WO2014195977A2 - Nouveaux polymorphes de vismodegib - Google Patents

Nouveaux polymorphes de vismodegib Download PDF

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Publication number
WO2014195977A2
WO2014195977A2 PCT/IN2014/000381 IN2014000381W WO2014195977A2 WO 2014195977 A2 WO2014195977 A2 WO 2014195977A2 IN 2014000381 W IN2014000381 W IN 2014000381W WO 2014195977 A2 WO2014195977 A2 WO 2014195977A2
Authority
WO
WIPO (PCT)
Prior art keywords
vismodegib
solvent
crystalline form
amorphous form
preparation
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.)
Ceased
Application number
PCT/IN2014/000381
Other languages
English (en)
Other versions
WO2014195977A3 (fr
Inventor
Bandi Parthasaradhi Reddy
Kura Rathnakar Reddy
Dasari Muralidhara Reddy
Itiyala Srinivas Reddy
Bandi Vamsi Krishna
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.)
Hetero Research Foundation
Original Assignee
Hetero Research Foundation
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 Hetero Research Foundation filed Critical Hetero Research Foundation
Publication of WO2014195977A2 publication Critical patent/WO2014195977A2/fr
Publication of WO2014195977A3 publication Critical patent/WO2014195977A3/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/36—Radicals substituted by singly-bound nitrogen atoms
    • C07D213/40—Acylated substituent nitrogen atom

Definitions

  • the present invention provides a novel crystalline Form of vismodegib, process for its preparation and pharmaceutical compositions comprising it.
  • the present invention also provides a novel amorphous Form of vismodegib, process for its preparation and pharmaceutical compositions comprising it.
  • Vismodegib is a drug for the treatment of basal-cell carcinoma (BCC). It is marketed by Genentech under the brand name ERIVEDGE ® .
  • Polymorphism is defined as "the ability of a substance to exist as two or more crystalline phases that have different arrangement and/or conformations of the molecules in the crystal Lattice.
  • polymorphs are different crystalline structures of the same pure substance in which the molecules have different arrangements and/or different configurations of the molecules.
  • Different polymorphs may differ in their physical properties such as melting point, solubility, X-ray diffraction patterns, etc. Although those differences disappear once the compound is dissolved, they can appreciably influence pharmaceutically relevant properties of the solid form, such as handling properties, dissolution rate and stability. Such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorph.
  • Polymorphic forms of a compound can be distinguished in the laboratory by analytical methods such as X-ray diffraction (XRD), Differential Scanning Calorimetry (DSC) and Infrared spectrometry (IR).
  • XRD X-ray diffraction
  • DSC Differential Scanning Calorimetry
  • IR Infrared spectrometry
  • Solvent medium and mode of crystallization play very important role in obtaining one polymorphic Form over the other.
  • Vismodegib can exist in different polymorphic Forms, which may differ from each other in terms of stability, physical properties, spectral data and methods of preparation.
  • crystalline solid of vismodegib was obtained by crystallizing vismodegib with acetone and ethyl acetate and recrystallized from hot slurry of isopropyl acetate.
  • the crystalline vismodegib obtained by the process of the prior art is herein after designated as vismodegib crystalline Form I.
  • Crystalline Form I is characterized by peaks in the powder x-ray diffraction spectrum having 2 ⁇ angle positions at about 10.3, 14.0, 18.1, 19.9, 20.6 and 23.3 ⁇ 0.2 degrees.
  • one object of the present invention is to provide a novel crystalline Form of vismodegib, process for its preparation and pharmaceutical compositions comprising it.
  • Another object of the present invention is to provide a novel amorphous Form of
  • the present invention provides a crystalline Form of vismodegib designated as Form II characterized by peaks in the powder x-ray diffraction spectrum having 2 ⁇ angle positions at about 6.5, 1 1.5, 15.5, 18.9, 19.6, 20.2, 21.2 and 22.7 ⁇ 0.2 degrees.
  • the present invention provides a process for the preparation of vismodegib crystalline Form II, which comprises: .
  • the present invention provides a pharmaceutical composition comprising crystalline Form II of vismodegib and pharmaceutically acceptable excipients.
  • the present invention provides an amorphous Form of vismodegib.
  • the present invention provides a process for the preparation of vismodegib amorphous Form, which comprises:
  • step (b) removing the solvent from the solution obtained in step (a) to obtain vismodegib amorphous Form.
  • the present invention provides a pharmaceutical composition comprising amorphous Form of vismodegib and pharmaceutically acceptable excipients.
  • Figure 1 is an X-ray powder diffraction spectrum of vismodegib crystalline Form
  • Figure 2 is an X-ray powder diffraction spectrum of vismodegib crystalline Form
  • Figure 3 is an X-ray powder diffraction spectrum of vismodegib amorphous
  • X-ray powder diffraction spectrum was measured on a bruker axs D8 advance X- ray powder diffractometer having a copper- ⁇ radiation. Approximately 500 gm of sample was gently flattered on a sample holder and scanned from 2 to 50 degrees two- theta, at 0.020 degrees two theta per step and a step time of 1 second. The sample was simply placed on the sample holder. The sample was rotated at 30 rpm at a voltage 40 KV and current 35 mA.
  • room temperature refers to temperature at about 25 to 35°C.
  • Form II Form of vismodegib designated as Form II characterized by peaks in the powder x-ray diffraction spectrum having 20 angle positions at about 6.5, 1 1.5, 15.5, 18.9, 19.6, 20.2, 21.2 and 22.7 ⁇ 0,2 degrees.
  • the powdered x-ray diffractogram (PXRD) of vismodegib crystalline Form II is shown in figure 2.
  • Vismodegib used in step (a) may preferably be vismodegib obtained by the known process.
  • the ester solvent used in step (a) may preferably be a solvent or a mixture of solvents selected from ethyl acetate, methyl acetate, isopropyl acetate, tert-butyl methyl acetate and ethyl ( formate, and more preferably the ester solvent is ethyl acetate.
  • Isolation of vismodegib crystalline Form II in step (b) can be performed by conventional methods such as removal of solvents, concentrating the reaction mass, filtration, centrifugation or extraction with a solvent.
  • a pharmaceutical composition comprising crystalline Form II of vismodegib and pharmaceutically acceptable excipients, and optionally other therapeutic ingredients.
  • the crystalline Form II may preferably be formulated into tablets, capsules, suspensions, dispersions, injectables or other pharmaceutical forms.
  • an amorphous Form of vismodegib there is provided an amorphous Form of vismodegib.
  • the powdered x-ray diffractogram (PXRD) of vismodegib amorphous Form is shown in figure 3.
  • a process for the preparation of vismodegib amorphous Form which comprises:
  • step (b) removing the solvent from the solution obtained in step (a) to obtain vismodegib amorphous Form.
  • Vismodegib used in step (a) may preferably be vismodegib obtained by the known process.
  • the ketonic solvent used in step (a) may preferably be a solvent or a mixture of solvents selected from acetone, methyl ethyl ketone, diethyl ketone and methyl isobutyl ketone. More preferably the ketonic solvent is methyl ethyl ketone.
  • the alcoholic solvent used in step (a) may be a solvent or a mixture of solvents selected from methanol, ethanol, isopropyl alcohol and n-butanol, and more preferably the alcoholic solvent is ethanol.
  • the solvent may be removed from the solution in step (b) by known methods, for example, distillation.
  • the distillation of the solvent may be carried out at atmospheric pressure or at reduced pressure.
  • the distillation may preferably be carried out until the solvent is almost completely distilled off.
  • a pharmaceutical composition comprising amorphous Form of vismodegib and pharmaceutically acceptable excipients, and optionally other therapeutic ingredients.
  • the amorphous Form may preferably be formulated into tablets, capsules, suspensions, dispersions, injectables or other pharmaceutical forms.
  • Vismodegib (5 gm) was dissolved in ethyl acetate (500 ml) at room temperature and filtered through hi-flow bed. The resulting filtrate was subjected to spray drying to obtain 2 gm of vismodegib crystalline Form II.
  • Example 1 was repeated using isopropyl acetate solvent instead of ethyl acetate solvent to obtain vismodegib crystalline Form II.
  • Vismodegib (5 gm) was dissolved in methyl ethyl ketone (200 ml) and filtered through hi-flow bed. The solvent was distilled off from the filtrate thus obtained under high vacuum at 45 to 50 C and maintained for 3 hours at 45 to 50 C to obtain 4.5 gm of vismodegib amorphous Form.
  • Example 3 was repeated using acetone solvent instead of methyl ethyl ketone solvent to obtain vismodegib amorphous Form.
  • Vismodegib (5 gm) was dissolved in ethanol (500 ml) and filtered through hi-flow bed. The solvent was distilled off from the filtrate thus obtained under high vacuum at 45 to 50°C and maintained for 3 hours at 45 to 50°C to obtain 4.6 gm of vismodegib amorphous Form.
  • Example 5 was repeated using methanol solvent instead of ethanol solvent to obtain vismodegib amorphous Form.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne une nouvelle forme cristalline de vismodegib, un procédé de préparation correspondant et des compositions pharmaceutiques contenant du vismodegib. La présente invention concerne une nouvelle forme amorphe de vismodegib, son procédé de préparation et des compositions pharmaceutiques contenant du vismodegib.
PCT/IN2014/000381 2013-06-05 2014-06-04 Nouveaux polymorphes de vismodegib Ceased WO2014195977A2 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN2449/CHE/2013 2013-06-05
IN2449CH2013 2013-06-05

Publications (2)

Publication Number Publication Date
WO2014195977A2 true WO2014195977A2 (fr) 2014-12-11
WO2014195977A3 WO2014195977A3 (fr) 2015-11-12

Family

ID=52008674

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2014/000381 Ceased WO2014195977A2 (fr) 2013-06-05 2014-06-04 Nouveaux polymorphes de vismodegib

Country Status (1)

Country Link
WO (1) WO2014195977A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022271109A1 (fr) * 2021-06-23 2022-12-29 Deva Holding Nouveau polymorphe de vismodégib et son procédé de préparation
WO2023140809A1 (fr) * 2022-01-20 2023-07-27 Deva Holding Nouveau polymorphe de vismodégib et procédé de préparation
WO2023194300A1 (fr) 2022-04-05 2023-10-12 Synthon B.V. Formes solides de vismodégib

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20200019263A (ko) * 2004-09-02 2020-02-21 제넨테크, 인크. 헤지호그 신호전달에 대한 피리딜 억제제
FR2948367A1 (fr) * 2009-07-24 2011-01-28 Centre Nat Rech Scient Derives d'acyl-guanidines modulateurs de la voie de signalisation des proteines hedgehog
US20120184529A1 (en) * 2011-01-14 2012-07-19 Demario Mark D Combination therapy

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2022271109A1 (fr) * 2021-06-23 2022-12-29 Deva Holding Nouveau polymorphe de vismodégib et son procédé de préparation
WO2023140809A1 (fr) * 2022-01-20 2023-07-27 Deva Holding Nouveau polymorphe de vismodégib et procédé de préparation
WO2023194300A1 (fr) 2022-04-05 2023-10-12 Synthon B.V. Formes solides de vismodégib

Also Published As

Publication number Publication date
WO2014195977A3 (fr) 2015-11-12

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