EP1089995A1 - Paroxetine ascorbate - Google Patents

Paroxetine ascorbate

Info

Publication number
EP1089995A1
EP1089995A1 EP99918151A EP99918151A EP1089995A1 EP 1089995 A1 EP1089995 A1 EP 1089995A1 EP 99918151 A EP99918151 A EP 99918151A EP 99918151 A EP99918151 A EP 99918151A EP 1089995 A1 EP1089995 A1 EP 1089995A1
Authority
EP
European Patent Office
Prior art keywords
paroxetine
ascorbate
paroxetine ascorbate
salt
solution
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Withdrawn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
EP99918151A
Other languages
German (de)
English (en)
French (fr)
Inventor
Michael Smithkline Beecham Pharma. Urquhart
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.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham 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 SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Publication of EP1089995A1 publication Critical patent/EP1089995A1/en
Withdrawn legal-status Critical Current

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/02Heterocyclic 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
    • C07D405/12Heterocyclic 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
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/445Non condensed piperidines, e.g. piperocaine
    • A61K31/4523Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
    • A61K31/4525Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/14Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16Anti-Parkinson drugs
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/22Anxiolytics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/24Antidepressants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00Drugs for disorders of the nervous system
    • A61P25/28Drugs 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 relates to a novel compound, to processes for preparing it and to its use in treating medical disorders.
  • paroxetine ascorbate According to the present invention there is provided paroxetine ascorbate.
  • novel salt of this invention is provided in non-crystalline form, which may a solid or an oil.
  • the oil is preferably absorbed on a solid carrier, especially a carrier that is usable as a component of a pharmaceutical composition
  • novel salt of this invention is provided in crystalline form.
  • each polymorph forms another aspect of this invention.
  • Paroxetine ascorbate may be prepared by contacting stoichiometric amounts of ascorbic acid and paroxetine free base.
  • the acid or base is in solution, more preferably both are in solution. Elevated temperature may be used to bring the acid into solution, but good yields of the salt are obtained by evaporation of some or all of the solvent or by controlled cooling, preferably in stages.
  • Most commonly used solvents are suitable for mobilizing paroxetine free base, for example toluene, alcohols such as
  • Suitable solvents for ascorbic acid include water and lower alcohols.
  • the salt may be isolated in solid form by conventional means from a solution thereof obtained as above.
  • the non-crystalline salt may be prepared by precipitation, spray drying, and freeze drying of solutions, or vacuum drying of oils, or solidification of melts obtained from reaction of the free base and the acid.
  • the crystalline salt may be prepared by crystallization or recrystallization from appropriate solvents.
  • Solvates may be returned to the unsolvated salt by heating, for example by oven-drying, or by treatment with a displacement solvent which does not form a solvate.
  • water Prior to the isolation of the paroxetine salt, water may be removed by azeotropic distillation to avoid the formation of hydrates or to obtain the product in anhydrous form.
  • suitable solvents for the solution of the salt are those which form an azeotrope with water such as toluene and propan-2-ol. It should also be appreciated that mixtures of solvents can also be used to aid the azeotropic removal of water.
  • crystallization may be carried out from any solvent which allows formation of the desired crystal structure, using seeds of the desired structure where necessary or desirable.
  • individual polymo ⁇ hs are preferably crystallized directly from a solution of the salt, although recrystallizing a solution of one polymo ⁇ h using seeds of another polymo ⁇ h may also be carried out.
  • Paroxetine free base may be prepared according to the procedures generally outlined in US Patent No 4,007,196 and EP-B-0 223403. Ascorbic acid is commercially available.
  • the compounds of this invention may be used to treat and prevent the following disorders:
  • the Disorders are herein after referred to as "the Disorders”.
  • the present invention further provides a method for treating and/or preventing any one or more of the Disorders by administering an effective and/or prophylactic amount of a salt of the invention to a sufferer in need thereof.
  • the present invention further provides a pharmaceutical composition for use in the treatment and/or prevention of the Disorders which comprises an admixture of a salt of the invention with a pharmaceutically acceptable carrier.
  • the present invention also provides the use of a salt of the invention for treating and/or preventing the Disorders.
  • the present invention also provides the use of a salt of the invention in the manufacture of a medicament for treating and/or preventing the Disorders.
  • the present invention is applied to the treatment of depression, OCD and panic.
  • compositions of this invention are usually adapted for oral administration, but formulations for dissolution for parental administration are also within the scope of this invention.
  • the composition is usually presented as a unit dose composition containing from 1 to 200mg of active ingredient calculated on a free base basis, more usually from 5 to lOOmg, for example 10 to 50mg such as 10, 12.5, 15, 20, 25, 30 or 40mg by a human patient. Most preferably unit doses contain 20mg of active ingredient calculated on a free base basis. Such a composition is normally taken from 1 to 6 times daily, for example 2, 3 or 4 times daily so that the total amount of active agent administered is within the range 5 to 400mg of active ingredient calculated on a free base basis. Most preferably the unit dose is taken once a day.
  • Preferred unit dosage forms include tablets or capsules.
  • compositions of this invention may be formulated by conventional methods of admixture such as blending, filling and compressing.
  • Suitable carriers for use in this invention include a diluent, a binder, a disintegrant, a colouring agent, a flavouring agent and/or preservative. These agents may be utilized in conventional manner, for example in a manner similar to that already used for marketed anti-depressant agents.
  • compositions include those described EP-B-0- 223403, and US 4,007,196 in which the products of the present invention may be used as the active ingredients.
  • Example 1 Preparation of paroxetine ascorbate
  • the tablets are made satisfactorily on a single punch or a Rotary press.
  • Dihydrate are screened and mixed together in a suitable mixer.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Psychology (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
EP99918151A 1998-04-25 1999-04-23 Paroxetine ascorbate Withdrawn EP1089995A1 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9808896.6A GB9808896D0 (en) 1998-04-25 1998-04-25 Novel compound
GB9808896 1998-04-25
PCT/GB1999/001244 WO1999055698A1 (en) 1998-04-25 1999-04-23 Paroxetine ascorbate

Publications (1)

Publication Number Publication Date
EP1089995A1 true EP1089995A1 (en) 2001-04-11

Family

ID=10831008

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99918151A Withdrawn EP1089995A1 (en) 1998-04-25 1999-04-23 Paroxetine ascorbate

Country Status (20)

Country Link
EP (1) EP1089995A1 (id)
JP (1) JP2002513019A (id)
KR (1) KR20010042977A (id)
CN (1) CN1297448A (id)
AP (1) AP2000001963A0 (id)
AU (1) AU3618499A (id)
BG (1) BG104940A (id)
BR (1) BR9909868A (id)
CA (1) CA2330055A1 (id)
EA (1) EA200001104A1 (id)
GB (1) GB9808896D0 (id)
HU (1) HUP0102116A3 (id)
ID (2) ID26083A (id)
IL (1) IL139081A0 (id)
NO (1) NO20005352L (id)
PL (1) PL343677A1 (id)
SK (1) SK15912000A3 (id)
TR (1) TR200003084T2 (id)
WO (1) WO1999055698A1 (id)
ZA (1) ZA200005912B (id)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0003232D0 (en) * 2000-02-11 2000-04-05 Smithkline Beecham Plc Novel composition
IL159280A0 (en) * 2001-06-14 2004-06-01 Teva Pharma A process for preparing paroxetine hcl which limits formation of pink colored compounds
EP2272501B1 (en) * 2002-01-09 2013-03-20 Emisphere Technologies, Inc. Polymorphs of sodium 4-((4-chloro-2-hydroxybenzoyl) amino) butanoate
CN110607554B (zh) * 2018-10-30 2024-03-22 中国科学院化学研究所 一种制备药物或药物中间体单晶或无定型物的方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB1422263A (en) * 1973-01-30 1976-01-21 Ferrosan As 4-phenyl-piperidine compounds
DE3688827T2 (de) * 1985-10-25 1994-03-31 Beecham Group Plc Piperidinderivat, seine Herstellung und seine Verwendung als Arzneimittel.
US5276042A (en) * 1993-04-16 1994-01-04 Crenshaw Roger T Treatment of premature ejaculation
ES2117557B1 (es) * 1996-02-29 1999-07-01 Ferrer Int Nuevo procedimiento de obtencion de (-)-trans -n-p-fluorobenzoilmetil-4-(p-fluorofenil)-3- ((3,4-(metilendioxi)fenoxi ) metil)-piperidina.

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9955698A1 *

Also Published As

Publication number Publication date
ID26654A (id) 2001-01-25
TR200003084T2 (tr) 2001-02-21
HUP0102116A2 (hu) 2002-05-29
SK15912000A3 (sk) 2001-04-09
KR20010042977A (ko) 2001-05-25
ID26083A (id) 2000-11-23
BR9909868A (pt) 2000-12-19
BG104940A (bg) 2001-09-28
NO20005352D0 (no) 2000-10-24
IL139081A0 (en) 2001-11-25
WO1999055698A1 (en) 1999-11-04
GB9808896D0 (en) 1998-06-24
JP2002513019A (ja) 2002-05-08
CN1297448A (zh) 2001-05-30
EA200001104A1 (ru) 2001-04-23
ZA200005912B (en) 2001-12-19
NO20005352L (no) 2000-10-24
AU3618499A (en) 1999-11-16
PL343677A1 (en) 2001-08-27
HUP0102116A3 (en) 2002-12-28
AP2000001963A0 (en) 2000-12-31
CA2330055A1 (en) 1999-11-04

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