EP1858847A1 - Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques - Google Patents

Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques

Info

Publication number
EP1858847A1
EP1858847A1 EP06710466A EP06710466A EP1858847A1 EP 1858847 A1 EP1858847 A1 EP 1858847A1 EP 06710466 A EP06710466 A EP 06710466A EP 06710466 A EP06710466 A EP 06710466A EP 1858847 A1 EP1858847 A1 EP 1858847A1
Authority
EP
European Patent Office
Prior art keywords
donepezil hydrochloride
donepezil
stable
polymorphic
hydrochloride
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Withdrawn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
EP06710466A
Other languages
German (de)
English (en)
Inventor
Asok Nath
Mohan Prasad
Yatendra Kumar
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.)
Ranbaxy Laboratories Ltd
Original Assignee
Ranbaxy 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 Ranbaxy Laboratories Ltd filed Critical Ranbaxy Laboratories Ltd
Publication of EP1858847A1 publication Critical patent/EP1858847A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/30—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom
    • C07D211/32—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by doubly bound oxygen or sulfur atoms or by two oxygen or sulfur atoms singly bound to the same carbon atom by oxygen atoms
    • 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
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia

Definitions

  • the present invention provides stable polymorphic Form I donepezil hydrochloride, processes for its preparation, use in pharmaceutical compositions and methods of treating Alzheimer's disease using the pharmaceutical compositions.
  • Donepezil is chemically, 2-[(l-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy indan- 1-one of Formula I and is used in the treatment of mild to moderate dementia of Alzheimer's type. It is commercially available as its hydrochloride salt.
  • US 4,895,841 provides a process for preparing donepezil hydrochloride by crystallizing crude donepezil hydrochloride from a mixture of methanol and diisopropyl ether. Although no particular polymorphic form is mentioned in the specification of the '841 patent, it is believed that Form I of donepezil hydrochloride is obtained by employing such crystallization.
  • US Application No 2004/0229914 provides a process for preparing crystalline Form VI of donepezil hydrochloride.
  • PCT Application WO 04/092137 provides crystalline donepezil hydrochloride Form Hl, Form H2, crystalline donepezil hydrochloride monohydrate and crystalline donepezil hydrochloride sesquihydrate.
  • US 6,734,195 provides processes for making amorphous donepezil hydrochloride.
  • PCT Patent Application WO 99/29668 provides a process for making crystal A, B and C of donepezil.
  • PCT Application WO 04/099142 provides the hydrobromide salt of donepezil. It further provides donepezil hydrobromide in solid state crystalline Forms I and II.
  • polymorphic Form I of donepezil hydrochloride when prepared as per the process reported in the prior art is not stable and has a tendency to convert to other polymorphic forms, especially Form III. It also was observed by the present inventors that after addition of ether to a solution of donepezil hydrochloride in methanol at a higher or ambient temperature, formation of Form I of donepezil is accompanied by contamination with Form III crystals if it takes more than forty five minutes to cool the resultant mass to less than 20 C. The so obtained Form I of donepezil hydrochloride, whenever stirred with water or any solvent at ambient temperature, converts to Form III at a much faster rate.
  • the present inventors have now obtained a stable polymorphic Form I donepezil hydrochloride having no or little tendency to convert to any other polymorphic form of donepezil hydrochloride.
  • a stable polymorphic Form I of donepezil hydrochloride may include one or more of the following features.
  • the donepezil hydrochloride may have no detectable quantity of other polymorphic forms of donepezil hydrochloride.
  • the donepezil hydrochloride may have 2% or less of other polymorphic forms of donepezil hydrochloride.
  • the donepezil hydrochloride may be incorporated into a dosage form with one or more pharmaceutically acceptable excipients.
  • the donepezil hydrochloride may have the pattern illustrated in Figures 1 and/or 2.
  • a process for preparing stable Form I of donepezil hydrochloride includes (a) adding an optionally pre-cooled anti- solvent to a solution of donepezil hydrochloride at 30°C or less; (b) rapidly cooling the resultant solution; and (c) isolating Form I of donepezil hydrochloride from the reaction mass thereof.
  • Embodiments of the process may include one or more of the following features.
  • the anti-solvent may be characterized by the donepezil hydrochloride being insoluble, practically insoluble or very slightly soluble in the anti-solvent.
  • the anti- solvent may be diisopropyl ether or diethyl ether.
  • step (b) may be cooled to 25°C or less.
  • the cooling may be effected in 30 minutes or less.
  • the donepezil hydrochloride may have no detectable quantity of other polymorphic forms of donepezil hydrochloride.
  • the donepezil hydrochloride may have 2% or less of other polymorphic forms of donepezil hydrochloride.
  • a pharmaceutical composition that includes stable polymorphic Form I of donepezil hydrochloride and one or more pharmaceutically acceptable excipients and diluents.
  • the donepezil hydrochloride has no tendency to convert to any other polymorphic form.
  • Embodiments of the pharmaceutical composition may include one or more of the following features.
  • the donepezil hydrochloride may have no detectable quantity of other polymorphic forms of donepezil hydrochloride.
  • the donepezil hydrochloride may have 2% or less of other polymorphic forms of donepezil hydrochloride.
  • a method of treating mild to moderate dementia of Alzheimer's type includes administering to a mammal in need thereof a therapeutically effective amount of stable polymorphic Form I of donepezil hydrochloride having no tendency to convert to any other polymorphic form.
  • the therapeutically effective amount of donepezil hydrochloride may be in the form of a pharmaceutical composition that includes one or more pharmaceutically acceptable excipients and diluents.
  • the donepezil hydrochloride may have no detectable quantity of other polymorphic forms of donepezil hydrochloride.
  • the donepezil hydrochloride may have 2% or less of other polymorphic forms of donepezil hydrochloride.
  • Figure 1 is an X-Ray Powder Diffraction Pattern of stable Form I donepezil hydrochloride
  • Figure 2 is a table of the two-theta values associated with the pattern of Figure 1.
  • a first aspect of the present invention provides stable polymorphic Form I of donepezil hydrochloride having no tendency to convert to any other polymorphic form.
  • the stable polymorphic Form I of donepezil hydrochloride of the present invention has 2% or less of other polymorphic forms of donepezil hydrochloride. More preferably the stable Form I of donepezil hydrochloride has no detectable quantity of any other known polymorphic form of donepezil hydrochloride.
  • the X-Ray powdered Diffraction (XRPD) pattern and associated two-theta values of stable Form I of donepezil hydrochloride is provided in Figures 1 and 2 of the accompanied drawing. The stability study performed on stable Form I of donepezil hydrochloride suggests that it is stable for more than 2 years under normal stability studies and for more than six months under accelerated stability studies.
  • Form I donepezil hydrochloride is stable and there is no change in the related substance content of Form I stored at 40 ⁇ 2 0 C at 75 ⁇ 5% relative humidity. There was no indication of a chemical degradation of Form I donepezil hydrochloride produced according the present invention.
  • a second aspect of the present invention provides a process for preparing stable Form I donepezil hydrochloride.
  • the process includes the steps of:
  • Donepezil hydrochloride to be used as the starting material can be prepared by any process known in the literature.
  • the so obtained donepezil hydrochloride then is dissolved in methanol by heating to reflux temperature.
  • the resultant solution can be clarified to remove foreign particulate matter or treated with activated charcoal to remove coloring and other related impurities.
  • the clear solution is cooled to a temperature of 3O 0 C or less and an optionally pre-cooled anti-solvent is added to it.
  • the anti-solvent is characterized by the fact that donepezil hydrochloride is insoluble, practically insoluble or very slightly soluble in the anti-solvent.
  • the terms insoluble, practically insoluble and very slightly soluble have their ordinary meanings as defined in United States Pharmacopoeia 2002.
  • Diisopropyl ether and diethyl ether are examples of anti-solvents that can be employed.
  • a third aspect of the present invention provides a pharmaceutical composition comprising as its active ingredient stable polymorphic Form I of donepezil hydrochloride having no tendency to convert to any other polymorphic form.
  • the pharmaceutical composition includes one or more pharmaceutically acceptable excipients/diluents.
  • the pharmaceutical composition of the present invention may be in the form of a solid or liquid dosage forms for oral, parenteral or topical use and may have immediate or sustained release characteristics.
  • the dosage forms possible include tablets, capsules, powders, granules, creams, lotions, ointments, injectables, ophthalmic or otic solutions, suspensions, elixirs and the like.
  • a fourth aspect of the present invention provides a method of treating mild to moderate dementia of Alzheimer's type by administering to a mammal in need thereof a therapeutically effective amount of stable polymorphic Form I of donepezil hydrochloride having no tendency to convert to any other polymorphic form.
  • the compounds described herein can be formulated into dosage forms that are suitable for administering to patients in need of the compound for treating a medical condition for which the compound is indicated, approved, or otherwise beneficial.
  • the stable Form I of donepezil hydrochloride can be formulated with one or more pharmaceutically acceptable excipients into a dosage form and administered to treat Alzheimer's type dementia.

Landscapes

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

Abstract

L'invention concerne le chlorhydrate de donépézil de formule I stable polymorphe, ses procédés de préparation, et son utilisation dans des compositions pharmaceutiques. Elle concerne également des procédés de traitement de la maladie d'Alzheimer faisant appel à ces compositions pharmaceutiques.
EP06710466A 2005-02-28 2006-02-28 Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques Withdrawn EP1858847A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN436DE2005 2005-02-28
PCT/IB2006/000416 WO2006090263A1 (fr) 2005-02-28 2006-02-28 Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques

Publications (1)

Publication Number Publication Date
EP1858847A1 true EP1858847A1 (fr) 2007-11-28

Family

ID=36654908

Family Applications (1)

Application Number Title Priority Date Filing Date
EP06710466A Withdrawn EP1858847A1 (fr) 2005-02-28 2006-02-28 Chlorhydrate de donepezil de formule i stable et son procede de preparation et d'utilisation dans des compositions pharmaceutiques

Country Status (2)

Country Link
EP (1) EP1858847A1 (fr)
WO (1) WO2006090263A1 (fr)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU227474B1 (en) * 2005-12-20 2011-07-28 Richter Gedeon Nyrt Process for industrial scale production of high purity donepezil hydrochloride polymorph i.
AR063319A1 (es) * 2006-10-16 2009-01-21 Medichem Sa Proceso mejorado para preparar la forma polimorfica i de clorhidrato de donepezilo (2,3-dihidro-5,6-dimetoxi-2-[[1-(fenilmetil)-4-piperidin]metil-1h-inden-1-ona)
DE102010010998A1 (de) 2010-03-10 2011-09-15 Stada Arzneimittel Ag Feste pharmazeutische Zusammensetzung, umfassend Donepezil-Hydrochlorid der kristallinen polymorphen Form I
CN103694164B (zh) * 2014-01-23 2015-08-12 天津大学 一种盐酸多奈哌齐新晶型及制备方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU731282B2 (en) * 1996-06-07 2001-03-29 Eisai Co. Ltd. Polymorphs of donepezil hydrochloride and process for production
JPH1053576A (ja) * 1996-06-07 1998-02-24 Eisai Co Ltd 塩酸ドネペジルの多形結晶およびその製造法
IL150509A (en) * 2002-07-01 2007-07-04 Joseph Kaspi Pharmaceutical preparations containing donafazil hydrochloride
EP1608371A1 (fr) * 2003-03-21 2005-12-28 Ranbaxy Laboratories, Ltd. Procede de preparation de donepezil et de ses derives
US7560560B2 (en) * 2003-04-16 2009-07-14 Hetero Drugs Limited Crystalline forms of donepezil hydrochloride

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO2006090263A1 *

Also Published As

Publication number Publication date
WO2006090263A1 (fr) 2006-08-31

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