EP1440074A1 - Olanzapin dihydrat-ii, verfahren zu ihrer herstellung und ihre anwendung - Google Patents

Olanzapin dihydrat-ii, verfahren zu ihrer herstellung und ihre anwendung

Info

Publication number
EP1440074A1
EP1440074A1 EP02778677A EP02778677A EP1440074A1 EP 1440074 A1 EP1440074 A1 EP 1440074A1 EP 02778677 A EP02778677 A EP 02778677A EP 02778677 A EP02778677 A EP 02778677A EP 1440074 A1 EP1440074 A1 EP 1440074A1
Authority
EP
European Patent Office
Prior art keywords
olanzapine
dihydrate
olanzapine dihydrate
product
methyl
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Withdrawn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
EP02778677A
Other languages
English (en)
French (fr)
Inventor
Janet I. Cord
Reguri Buchi Reddy
Chakka Ramesh
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.)
Dr Reddys Laboratories Ltd
Original Assignee
Dr Reddys 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 Dr Reddys Laboratories Ltd filed Critical Dr Reddys Laboratories Ltd
Publication of EP1440074A1 publication Critical patent/EP1440074A1/de
Withdrawn legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
    • C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D495/04—Ortho-condensed systems

Definitions

  • the present invention relates to novel dihydrate form of 2-methyl-4-(4- metl ⁇ yl-l-piperazinyl)-10H-thieno[2,3-b][l,5]benzodiazepine (hereinafter referred to as Olanzapine dihydrate-II), a process for its preparation and its conversion to Olanzapine Form-II.
  • the present invention also relates to compositions containing Olanzapine dihydrate II and the use of Olanzapine dihydrate II and compositions containing Olanzapine dihydrate II for treating disorders of the central nervous system.
  • Olanzapine is represented by the following structure:
  • Olanzapine is useful for treating psychotic patients and patients with mild-anxiety states.
  • Preparation of Olanzapine and its acid addition salts, having pharmaceutical properties, particularly in the treatment of disorders of the central nervous system is disclosed in U.S. 5,229,382.
  • EP 733635B1 discloses Olanzapine Form-II and designates the product obtained according to the process described in U.S. 5,229,382 as Olanzapine Form-I characterizing both Form-I and Form-II with their XRD patterns.
  • EP 831098B1 discloses Olanzapine Form-II as the most stable anhydrous form of Olanzapine, providing a stable anhydrous formulation with pharmaceutically desired characteristics. The patent further discloses that substantially pure Olanzapine Form-II, which can be prepared using an Olanzapine dihydrate.
  • the patent discloses the preparation of a series of dihydrates of Olanzapine namely Dihydrate B, Dihydrate D and Dihydrate E characterized by their XRD pattern which serve as intermediates for the preparation of Olanzapine Form-II.
  • the present invention hence provides a novel Olanzapine dihydrate-II, which is useful in the preparation of Olanzapine Form-II.
  • the Olanzapine dihydrate-II is prepared using an eco-friendly process. Conversion of Olanzapine dihydrate-II to Olanzapine Form-II, is specially advantageous since the novel Olanzapine dihydrate-II is prepared in water and subsequently dried to provide Olanzapine Form-II, thus providing assurance that the Form-II material is substantially free from all organic solvent residues.
  • the present invention is directed to novel Olanzapine dihydrate-II.
  • the present invention further provides an eco-friendly and a commercially viable process for the preparation of novel Olanzapine dihydrate-II, comprising stirring Olanzapine form-I with water, followed by filtration and drying to afford the novel Olanzapine dihydrate -II.
  • the present invention also provides a process for the conversion of novel Olanzapine dihydrate-II to Olanzapine Form-II comprising further drying of Olanzapine dihydrate-II to constant weight, thereby yielding Olanzapine Form-II.
  • the present invention also provides for the use of Olanzapine dihydrate- II for treating disorders of the central nervous system and for the use of Olanzapine dihydrate-II in compositions.
  • Fig 1 is an X Ray Powder Diffractogram of novel Olanzapine dihydrate- II.
  • Fig 2 is an Infrared Absorption Spectrum of Olanzapine dihydrate-II.
  • Fig 3 is a Differential Scanning Calorimetry Thermogram of Olanzapine dihydrate-II.
  • Fig 4 is an X Ray Powder Diffractogram of Olanzapine Form-II obtained from novel Olanzapine dihydrate —II. Detailed Description Of The Invention
  • the Olanzapine dihydrate-II of the present invention can be prepared by the treatment of Form I of 2-methyl-4-(4-methyl-l- ⁇ iperazinyl)-10H-thieno[2,3- b][l,5]benzodiazepine i.e. Olanzapine Form-I with water by stirring at 25 - 35°C for 72 to 120 hours. Subsequent filtration and drying the product renders the desired Olanzapine dihydrate-II. The drying can be achieved under vacuum at 25-50°C for 1 - 2 hours, in an oven at 60-70°C for 1-2 hours, or air-drying at ambient temperature for 5- 24 hours.
  • This isolated Olanzapine dihydrate-II on further drying in oven at 60-70°C, to constant weight, renders Olanzapine Form-II.
  • the novel Olanzapine dihydrate-II of the present invention is well distinguished from the crystal modifications reported in the prior art.
  • Form-I used in the preparation of Olanzapine dihydrate-II can be prepared as per the process disclosed in U.S. 5,229,382, Indian Patent Application No. 709/MAS/2000 or PCT Application No. WO 02/18390A1, the subject matter of which is incorporated herein by reference.
  • Olanzapine dihydrate II can be used as a drug and in compositions, including compositions that can be administered to mammals including humans.
  • Pharmaceutical compositions of this invention can contain and/or comprise a therapeutically effective amount of the active ingredient, together with inorganic or organic, solid or liquid, pharmaceutically acceptable carriers or excipients, which are suitable for enteral, for example oral, parenteral or topical administration.
  • the pharmaceutical compositions may be sterilized and/or may comprise of one or more excipients, for example preservatives, stabilizers, wetting agents and/or emulsifiers, solubilizers, salts for regulating the osmotic pressure and/or buffers.
  • compositions are formulated in unit dosage form, each dosage containing from 0.1 mg to 20 mg or 0.5 to 10 mg of active ingredient.
  • the dosage of Olanzapine dihydrate II depends on various factors, such as method of administration, species, age and/or individual condition.
  • the doses to be administered daily are between 0.5 mg and about 100 mg, preferably between 1 mg to
  • compositions of this invention can be used to treat disorders of the central nervous system including schizophrenia and psychosis.
  • Olanzapine Form-I (25.0 g) and water (125 ml) were stirred at 25 - 30°C for 120 hours. It was then filtered and dried under vacuum at 32 - 44°C for about 1-2 hours to render the desired Olanzapine dihydrate - II.
  • the Olanzapine dihydrate-II (5.0g) obtained as per Example 1 is dried in oven at 60-70°C to constant weight rendering Form II of Olanzapine.
  • TGA 0.310%.
  • Olanzapine Form-I (25.0 g) and water (125 ml) were stirred at 25 - 30°C for 120 hours.
  • the remaining part was air dried for about 6-7 hours at ambient temperature, to render the desired Olanzapine dihydrate - H.
  • Fig. 1 is a characteristic X-Ray powder diffraction pattern of Olanzapine dihydrate-II (Vertical axis: Intensity (CPS); Horizontal axis: Two Theta (degrees). The significant d values obtained are 9.9949, 9.5838, 9.4007, 7.6884, 7.4184, 5.2052, 4.9678, 4.8756, 4.7767, 4.4271, 4.3881, 4.3414, 4.2752, 4.1145, 3.7762 and 3.3682.
  • Fig. 2 is a characteristic infrared absorption spectrum in potassium bromide of Olanzapine dihydrate-II [Vertical axis, Transmission (%); Horizontal axis:
  • Fig. 3 is a characteristic of differential scanning calorimetry thermogram of Olanzapine dihydrate-II. Vertical axis ' : mW; Horizontal axis: Temperature (°C). The
  • DSC thermogram exhibits a significant endo - endo pattern at 69.50-195.38°C, which is characteristic of Olanzapine dihydrate-II.
  • the heating rate is 5°C/minute.
  • Fig 4 is an X ray powder diffractogram of Olanzapine Form-II obtained from novel Olanzapine dihydrate - II.
  • Vertical axis Intensity (CPS); Horizontal axis: Two Theta (degrees).
  • the significant d values obtained are 10.3696, 8.6314, 7.1668, 5.2296, 4.7869, 4.4937, 4.2468, 4.1526, 4.0046, 3.7324 and 3.5449.
  • the present invention therefore provides novel Olanzapine dihydrate-II and a process for the preparation thereof.
  • the novel Olanzapine dihydrate-II of the present invention is an important intermediate for the preparation of Olanzapine Form- II, which is disclosed as the most stable anhydrous form of Olanzapine, providing a stable anhydrous formulation with pharmaceutically desired characteristics.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
EP02778677A 2001-10-29 2002-10-29 Olanzapin dihydrat-ii, verfahren zu ihrer herstellung und ihre anwendung Withdrawn EP1440074A1 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
IN877CH2001 2001-10-29
INCH08772001 2001-10-29
PCT/US2002/034701 WO2003037903A1 (en) 2001-10-29 2002-10-29 Olanzapine dihydrate-ii a process for its preparation and use thereof

Publications (1)

Publication Number Publication Date
EP1440074A1 true EP1440074A1 (de) 2004-07-28

Family

ID=11097012

Family Applications (1)

Application Number Title Priority Date Filing Date
EP02778677A Withdrawn EP1440074A1 (de) 2001-10-29 2002-10-29 Olanzapin dihydrat-ii, verfahren zu ihrer herstellung und ihre anwendung

Country Status (4)

Country Link
EP (1) EP1440074A1 (de)
AU (1) AU2002340328A1 (de)
CA (1) CA2464306A1 (de)
WO (1) WO2003037903A1 (de)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SI1513846T1 (sl) 2002-05-31 2011-11-30 Sandoz Ag Postopek za pripravo olanzapina form I
EP1575962A1 (de) * 2002-12-24 2005-09-21 Teva Pharmaceutical Industries Limited Neue kristallformen von olanzapin, verfahren zu deren herstellung und verfahren zur herstellung bekannter kristallformen von olanzapin
DE05783995T1 (de) * 2004-07-14 2007-10-11 Shasun Chemicals and Drugs Ltd., Chennai Verbessertes verfahren zur herstellung von form i aus olanzapin
SI1838716T1 (sl) 2005-01-05 2011-10-28 Lilly Co Eli Olanzapin pamoat dihidrat
CN103185759A (zh) * 2011-12-27 2013-07-03 天津药物研究院 奥氮平中溶剂残留的检测方法及其应用
CN103848847B (zh) * 2012-12-04 2018-02-06 广东东阳光药业有限公司 一种改进制备奥氮平及其晶型ii的方法
JP6008734B2 (ja) * 2012-12-20 2016-10-19 株式会社トクヤマ オランザピンｉｉ型結晶の製造方法

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5229382A (en) * 1990-04-25 1993-07-20 Lilly Industries Limited 2-methyl-thieno-benzodiazepine
EG23659A (en) * 1995-03-24 2007-03-26 Lilly Co Eli Process and crystal forms of methyl-thieno-benzodiazepine
ZA978515B (en) * 1996-09-23 1999-03-23 Lilly Co Eli Intermediates and process for preparing olanzapine
AU720366B2 (en) * 1996-09-23 2000-06-01 Eli Lilly And Company Olanzapine dihydrate D
WO2002018390A1 (en) * 2000-08-31 2002-03-07 Dr. Reddy's Laboratories Ltd. Process for preparation of hydrates of olanzapine and their conversion into crystalline forms of olanzapine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO03037903A1 *

Also Published As

Publication number Publication date
AU2002340328A1 (en) 2003-05-12
CA2464306A1 (en) 2003-05-08
WO2003037903A8 (en) 2004-02-12
WO2003037903A1 (en) 2003-05-08

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