WO2014064715A2 - Forme amorphe de chlorhydrate de vilazodone et son procédé de préparation - Google Patents

Forme amorphe de chlorhydrate de vilazodone et son procédé de préparation Download PDF

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Publication number
WO2014064715A2
WO2014064715A2 PCT/IN2013/000643 IN2013000643W WO2014064715A2 WO 2014064715 A2 WO2014064715 A2 WO 2014064715A2 IN 2013000643 W IN2013000643 W IN 2013000643W WO 2014064715 A2 WO2014064715 A2 WO 2014064715A2
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WO
WIPO (PCT)
Prior art keywords
vilazodone hydrochloride
amorphous form
vilazodone
hydrochloride
ball milling
Prior art date
Application number
PCT/IN2013/000643
Other languages
English (en)
Other versions
WO2014064715A3 (fr
Inventor
Shri Prakash Dhar Dwivedi
Ramesh Chandra SINGH
Kishorkumar Maneklal Vinchhi
Sachin Ashokrao PATIL
Original Assignee
Cadila Healthcare Limited
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 Cadila Healthcare Limited filed Critical Cadila Healthcare Limited
Publication of WO2014064715A2 publication Critical patent/WO2014064715A2/fr
Publication of WO2014064715A3 publication Critical patent/WO2014064715A3/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants

Definitions

  • the present invention provides substantially pure amorphous form : of vilazodone hydrochloride having polymorphic purity greater than 99.9% with no detectable amount of any other crystalline forms.
  • a process for the preparation of amorphous form of vilazodone hydrochloride of Formula (I) includes grinding vilazodone hydrochloride in a grinder for sufficient time and interval and isolating amorphous form of vilazodone hydrochloride.
  • step (i) adding vilazodone hydrochloride obtained in step (i) in a ball miller;
  • step (i) adding vilazodone hydrochloride obtained in step (i) in a ball miller;
  • a stable amorphous form of vilazodone hydrochloride thereof which is stable during storage and drying.
  • a pharmaceutical composition comprising the stabilized amorphous solid dispersion of vilazodone hydrochloride together with one or more pharmaceutically acceptable carriers, optionally with one or more pharmaceutically acceptable excipients.
  • the term "storage stable” includes the amorphous form of vilazodone hydrochloride after exposure to a relative humidity of 75% at 40°C or relative humidity of 60% at 25°C, for a period of at least three months shows no change in the polymorphic form by X- ray powder diffraction.
  • amorphous form of vilazodone hydrochloride may be obtained by milling the solid mixture of vilazodone hydrochloride.
  • the milling step may be traditionally carried out in pharmacy practice by compounding using a ball milling, pestle and mortar or a - " f common mixer grinder.
  • milling machines that work on substantially the same principle may be used in the present process. Examples of such milling machines include various makes of ball mills, roller mills, gyratory mills, multi-mills, Jet- mills, and the like.
  • amorphous form of vilazodone hydrochloride may be obtained by using grinding technique.
  • the process parameter includes adding vilazodone hydrochloride in a grinder.
  • a specific grinder used can be small-scale to large-scale mixer grinder which can easily prepare the homogeneous mixture.
  • Quadro dry mixing apparatus for providing lump-free homogenous blending to ensure proper mixing.
  • This grinding apparatus may consists of a water cooled jacketed bowl with the inside surface made of a suitable material such as Zirconium oxide, stainless steel, tungsten carbide, or aluminum oxide.
  • the speed of rotation of the main shaft and the effective volume of the grinding chamber may vary.
  • the period of milling using the mill may vary depending on the size of the mill, the speed of rotation of the main shaft, the type of feed material, and the quantity of feed material. The effects of these variables are well known in the art and the invention may be worked over a range of these variables. Typically, the period of milling ranges from about 15 minutes to 500 minutes.
  • such a mixture may be cooled below 60°C and again the solid mixture may be ball milled below 60°C.
  • the repetition of about two to three ball milling cycles followed by crushing of the solid mixture or sieving of the solid mixture results in substantially pure amorphous form of vilazodone hydrochloride characterized by XRD as depicted in FIG.1.
  • the sieving step is followed by subjecting vilazodone hydrochloride to a ball miller in pharmacy practice.
  • the ball milling step may be performed below 60°C.
  • the ball milling step may be performed using a ball mill at a temperature of about 30°C to 50°C.
  • the preferred temperature for ball milling may be from 40°C to 50°C.
  • the ball milling cycles may be repeated for two or more times after an interval of 2 hours.
  • the time duration between the two cycles of ball milling may vary from 60 minutes to 700 minutes.
  • the ball milling may be performed for about 30 minutes to 900 minutes.
  • reaction being an exothermic reaction, results in rise of temperature.
  • a mixture may be cooled below 60°C and again the solid mixture may be ball milled below 60 6 C.
  • the repetition of about two to three ball milling cycles followed by crushing of the solid mixture or sieving of the solid mixture results in amorphous form of vilazodone hydrochloride.
  • Vilazodone hydrochloride obtained after ball milling leads to substantially pure amorphous vilazodone hydrochloride as depicted in FIG.1.
  • step (i) adding the reaction mass of step (i) into a ternary solvent system and hydrochloric acid to obtain vilazodone hydrochloride; iii) purifying vilazodone hydrochloride in an organic solvent to obtain pure vilazodone hydrochloride;
  • the suitable solvent for step (i) comprises one or more of hydrocarbons, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises toluene, xylene, ethylbenzene dimethyl formamide, dimethyl sulfoxide, dimethyl acetamide, acetonitrile, C 1 -C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate and butyl acetate and the like.
  • the solvent may be dimethyl sulfoxide.
  • the preferred solvent for isolation of vilazodone hydrochloride may be methanol.
  • the suitable solvent for purifying vilazodone hydrochloride in step (iii) may be selected from one or more of hydrocarbons, nitriles, amides, alcohol, ketones, ester and the like.
  • the suitable solvent comprises toluene, xylene, ethylbenzene dimethyl formamide, dimethyl sulfoxide, dimethyl acetamide, acetonitrile, C 1 -C4 straight chain or branched alcohols, acetone, methyl isobutyl ketone, methyl ethyl ketone, ethyl acetate, isopropyl acetate, butyl acetate and mixture thereof.
  • the solvent may be mixture of acetone-water.
  • vilazodone hydrochloride prepared by one pot process as per the present invention, in the preparation of amorphous form of vilazodone hydrochloride.
  • step (i) adding vilazodone hydrochloride obtained in step (i) in grinder or miller;
  • the ball milling may be performed at a temperature of about 20°C to 40°C for about 30 minutes to 900 minutes for two or more cycles.
  • the milling step may be performed using a jet mill with feeding pressure of about 3 kg and grinding pressure of about 4 kg.
  • the grinding or jet milling cycles may vary from 1 to 5 cycles to obtain substantially pure amorphous form of vilazodone hydrochloride as depicted in FIG. l
  • step (i) adding the reaction mass of step (i) into a ternary solvent system (ethyl acetate: methanol: acetone with mole ratio of 1.5: 1 : 1 respectively) and hydrochloric acid to obtain vilazodone hydrochloride;
  • a ternary solvent system ethyl acetate: methanol: acetone with mole ratio of 1.5: 1 : 1 respectively
  • step (i) adding vilazodone hydrochloride obtained in step (i) in a ball miller;
  • the suitable base for step (i) comprises of an organic or inorganic base.
  • the base may be diisopropylethylamine.
  • the suitable solvent for purifying vilazodone hydrochloride in step (iii) may be selected from one or more of hydrocarbons, nitriles, amides, alcohol, ketones, ester and the like. Particularly, the solvent may be mixture of acetone-water.
  • the ball milling cycles may be repeated for two or more times after an interval of 2 hours.
  • the ball milling may be performed for about 30 minutes to 900 minutes.
  • the stable amorphous form of vilazodone hydrochloride is stored under nitrogen atmosphere and packed in a double polythene bag tied with a thread, keeping primary packing containing amorphous vilazodone hydrochloride or salts thereof inside a black color polyethylene bag containing oxygen busters and sealing it, placing above the double polyethylene bag inside a triple laminated bag optionally containing oxygen busters and sealing it, and placing the sealed triple laminated bag inside a closed high density polyethylene (HDPE) container and storing in controlled environment chamber at about 25°C and/or 40°C.
  • HDPE high density polyethylene
  • compositions containing the vilazodone hydrochloride of the invention may be prepared by using diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, surface active agents, and lubricants.
  • diluents or excipients such as fillers, bulking agents, binders, wetting agents, disintegrating agents, surface active agents, and lubricants.
  • modes of administration of the pharmaceutical compositions of the invention can be selected depending on the therapeutic purpose, for example tablets, pills, powders, liquids, suspensions, emulsions, granules, capsules, suppositories, or injection preparations.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une forme amorphe de chlorhydrate de vilazodone et des procédés pour la préparation de la forme amorphe de chlorhydrate de vilazodone. La présente invention concerne également des compositions pharmaceutiques qui comprennent une quantité thérapeutiquement efficace de la forme amorphe de chlorhydrate de vilazodone et l'utilisation desdites compositions pour le traitement d'un trouble dépressif majeur (MDD).
PCT/IN2013/000643 2012-10-22 2013-10-21 Forme amorphe de chlorhydrate de vilazodone et son procédé de préparation WO2014064715A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN3075MU2012 2012-10-22
IN3075/MUM/2012 2012-10-22

Publications (2)

Publication Number Publication Date
WO2014064715A2 true WO2014064715A2 (fr) 2014-05-01
WO2014064715A3 WO2014064715A3 (fr) 2014-09-12

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PCT/IN2013/000643 WO2014064715A2 (fr) 2012-10-22 2013-10-21 Forme amorphe de chlorhydrate de vilazodone et son procédé de préparation

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WO (1) WO2014064715A2 (fr)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105601536A (zh) * 2014-11-19 2016-05-25 北京凯莱天成医药科技有限公司 一种维拉佐酮中间体的制备方法
US9382233B2 (en) 2012-06-13 2016-07-05 Apotex Inc. Forms of vilazodone and processes for the preparation thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5532241A (en) 1993-09-30 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Piperidines and piperazines
WO2000072832A2 (fr) 1999-05-27 2000-12-07 Merck Patent Gmbh Nouvelle utilisation de 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine et de ses sels physiologiquement acceptables
US7381726B2 (en) 2001-06-19 2008-06-03 Merck Patentgesellschaft Mit Beschrankter Haftung Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl)piperazine hydrochloride
WO2012131706A1 (fr) 2011-03-20 2012-10-04 Cadila Healthcare Limited Forme amorphe du chlorhydrate de vilazodone et son procédé de préparation

Family Cites Families (5)

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Publication number Priority date Publication date Assignee Title
DE19514567A1 (de) * 1995-04-20 1996-10-24 Merck Patent Gmbh Benzofurane
DE102005019670A1 (de) * 2005-04-26 2006-11-02 Merck Patent Gmbh Verfahren zur Herstellung von (5-(4-[4-(5-Cyano-3-indolyl)-butyl)-1-piperazinyl)-benzofuran-2-carboxamid
WO2013078361A1 (fr) * 2011-11-23 2013-05-30 Assia Chemical Industries Ltd. Formes à l'état solide de vilazodone et de chlorhydrate de vilazodone
WO2013114338A1 (fr) * 2012-02-01 2013-08-08 Ranbaxy Laboratories Limited Procédé pour la préparation de vilazodone ou de ses sels pharmaceutiquement acceptables
WO2013168126A1 (fr) * 2012-05-11 2013-11-14 Dr.Reddys Laboratories Limited Formes cristallines du chlorhydrate de vilazodone et de la base libre de la vilazodone

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5532241A (en) 1993-09-30 1996-07-02 Merck Patent Gesellschaft Mit Beschrankter Haftung Piperidines and piperazines
WO2000072832A2 (fr) 1999-05-27 2000-12-07 Merck Patent Gmbh Nouvelle utilisation de 1-[4-(5-cyanoindol-3-yl)butyl]-4-(2-carbamoyl-benzofuran-5-yl)-piperazine et de ses sels physiologiquement acceptables
US7381726B2 (en) 2001-06-19 2008-06-03 Merck Patentgesellschaft Mit Beschrankter Haftung Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl)piperazine hydrochloride
US7834020B2 (en) 2001-06-19 2010-11-16 Merck Patent Gesellschaft Polymorphic forms of 1-′4-(5-cyanoindol-3-yl)butyl-4-(2-carbamoylbenzofuran-5-yl) piperazine hydrochloride
WO2012131706A1 (fr) 2011-03-20 2012-10-04 Cadila Healthcare Limited Forme amorphe du chlorhydrate de vilazodone et son procédé de préparation

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
"Perry's Chemical Engineers' Handbook"
ECONNO T., CHEM. PHARM. BULL., vol. 38, 1990, pages 2003 - 2007

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9382233B2 (en) 2012-06-13 2016-07-05 Apotex Inc. Forms of vilazodone and processes for the preparation thereof
CN105601536A (zh) * 2014-11-19 2016-05-25 北京凯莱天成医药科技有限公司 一种维拉佐酮中间体的制备方法
CN105601536B (zh) * 2014-11-19 2017-10-13 北京凯莱天成医药科技有限公司 一种维拉佐酮中间体的制备方法

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Publication number Publication date
WO2014064715A3 (fr) 2014-09-12

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