DESC:SOLID FORMS OF LESINURAD

INTRODUCTION
Aspects of the present application relate to solid forms of Lesinurad, their processes and pharmaceutical compositions thereof. Specific aspects of the present application relate to novel crystalline forms of Lesinurad and their preparative processes.
Lesinurad is a selective uric acid re-absorption inhibitor (SURI). Lesinurad is used for reducing serum uric acid level and for the treatment of gout and hyperurecemia. Lesinurad is chemically known as 2-(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-ylthio)acetic acid and has following structural formula (I).

I
US8546436B2 discloses crystalline Forms 1 and 2 of Lesinurad and their processes for preparation. Similarly, US8524754B2 discloses crystalline forms A, B, B’, C, D and E of Lesinurad sodium and their processes for preparation.
WO2015075561A1 assigned to Crystal Pharmatech Co Ltd & Suzhou pengxu harmatech co. ltd., discloses crystalline forms III, IV, V, and VI of Lesinurad and their process for preparation.
CN104557748 A assigned to Guangdong East Sunshine Pharmaceutical Co., Ltd., discloses crystalline forms a, ß of Lesinurad and their process for preparation.
In general, polymorphism refers to the ability of a substance to exist as two or more crystalline phases that have different spatial arrangements and/or conformations of molecules in their crystal lattices. Thus, “polymorphs” refer to different crystalline forms of the same pure substance in which the molecules have different spatial arrangements of the molecules, atoms, and/or ions forming the crystal. Different polymorphs may have different physical properties such as melting points, solubilities, etc. The variation in solid forms may appreciably influence the pharmaceutical properties, such as bioavailability, handling properties, dissolution rate, and stability, and in turn such properties can significantly influence the processing, shelf life, and commercial acceptance of a polymorphic form. For these reasons, regulatory authorities require drug manufacturing companies to put efforts into identifying all different solid forms, e.g., crystalline, amorphous, solvates, stable dispersions with a pharmaceutically acceptable carriers, etc., of new drug substances.
The existence and possible numbers of polymorphic forms for a given compound cannot be predicted, and there are no “standard” procedures that can be used to prepare polymorphic forms of a substance. This is well-known in the art, as reported, for example, by A. Goho, “Tricky Business,” Science News, Vol. 166(8), August 2004.
Hence, there remains a need for alternate solid forms, particularly, need for alternate crystalline forms of Lesinurad, which are stable, reproducible and can be prepared through an industrially viable manner.

SUMMARY
In an aspect, the present application provides a crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB1 of Lesinurad, characterized by a PXRD having additional peaks at about, 11.57, 20.23 and 22.81± 0.2° 2?.
In another aspect, the present application provides a crystalline form RB2 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.30, 14.20, 14.65 and 25.91 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB2 of Lesinurad, characterized by a PXRD having additional peaks at about, 15.18, 16.99, 17.84, 20.71, 22.85 and 27.02 ± 0.2° 2?.
In another aspect, the present application provides a crystalline form RB3 of Lesinurad, characterized by a PXRD comprising the peaks at about 11.09 and 14.99 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB3 of Lesinurad, characterized by a PXRD having additional peaks at about, 16.40, 22.10, 24.75, 25.79, 28.68, 31.02, 33.45 and 35.28 ± 0.2° 2?.
In another aspect, the present application provides a crystalline form RB4 of Lesinurad, characterized by a PXRD comprising the peaks at about 9.40, 14.82 and 22.11 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB4 of Lesinurad, characterized by a PXRD having additional peaks at about, 15.55, 16.34, 19.97 and 27.07 ± 0.2° 2?.
In another aspect, the present application provides a crystalline form RB5 of Lesinurad, characterized by a PXRD comprising the peaks at about 8.42, 11.27, 15.52 and 33.15 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB5 of Lesinurad, characterized by a PXRD having additional peaks at about, 10.64, 15.84, 18.79, 20.26, 21.57, 22.84, 23.28, 25.03 and 27.41 ± 0.2° 2?.
In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising the step of crystallizing Lesinurad form RB1 from the solution comprising Lesinurad and N,N-dimethyl acetamide .

In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl acetamide;
b) optionally, seeding Lesinurad to the solution of step a);
c) adding water to the material obtained from step b) to get free material;
d) optionally, drying crystalline form RB1 at suitable temperature.

In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl acetamide;
b) optionally, heating the solution of step a);
c) adding diethyl ether as an anti-solvent to the solution of Lesinurad; or adding solution of Lesinurad to diethyl ether;
d) isolating the solid of crystalline form RB1 of Lesinurad;
e) optionally, drying the product at suitable temperature.

In another aspect, the present application provides a process for the preparation of crystalline form RB2 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.30, 14.20, 14.65 and 25.91 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl formamide;
b) optionally, heating the solution of step a);
c) adding diethyl ether as an anti-solvent to the solution of Lesinurad; or adding solution of Lesinurad to diethyl ether;
d) isolating the solid of crystalline form RB2 of Lesinurad;
e) optionally, drying the product at suitable temperature.

In another aspect, the present application provides a process for the preparation of crystalline form RB3 of Lesinurad, characterized by a PXRD comprising the peaks at about 11.09 and 14.99 ± 0.2° 2? comprising the step of treating Lesinurad with solvent or solvent mixture comprising acetic acid.

In another aspect, the present application provides a process for the preparation of crystalline form RB4 of Lesinurad, characterized by a PXRD comprising the peaks at about 9.40, 14.82 and 22.11 ± 0.2° 2? comprising the step of crystallizing Lesinurad from solvent or solvent mixtures comprising morpholine.
In another aspect, the present application provides a process for the preparation of crystalline form RB5 of Lesinurad, characterized by a PXRD comprising the peaks at about 8.42, 11.27, 15.52 and 33.15 ± 0.2° 2? comprising the step of crystallizing Lesinurad from solvent or solvent mixtures comprising formamide.
In another aspect, the present application provides a pharmaceutical composition comprising crystalline Form of Lesinurad selected from the group comprising form RB1, form RB2, form RB3, form RB4, form RB5 or mixtures thereof together with at least one pharmaceutically acceptable excipient.

BRIEF DESCRIPTION OF THE DRAWING
Figure 1 is an illustrative X-ray powder diffraction of crystalline
Form RB1 of Lesinurad prepared by the method of Example-3.
Figure 2 is an illustrative X-ray powder diffraction of crystalline
Form RB2 of Lesinurad prepared by the method of Example-4.
Figure 3 is an illustrative X-ray powder diffraction of crystalline
Form RB3 of Lesinurad prepared by the method of Example-5.
Figure 4 is an illustrative X-ray powder diffraction of crystalline
Form RB4 of Lesinurad prepared by the method of Example-6.
Figure 5 is an illustrative X-ray powder diffraction of crystalline
Form RB5 of Lesinurad prepared by the method of Example-7.

DETAILED DESCRIPTION
In an aspect, the present application provides a crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB1 of Lesinurad, characterized by a PXRD having additional peaks at about, 11.57, 20.23 and 22.81± 0.2° 2?.
In an embodiment, the present application provides crystalline form RB1 of Lesinurad, characterized by a PXRD substantially as shown in figure 1.

In another aspect, the present application provides a crystalline form RB2 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.30, 14.20, 14.65 and 25.91 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB2 of Lesinurad, characterized by a PXRD having additional peaks at about, 15.18, 16.99, 17.84, 20.71, 22.85 and 27.02 ± 0.2° 2?.
In an embodiment, the present application provides crystalline form RB2 of Lesinurad, characterized by a PXRD substantially as shown in figure 2.

In another aspect, the present application provides a crystalline form RB3 of Lesinurad, characterized by a PXRD comprising the peaks at about 11.09 and 14.99 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB3 of Lesinurad, characterized by a PXRD having additional peaks at about, 16.40, 22.10, 24.75, 25.79, 28.68, 31.02, 33.45 and 35.28 ± 0.2° 2?.
In an embodiment, the present application provides crystalline form RB3 of Lesinurad, characterized by a PXRD substantially as shown in figure 3.

In another aspect, the present application provides a crystalline form RB4 of Lesinurad, characterized by a PXRD comprising the peaks at about 9.40, 14.82 and 22.11 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB4 of Lesinurad, characterized by a PXRD having additional peaks at about, 15.55, 16.34, 19.97 and 27.07 ± 0.2° 2?.
In an embodiment, the present application provides crystalline form RB4 of Lesinurad, characterized by a PXRD substantially as shown in figure 4.

In another aspect, the present application provides a crystalline form RB5 of Lesinurad, characterized by a PXRD comprising the peaks at about 8.42, 11.27, 15.52 and 33.15 ± 0.2° 2?. In an embodiment, the application provides crystalline form RB5 of Lesinurad, characterized by a PXRD having additional peaks at about, 10.64, 15.84, 18.79, 20.26, 21.57, 22.84, 23.28, 25.03 and 27.41 ± 0.2° 2?.
In an embodiment, the present application provides crystalline form RB5 of Lesinurad, characterized by a PXRD substantially as shown in figure 5.

Lesinurad that is used as starting material for the preparation of any of the solid forms of present application may be purified before using employing any of the purification techniques known in the art such as recrystallization, slurrying or chromatography or according to the procedures described or exemplified in the instant application.
Starting material may be either in a crystalline or amorphous state. In embodiments, crystalline form of Lesinurad that may be used may include but not limited to crystalline form 1 or crystalline form 2 of Lesinurad or an alternate crystalline form of Lesinurad known in the art.

In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising the step of crystallizing Lesinurad form RB1 from the solution comprising Lesinurad and N,N-dimethyl acetamide .
In an embodiment, solution comprising Lesinurad and N,N-dimethyl acetamide may obtained by dissolving Lesinurad in a solvent or mixture of solvents comprising N,N-dimethyl acetamide, optionally by heating.
In an embodiment, dissolution of Lesinurad may be carried out by optionally heating a mixture of Lesinurad and a solvent or mixture of solvents comprising N,N-dimethyl acetamide at about 60°C to reflux temperature of the solvent. The solution may be made particle free by filtering the solution, optionally the solution may be treated with carbon, hydrose or any decolorizing agent before filtration.
In an embodiment, crystallization of Lesinurad form RB1 may be carried out according to any methods known in the art for the reduction of solubility of Lesinurad such as lowering the temperature (i.e., cooling crystallization) of the solution; adding anti-solvent to the solution; slow evaporating the solvent from the solution; or the combinations thereof.
Isolation of crystalline form RB1 of Lesinurad may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, crystalline form RB1 may be isolated by employing any of the techniques, but not limited to: decantation, filtration by gravity or suction, centrifugation, adding solvent to make slurry followed by filtration, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.

In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl acetamide;
b) optionally, seeding Lesinurad to the solution of step a);
c) adding water to the material obtained from step b) to get free material;
d) optionally, drying crystalline form RB1 at suitable temperature.

In embodiments of step a) involves the solution may optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution.
In an embodiment, water as an anti-solvent may be added to the reaction solution obtained in either step (a) or step (b) of the present invention by drop wise or in a single lot. Optionally, the solution obtained in step (a) or step (b) may be added to water.
The temperature at which the above steps may be carried out in between about 20 °C and about 100 °C, preferably at about 25°C and about 75°C.
The isolation of step d) can be effected, if desired, by any suitable separation methods such as precipitation, filtration, centrifugation, extraction, acid-base treatment, conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures.

In another aspect, the present application provides a process for the preparation of crystalline form RB1 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl acetamide;
b) optionally, heating the solution of step a);
c) adding diethyl ether as an anti-solvent to the solution of Lesinurad; or adding solution of Lesinurad to diethyl ether;
d) isolating the solid of crystalline form RB1 of Lesinurad;
e) optionally, drying the product at suitable temperature.

In embodiments of step a) involves the solution may optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution.
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. The solution may be filtered by passing thourough paper, glass fiber, 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 crystallization.
In embodiments of step c) involves adding diethyl ether to the solution obtained in step b), or adding the solution obtained in step b) to the diethyl ether, wherein the solution is made in step b) with only N,N-dimethyl acetamide. After adding diethyl ether, the reaction mass may be maintained from 15 minutes to 24 hours.
The isolation of step d) can be effected, if desired, by any suitable separation methods such as precipitation, filtration, centrifugation, extraction, acid-base treatment, by scraping, or by shaking the container conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures.

In another aspect, the present application provides a process for the preparation of crystalline form RB2 of Lesinurad, characterized by a PXRD comprising the peaks at about 7.30, 14.20, 14.65 and 25.91 ± 0.2° 2? comprising:
a) dissolving Lesinurad in N,N-dimethyl formamide;
b) optionally, heating the solution of step a);
c) adding diethyl ether as an anti-solvent to the solution of Lesinurad; or adding solution of Lesinurad to diethyl ether;
d) isolating the solid of crystalline form RB2 of Lesinurad;
e) optionally, drying the product at suitable temperature.

In embodiments of step a) involves the solution may optionally be treated with carbon, flux-calcined diatomaceous earth (Hyflow), or any other suitable material to remove color and/or to clarify the solution.
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. The solution may be filtered by passing thourough paper, glass fiber, 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 crystallization.
In embodiments of step c) involves adding diethyl ether to the solution obtained in step b), or adding the solution obtained in step b) to the diethyl ether, wherein the solution is made in step b) with only N,N-dimethyl formamide. After adding diethyl ether, the reaction mass may be maintained from 15 minutes to 24 hours.
The isolation of step d) can be effected, if desired, by any suitable separation methods such as precipitation, filtration, centrifugation, extraction, acid-base treatment, by scraping, or by shaking the container conventional isolation and refining means such as concentration, concentration under reduced pressure or by a combination of these procedures.

In another aspect, the present application provides a process for the preparation of crystalline form RB3 of Lesinurad, characterized by a PXRD comprising the peaks at about 11.09 and 14.99 ± 0.2° 2? comprising the step of treating Lesinurad with solvent or solvent mixture comprising acetic acid.
In an embodiment, crystalline form RB3 of Lesinurad may be obtained by treating Lesinurad with solvent or solvent mixture comprising acetic acid, wherein the mixture of Lesinurad and the solvent is either heterogeneous or homogeneous.
In an embodiment, crystalline form RB3 of Lesinurad may be obtained by suspending Lesinurad in a solvent or mixture of solvents comprising acetic acid for at suitable temperature and sufficient time.
In an embodiment, crystalline form RB3 of Lesinurad may be obtained by crystallizing it from the solution comprising Lesinurad and solvent or mixture of solvents comprising acetic acid.
In embodiments, crystallization of Lesinurad form RB3 may be carried out according to any method known in the art for the reduction of solubility of Lesinurad such as lowering the temperature (i.e., cooling crystallization) of the solution; adding anti-solvent to the solution; evaporating the solvent from the solution; or the combinations thereof. Crystallization may be carried out by any method described in any aspect or according to procedures exemplified in the instant application.

In an embodiment, crystallization of Lesinurad form RB3 may be carried out by lowering the temperature of the solution comprising Lesinurad and solvent or mixture of solvents comprising acetic acid to a suitable temperature of about 15°C and below. In an embodiment, crystallization may be carried out by lowering the temperature of the solution to 10°C and below.
In an embodiment, temperature lowering may be carried out slowly or drastically. In an embodiment, drastic lowering of temperature may be effected by placing the solution in a pre-cooled bath. In further embodiments, temperature lowering may be carried out in gradually in single step or stepwise in multiple steps.
In an embodiment, after lowering the temperature, the solution comprising Lesinurad and solvent or mixture of solvents comprising acetic acid may be stirred at the same temperature for time sufficient to obtain crystalline form RB3 of Lesinurad.
Isolation of crystalline form RB3 of Lesinurad may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, crystalline form RB3 may be isolated by employing any of the techniques, but not limited to: decantation, filtration by gravity or suction, centrifugation, adding solvent to make slurry followed by filtration, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.
In an embodiment, isolated crystalline form RB3 of Lesinurad may be optionally dried in a suitable drying equipment for times sufficient to achieve desired quality of product at suitable temperatures.

In another aspect, the present application provides a process for the preparation of crystalline form RB4 of Lesinurad, characterized by a PXRD comprising the peaks at about 9.40, 14.82 and 22.11 ± 0.2° 2? comprising the step of crystallizing Lesinurad from solvent or solvent mixtures comprising morpholine.
In an embodiment, solution comprising Lesinurad and solvent or mixture of solvents comprising morpholine may obtained by dissolving Lesinurad in a solvent or mixture of solvents, optionally by heating.
In an embodiment, dissolution of Lesinurad may be carried out by optionally heating a mixture of Lesinurad and a solvent or mixture of solvents comprising morpholine at about 50°C to reflux temperature of the solvent. The solution may be made particle free by filtering the solution, optionally the solution may be treated with carbon, hydrose or any decolorizing agent before filtration.
In an embodiment, crystallization of Lesinurad form RB4 may be carried out according to any methods known in the art for the reduction of solubility of Lesinurad such as lowering the temperature (i.e., cooling crystallization) of the solution; adding anti-solvent to the solution; evaporating the solvent from the solution; or the combinations thereof.
In an embodiment, crystallization of Lesinurad form RB4 may be carried out by lowering the temperature of the solution comprising Lesinurad and morpholine to a suitable temperature of about 25°C and below. In an embodiment, crystallization may be carried out by lowering the temperature of the solution to 0°C and below.
In an embodiment, temperature lowering may be carried out slowly or drastically. In an embodiment, drastic lowering of temperature may be effected by placing the solution in a pre-cooled bath. In further embodiments, temperature lowering may be carried out in gradually in single step or stepwise in multiple steps.
In an embodiment, after lowering the temperature, the solution comprising Lesinurad and morpholine may be stirred at the same temperature for time sufficient to obtain crystalline form RB4 of Lesinurad.
Isolation of crystalline form RB4 of Lesinurad may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, crystalline form RB4 may be isolated by employing any of the techniques, but not limited to: decantation, filtration by gravity or suction, centrifugation, adding solvent to make slurry followed by filtration, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.

In another aspect, the present application provides a process for the preparation of crystalline form RB5 of Lesinurad, characterized by a PXRD comprising the peaks at about 8.42, 11.27, 15.52 and 33.15 ± 0.2° 2? comprising the step of crystallizing Lesinurad from solvent or solvent mixtures comprising formamide.
In an embodiment, solution comprising Lesinurad and solvent or mixture of solvents comprising formamide may obtained by dissolving Lesinurad in a solvent or mixture of solvents, optionally by heating.
In an embodiment, dissolution of Lesinurad may be carried out by optionally heating a mixture of Lesinurad and a solvent or mixture of solvents comprising formamide at about 30°C to reflux temperature of the solvent. The solution may be made particle free by filtering the solution, optionally the solution may be treated with carbon, hydrose or any decolorizing agent before filtration.
In an embodiment, crystallization of Lesinurad form RB5 may be carried out according to any methods known in the art for the reduction of solubility of Lesinurad such as lowering the temperature (i.e., cooling crystallization) of the solution; adding anti-solvent to the solution; evaporating the solvent from the solution; or the combinations thereof.
In an embodiment, crystallization of Lesinurad form RB5 may be carried out by lowering the temperature of the solution comprising Lesinurad and formamide to a suitable temperature of about 25°C and below. In an embodiment, crystallization may be carried out by lowering the temperature of the solution to 0°C and below.
In an embodiment, temperature lowering may be carried out slowly or drastically. In an embodiment, drastic lowering of temperature may be effected by placing the solution in a pre-cooled bath. In further embodiments, temperature lowering may be carried out in gradually in single step or stepwise in multiple steps.
In an embodiment, after lowering the temperature, the solution comprising Lesinurad and formamide may be stirred at the same temperature for time sufficient to obtain crystalline form RB5 of Lesinurad.
Isolation of crystalline form RB5 of Lesinurad may be carried out by any methods known in the art or procedures described in the present application. In an embodiment, crystalline form RB5 may be isolated by employing any of the techniques, but not limited to: decantation, filtration by gravity or suction, centrifugation, adding solvent to make slurry followed by filtration, or other techniques specific to the equipment used and the like, and optionally washing with a solvent.
Drying in the embodiments of the present invention may be suitably carried out by using any of an air tray dryer, vacuum tray dryer, fluidized bed dryer, spin flash dryer, flash dryer, and the like. The drying may be carried out at atmospheric pressure or above, or under reduced pressures, specifically at temperatures less than about 80 °C and more specifically less than about 60 °C. The drying may be carried out for any time period required for obtaining a desired product quality, such as from about 30 minutes to about 24 hours, or longer.

In another aspect, the present application provides a pharmaceutical composition comprising crystalline Form of Lesinurad selected from the group comprising form RB1, form RB2, form RB3, form RB4, form RB5 or mixtures thereof together with at least one pharmaceutically acceptable excipient.
In another aspect, the present application provides crystalline forms of Lesinurad or their pharmaceutical compositions comprising Lesinurad having a chemical purity of at least 99% by HPLC or at least 99.5% by HPLC or at least 99.9% by HPLC.
All PXRD data reported herein are obtained using a PANalytical X-ray Diffractometer and Bruker D8 advance X-ray Diffractometer, with copper Ka radiation.
DEFINITIONS
The following definitions are used in connection with the present application unless the context indicates otherwise.
The terms "about," "general, ‘generally," and 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.
The terms “crystalline form" indicates that the Lesinurad is present in substantially crystalline Form. "Substantially" crystalline denotes that at least 80 %, preferably 90 % or 95 %, more preferably all of the Lesinurad is crystalline form. In other words, "crystalline form" of Lesinurad denotes Lesinurad, which does not contain substantial amounts, preferably does not contain noticeable amounts, of any other crystalline portions of Lesinurad e.g. measurable upon X-ray powder diffraction analysis.
The term “optional” or “optionally” is taken to mean that the event or circumstance described in the specification may or may not occur, and that the description includes instances where the event occurs and instances where it does not.
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. Variations of the described procedures, as will be apparent to those skilled in the art, are intended to be within the scope of the present application.
EXAMPLES

Example-1: Preparation of crystalline form RB1 of Lesinurad.
Lesinurad (100 mg) was dissolved in N, N-dimethyl acetamide (1 mL) at 60°C. The reaction mixture was allowed to slow evaporation to obtain the title compound.
Example-2: Preparation of crystalline form RB1 of Lesinurad.
Lesinurad (1.004 g) was dissolved in N, N-dimethyl acetamide (0.8 mL) at 25°C. Seed material was added to the reaction mixture at 25°C and stirred for 10-20 minutes. Water (0.6 mL) was added to the reaction mass and stirred for 10-20 minutes. The solid was filtered and dried under vacuum for 2 hours at 60°C to obtain title compound.

Example-3: Preparation of crystalline form RB1 of Lesinurad.
Lesinurad (2.008 g) was dissolved in N, N-dimethyl acetamide (2 mL) at 25°C and rapidly heated to 60°C to get clear solution. The reaction mixture was cooled to 30°C. Diethyl ether (20 mL) was added to the reaction mass and stirred for 10-50 minutes. The solid was filtered through hyflow bed and washed with diethyl ether to obtain 1.945 g of the title compound.
Example-4: Preparation of crystalline form RB2 of Lesinurad.
Lesinurad (3.0014 g) was dissolved in N, N-dimethyl formamide (3 mL) at 25°C and rapidly heated to 70°C. The reaction mixture was cooled to 60°C. Diethyl ether (30 mL) was added to the reaction mass at 60°C and stirred for 10-20 minutes. The solid was filtered and dried under vacuum to obtain the title compound.
Example-5: Preparation of crystalline form RB3 of Lesinurad.
Lesinurad (1.013 g) was dissolved in acetic acid (5 mL) at 80°C and rapidly cooled to 30°C and was filtered to remove any particulate matter. The beaker was closed with a cover and kept in refrigerator at 10-11°C for recrystallization. Decanted the solution and scratched the powder to obtain the title compound.
Example-6: Preparation of crystalline form RB4 of Lesinurad.
Lesinurad (100 mg) was charged into each well (12wells) of crissy block. Morpholine (0.1 mL) was added into each well and stirred at 50°C for about 5 hours. The reaction mixture was cooled to -5°C and stirred for 2 days 15 hours. The solvent from the reaction mass was slowly evaporated at 27°C for 27 hours to obtain the title compound.
Example-7: Preparation of crystalline form RB5 of Lesinurad.
Lesinurad (2.004 g), formamide (8 mL) were charged in to the glass vial at 25°C and stirred for 2-3 hours. The solid was filtered and dried under vacuum to obtain the title compound.
,CLAIMS:1) Crystalline form RB1 of Lesinurad characterized by an X-ray Powder Diffraction Pattern (PXRD) having the peaks at about 7.14, 14.91, 16.55 and 28.27 ± 0.20° 2?.
2) Crystalline form RB2 of Lesinurad characterized by an X-ray Powder Diffraction Pattern (PXRD) having the peaks at about 7.30, 14.20, 14.65 and 25.91 ± 0.20° 2?.
3) Crystalline form RB3 of Lesinurad characterized by an X-ray Powder Diffraction Pattern (PXRD) having the peaks at about 11.09 and 14.99 ± 0.20° 2?.
4) Crystalline form RB4 of Lesinurad characterized by an X-ray Powder Diffraction Pattern (PXRD) having the peaks at about 9.40, 14.82 and 22.11 ± 0.20° 2?.
5) Crystalline form RB5 of Lesinurad characterized by an X-ray Powder Diffraction Pattern (PXRD) having the peaks at about 8.42, 11.27, 15.52 and 33.15 ± 0.20° 2?.