DESC:
FIELD OF THE APPLICATION
The present application relates to solid state forms of Cediranib Maleate and processes for preparation thereof.
The drug compound having the adopted name “Cediranib” and it has chemical name: 4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-6-methoxy-7-[3-(pyrrolidin-1-yl) propoxy]quinazoline; and a structure depicted by Formula I.

Formula I
International Patent Application Publication No. WO2000047212A1, which is incorporated herein in its entirety reported Cediranib and its related compounds as inhibitors of vascular endothelial growth factor (VEGF)-2 receptor tyrosine kinases. International Patent Application Publication Nos. WO2003064413A1 and WO2008053221A2 disclose processes for preparing Cediranib and its intermediates.
International Patent Application Publication No. WO2005061488A1 disclose crystalline forms of Cediranib maleate.
Isolating a pharmaceutical compound in crystalline form may provide advantages with desirable processing properties, such as ease of handling, ease of processing, storage stability and ease of purification. Such properties may significantly influence the processing, shelf life, and commercial acceptance of a product.
There remains a need to provide crystalline forms of Cediranib maleate and process for making the same.

SUMMARY OF THE APPLICATION
In the first embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM1.
In the second embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM2.
In the third embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM3.
In the fourth embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM4.
In the fifth embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM5.
In the sixth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM1, comprising the steps of:
a) providing a solution of Cediranib maleate in acetonitrile; and
b) isolating Cediranib maleate, designated as Form CM1.
In the seventh embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM2, comprising the steps of:
a) providing a solution of Cediranib maleate in acetic acid; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM2.
In the eighth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM3, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid;
b) adding anti-solvent, methyl acetate to the solution obtained in step a); and
c) isolating crystalline form of Cediranib maleate, designated as Form CM3, by drying in vacuum tray dryer (VTD).
In the eighth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM4, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid;
b) adding anti-solvent, methyl acetate to the solution obtained in step a); and
c) isolating crystalline form of Cediranib maleate, designated as Form CM4, by drying in air tray dryer (ATD).
In the tenth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM5, comprising the steps of:
a) providing a solution of Cediranib maleate in nitromethane; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM5.
In the eleventh embodiment, the present application provides a pharmaceutical composition comprising crystalline form of Cediranib maleate, designated as Form CM1, CM2, CM3, CM4 or CM5 or mixtures thereof and one or more pharmaceutically acceptable excipients.
BRIEF DESCRIPTION OF THE DRAWING
FIG. 1 is an illustration of powder X-ray diffraction (“PXRD”) pattern of crystalline form of Cediranib maleate, designated as Form CM1.
FIG. 2 is an illustration of powder X-ray diffraction (“PXRD”) pattern of crystalline form of Cediranib maleate, designated as Form CM2.
FIG. 3 is an illustration of powder X-ray diffraction (“PXRD”) pattern of crystalline form of Cediranib maleate, designated as Form CM3.
FIG. 4 is an illustration of powder X-ray diffraction (“PXRD”) pattern of crystalline form of Cediranib maleate, designated as Form CM4.
FIG. 5 is an illustration of powder X-ray diffraction (“PXRD”) pattern of crystalline form of Cediranib maleate, designated as Form CM5.

DESCRIPTION OF THE APPLICATION
In the first embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM1.
In an aspect, the present application provides a crystalline form of Cediranib maleate, designated as Form CM1 that can be characterized by its PXRD pattern as illustrated by Figure 1.
In an aspect, the present application provides crystalline Form CM1 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 20.25 and 26.11±0.2°.
In an aspect, the present application provides crystalline Form CM1 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 9.15, 10.05 and 10.74±0.2°.
In an aspect, the present application provides crystalline Form CM1 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 7.72, 8.14, 16.17 and 20.75±0.2°.
In the second embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM2.
In an aspect, the present application provides a crystalline form of Cediranib maleate, designated as Form CM2 that can be characterized by its PXRD pattern as illustrated by Figure 2.
In an aspect, the present application provides crystalline Form CM2 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 4.03, 7.98, 9.07 and 29.06±0.2°.
In an aspect, the present application provides crystalline Form CM2 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 13.66, 22.65 and 23.62±0.2°.
In an aspect, the present application provides crystalline Form CM2 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 7.52, 12.85, 16.18, 17.26, 20.22 and 27.50±0.2°.
In the third embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM3.
In an aspect, the present application provides a crystalline form of Cediranib maleate, designated as Form CM3 that can be characterized by its PXRD pattern as illustrated by Figure 3.
In an aspect, the present application provides crystalline Form CM3 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 4.27, 18.94 and 27.59±0.2°.
In an aspect, the present application provides crystalline Form CM3 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 8.39, 9.74, 19.35 and 25.95±0.2°.
In the fourth embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM4.
In an aspect, the present application provides a crystalline form of Cediranib maleate, designated as Form CM4 that can be characterized by its PXRD pattern as illustrated by Figure 4.
In an aspect, the present application provides crystalline Form CM4 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 8.44 and 18.31±0.2°.
In an aspect, the present application provides crystalline Form CM4 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 7.53, 12.17, 13.11, 16.69, 19.31, 21.69 and 29.89±0.2°.
In the fifth embodiment, the present application provides a crystalline form of Cediranib maleate, designated as Form CM5.
In an aspect, the present application provides a crystalline form of Cediranib maleate, designated as Form CM5 that can be characterized by its PXRD pattern as illustrated by Figure 5.
In an aspect, the present application provides crystalline Form CM5 characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 20.20 and 23.98±0.2°.
In an aspect, the present application provides crystalline Form CM5 further characterized by an X-ray powder diffraction pattern having peaks expressed in degrees 2? at about 9.89, 15.27, 16.13 and 23.20±0.2°.
In the sixth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM1, comprising the steps of:
a) providing a solution of Cediranib maleate in acetonitrile; and
b) isolating Cediranib maleate, designated as Form CM1.
Any physical form of Cediranib maleate may be utilized for providing the solution of Cediranib maleate in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of Cediranib maleate is obtained without affecting its quality.
The solution obtained in step a) may be optionally treated with carbon, flux-calcined diatomaceous earth (Hyflow) or any other suitable material to remove color, insoluble materials, improve clarity of the solution, and/or remove impurities adsorbable on such material. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step b) involves isolating the Cediranib maleate, designated as Form CM1. In one aspect present application involves isolation of Cediranib maleate by removing solvent from a solution obtained in step a).
The isolated solid may be optionally further dried to afford Form CM1. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The tray dryer may be air tray dryer or vacuum tray dryer. The drying can be carried out at temperatures of less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Cediranib maleate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In the seventh embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM2, comprising the steps of:
a) providing a solution of Cediranib maleate in acetic acid; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM2.
Any physical form of Cediranib maleate may be utilized for providing the solution of Cediranib maleate in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of Cediranib maleate is obtained without affecting its quality.
The solution obtained in step a) may be optionally treated with carbon, flux-calcined diatomaceous earth (Hyflow) or any other suitable material to remove color, insoluble materials, improve clarity of the solution, and/or remove impurities adsorbable on such material. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step b) involves isolating the Cediranib maleate, designated as Form CM2. In one aspect present application involves isolation of Cediranib maleate by removing solvent from a solution obtained in step a).
The isolated solid may be optionally further dried to afford Form CM2. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures of less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Cediranib maleate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In the eighth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM3, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid; and
b) adding anti-solvent, methyl acetate to the solution obtained in step a)
c) isolating crystalline form of Cediranib maleate, designated as Form CM3, by drying in vacuum tray dryer (VTD).
Any physical form of Cediranib maleate may be utilized for providing the solution of Cediranib maleate in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of Cediranib maleate is obtained without affecting its quality.
The solution obtained in step a) may be optionally treated with carbon, flux-calcined diatomaceous earth (Hyflow) or any other suitable material to remove color, insoluble materials, improve clarity of the solution, and/or remove impurities adsorbable on such material. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step b) involves addition of an anti-solvent, methyl acetate to the solution obtained in step a). In step c) the Form CM3 may be isolated by drying in vacuum tray dryer (VTD). The drying can be carried out at temperatures of less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Cediranib maleate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In the ninth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM4, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid;
b) adding anti-solvent, methyl acetate to the solution obtained in step a); and
c) isolating crystalline form of Cediranib maleate, designated as Form CM4, by drying in air tray dryer (ATD).
Any physical form of Cediranib maleate may be utilized for providing the solution of Cediranib maleate in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of Cediranib maleate is obtained without affecting its quality.
The solution obtained in step a) may be optionally treated with carbon, flux-calcined diatomaceous earth (Hyflow) or any other suitable material to remove color, insoluble materials, improve clarity of the solution, and/or remove impurities adsorbable on such material. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step b) involves addition of an anti-solvent, methyl acetate to the solution obtained in step a). In step c) the Form CM4 may be isolated by drying in air tray dryer (ATD). The drying can be carried out at temperatures of less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Cediranib maleate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In the tenth embodiment, the present application provides a process for preparing crystalline form of Cediranib maleate, designated as Form CM5, comprising the steps of:
a) providing a solution of Cediranib maleate in nitromethane; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM5.
Any physical form of Cediranib maleate may be utilized for providing the solution of Cediranib maleate in step a).
The dissolution temperatures may range from about 0°C to about the reflux temperature of the solvent, or less than about 150°C, less than about 130°C, less than about 100°C, less than about 70°C, less than about 40°C, less than about 20°C, less than about 0°C, or any other suitable temperatures, as long as a clear solution of Cediranib maleate is obtained without affecting its quality.
The solution obtained in step a) may be optionally treated with carbon, flux-calcined diatomaceous earth (Hyflow) or any other suitable material to remove color, insoluble materials, improve clarity of the solution, and/or remove impurities adsorbable on such material. Optionally, the solution obtained above may be filtered to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflow. Depending upon the equipment used and the concentration and temperature of the solution, the filtration apparatus may need to be preheated to avoid premature precipitation of solid.
Step b) involves isolating the Cediranib maleate, designated as Form CM5. In one aspect present application involves isolation of Cediranib maleate by removing solvent from a solution obtained in step a).
The isolated solid may be optionally further dried to afford Form CM5. Drying can be carried out in a tray dryer, vacuum oven, air oven, cone vacuum dryer, rotary vacuum dryer, fluidized bed dryer, spin flash dryer, flash dryer, or the like. The drying can be carried out at temperatures of less than about 100°C, less than about 70°C, less than about 40°C, less than about 30°C, less than about 20°C, or any other suitable temperatures; at atmospheric pressure or under a reduced pressure; as long as the Cediranib maleate is not degraded in its quality. The drying can be carried out for any desired times until the required product quality is achieved. Suitable time for drying can vary from few minutes to several hours for example from about 30 minutes to about 24 or more hours.
In an aspect, the present application provides pharmaceutical formulations comprising crystalline forms of Cediranib maleate designated as CM1, CM2, CM3, CM4 and/or CM5. Cediranib maleate together with one or more pharmaceutically acceptable excipients of the present application may be formulated as: solid oral dosage forms such as, but not limited to, powders, granules, pellets, tablets, and capsules; liquid
oral dosage forms such as, but not limited to, syrups, suspensions, dispersions, and emulsions; and injectable preparations such as, but not limited to, solutions, dispersions, and freeze dried compositions. Formulations may be in the forms of immediate release, delayed release, or modified release. Further, immediate release compositions may be conventional, dispersible, chewable, mouth dissolving, or flash melt preparations, and modified release compositions that may comprise hydrophilic or hydrophobic, or combinations of hydrophilic and hydrophobic, release rate controlling substances to form matrix or reservoir or combination of matrix and reservoir systems. The compositions may be prepared using any one or more of techniques such as direct blending, dry granulation, wet granulation, and extrusion and spheronization.
Compositions may be presented as uncoated, film coated, sugar coated, powder coated, enteric coated, and modified release coated. Pharmaceutically acceptable excipients that are useful in the present application include, but are not limited to: diluents such as starches, pregelatinized starches, lactose, powdered celluloses, microcrystalline celluloses, dicalcium phosphate, tricalcium phosphate, mannitol, sorbitol, sugar, and the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methyl celluloses, pregelatinized starches, and the like; disintegrants such as starches, sodium starch glycolate, pregelatinized starches, crospovidones, croscarmellose sodium, colloidal silicon dioxide, and the like; lubricants such as stearic acid, magnesium stearate, zinc stearate, and the like; glidants such as colloidal silicon dioxide and the like; solubility or wetting enhancers such as anionic, cationic, or neutral surfactants; complex forming agents such as various grades of cyclodextrins and resins; and release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes, and the like. Other pharmaceutically acceptable excipients that are useful include, but are not limited to, film formers, plasticizers, colorants, flavoring agents, sweeteners, viscosity enhancers, preservatives, antioxidants, and the like.
The pharmaceutical dosage form according to the present invention may be coated with one or more coating materials or uncoated. The coating materials are not particularly limited and are known to the person skilled in the art.
The pharmaceutical dosage form according to the present invention can further comprise additional excipients and adjuvants, which are pharmaceutically acceptable and general coating materials, which are preferably applied as a coating to the pharmaceutical dosage form of the present invention. Such further excipients and adjuvants are known to the person skilled in the art.
The pharmaceutical compositions of the present invention are generally administered orally to patients, which include, but are not limited to, mammals, for example, humans, in the form of, for example, a hard or soft gelatin capsule, a tablet, a caplet, pills, granules or a suspension. The pharmaceutical dosage form can be prepared by methods known in the art.
The solid form of Cediranib maleate of the present application may be characterized by means of Powder X-ray Diffraction Pattern (PXRD). Other techniques, such as solid state NMR, Fourier Transform Infrared (FTIR), differential scanning calorimetry (DSC) may also be used.
The polymorphs of this application are best characterized by the X-ray powder diffraction pattern determined in accordance with procedures that are known in the art.
PXRD data reported herein was obtained using CuKa radiation, having the wavelength 1.5406 Å and were obtained using a PANalytical X’Pert PRO instrument.
DEFINITIONS
The following definitions are used in connection with the present application unless the context indicates otherwise. Polymorphs are drug substances that exist in different crystalline forms and differ in their physical properties. Polymorphs may also include solvation or hydration products (also known as pseudopolymorphs) and amorphous forms.
All percentages and ratios used herein are by weight of the total composition, unless the context indicates otherwise. All temperatures are in degrees Celsius unless specified otherwise and all measurements are made at 25oC and normal pressure unless otherwise designated. The present disclosure can comprise the components discussed in the present disclosure as well as other ingredients or elements described herein.
As used herein, "comprising" means the elements recited, or their equivalents in structure or function, plus any other element or elements which are not recited. The terms "having" and "including" are also to be construed as open ended unless the context suggests otherwise.
All ranges recited herein include the endpoints, including those that recite a range "between" two values.
Terms such as "about," "generally," "substantially," or the like are to be construed as modifying a term or value such that it is not an absolute. Such terms will be defined by the circumstances and the terms that they modify, as those terms are understood by those of skill in the art. This includes, at very least, the degree of expected experimental error, technique error and instrument error for a given technique used to measure a value.
Where this document refers to a material, such as in this instance, Cediranib maleate and its solid state forms thereof by reference to patterns, spectra or other graphical data, it may do so by qualifying that they are "substantially" shown or as depicted in a Figure, or by one or more data points. By "substantially" used in such a context, it will be appreciated that patterns, spectra and other graphical data can be shifted in their positions, relative intensities and/or values due to a number of factors known to those of skill in the art.
In addition, where a reference is made to a figure, it is permissible to, and this document includes and contemplates, the selection of any number of data points illustrated in the figure which uniquely define that solid state form, within any associated and recited margin of error, for purposes of identification.
As used herein, the term "room temperature" refers to a temperature of from about 20oC to about 35oC, from about 25oC to about 35oC, from about 25oC to about 30oC, or for example, about 25oC.
As used herein, the term "overnight" refers to a time interval from about 14 hours to about 24 hours, or about 14 hours to about 20 hours, for example, about 16 hours.
The "polymer" or “carrier” or “excipient” as used herein interchangeably refers to any substance or mixture of substances which are pharmaceutically acceptable inactive ingredients.
Certain specific aspects and embodiments of the present application will be explained in greater detail with reference to the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner. Reasonable variations of the described procedures are intended to be within the scope of the present application. While particular aspects of the present application have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the application. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this application.
EXAMPLES
EXAMPLE 1: PREPARATION OF CEDIRANIB MALEATE FORM-CM1
Cediranib maleate (2 gm) was added to hot acetonitrile (100 ml) at 85°C under stirring in an easymax reactor. After significant dissolution, the solution was filtered hot under vacuum. This filtrate was added to a fresh reaction vessel and continued stirring at 85°C and 650 RPM. After 10 minutes the temperature was cooled down to –5°C, over a period of 15 minutes. After 4 hours the suspension was filtered under vacuum for 10 minutes. Kept for drying in ATD at 45°C for 24 hours to give titled compound.
The Powder X-ray diffraction (PXRD) pattern of Cediranib maleate obtained herein is in accordance with Figure 1.
EXAMPLE 2: PREPARATION OF CEDIRANIB MALEATE FORM-CM2
Cediranib maleate (2 gm) was added to hot acetic acid (1.5 ml) at 90°C under stirring in glass vial on magnetic stirrer. The stirring was maintained for 15 hours. After 15 hours the wet mass was isolated, kept for drying in VTD at 30°C for 3 hours to give titled compound.
The Powder X-ray diffraction (PXRD) pattern of Cediranib maleate obtained herein is in accordance with Figure 2.
EXAMPLE 3: PREPARATION OF CEDIRANIB MALEATE FORM-CM3
Cediranib maleate (5 gm) was added to hot propionic acid (10 ml) at 85°C under stirring in an easymax reactor. After complete dissolution, methyl acetate (50 ml) was added to propionic acid solution. After 2 hours the suspension obtained was filtered under vacuum for 15 minutes. Kept for drying in VTD at 45°C for 16 hours to give titled compound.
The Powder X-ray diffraction (PXRD) pattern of Cediranib maleate obtained herein is in accordance with Figure 3.
EXAMPLE 4: PREPARATION OF CEDIRANIB MALEATE FORM-CM4
Cediranib maleate (5 gm) was added to hot propionic acid (10 ml) at 85°C under stirring in an easymax reactor. After complete dissolution, methyl acetate (50 ml) was added to propionic acid solution. After 2 hours the suspension obtained was filtered under vacuum for 15 minutes. Kept for drying in ATD at 45°C for 16 hours to give titled compound.
The Powder X-ray diffraction (PXRD) pattern of Cediranib maleate obtained herein is in accordance with Figure 4.
EXAMPLE 5: PREPARATION OF CEDIRANIB MALEATE FORM-CM5
Cediranib maleate (2.5 gm) was added to hot nitromethane (30 ml) at 90°C under stirring in an easymax reactor. After significant dissolution the solution was filtered hot under vacuum. This filtrate was added to a fresh reaction vessel and continued stirring at 90°C and 500 RPM for 5 minutes. After 5 minutes the temperature was cooled down to 0°C over a period of 3 hours. After 3 hours the suspension was filtered under vacuum for 40 minutes. Kept for drying in ATD at 45°C for 26 hours to give titled compound.
The Powder X-ray diffraction (PXRD) pattern of Cediranib maleate obtained herein is in accordance with Figure 5.
,CLAIMS:Claims

Claim 1: A process for preparing crystalline Form CM1 of Cediranib Maleate, comprising the steps of:
a) providing a solution of Cediranib maleate in acetonitrile; and
b) isolating Cediranib maleate, designated as Form CM1.

Claim 2: A pharmaceutical composition comprising the crystalline Form CM1 of Cediranib maleate and pharmaceutically acceptable excipient.

Claim 3: A process for preparing crystalline Form CM2 of Cediranib Maleate, comprising the steps of:
a) providing a solution of Cediranib maleate in acetic acid; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM2.

Claim 4: A pharmaceutical composition comprising the crystalline Form CM2 of Cediranib maleate and pharmaceutically acceptable excipient.

Claim 5: A process for preparing crystalline Form CM3 of Cediranib Maleate, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid; and
b) adding anti-solvent, methylacetate to the solution obtained in step a)
c) isolating and drying in vacuum tray dryer (VTD).

Claim 6: A pharmaceutical composition comprising the crystalline Form CM3 of Cediranib maleate and pharmaceutically acceptable excipient.

Claim 7: A process for preparing crystalline Form CM4 of Cediranib Maleate, comprising the steps of:
a) providing a solution of Cediranib maleate in propionic acid;
b) adding anti-solvent, methylacetate to the solution obtained in step a); and
c) isolating and drying in air tray dryer (ATD).

Claim 8: A pharmaceutical composition comprising the crystalline Form CM4 of Cediranib maleate and pharmaceutically acceptable excipient.

Claim 9: A process for preparing crystalline Form CM5 of Cediranib Maleate, comprising the steps of:
a) providing a solution of Cediranib maleate in nitromethane; and
b) isolating crystalline form of Cediranib maleate, designated as Form CM5.

Claim 10: A pharmaceutical composition comprising the crystalline Form CM5 of Cediranib maleate and pharmaceutically acceptable excipient.