Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph.
  • Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Infrared spectrometry (IR).
  • XRD X-ray diffraction
  • DSC Differential Scanning calorimetry
  • IR Infrared spectrometry
  • Darunavir can exist in different polymorphic forms, which differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
  • U.S. Patent Application No. 2005/0250845 described Amorphous Form, Form A (ethanolate), Form B (hydrate), Form C (methanolate), Form D (acetonate), Form E (dichloromethanate), Form F (ethylacetate solvate), Form G (1-ethoxy-2-propanolate), Form H (anisolate), Form I (tetrahydrofuranate), Form J (isopropanolate) and Form K (mesylate) of darunavir.
  • One object of the present invention is to provide novel solvated forms of darunavir and processes for their preparation.
  • Another object of the present invention is to provide a novel process for preparation of darunavir amorphous form and pharmaceutical compositions comprising them.
  • the present invention provided darunavir C 5 -C 8 alcohol solvate.
  • the present invention provides a process for preparing darunavir C 5 -C 8 alcohol solvate, which comprises crystallizing darunavir C 5 -C 8 alcohol solvate from a solution of darunavir in C 5 -C 8 alcohol solvent.
  • the present invention provides a process for preparing darunavir amorphous form, which comprises:
  • the present invention provides a pharmaceutical composition comprising darunavir amorphous form and a pharmaceutically acceptable excipient.
  • FIG. 1 is X-ray powder diffraction spectrum of darunavir 2-methyl-2-butanol solvate.
  • FIG. 2 is X-ray powder diffraction spectrum of darunavir n-pentanol solvate.
  • FIG. 3 is X-ray powder diffraction spectrum of darunavir amorphous form.
  • X-ray powder diffraction spectrum was measured on a bruker axs D8 advance X-ray powder diffractometer having a copper-K ⁇ radiation. Approximately 1 gm of sample was gently flattered on a sample holder and scanned from 2 to 50 degrees two-theta, at 0.02 degrees to theta per step and a step of 10.4 seconds. The sample was simply placed on the sample holder. The sample was rotated at 30 rpm at a voltage 40 KV and current 35 mA.
  • darunavir C 5 -C 8 alcohol solvate there is provided darunavir C 5 -C 8 alcohol solvate.
  • a process for preparing darunavir C 5 -C 8 alcohol solvate which comprises crystallizing darunavir C 5 -C 8 alcohol solvate from a solution of darunavir in C 5 -C 8 alcohol solvent.
  • Solvates can occur in different ratios of solvation.
  • the ratio of darunavir to the C 5 -C 8 alcohol solvent may range between 1:0.3 and 1:1.3. In particular, the ratio may range from about 0.5 to about 1 molecules of C 5 -C 8 alcohol solvent per 1 molecule of darunavir, preferably the ratio is 1 molecule of C 5 -C 8 alcohol solvent per 1 molecule of darunavir.
  • the C 5 -C 8 alcohol solvent is selected from 2-methyl-2-butanol or n-pentanol.
  • Darunavir 2-methyl-2-butanol solvate characterized by peaks in the powder x-ray diffraction spectrum having 2 ⁇ angle positions at about 6.8, 8.8, 11.1, 13.7, 16.3, 16.7, 19.6, 20.9 and 22.3 ⁇ 0.2 degrees.
  • the powdered x-ray diffractogram (PXRD) of darunavir 2-methyl-2-butanol solvate is shown in FIG. 1 .
  • Darunavir n-pentanol solvate characterized by peaks in the powder x-ray diffraction spectrum having 2 ⁇ angle positions at about 6.9, 9.1, 11.2, 13.7, 16.4, 17.1, 20.3, 20.6, 21.1 and 22.6 ⁇ 0.2 degrees.
  • the powdered x-ray diffractogram (PXRD) of darunavir n-pentanol solvate is shown in FIG. 2 .
  • the solvates of the present invention are useful intermediates for obtaining pure darunavir.
  • the solvates of darunavir of the present invention can be used to obtain known polymorphs of darunavir.
  • a process for the preparation of darunavir amorphous form which comprises:
  • Darunavir used in step (a) is darunavir in any solvated or hydrated or anhydrous form.
  • darunavir used in step (a) is darunavir C 5 -C 8 alcohol solvate such as 2-methyl-2-butanol solvate or n-pentanol solvate.
  • the solvent used in step (a) may be a solvent or mixture of solvents selected from the group consisting of a dichloromethane, ethylene dichloride, chloroform and ethyl acetate.
  • a dichloromethane ethylene dichloride, chloroform and ethyl acetate.
  • Preferable solvent is dichloromethane.
  • the distillation of the solvent may be carried out in step (b) at atmospheric pressure or at reduced pressure.
  • the distillation may preferably be carried out until the solvent is almost completely distilled off.
  • the aliphatic solvent or aromatic solvent used in step (c) may be a solvent or a mixture of solvents selected from the group consisting of a cyclohexane, hexane, n-heptane, toluene and xylene.
  • Preferable aliphatic solvent is cyclohexane.
  • the isolation of darunavir amorphous form may be performed by conventional techniques such as centrifugation and filtration.
  • a pharmaceutical composition comprising a darunavir amorphous form and a pharmaceutically acceptable excipient.
  • the pharmaceutically acceptable inert carrier which can be used may be a solid dosage forms.
  • the solid dosage forms for oral administration may include capsules, tablets, pills, powders and granules.
  • the ethyl acetate layer was washed with 10% sodium bicarbonate (100 ml), 2% sulfuric acid (100 ml), 10% sodium sulfate (100 ml) and 10% sodium chloride solution (100 ml). The layer was dried over sodium sulfate. The layer was treated with carbon and distilled off the solvent under vacuum at below 45° C. to obtain 85 gm of darunavir.
  • Darunavir (85 gm) as obtained in preparative example was added to n-pentanol (50 ml) and distilled off the solvent under vacuum at below 45° C. to obtain a residue.
  • n-pentanol (150 ml) was added to the residue.
  • the reaction mass was slowly cooled to room temperature and stirred for 24 hours.
  • the reaction mass further cooled to 0° C. and stirred for 1 hour at 0 to 5° C., filtered.
  • the solid obtained was washed with n-pentanol and dried the solid under vacuum at 50° C. to obtain 61 gm of darunavir n-pentanol solvate.
  • Darunavir 2-methyl-2-butanol solvate (5 gm) as obtained in example 1 was dissolved in methylene dichloride (50 ml), methylene dichloride layer was dried over sodium sulfate. The layer was treated with carbon and distilled off the solvent under vacuum at 45° C. to obtain foam like residue. Cyclohexane (2 ⁇ 25 ml) was added to the residue, distilled off the solvent and the residue was collected. To the residue obtained was added cyclohexane (50 ml), stirred for 30 hours at 20 to 25° C. The separated solid was filtered, washed with cyclohexane and then dried under vacuum at 50° C. for 12 hours to obtain 4.2 gm of darunavir amorphous form.
  • Darunavir n-pentanol solvate (5 gm) as obtained in example 2 was dissolved in methylene dichloride (50 ml), methylene dichloride layer was dried over sodium sulfate. The layer was treated with carbon and distilled off the solvent under vacuum at 45° C. to obtain foam like residue. Cyclohexane (2 ⁇ 25 ml) was added to the residue, distilled off the solvent and the residue was collected. To the residue obtained was added cyclohexane (50 ml), stirred for 30 hours at 20 to 25° C., filtered, washed with cyclohexane and dried under vacuum at 50° C. for 12 hours to obtain 4.2 gm of darunavir amorphous form.
  • Example 3 was repeated using darunavir ethanolate form A instead of darunavir 2-methyl-2-butanol solvate to obtain darunavir amorphous form.
  • Example 3 was repeated using darunavir hydrated form B instead of darunavir 2-methyl-2-butanol solvate to obtain darunavir amorphous form.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Oncology (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Steroid Compounds (AREA)
US13/128,157 2009-12-16 2009-12-16 Polymorphs of darunavir Abandoned US20110313035A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
INPCT/IN2009/000724 2009-12-16
PCT/IN2009/000724 WO2011073993A1 (en) 2009-12-16 2009-12-16 Polymorphs of darunavir

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2009/000724 A-371-Of-International WO2011073993A1 (en) 2009-12-16 2009-12-16 Polymorphs of darunavir

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US13/530,844 Continuation-In-Part US9624236B2 (en) 2009-12-16 2012-06-22 Amorphous darunavir
US14/047,243 Division US9580440B2 (en) 2009-12-16 2013-10-07 Polymorphs of darunavir

Publications (1)

Publication Number Publication Date
US20110313035A1 true US20110313035A1 (en) 2011-12-22

Family

ID=44166823

Family Applications (3)

Application Number Title Priority Date Filing Date
US13/128,157 Abandoned US20110313035A1 (en) 2009-12-16 2009-12-16 Polymorphs of darunavir
US13/530,844 Active 2031-10-11 US9624236B2 (en) 2009-12-16 2012-06-22 Amorphous darunavir
US14/047,243 Active 2031-09-26 US9580440B2 (en) 2009-12-16 2013-10-07 Polymorphs of darunavir

Family Applications After (2)

Application Number Title Priority Date Filing Date
US13/530,844 Active 2031-10-11 US9624236B2 (en) 2009-12-16 2012-06-22 Amorphous darunavir
US14/047,243 Active 2031-09-26 US9580440B2 (en) 2009-12-16 2013-10-07 Polymorphs of darunavir

Country Status (7)

Country Link
US (3) US20110313035A1 (de)
EP (1) EP2513116B1 (de)
CN (1) CN102686594A (de)
CA (1) CA2784131C (de)
ES (1) ES2546866T3 (de)
PT (1) PT2513116E (de)
WO (1) WO2011073993A1 (de)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2013108105A2 (en) 2012-01-18 2013-07-25 Aurobindo Pharma Limited Novel solvates of darunavir
US8853430B2 (en) 2010-05-20 2014-10-07 Hetero Research Foundation Crystalline hydrochloride salt of darunavir
US9580440B2 (en) 2009-12-16 2017-02-28 Hetero Research Foundation Polymorphs of darunavir

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8921415B2 (en) 2009-01-29 2014-12-30 Mapi Pharma Ltd. Polymorphs of darunavir
WO2011083287A2 (en) * 2010-01-05 2011-07-14 Cipla Limited Darunavir polymorph and process for preparation thereof
WO2011092687A1 (en) 2010-01-28 2011-08-04 Mapi Pharma Hk Limited Process for the preparation of darunavir and darunavir intermediates
WO2012107889A1 (en) * 2011-02-10 2012-08-16 Ranbaxy Laboratories Limited Process for the preparation of amorphous darunavir
CN103509031B (zh) * 2012-06-20 2016-04-27 上海迪赛诺药业有限公司 制备达芦那韦无定形物的方法
ES2969589T3 (es) 2012-07-24 2024-05-21 Laurus Labs Ltd Solvato de Propionato de Darunavir
WO2016092525A1 (en) * 2014-12-12 2016-06-16 Lupin Limited Darunavir n-propanol solvate and process for preparation thereof
CN106854212A (zh) * 2015-12-08 2017-06-16 浙江九洲药业股份有限公司 一种达芦那韦无定型的制备方法
CN107235987A (zh) * 2016-03-28 2017-10-10 浙江九洲药业股份有限公司 一种地瑞那韦甲醇溶剂化物及其制备方法和用途
EP3532478B1 (de) 2016-10-27 2021-05-26 Gilead Sciences, Inc. Crystalline form von darunavir freie base
CN108794498A (zh) * 2017-05-03 2018-11-13 江苏瑞科医药科技有限公司 一种达芦那韦无定型的制备方法

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4670578A (en) * 1983-08-29 1987-06-02 Merck & Co., Inc. Process for crystalline salts of L or (S)-3-(3,4-dihydroxyphenyl)-2-methylalanine esters
US5315016A (en) * 1992-10-13 1994-05-24 Nycomed Dak A/S Process for preparing pure podophyllotoxin
WO2003106461A2 (en) * 2002-05-16 2003-12-24 Tibotec Pharmaceuticals Ltd Pseudopolymorphic forms of a hiv protease inhibitor
US20090111796A1 (en) * 2004-12-02 2009-04-30 Tsuyoshi Muto 7-membered ring compound and method of production and pharmaceutical application thereof
US7649010B2 (en) * 2002-06-27 2010-01-19 SmithKline Beechman Cork Limited Carvedilol hydrobromide
US20120088808A1 (en) * 2009-04-09 2012-04-12 Sandoz Ag Crystal forms of saxagliptin

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL7310889A (de) 1972-08-12 1974-02-14
US4692438A (en) * 1984-08-24 1987-09-08 Hoffmann-La Roche Inc. Pyridazo-diazepines, diazocines, and -triazepines having anti-hypertensive activity
US5968942A (en) * 1992-08-25 1999-10-19 G. D. Searle & Co. α- and β-amino acid hydroxyethylamino sulfonamides useful as retroviral protease inhibitors
ATE174587T1 (de) 1993-08-24 1999-01-15 Searle & Co Hydroxyaminosulfonamide verwendbar als inhibitoren retroviraler proteasen
CA2336160C (en) 1998-06-23 2015-02-17 The United States Of America, Represented By The Secretary, Department Of Health And Human Services Use of compounds for treating hiv
US20030125336A1 (en) 2001-05-30 2003-07-03 Fleitz Fred J. Hydrohalide salts of an HIV protease inhibitor
WO2006067795A2 (en) * 2004-12-23 2006-06-29 Jubilant Organosys Limited Novel polymorphic forms of atorvastatin lactone and process for preparing the same
EP1963254A2 (de) * 2005-09-21 2008-09-03 Torrent Pharmaceuticals Ltd Verfahren zur herstellung von lercanidipin und einer amorphen form von lercanidipin-hypochlorid
TWI385173B (zh) 2005-11-28 2013-02-11 Tibotec Pharm Ltd 作為ｈｉｖ蛋白酶抑制劑之經取代的胺基苯基磺醯胺化合物
PL2089371T3 (pl) 2006-11-09 2011-06-30 Janssen Sciences Ireland Uc Sposoby wytwarzania heksahydrofuro[2,3-b]furan-3-olu
PL2381786T3 (pl) 2009-01-29 2015-06-30 Mapi Pharma Ltd Dimetylosulfotlenkowy solwat darunawiru
US8921415B2 (en) 2009-01-29 2014-12-30 Mapi Pharma Ltd. Polymorphs of darunavir
CN102686594A (zh) 2009-12-16 2012-09-19 熙德隆研究基金会 地瑞那韦的多晶型物
US8853430B2 (en) 2010-05-20 2014-10-07 Hetero Research Foundation Crystalline hydrochloride salt of darunavir

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4670578A (en) * 1983-08-29 1987-06-02 Merck & Co., Inc. Process for crystalline salts of L or (S)-3-(3,4-dihydroxyphenyl)-2-methylalanine esters
US5315016A (en) * 1992-10-13 1994-05-24 Nycomed Dak A/S Process for preparing pure podophyllotoxin
WO2003106461A2 (en) * 2002-05-16 2003-12-24 Tibotec Pharmaceuticals Ltd Pseudopolymorphic forms of a hiv protease inhibitor
US7649010B2 (en) * 2002-06-27 2010-01-19 SmithKline Beechman Cork Limited Carvedilol hydrobromide
US20090111796A1 (en) * 2004-12-02 2009-04-30 Tsuyoshi Muto 7-membered ring compound and method of production and pharmaceutical application thereof
US20120088808A1 (en) * 2009-04-09 2012-04-12 Sandoz Ag Crystal forms of saxagliptin

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
Vippagunta et. al. (Advanced Drug Delivery Reviews (2001) 48:3-26). *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9580440B2 (en) 2009-12-16 2017-02-28 Hetero Research Foundation Polymorphs of darunavir
US9624236B2 (en) 2009-12-16 2017-04-18 Hetero Research Foundation Amorphous darunavir
US8853430B2 (en) 2010-05-20 2014-10-07 Hetero Research Foundation Crystalline hydrochloride salt of darunavir
US9175005B2 (en) 2010-05-20 2015-11-03 Hetero Research Foundation Crystalline hydrochloride salt of darunavir
WO2013108105A2 (en) 2012-01-18 2013-07-25 Aurobindo Pharma Limited Novel solvates of darunavir

Also Published As

Publication number Publication date
EP2513116B1 (de) 2015-08-19
CN102686594A (zh) 2012-09-19
EP2513116A1 (de) 2012-10-24
WO2011073993A1 (en) 2011-06-23
US20120288563A1 (en) 2012-11-15
CA2784131A1 (en) 2011-06-23
CA2784131C (en) 2017-07-11
EP2513116A4 (de) 2013-05-08
US9580440B2 (en) 2017-02-28
US9624236B2 (en) 2017-04-18
US20140200356A1 (en) 2014-07-17
PT2513116E (pt) 2015-10-14
ES2546866T3 (es) 2015-09-29

Similar Documents

Publication Publication Date Title
US9580440B2 (en) Polymorphs of darunavir
US9175005B2 (en) Crystalline hydrochloride salt of darunavir
US20150141383A1 (en) Darunavir Polymorph and Process for Preparation Thereof
US10544157B2 (en) Process for preparation of Darunavir
US9216990B2 (en) Crystalline Darunavir
US9624207B2 (en) Polymorphs of azilsartan medoxomil
US8962833B2 (en) Salts of raltegravir
US8445506B2 (en) Polymorphs of lopinavir
US20150025040A1 (en) Novel polymorphs of fosamprenavir calcium
CA2808731A1 (en) Crystalline forms of maraviroc phosphate and process for maraviroc amorphous form
US20120035211A1 (en) Novel polymorphs of saquinavir
WO2011016044A1 (en) Novel polymorphs of adefovir dipivoxil
WO2014024210A2 (en) Novel polymorphs of doxercalciferol

Legal Events

Date Code Title Description
AS Assignment

Owner name: HETERO RESEARCH FOUNDATION, INDIA

Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:PARTHASARADHI REDDY, BANDI;RATHNAKAR REDDY, KURA;MURALIDHARA REDDY, DASARI;AND OTHERS;REEL/FRAME:026542/0092

Effective date: 20110617

STCB Information on status: application discontinuation

Free format text: ABANDONED -- FAILURE TO RESPOND TO AN OFFICE ACTION