Novel etrasimod l-arginine polymorphs and amorphous forms and processes for the same

Abstract

The present invention relates to novel Etrasimod L-Arginine polymorphs and amorphous forms and to the processes of preparation thereof.

Description

[0001] NOVEL ETRASIMOD L-ARGININE POLYMORPHS AND AMORPHOUS FORMS AND PROCESSES FOR THE SAME

[0002] TECHNICAL FIELD OF THE INVENTION

[0003] The present invention is related to novel Etrasimod L-Arginine polymorphs and amorphous forms and to the processes for preparation of the same.

[0004] BACKGROUND AND PRIOR ART

[0005] Etrasimod arginine, chemically known as (2S)-2-amino-5- (diaminomethylideneamino) pentanoic acid;2-[(3R)-7- [[4-cyclopentyl-3- (trifluoro methyl) phenyl] methoxy]-l,2,3,4-tetrahydrocyclopenta[b]indol-3-yl] acetic acid is an organoammonium salt obtained by combining etrasimod with one molar equivalent of L-arginine. It is a sphingosine 1 -phosphate receptor modulator approved for the treatment of moderately to severely active ulcerative colitis in adults. It has a role as an anti-inflammatory drug, an immunosuppressive agent and a sphingosine- 1 -phosphate receptor 1 antagonist. It contains a L- argininium (1+) and an etrasimod (1-).

[0006] The sphingosine- 1 -phosphate (SIP) receptors 1-5 constitute a family of G protein- coupled receptors with a seven-transmembrane domain. These receptors, referred to as S1P1 to S 1P5 (formerly termed endothelial differentiation gene (EDG) receptor-1, -5, -3, -6 and -8, respectively; Chun et al., Pharmacological Reviews, 54:265-269, 2002), are activated via binding by sphingosine-1 -phosphate, which is produced by the sphingosine kinase-catalyzed phosphorylation of sphingosine. S1P1, SI P4 and S1P5 receptors activate Gi but not Gq, whereas S1P2 and S1P3 receptors activate both Gi and Gq. The S1P3 receptor, but not the S1P1 receptor, responds to an agonist with an increase in intracellular calcium.

[0007] Etrasimod L- Arginine has been approved in 2023 by USFDA for immune- mediated diseases like ulcerative colitis, with high level of inflammatory T cells in the gastro-intestinal tract, causing diffuse mucosal inflammation. The earliest patent US8580841 has been assigned to Arena Pharmaceuticals. US’841 relates to certain substituted l,2,3,4-tetrahydrocyclopenta[b]indol-3-yl) V T acetic acid derivatives of Formula (la) and pharmaceutically acceptable salts thereof, which exhibit useful pharmacological properties, for example, as agonists of the SIP 1 receptor. wherein the variables are as defined therein. Further, Preparation of 1, 2,3,4- tetrahydrocyclopenta[b]indol-3-yl) acetic acid derivatives useful in treatment of autoimmune and inflammatory diseases has been described therein.

[0008] Crystalline L-Arginine salt of (R)-2-(7-(4-cyclopentyl-3 (trifluoromethyl) benzyloxy)-l,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl) acetic acid (Compundl) for use in SIPI receptor-associated disorders was described in W02016209809. Crystalline spherulite forms of the arginine salt and crystalline free-plate habit and processes thereof have been described therein. WO20 16209809 relates to a crystalline free-plate habit of L-arginine salt of (R)-2- (7-(4-cyclopentyl-3- (trifluoromethyl)benzyloxy)-l ,2,3,4-tetrahydrocyclopenta [b]indol-3-yl)acetic acid in the treatment of SIP receptor-associated disorders, further having a powder X-ray diffraction pattern comprising peaks, 2 9 at 8.2° ± 0.2°, 16.4° ± 0.2°, 20.5° ± 0.2°, and 24.6° ± 0.2°.

[0009] The amorphous form of Etrasimod L-Arginine which was produced using cryogenic ball milling and characterized by PXRD, Solid State NMR and FT- Raman spectroscopy is disclosed in the published article titled Etrasimod L- Arginine Amorphous Form, IPCOM000273435D published on December 05, 2023.

[0010] Considering the scope of Etrasimod L- Arginine and its array in the treatment of immune-mediated diseases like ulcerative colitis, with high level of inflammatory T cells in the gastro-intestinal tract, causing diffuse mucosal inflammation there still exists a need for development of newer forms of Etrasimod L- Arginine which remains the objective of the present invention.

[0011] Accordingly, the inventors of the present invention have provided novel forms of Etrasimod L- Arginine and to the processes for preparation thereof.

[0012] SUMMARY OF THE INVENTION

[0013] In an aspect, the present invention provides Etrasimod L- Arginine in the form of;

[0014] (i) Crystalline DMF solvate of Etrasimod L- Arginine Form Cl;

[0015] (ii) Crystalline Etrasimod L-Arginine Form C2; and

[0016] (iii) Amorphous Etrasimod L-Arginine.

[0017] In an aspect, the present invention provides Crystalline DMF solvate of Etrasimod L-Arginine Form Cl having the PXRD peaks at 7.43±0.2°, 15.45±0.2°, 16.74±0.2°, 18.22±0.2° and 20.5 ±0.2° 29 and further characterized by the peaks as depicted in Fig 1. In another aspect, the crystalline DMF solvate of Etrasimod L- Arginine Form Cl exhibits a DSC having thermogram as depicted in Fig 2.

[0018] In yet another aspect, the crystalline DMF solvate of Etrasimod L- Arginine Form Cl exhibits the TGA as depicted in Fig 3.

[0019] In another aspect, the present invention provides a novel crystalline Etrasimod L- Arginine Form C2 having the PXRD peaks at 7.83±0.2°, 15.27±0.2°, 17.22±0.2°, 19.75±0.2° and 23.0±0.2° 29 and further characterized by the peaks as depicted in Fig 4.

[0020] In yet another aspect, the present invention provides a novel crystalline Etrasimod L- Arginine Form C2 having the PXRD peaks as depicted in Fig 5.

[0021] In another aspect, the crystalline Etrasimod L-Arginine Form C2 exhibits a DSC having thermogram as depicted in Fig 6.

[0022] In yet another aspect, the crystalline Etrasimod L-Arginine Form C2 exhibits the TGA as depicted in Fig 7.

[0023] In another aspect, the present invention provides Etrasimod L-Arginine amorphous form as depicted in Fig 8.

[0024] In another aspect, the present invention relates to the process for preparation of said crystalline DMF solvate of Etrasimod L-Arginine Form Cl and crystalline Form C2 thereof.

[0025] Accordingly, the process for preparation of crystalline DMF solvate of Etrasimod L-Arginine Form Cl comprises the following steps: i. Stirring Etrasimod Free acid and L-Arginine or Etrasimod L-Arginine salt in DMF; ii. Adding another suitable solvent to the mixture of step (i) and stirring; iii. Isolating the solids by filtration under vacuum to obtain the DMF solvate of Etrasimod L- Arginine Form Cl; and iv. Optionally re-slurrying the filtered material of step (iii) in suitable solvent followed by filtering under vacuum to obtain the title compound.

[0026] In another aspect, the process for preparation of crystalline Form C2 of Etrasimod L- Arginine comprises drying the DMF solvate of Form Cl in a vacuum tray dryer at 60-75°C for about 24 hours.

[0027] In an alternate aspect, crystalline Form C2 of Etrasimod L- Arginine was prepared by the process comprising. i. Suspending Etrasimod L-arginine in a solvent or mixture of solvents, stirring and heating the reaction mixture to a temperature ranging between 40-45°C; ii. Cooling the reaction mixture of step (i) to a temperature ranging between 25-30°C and stirring for a period of 10-12 hours followed by heating to a temperature ranging between 40-45°C and stirring; iii. Cooling the reaction mixture of step (ii) to a temperature ranging between 25-30°C, followed by the steps of filtering and washing(s) in suitable solvent and drying to obtain the desired Form C2.

[0028] In yet another aspect, the present invention relates to the process for preparation of Etrasimod L- Arginine amorphous form comprising; i. Dissolving Etrasimod L-Arginine in a suitable solvent and filtering to remove the undissolved particulate; ii. Adding a suitable solvent cooled to below -5°C to the solution of step (i) and marinating at the temperature for 2-3 hours; iii. Filtering the mixture of step (ii) under pressure in nitrogen atmosphere followed by drying to obtain the desired product. In yet another aspect, the present invention relates to a pharmaceutical composition comprising crystalline DMF solvate of Etrasimod L-Arginine Form Cl or Crystalline Etrasimod L-Arginine Form C2 with pharmaceutically acceptable excipients.

[0029] In another aspect, the present invention relates to a pharmaceutical composition comprising amorphous Etrasimod L-Arginine with pharmaceutically acceptable excipients.

[0030] DESCRIPTION OF FIGURES

[0031] Fig 1: Depicts PXRD of Etrasimod L-Arginine Form Cl

[0032] Fig 2: Depicts DSC of Etrasimod L-Arginine Form Cl

[0033] Fig 3: Depicts TGA of Etrasimod L-Arginine Form Cl

[0034] Fig 4: Depicts PXRD of Etrasimod L-Arginine Form C2 Example-2

[0035] Fig 5: Depicts PXRD of Etrasimod L-Arginine Form C2 Example-4

[0036] Fig 6: Depicts DSC of Etrasimod L-Arginine Form C2

[0037] Fig 7: Depicts TGA of Etrasimod L-Arginine Form C2

[0038] Fig 8: Depicts the PXRD of Etrasimod L-Arginine Amorphous

[0039] Fig 9: Depicts SEM image of Etrasimod L-Arginine Form C2 Example 6

[0040] Fig 10: Depicts SEM image of Etrasimod L-Arginine Form C2 Example 7

[0041] Fig 11: Depicts DVS data of Etrasimod L-Arginine Form C2

[0042] Fig 12: Depicts DVS data of Etrasimod L-Arginine Form C2

[0043] DESCRIPTION OF THE INVENTION

[0044] The invention will now be described in detail in its preferred and optional embodiments however should not be construed to limit the scope of the invention. Unless specified otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, to which this invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, the preferred methods and materials are described. Unless stated to the contrary, any of the words “contains”, “containing”, "including," "includes," "comprising," and "comprises" mean "including without limitation" and shall not be construed to limit any general statement that it follows to the specific or similar items or matters immediately following it. Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention.

[0045] Further, words like “a”, “an”, “at least” and “the” should be construed to not only cover singular quantities but also plural quantities of the elements immediately following them.

[0046] ‘Polymorphs’ as referred to herein are the Crystalline forms Form Cl and Form C2 of Etrasimod L- Arginine.

[0047] ‘Form Cl’ refer to the crystalline DMF solvate of Etrasimod L- Arginine.

[0048] In an embodiment, the present invention relates to a novel crystalline DMF solvate of Etrasimod L-Arginine Form Cl having the PXRD peaks at 7.43, 15.45, 16.74, 18.22 and 20.5 ±0.2° 20.

[0049] In another embodiment, the crystalline DMF solvate of Etrasimod L-Arginine Form Cl exhibits an endothermic peak with onset at 193.63°C and a peak at a temperature of 199.01°C as measured by differential scanning calorimetry DSC depicted in Fig 2.

[0050] In yet another embodiment, the crystalline DMF solvate of Etrasimod L-Arginine Form Cl depicts a weight loss of 3.314% as determined by thermogravimetric analysis (TGA) depicted in Fig 3. In another embodiment, the present invention provides a novel crystalline Etrasimod L-Arginine Form C2 having the PXRD peaks at 7.83, 15.27, 17.22, 19.75 and 23.0±0.2° 26.

[0051] In yet another embodiment, the present invention provides a novel crystalline Etrasimod L-Arginine Form C2 having the PXRD peaks at 7.83, 15.27, 17.22, 19.75 and 23.0±0.2° 26 as depicted in Fig 5.

[0052] In another embodiment, the crystalline Etrasimod L-Arginine Form C2 exhibits an endothermic peak with onset at 197.61°C and a peak at a temperature of 200.65°C as measured by DSC depicted in Fig 6.

[0053] In yet another embodiment, the crystalline Etrasimod L-Arginine Form C2 exhibits the weight loss of 6.258% as determined by TGA depicted in Fig 7.

[0054] In another embodiment, the present invention discloses a process for the preparation of crystalline DMF solvate of Etrasimod L-Arginine Form Cl comprising the following steps: i. Stirring Etrasimod Free acid and L-Arginine or Etrasimod L-Arginine salt in DMF; ii. Adding suitable solvent to the mixture of step (i) and stirring; iii. Isolating the solids by filtration under vacuum to obtain the Cl form of Etrasimod L-Arginine; iv. Optionally re-slurrying the filtered material of step iii in suitable solvent followed by filtering under vacuum to obtain the title compound.

[0055] The process of step (i) was carried out at room temperature with stirring for a period of 16-12 hours.

[0056] The reaction mixture in the process step (ii) after addition of the solvent was further stirred for a period of 5-7 hours at room temperature. In an embodiment, the solvent for the process is selected from water, C1-C5 alcohols, Acetonitrile, esters such as ethyl acetate, isopropyl acetate alone or combination thereof.

[0057] In yet another embodiment, the present invention provides a process for the preparation of crystalline Form C2 of Etrasimod L-Arginine comprising drying the Form Cl in a vacuum tray dryer at 60-75°C for 20-24 hours.

[0058] In an alternate embodiment, the process for preparation of crystalline Form C2 of Etrasimod L-Arginine comprising; i. Suspending Etrasimod L-arginine in a solvent or mixture of solvents, stirring and heating the reaction mixture to a temperature ranging between 40-45°C; ii. Cooling the reaction mixture of step (i) to a temperature ranging between 25-30°C and stirring for a period of 10-12 hours followed by heating to a temperature ranging between 40-45°C and stirring; iii. Cooling the reaction mixture of step (ii) to a temperature ranging between 25-30°C, followed by the steps of filtering and washing(s) in suitable solvent and drying to obtain the desired Form C2.

[0059] In an embodiment, the process step (i) may optionally be carried out in presence of an anti-oxidant such as Butylated hydroxytoluene (BHT), Butylated hydroxy anisole (BHA) and the like.

[0060] In an embodiment, the solvent for the process is selected from water, C1-C5 alcohols, DMF, THF, esters such as ethyl acetate, isopropyl acetate; acetonitrile alone or combination thereof.

[0061] In an embodiment, the reaction mixture of step (i) was stirred for a period of 3-4 hours.

[0062] In another embodiment, the reaction mixture of step (ii) on heating to temperature 40-45°C was stirred for a period of 4-8 hours. In another embodiment, alternately, to the stirred mixture of step (ii) was added solvent or solvent mixture in the desired ratio and further stirred for about 1 hour. The reaction mixture was then heated to 40-45°C for a period of about 3 hours and stirred for another 1-2 hours.

[0063] After filtration and washing in suitable solvent the wet material in step (iii) was suck dried under nitrogen pressure for a period of about 30 minutes, and further dried in VTD at 50-60°C for 15-20 hours, optionally further dried at 65-70°C for 30-35 hours to obtain the desired Etrasimod L- Arginine Form C2.

[0064] In an embodiment, the Etrasimod L-Arginine Form C2 has the BET specific surface area in the range of 16-17m2 / g.

[0065] The Etrasimod L-Arginine Form C2 was observed to be stable at temperature of 2-8°C for a period of six months; at 25°C and 60%RH and at accelerated conditions of 40°C and 75%RH for six months as shown in table below.

[0066] In an embodiment, the degradation studies showed that Etrasimod L-Arginine Form C2 is stable under 25°C and 60%RH, 40°C and 75%RH, 60°C / 80%RH and when exposed to UV light and at high temperature conditions as shown in the table below.

[0067] In yet another embodiment, the present invention discloses Etrasimod L-Arginine Amorphous form having PXRD as depicted in Fig 8.

[0068] In another embodiment, the present invention relates to a process for preparation of Etrasimod L-Arginine Amorphous comprising; i. Dissolving Etrasimod L-Arginine in a suitable solvent and filtering to remove the undissolved particulate; ii. Adding a suitable solvent cooled to below -5°C to the solution of step (i) and marinating at the temperature for 2-3 hours; iii. Filtering the mixture of step (ii) under pressure in nitrogen atmosphere followed by drying to obtain the desired product.

[0069] The solvent for the preparation of the amorphous form of Etrasimod L- Arginine is selected from DMSO, acetonitrile, THF, DMF, acetone alone or combination thereof.

[0070] In yet another embodiment, the present invention relates to a pharmaceutical composition containing DMF solvate of Etrasimod L- Arginine Form Cl or Etrasimod L- Arginine Form C2 prepared by the process of the present invention together with pharmaceutically acceptable excipients.

[0071] In another embodiment, the present invention relates to a pharmaceutical composition containing Etrasimod L- Arginine amorphous prepared by the process of the present invention together with pharmaceutically acceptable excipients.

[0072] The following examples will further describe certain specific aspects and embodiments of the invention in greater details and are not intended to limit the scope of invention.

[0073] Example-1:

[0074] Process for the preparation of DMF solvate of Etrasimod L-Arginine Form Cl:

[0075] Etrasimod Free acid (5 g) and L-Arginine 1.9 g (1.0 eq) were suspended in 15.0 ml (3 volumes) of Dimethyl formamide at room temperature and stirred for 12 hours, followed by addition of 75.0 ml (15 volumes) of Iso propyl acetate and stirred for 6 hours at room temperature. The solids were isolated by filtration under vacuum to obtain the title compound.

[0076] Yield: 6.5 g

[0077] Example-2:

[0078] Process for the preparation of Etrasimod L-Arginine Form C2: Form-Cl obtained as per example-1 was dried in a vacuum tray dryer at 70 °C for 24 hours to obtain the title compound.

[0079] Example-3:

[0080] Process for the preparation of DMF solvate of Etrasimod L-Arginine Form Cl:

[0081] Etrasimod L-Arginine salt 5.0 g suspended in 25.0 ml (5 volumes) of Dimethyl formamide and 0.5 ml of water (0.1 volume) mixture was heated to 50 °C and stirred at this temperature for 12 hrs, then cooled to room temperature and maintained at this temperature for 3 hours, then added 150.0 ml (15 volumes) of Iso propyl acetate and stirred for 1-2 hours at room temperature. The resulted material filtered and re-slurried in 6 vol of Iso propyl acetate followed by filtration under vacuum to obtain the title compound.

[0082] Yield: 4.5 g

[0083] Example-4:

[0084] Process for the preparation of Etrasimod L-Arginine Form C2:

[0085] Form-Cl obtained as per the example-3 was dried in a vacuum tray dryer at 70 °C for 24 hours to obtain the title compound.

[0086] Example 5: Process for the preparation of Etrasimod L-Arginine Amorphous Dissolved Etrasimod L- Arginine (3 g) in DMSO (9 ml) at 50°C and then filtered it to remove undissolved particulate. In another RBF, taken 60 ml of Acetonitrile and cooled it to below -5 °C and then slowly added the above Etrasimod L- Arginine clear solution and maintained at -5°C for about 3hrs, followed by pressure Nutsche filtration under nitrogen atmosphere and drying under vacuum at 60 °C for 12 hrs resulting in the title compound.

[0087] Yield: 2.8 g.

[0088] Example 6: Process for the preparation of Etrasimod L-arginine Form C2. Suspended 2.5 gm of Etrasimod L-arginine in mixture of 12.5 ml of DMF and 0.125 ml of water and stirred for 10-15 minutes, heated the reaction mass to 45 °C. Stirred the reaction mass at 45°C for 3 hours. Cooled the reaction mass to 25 °C and stirred the reaction mass for 10 hours. Heated to 45°C and stirred at 45°C for 5 hours. Cooled the reaction mass to 25°C. Filtered the reaction mass in PNF under nitrogen pressure and washed the material with 5ml of isopropyl acetate and kept the material under nitrogen pressure for 30 min. Unloaded the material (weight: 2.1 gm). Suspended 2.0 gm wet material in 20ml isopropyl acetate and stirred at 23 °C for 2 hours, filtered the material in PNF under nitrogen pressure and washed with 6 ml of isopropyl acetate. Suck dried the material under nitrogen pressure for 30 min, unloaded the material and dried the material in vacuum tray dryer (VTD) at 50°C for 18 hours and then at 70°C for 32 hours to obtain Etrasimod L-arginine form C2.

[0089] Yield: 1.8gm

[0090] PXRD: Form C2

[0091] Purity: 99.88%

[0092] SSA by BET: 16.9124 m2 / g

[0093] The SEM image has been depicted in Fig 9

[0094] Example 7: Process for the preparation of Etrasimod L-arginine Form C2.

[0095] Suspended 5.0 gm of Etrasimod L-arginine in 25 ml of DMF and 0.25 ml of water, charged 25 mg of BHT, stirred for 15 minutes, heated the reaction mass to 45°C. Stirred the reaction mass at 45°C for 4 hours. Cooled the reaction mass to 25°C and stirred the reaction mass for 10 hours. Again, heated the reaction mass to 45°C and stirred at 45°C for 8 hours. Cooled the reaction mass to 25°C and stirred the reaction mass for 4-5 hours, added 50 ml of Acetonitrile and methanol (9: 1 ratio) mixture and stirred for 1 hr, then heated to 40±5 °C and stirred at 40±5 °C for 3 hours, cooled to 25±5 °C and stirred for 1 hour. Filtered the reaction mass in Pressure Nutsche Filter (PNF) under nitrogen pressure and washed the material with 10.0 ml of Acetonitrile. Dried the material in VTD at 60 °C for 14 hours. The dried material was further slurried in 20 V of mixture of acetonitrile and methanol (9.5:0.5 ratio) at 45±5 °C for 5 hours then cooled to 25±5 °C and stirred for 1 hour, filtered the material in PNF under nitrogen pressure and washed the material with 10 ml of Acetonitrile. Dried the material in VTD at 60 °C for 25 hours to obtain Etrasimod L-arginine Form C2. Yield; 3.5gm

[0096] PXRD: Form C2

[0097] Purity: 99.91%

[0098] SSA by BET: 16.3811 m2 / g

[0099] SEM image has been depicted in Fig 10. Example 8: Etrasimod L-Arginine Form C2 stability

[0100] Example 9:

[0101] Etrasimod L-Arginine Form C2 solid state forced degradation study:

Claims

We Claim1. An Etrasimod L- Arginine in the form of;(i) Crystalline DMF solvate of Etrasimod L- Arginine Form Cl;(ii) Crystalline Etrasimod L- Arginine Form C2; and(iii)Amorphous Etrasimod L- Arginine.

2. The crystalline DMF solvate of Etrasimod L- Arginine Form Cl as claimed in claim 1, characterized by the PXRD peaks at 7.43±0.2°, 15.45±0.2°,16.74±0.2°, 18.22±0.2° and 20.5 ±0.2° 20.

3. The crystalline DMF solvate of Etrasimod L- Arginine Form Cl as DMF solvate as claimed in claim 1, wherein (i) DSC curve comprising an endothermic peak with onset at 193.63°C and a peak at a temperature of 199.01°C; (ii) TGA curve exhibiting a weight loss of 3.314%.

4. The crystalline Etrasimod L-Arginine Form C2 as claimed in claim 1, characterized by the PXRD peaks at 7.83, 15.27, 17.22, 19.75 and 23.0±0.2° 20.

5. The crystalline Etrasimod L-Arginine Form C2 as claimed in claim 1, wherein (i) DSC curve comprising an endothermic peak with onset at 197.61°C and a peak at a temperature of 200.65°C; (ii) TGA curve exhibiting the weight loss of 0.258%.

6. A process for preparation of the crystalline DMF solvate of Etrasimod L- Arginine Form Cl comprising; i. Stirring Etrasimod Free acid and L-Arginine or Etrasimod L- Arginine salt in DMF; ii. Adding suitable solvent to the mixture of step (i) and stirring;iii. Isolating the solids by filtration under vacuum to obtain the Cl Form of Etrasimod L- Arginine. iv. Optionally re-slurrying the filtered material of step 3 iii in suitable solvent followed by filtering under vacuum to obtain the titled compound.

7. The process as claimed in claim 6, wherein the solvent for the process is selected from water, C1-C5 alcohols, Acetonitrile, DMF, esters such as ethyl acetate, isopropyl acetate alone or combination thereof.

8. The process as claimed in claim 6, wherein the process is carried out at room temperature.

9. A process for preparation of Etrasimod L-Arginine Form C2 comprising drying Etrasimod L-Arginine Form Clas claimed in claim 6 in a vacuum tray drier dryer at 60-75°C for 20- 24 hours.

10. A process for preparation of Etrasimod L-Arginine Form C2, comprising; i. Suspending Etrasimod L-arginine in a solvent or mixture of solvents, stirring and heating the reaction mixture to a temperature ranging between 40-45°C; ii. Cooling the reaction mixture of step (i) to a temperature ranging between 25-30°C and stirring for a period of 10-12 hours followed by heating to a temperature ranging between 40-45°C and stirring. iii. Cooling the reaction mixture of step (ii) to a temperature ranging between 25-30°C, followed by the steps of filtering and washing(s) in suitable solvent and drying to obtain the desired Form C2.

11. The process as claimed in claim 10, wherein the solvent for the process is selected from water, C1-C5 alcohols, DMF, THF, esters such as ethyl acetate, isopropyl acetate; acetonitrile alone or combination thereof.

12. The process as claimed in claim 10, wherein the process step (i) may optionally be carried out in presence of an anti-oxidant such as Butylated hydroxytoluene (BHT), Butylated hydroxy anisole (BHA) and the like.

13. A process for preparation of Etrasimod L- Arginine amorphous form as claimed in claim 1, comprising; i. Dissolving Etrasimod L-Arginine in a suitable solvent and filtering to remove the undissolved particulate; ii. Adding a suitable solvent cooled to below -5°C to the solution of step (i) and marinating at the temperature for about 2-3 hours; iii. Filtering the mixture of step (ii) under pressure in nitrogen atmosphere followed by drying to obtain the desired product.

14. The process as claimed in claim 13, wherein the solvent for the process is selected from DMSO, acetonitrile, THF, DMF, acetone alone or combination thereof.

15. A pharmaceutical composition comprising crystalline DMF solvate of Etrasimod L-Arginine Form Cl or crystalline Etrasimod L-Arginine Form C2 as claimed in any one of the preceding claims 1 to 12 along with pharmaceutically acceptable excipients.

16. A pharmaceutical composition comprising amorphous form of Etrasimod L-Arginine as claimed in any one of the preceding claims 13- 14 along with pharmaceutically acceptable excipients.

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