DESC:The following specification particularly describes the invention and the manner in which it is to be performed:

SOLID FORMS OF ROXADUSTAT AND ITS PROCESS

INTRODUCTION

The present invention provides crystalline form RO of Roxadustat with oxalic acid and its process for the preparation.

BACKGROUND

Roxadustat (I) or FG-4592 is chemically known as [(4-Hydroxy-1-methyl-7-phenoxy-isoquinoline-3-carbonyl)-amino]-acetic acid.It is an oral small molecule inhibitor of Hypoxia-Inducible Factor-prolyl hydroxylases, or HIF-PHs, in Phase 3 clinical development for treating and preventing disorders associated with HIF, including anemia in chronic kidney disease or CKD, ischemia, and hypoxia.
(I)
The US patent number 7323475 B2, Example D-81 (e), by referring Example D-78 (d), discloses a process for preparation followed by isolation of Roxadustat by concentration of organic phases (EtOAc/Methanol) under vacuum.
The US patent number 8883823 B2 discloses crystalline Forms of Roxadustat and their processes for the preparation. The crystalline forms are designated as Form A, Form B (hemihydrate), Form C (hexafluropropan-2-ol solvate) and Form D (DMSO: Water solvate). It further discloses various salts of Roxadustat and amorphous form Roxadustat.
The US patent number 9206134 B2 discloses various crystalline Forms of Roxadustat and their processes for the preparation. The crystalline forms are designated as Form I, Form II, Form III, Form IV, Form V, Form VI and Form VII.
Different forms of Active pharmaceutical ingredients (API) in pharmaceutical compositions can be prepared. For example, API may be prepared in amorphous form, crystalline forms, solvate or hydrate and salt form. This variation in solid forms may be significant and may result in differences in pharmaceutical products with respect to solubility, bioavailability, stability and other properties.Accordingly, variation of the crystalline state of Roxadustat is one way in which physical properties of the Roxadustat can be modulated.It has now been found that new solid state form i.e., crystalline form of Roxadustat can be obtained which may modify the properties of Roxadustat as compared to traditional solid forms such as salts, polymorphs, hydrates, solvates etc.
SUMMARY OF THE INVENTION
In the first aspect, the present application provides a crystalline formRO of Roxadustat with oxalic acid,characterized by a PXRD pattern comprising the peaks at about 6.51, 10.32 and 25.46± 0.2° 2?.In an embodiment, the application provides a crystalline form RO of Roxadustat with oxalic acid,characterized by a PXRD having additional peaks at about 12.09, 14.06, 17.10, 20.59 and 27.22± 0.2° 2?.
In the second aspect, the present application provides a process for the preparation of crystalline Form RO of Roxadustat with oxalic acid, comprising a step of grinding the mixture Roxadustat and oxalic acid in a ball mill, optionally in the presence of organic solvent.
In the third aspect, the present application provides a pharmaceutical composition comprising crystalline Form ROof Roxadustat with oxalic acidwith at least one pharmaceutically acceptable excipient.

BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is an illustrative X-ray powder diffraction of crystallineForm RO of Roxadustat with oxalic acid prepared by the method of Example-1.

DETAILED DESCRIPTION
Aspects of the present application relate to solid forms ofRoxadustat and pharmaceutical compositions of thereof. Specific aspects relate to the crystalline forms of Roxadustat with oxalic acid. Further, aspects of the application relate to processes for the preparation of said solid form.
In the first aspect, the present application provides a crystalline form RO of Roxadustat with oxalic acid, characterized by a PXRD pattern comprising the peaks at about 6.51, 10.32 and 25.46 ± 0.2° 2?.In an embodiment, the application provides a crystalline form RO of Roxadustat with oxalic acid, characterized by a PXRD having additional peaks at about 12.09, 14.06, 17.10, 20.59 and 27.22± 0.2° 2?.
In an embodiment, the application provides crystalline Form RO of Roxadustat with oxalic acid, characterized by a PXRD pattern of figure 1.
In the second aspect, the present application provides a process for the preparation of crystalline Form RO of Roxadustat with oxalic acid, comprising a step of grinding the mixture Roxadustat and oxalic acid in a ball mill, optionally in the presence of organic solvent.
In embodiments, the mixture of Roxadustat and oxalic acid may be ground under suitable grinding conditions in a ball mill to obtain crystalline Form RO. In embodiments, a mixture of Roxadustat and oxalic acid may be ground at temperature of about 15°C or above and for at least 5 minutes or longer. In embodiments, the mixture of Roxadustat and oxalic acid may be ground in a ball mill with a frequency of at least 10 Hz or more.
In alternate embodiments, the mixture of Roxadustat and oxalic acid may be ground in other grinding apparatus such as planetary mill and the like.
In embodiments, the mixture may be ground in the presence of organic solvent. organic solvent may be one or more solvents selected from the group comprising of acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, methanol, ethanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, acetonitrile, propionitrile, tetrahydrofuron, 1,4-dioxane, dichloromethane, chloroform and the mixtures thereof.
In embodiments, the mixture Roxadustat and oxalic acid may be dried after grinding under suitable drying conditions such as aerial drying, drying under vacuum or inert gas at a suitable temperature of about 25°C or above.
In embodiments, the crystalline Form RO of Roxadustat with oxalic acid obtained by the process of this aspect may be characterized by a PXRD pattern comprising the peaks at about 6.51, 10.32 and 25.46 ± 0.2° 2?. In an embodiment, crystalline Form ROmay be characterized by a PXRD pattern having one or more additional peaks at about 12.09, 14.06, 17.10, 20.59 and 27.22 ± 0.2° 2?. In an embodiment, crystalline Form RO may be characterized by a PXRD pattern of figure 1.
In embodiments, the crystalline form RO of Roxadustat with oxalic acid may be isolated by solution crystallization and separating the solids from the solvent through suitable techniques known in the art such as filtration, decantation and the like. The isolated solids may be dried under suitable drying conditions such as aerial drying, drying under vacuum or inert gas at a suitable temperature of about 25°C or above.
Starting material may be either in a crystalline or amorphous state or an alternate crystalline form of Roxadustat known in the art.
In the third aspect, the present application provides a pharmaceutical composition comprising crystalline Form RO of Roxadustat with oxalic acid with at least one pharmaceutically acceptable excipient.
In another aspect, the present application provides solid forms ofRoxadustat with oxalic acid selected from crystalline form RO according to instant application and pharmaceutical compositions thereof, wherein the chemical purity of Roxadustat may be more than 99% by HPLC or more than 99.5% by HPLC or more than 99.9% by HPLC.

Certain specific aspects and embodiments of the presentapplication will beexplained in greater detail with reference to thefollowing examples, which are provided only for purposes of illustrationand should not be construed as limiting the scope of the application in anymanner. Variations of the described procedures, as will be apparent tothose skilled in the art, are intended to be within the scope of the presentapplication.

EXAMPLES

Example-1: Preparation of crystalline form RO of Roxadustat with oxalic acid.
A mixture of Roxadustat (300 mg), oxalic acid (192 mg) and methyl ethyl ketone (150 µL) were ground for 60 minutes with a frequency of 25Hz in ball mill to obtain the title compound.
Yield: 84%
,CLAIMS:WE CLAIM:

1) A crystalline form RO of Roxadustat with oxalic acid, characterized by a X-ray powder diffraction pattern having the peaks at about 6.51, 10.32 and 25.46 ± 0.2° 2?.
2) The crystalline form according to claim 1, Roxadustat Form RO, characterized by a X-ray powder diffraction pattern having additional peaks at about 12.09, 14.06, 17.10, 20.59 and 27.22± 0.2° 2?.
3) Crystalline Roxadustat Form-RO substantially as shown in Figure-1.
4) A process for the preparation of crystalline Form RO of Roxadustat with oxalic acid, comprising a step of grinding the mixture Roxadustat and oxalic acid in a ball mill, optionally in the presence of organic solvent.
5) The process according to claim 4, wherein organic solvent comprising acetone, ethyl methyl ketone, diethyl ketone, methyl isobutyl ketone, methanol, ethanol, 2-propanol, 1-butanol, 2-butanol, 1-pentanol, 2-pentanol, 3-pentanol, acetonitrile, propionitrile, tetrahydrofuron, 1,4-dioxane, dichloromethane, chloroform.