WO2005100348A1 - Amorphous ziprasidone hydrochloride - Google Patents

Amorphous ziprasidone hydrochloride Download PDF

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Publication number
WO2005100348A1
WO2005100348A1 PCT/IN2005/000115 IN2005000115W WO2005100348A1 WO 2005100348 A1 WO2005100348 A1 WO 2005100348A1 IN 2005000115 W IN2005000115 W IN 2005000115W WO 2005100348 A1 WO2005100348 A1 WO 2005100348A1
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Prior art keywords
ziprasidone hydrochloride
ziprasidone
hydrochloride
amorphous
solution
Prior art date
Application number
PCT/IN2005/000115
Other languages
French (fr)
Inventor
Om Dutt Tyagi
Tushar Kumar Srivastava
Yuvraj Atmaram Chavan
Original Assignee
Lupin Limited
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Filing date
Publication date
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Publication of WO2005100348A1 publication Critical patent/WO2005100348A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 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
    • A61P25/06—Antimigraine agents
    • 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
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • 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
    • A61P25/22—Anxiolytics

Definitions

  • the present invention relates to amorphous ziprasidone hydrochloride of formula (I) and process for preparation thereof.
  • Ziprasidone hydrochloride of formula (I), chemically known as 5-[2-[4-(1 ,2- benzisothiaol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride is a potent seretonin and dopamine antagonist, effective as an antipsychotic drug with negligible side effects for treating various disorders including schizophrenia, anxiety, migraine etc.
  • Ziprasidone hydrochloride is commercially sold under the brand names of Zeldox, Geodon etc for oral administration.
  • Ziprasidone and its acid addition salts, including the hydrochloride salt was first disclosed by Lowe J.A. et. al in US Patent No. 4 831 031.
  • This patent discloses a method for preparation of the ziprasidone hydrochloride hemihydrate by solvent precipitation method comprising addition of diethyl ether containing dissolved hydrogen chloride gas to a solution of ziprasidone in methylene chloride.
  • US Patent No. 5 312 925 discloses a method for preparation of crystalline ziprasidone hydrochloride monohydrate by heating an aqueous mixture of ziprasidone free base in presence of concentrated hydrochloric acid at 60-65°C. This patent provides x-ray powder diffraction and infra-red spectral data indicating the crystalline nature of ziprasidone hydrochloride monohydrate.
  • US Patent No. 6 110 918 discloses a method for preparation of mesylate trihydrate salt by addition of an aqueous solution of methanesulfonic acid to a slurry of ziprasidone free base in an organic solvent followed by formation of the mesylate salt under reflux.
  • the presence of the mesylate salt in four distinct forms viz. trihydrate, dihydrate (lath), dihydrate (needle), and anhydrous form is indicated by x-ray diffraction powder spectrum.
  • the present invention relates to method for preparation of ziprasidone hydrochloride, which is substantially amorphous and of high purity and stability.
  • the object of the present invention is to provide an efficient and economically advantageous process for preparation of ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.
  • An aspect of the invention relates to ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.
  • Another aspect of the invention relates to providing a process for preparation of substantially amorphous ziprasidone hydrochloride of formula (I), by different methods such as spray-drying, lyophilisation, freeze drying, solvent precipitation, jet-milling etc.
  • amorphous ziprasidone hydrochloride is be prepared by spray drying a solution of of ziprasidone hydrochloride in a mixture of alcoholic solvent such as methanol, ethanol, isoproanol, or tert-butyl alcohol with acetonitrile.
  • alcoholic solvent such as methanol, ethanol, isoproanol, or tert-butyl alcohol with acetonitrile.
  • the solution of ziprasidone hydrochloride is prepared in a mixture of methanol and acetonitrile.
  • the amount of methanol is used in an amount of 3-5 times the volume of acetonitrile, preferably, 4 times the volume of acetonitrile.
  • the solution of ziprasidone hydrochloride is spray dried maintaining the inlet temperature between 70 to 90 °C and outlet temperature between 50 to 75 °C.
  • the X-ray powder diffraction pattern of the product obtained by spray drying is as depicted in Fig.1. It is without any diffraction peaks. This demonstrates amorphous nature of the product formed by the process of present invention.
  • a substantially amorphous form of ziprasidone hydrochloride of formula (I) having high purity and stability could be prepared by utilizing the method of spray-drying given below:
  • Ziprasidone hydrochloride (10gms) was dissolved in a mixture of acetonitrile (725ml) and methanol (2900ml). The resulting mixture was spray dried at a temperature between 65°C and 90°C. The product separating out was dried at ambient temperature to give substantially amorphous ziprasidone hydrochloride. Yield: 4.0gms.

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

Abstract

A process for preparation of ziprasidone hydrochloride which is in amorphous form. The process comprises providing a ziprasidone hydrochloride solution in a mixture of alcoholic solvent and acetonitrile and spray drying the solution of ziprasidone hydrochloride.

Description

AMORPHOUS ZIPRASIDONE HYDROCHLORIDE
FIELD OF INVENTION
The present invention relates to amorphous ziprasidone hydrochloride of formula (I) and process for preparation thereof.
BACKGROUND OF THE INVENTION
Ziprasidone hydrochloride of formula (I), chemically known as 5-[2-[4-(1 ,2- benzisothiaol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-2H-indol-2-one hydrochloride is a potent seretonin and dopamine antagonist, effective as an antipsychotic drug with negligible side effects for treating various disorders including schizophrenia, anxiety, migraine etc.
Figure imgf000002_0001
Ziprasidone hydrochloride is commercially sold under the brand names of Zeldox, Geodon etc for oral administration.
Ziprasidone and its acid addition salts, including the hydrochloride salt was first disclosed by Lowe J.A. et. al in US Patent No. 4 831 031. This patent discloses a method for preparation of the ziprasidone hydrochloride hemihydrate by solvent precipitation method comprising addition of diethyl ether containing dissolved hydrogen chloride gas to a solution of ziprasidone in methylene chloride.
There is no mention in the above patent about the solid-state characteristics of ziprasidone hydrochloride to indicate whether ziprasidone hydrochloride is crystalline or amorphous. US Patent No. 5 312 925 (Allen J.M.A et. al) discloses a method for preparation of crystalline ziprasidone hydrochloride monohydrate by heating an aqueous mixture of ziprasidone free base in presence of concentrated hydrochloric acid at 60-65°C. This patent provides x-ray powder diffraction and infra-red spectral data indicating the crystalline nature of ziprasidone hydrochloride monohydrate.
US Patent No. 6 110 918 (Busch F.R. et. al) discloses a method for preparation of mesylate trihydrate salt by addition of an aqueous solution of methanesulfonic acid to a slurry of ziprasidone free base in an organic solvent followed by formation of the mesylate salt under reflux. The presence of the mesylate salt in four distinct forms viz. trihydrate, dihydrate (lath), dihydrate (needle), and anhydrous form is indicated by x-ray diffraction powder spectrum.
The present invention relates to method for preparation of ziprasidone hydrochloride, which is substantially amorphous and of high purity and stability.
OBJECT OF THE INVENTION
The object of the present invention is to provide an efficient and economically advantageous process for preparation of ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.
SUMMARY OF THE INVENTION
An aspect of the invention relates to ziprasidone hydrochloride of formula (I), which is substantially amorphous and of high purity and stability.
Figure imgf000003_0001
Another aspect of the invention relates to providing a process for preparation of substantially amorphous ziprasidone hydrochloride of formula (I), by different methods such as spray-drying, lyophilisation, freeze drying, solvent precipitation, jet-milling etc.
In a preferred embodiment, amorphous ziprasidone hydrochloride is be prepared by spray drying a solution of of ziprasidone hydrochloride in a mixture of alcoholic solvent such as methanol, ethanol, isoproanol, or tert-butyl alcohol with acetonitrile.
In a particularly preferred embodiment, the solution of ziprasidone hydrochloride is prepared in a mixture of methanol and acetonitrile. The amount of methanol is used in an amount of 3-5 times the volume of acetonitrile, preferably, 4 times the volume of acetonitrile.
The solution of ziprasidone hydrochloride is spray dried maintaining the inlet temperature between 70 to 90 °C and outlet temperature between 50 to 75 °C.
BRIEF DESCRIPTION OF ACCOMPANYING DRAWING Figure 1: X ray diffraction pattern of the amorphous form of compound of formulal obtained by spray drying of present invention.
DETAILED DESCRIPTION OF ACCOMPANYING DRAWING
The X-ray powder diffraction pattern of the product obtained by spray drying is as depicted in Fig.1. It is without any diffraction peaks. This demonstrates amorphous nature of the product formed by the process of present invention.
For example, a substantially amorphous form of ziprasidone hydrochloride of formula (I) having high purity and stability could be prepared by utilizing the method of spray-drying given below: Example-01
Ziprasidone hydrochloride (10gms) was dissolved in a mixture of acetonitrile (725ml) and methanol (2900ml). The resulting mixture was spray dried at a temperature between 65°C and 90°C. The product separating out was dried at ambient temperature to give substantially amorphous ziprasidone hydrochloride. Yield: 4.0gms.

Claims

1. A process for preparation of an amorphous form of Ziprasidone hydrochloride, said process comprising: a. providing a ziprasidone hydrochloride solution in a mixture of alcoholic solvent and acetonitrile b. spray drying the solution of ziprasidone hydrochloride.
2. The process according claim 1 , wherein said alcoholic solvent is selected from methanol, ethanol, isoprpanol and tert-butyl alcohol
3. The process according to claim 1 or 2, wherein the alcoholic solvent is methanol.
PCT/IN2005/000115 2004-04-15 2005-04-15 Amorphous ziprasidone hydrochloride WO2005100348A1 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN450MU2004 2004-04-15
IN450/MUM/2004 2004-04-15

Publications (1)

Publication Number Publication Date
WO2005100348A1 true WO2005100348A1 (en) 2005-10-27

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0586191A1 (en) * 1992-09-01 1994-03-09 Pfizer Inc. Monohydrate of 5-(2-(4-(1,2 Benzisothiazol-3-YL)-1-Piperazinyl)-Ethyl)-6-Chloro-1,3-Dihydro-2H-indol-2-one Hydrochloride
WO2000059489A2 (en) * 1999-04-06 2000-10-12 Sepracor Inc. Methods and compositions for the treatment of psychotic and related disorders using ziprasidone metabolites
WO2004050655A1 (en) * 2002-12-04 2004-06-17 Dr. Reddy's Laboratories Limited Polymorphic forms of ziprasidone and its hydrochloride
WO2004089948A1 (en) * 2003-04-11 2004-10-21 Hetero Drugs Limited Novel crystalline forms of ziprasidone hydrochloride
US20050043324A1 (en) * 2003-06-03 2005-02-24 Tamas Koltai Polymorphic forms of ziprasidone HCI and processes for their preparation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0586191A1 (en) * 1992-09-01 1994-03-09 Pfizer Inc. Monohydrate of 5-(2-(4-(1,2 Benzisothiazol-3-YL)-1-Piperazinyl)-Ethyl)-6-Chloro-1,3-Dihydro-2H-indol-2-one Hydrochloride
WO2000059489A2 (en) * 1999-04-06 2000-10-12 Sepracor Inc. Methods and compositions for the treatment of psychotic and related disorders using ziprasidone metabolites
WO2004050655A1 (en) * 2002-12-04 2004-06-17 Dr. Reddy's Laboratories Limited Polymorphic forms of ziprasidone and its hydrochloride
WO2004089948A1 (en) * 2003-04-11 2004-10-21 Hetero Drugs Limited Novel crystalline forms of ziprasidone hydrochloride
US20050043324A1 (en) * 2003-06-03 2005-02-24 Tamas Koltai Polymorphic forms of ziprasidone HCI and processes for their preparation

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
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, January 1997 (1997-01-01), pages 1 - 12, XP000929450, ISSN: 0022-3549 *

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