WO2025115040A1

WO2025115040A1 - Novel co-crystals of saroglitazar and saroglitazar mg salt

Info

Publication number: WO2025115040A1
Application number: PCT/IN2024/052314
Authority: WO
Inventors: Harikishore Pingali; Kaushik BANERJEE; Pandurang Zaware; Sanjay Kumar
Original assignee: Zydus Lifesciences Ltd
Current assignee: Zydus Lifesciences Ltd
Priority date: 2023-12-01
Filing date: 2024-11-30
Publication date: 2025-06-05
Anticipated expiration: 2026-06-01

Abstract

The present invention relates to co-crystal of Saroglitazar of formula (I) and Saroglitazar magnesium of formula (Ia), processes for the preparation of these novel co-crystal, use thereof and pharmaceutical composition comprising the same.

Description

Novel co-crystals of Saroglitazar and Saroglitazar Mg salt

FIELD OF THE INVENTION:

The present invention relates to co-crystal of Saroglitazar of formula (I) and Saroglitazar magnesium of formula (la), processes for the preparation of these novel co-crystal, use thereof and pharmaceutical composition comprising the same.

BACKGROUND OF THE INVENTION

Saroglitazar, (S) 2-Ethoxy-3-(4-{2-[2-methyl-5-(4-methylthiophenyl)-pyrrol-l-yl]-ethoxy}- phenyl)-propionic acid, shown below as formula (I), is peroxisome proliferator-activated receptor (PPAR) agonist. Its synthesis was first described in WO 03009841.

Saroglitazar was approved by the Drug Controller General of India for the treatment of diabetic dyslipidemia and hypertriglyceridemia that is not controlled by statin and non-cirrhotic nonalcoholic steatohepatitis (NASH).

WO 03009841 discloses compounds of the following general formula:

These compounds are reported to be hypolipidemic agents also include Saroglitazar of formula (I).

formula (I) WO2012104869 discloses Saroglitazar Magnesium salt. Saroglitazar magnesium was approved by the Drug Controller General of India for the treatment of Diabetic Dyslipidemia, a condition in which a patient has diabetes and has elevated levels of the total cholesterol, the bad LDL cholesterol and triglycerides and a decrease in good HDL cholesterol in blood, and non-cirrhotic non-alcoholic steatohepatitis (NASH).

The Saroglitazar of formula (I) is a thick liquid which is difficult to isolate, purify and develop into a pharmaceutical formulation. It is therefore necessary to isolate the acid in a form that is easy to purify, handle, scale up and develop into suitable pharmaceutical formulation. Several attempts have been made to purify, stabilize the acid and obtain it in a solid form. Such efforts are reported in W02020183379. However, most of these efforts have not been successful in obtaining the acid in a stable solid form for further commercial development. Thus, there is a continuing need to obtain solid form of Saroglitazar of formula (I) having improved physical and/or chemical properties. The present invention satisfies this need by providing novel cocrystal of Saroglitazar of formula (I).

Further the Saroglitazar as disclosed in W003009841 was always obtained in liquid form. When its stability studies were conducted, it was found to be less suitable for further development due to its purity as well as stability concerns as shown below tabular form:

The experimental data in above table shows there is a rise in impurity after 6 and 17 days for the Saroglitazar free acid (compound of formula (I) ). Further, the Saroglitazar was found to be less stable at room temperature conditions and hence could not be developed further. Hence there is unmet need for additional solid stable form of Saroglitazar that are stable upon storage to allow the potential of Saroglitazar to be fully explored.

WO2012104869 discloses Saroglitazar Magnesium salt being effective in the treatment of lipohypertrophy, lipoatrophy and metabolic abnormalities in HIV patients.

WO2014174524 discloses the use of Saroglitazar and its pharmaceutically acceptable salts for the treatment of Non-alcoholic Fatty Liver Diseases (NAFLD) & Nonalcoholic Steatohepatitis (NASH). W02016181409 discloses the use of Saroglitazar and its pharmaceutically acceptable salts for the treatment of Chylomicronemia. WO2017089979 discloses the use of the Saroglitazar and its pharmaceutically acceptable salts for the treatment of diabetic nephropathy. WO2017089980 discloses the use of the Saroglitazar and its pharmaceutically acceptable salts for the treatment of diabetic retinopathy. Disclosed herein are the use of the Saroglitazar or its pharmaceutically acceptable salts for the treatment of polycystic ovarian syndrome (PCOS).

Although therapeutic efficacy is the primary concern for an active pharmaceutical ingredient (API), the chemical composition and solid-state form (i.e., the crystalline or amorphous form) of the API can be critical to its pharmacological properties, such as bioavailability, and to its development as a viable drug candidate. Compositions and crystalline forms of some API's have been used to alter the API's physicochemical properties. Each composition or crystalline form can have different solid state (physical and chemical) properties. The differences in physical properties exhibited by a novel solid-state forms (such as, for example, a polymorph of the API or a co-crystal containing the API, discussed below) may affect pharmaceutical and pharmacological properties such as storage stability, compressibility and density (important in formulation and product manufacturing), and/or solubility and dissolution rates (important factors in determining bioavailability). For example, the rate of dissolution of an active ingredient in a patient's stomach fluid may have therapeutic consequences since it impacts the rate at which an orally administered active ingredient may reach the patient's bloodstream. Because these practical properties are influenced by the solid-state properties, e.g. the crystalline form of the API, they can impact the selection of a particular compound as an API, the ultimate pharmaceutical dosage form, the optimization of manufacturing processes, and absorption in the body.

Physical properties of an API also have a major influence on the ability to deliver a drug by a desired method. For example, if a drug is delivered by inhalation physical properties relating to the API as a particle, such as morphology, density, surface energy, charge, hygroscopicity, stability, dispersive properties and/or agglomeration, can come into play. The solid-state form of the API, and as described below, co-crystals of the API, provide opportunities to address, engineer and/or improve upon one or more of such properties and thereby upon methods of delivery.

It may be possible to achieve more desirable properties of a particular API by forming a cocrystal of the API. A co-crystal of an API is a distinct chemical composition of the API and coformer(s) and generally possesses distinct crystallographic and spectroscopic properties when compared to those of the API and coformer(s) individually. Crystallographic and spectroscopic properties of crystalline forms are typically measured by X-ray powder diffraction (XRPD) and single crystal X-ray crystallography, among other techniques. Co-crystals often also exhibit distinct thermal behavior. Thermal behavior is measured in the laboratory by such techniques as capillary melting point, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). Co-crystals often possess more favorable solid state, physical, chemical, pharmaceutical and/or pharmacological properties or be easier to process than known forms or formulations of the API. For example, a co-crystal may have different dissolution and/or solubility properties than the API and can therefore be more effective in therapeutic delivery. Formation of a co- crystal can be used as a way to avoid polymorph formation of the drug. New pharmaceutical compositions comprising a co-crystal of a given API may therefore have different or superior properties as compared to its existing drug formulations.

Unlike salts, which possess a neutral net charge, but which are comprised of charge-balanced components, co-crystals are comprised of neutral species. Thus, unlike a salt, one cannot determine the stoichiometry of a co-crystal based on charge balance. Indeed, one can often obtain co-crystals having stoichiometric ratios of drug to coformer of greater than or less than 1: 1. The stoichiometric ratio of an API to coformer is a generally unpredictable feature of a cocrystal.

Without limiting the disclosed invention to any particular definition because others may define the term differently, the term ‘co-crystal’ may be thought of as a multi-component crystal composed of neutral molecules. These multi-component assemblies are continuing to excite and find usefulness, particularly within the pharmaceutical field, for their ability to alter physicochemical properties. More specifically, co-crystals have been reported to alter melting point, make a compound in liquid to solid form, aqueous solubility and/or dissolution rates, increase stability and improve bioavailability of active pharmaceutical ingredients.

This is because a co-crystal form may have improved dissolution or solubility properties or advantageous storage stability, melting point, hygroscopicity, etc. For a pharmaceutical cocrystal of Saroglitazar to be used as an alternative marketed form of Saroglitazar it is important that the coformer used is ‘inactive’ and that it possesses regulatory acceptability for use in a pharmaceutical formulation.

These co-crystals may be present either in substantially crystalline or amorphous forms or may be present as partially crystalline forms. In another embodiment, the co-crystal are present in non-solvated/unsolvated form or in a solvent free form. In another embodiment, the co-crystals are present in solvated/hydrated form. In yet another embodiment the co-crystal are present in their anhydrous form. OBJECT OF THE INVENTION:

In one embodiment of the present invention, there is provided a co-crystal of Saroglitazar of formula (I).

In yet another embodiment of the present invention, there is provided a co-crystal of Saroglitazar of formula (I) with a suitable one or more coformer.

In a still further embodiment is provided a pharmaceutical composition comprising, the therapeutically effective amount of a co-crystal of Saroglitazar of formula (I), prepared according to the present invention, along with at least one suitable pharmaceutically acceptable excipient known in the art for the treatment of dyslipidemia or hyperglycemia.

Use of a co-crystal of Saroglitazar of formula (I) for the treatment of dyslipidemia or hyperglycemia.

In a further embodiment is provided a process for the prep aration of co-crystal of Saroglitazar.

In an embodiment invention is further relates Saroglitazar isonicotinamide co-crystals.

In an embodiment the invention relates to a Saroglitazar isonicotinamide co-crystals in ratio (1: 1), a Saroglitazar isonicotinamide co-crystals in ratio (1:2) and a Saroglitazar isonicotinamide co-crystals in ratio (1 :3).

In an embodiments invention is further relates to Saroglitazar L-proline co-crystal.

In an embodiment the invention relates to a Saroglitazar L-proline co-crystals in ratio (1: 1), a Saroglitazar L-proline co-crystals in ratio (1:2) and a Saroglitazar L-proline co-crystals in ratio (1:3).

In one embodiment of the present invention, there is provided a co-crystal of Saroglitazar magnesium of formula (la).

In yet another embodiment of the present invention, there is provided a co-crystal of Saroglitazar magnesium of formula (la) with a suitable one or more coformer. In a still further embodiment is provided a pharmaceutical composition comprising, the therapeutically effective amount of a co-crystal of Saroglitazar magnesium of formula (la), prepared according to the present invention, along with at least one suitable pharmaceutically acceptable excipient known in the art for the treatment of dyslipidemia or hyperglycemia.

Use of a co-crystal of Saroglitazar magnesium of formula (la) for the treatment of dyslipidemia or hyperglycemia.

In a further embodiment is provided a process for the preparation of co-crystal of Saroglitazar magnesium.

In an embodiment invention is further relates Saroglitazar magnesium Isonicotinamide cocrystals.

In an embodiment invention is further relates Saroglitazar magnesium nicotinamide co-crystals.

In an embodiments invention is further relates to Saroglitazar magnesium L-proline co-crystal.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG.1 shows a DSC trace for the co-crystal of Saroglitazar with Isonicotinamide (1.5:1)

FIG.2 shows a DSC trace for the co-crystal of Saroglitazar with L-proline (1: 1)

FIG.3 shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1: 1)

FIG.4 shows an IR diagram of the co-crystal of Saroglitazar with L-proline (1 :2)

FIG.5 shows a DSC trace for the co-crystal of Saroglitazar with L-proline (1:3)

FIG.6 shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:3)

FIG.7 shows a DSC trace for the Co-crystal of Saroglitazar with L-proline (1:4)

FIG.8 shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:4)

FIG 9. shows a DSC trace for the Co-crystal of Saroglitazar with L-proline (1 :5)

FIG 10. shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:5)

FIG 11. shows a DSC trace for the Co-crystal of Saroglitazar with L-proline (1:6)

FIG 12. shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:6)

FIG 13. shows a DSC trace for the Co-crystal of Saroglitazar with L-proline (1:7) FIG 14. shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:7)

FIG 15. shows a DSC trace for the Co-crystal of Saroglitazar with L-proline (1:8)

FIG 16. shows an XRPD diagram of the co-crystal of Saroglitazar with L-proline (1:8)

FIG 17. shows an XRPD diagram of the Co-crystal of s Saroglitazar magnesium with L-proline (1: 1)

FIG 18. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with L-proline (1: 1)

FIG 19. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with L-proline (1:2)

FIG 20. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with L-proline (1:2)

FIG 21. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with L-proline (1:3)

FIG 22. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with L-proline (1:3)

FIG 23. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with L-proline (1:4)

FIG 24. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with L-proline (1:4)

FIG 25. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with L-proline (1:5)

FIG 26. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with L-proline (1:5)

FIG 27. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1: 1)

FIG 28. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1: 1)

FIG 29. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:2)

FIG 30. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:2)

FIG 31. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:3)

FIG 32. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:3)

FIG 33. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:4) FIG 34. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:4)

FIG 35. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:5)

FIG 36. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Isonicotinamide (1:5)

FIG 37. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Nicotinamide (1: 1)

FIG 38. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinamide (1: 1)

FIG 39. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Nicotinamide (1:2)

FIG 40. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinamide (1:2)

FIG 41. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with

Nicotinamide (1:3)

FIG 42. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinamide (1:3)

FIG 43. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with

Nicotinamide (1:4)

FIG 44. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinamide (1:4)

FIG 45. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with

Nicotinamide (1:5)

FIG 46. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinamide (1:5)

FIG 47. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Benzamide (1:3)

FIG 48. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Benzamide (1:3)

FIG 49. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Acetamide (1:3)

FIG 50. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Acetamide (1 :3) FIG 51. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with Nicotinic acid (1:3)

FIG 52. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with Nicotinic acid

(1:3)

FIG 53. shows an XRPD diagram of the Co-crystal of Saroglitazar magnesium with (E)-3-(4- hy dr oxy-3 -methoxyphenyl)acrylic acid (1 :3)

FIG 54. shows a DSC trace for the Co-crystal of Saroglitazar magnesium with (E)-3-(4-hydroxy- 3-methoxyphenyl)acrylic acid (1 :3)

DETAILED DESCRIPTION OF THE INVENTION:

Saroglitazar L-proline co-crystal

As herein used the term Saroglitazar or Saroglitazar free acid or Saroglitazar base or (S) 2- Ethoxy-3-(4-{2-[2-methyl-5-(4-methylthiophenyl)-pyrrol-l-yl]-ethoxy}-phenyl)-propionic acid or formula (I) in acid form is the compound having the following formula

SCH₃ formula (I)

The present invention provides novel co-crystal of Saroglitazar. Co-crystal of Saroglitazar comprising; a) Saroglitazar and; b) Suitable one or more coformers.

As used herein, a "coformer" is a non-ionized molecule that can form a co-crystal with Saroglitazar.

Specific examples include organic acids, amino acids, amines, and amides, with nonvolatile organic acids or amino acids being preferred. The molar ratio of Saroglitazar to coformer can take any value depending on the coformer, for example, 1 to 2 : 1 to 15.

The molar ratio of Saroglitazar to coformer can take any value depending on the coformer, for example, 1:0.5 to 1:15, 1.5:1 to 1.5: 15, 1: 1.5 to 1:5, 1:3 to 1:8 preferably 1:3.

The molar ratio of Saroglitazar to conformer is selected from 1: 1, 1 :2, 1:3, 1:4, 1 :5, 1:6, 1:7, 1:8, 1:9, 1: 10, 1.5: 1, 1.5:2, 1.5:3, 1.5:4, 1.5:5.

The molar ratio of coformer to Saroglitazar can take any value depending on the coformer, for example, 1:0.5 to 1:15, 1.5:1 to 1.5: 15, 1: 1.5 to 1:5, 1 :3 to 1:8 preferably 1:3.

The molar ratio of conformer to Saroglitazar is selected from 1: 1, 1 :2, 1:3, 1:4, 1 :5, 1:6, 1:7, 1:8, 1:9, 1: 10, 1.5: 1, 1.5:2, 1.5:3, 1.5:4, 1.5:5.

In some embodiments, the coformer may elute from the crystal lattice of the co-crystal under certain conditions, thereby rendering Saroglitazar supersaturated and increasing its solubility.

In this case, the coformer is preferably water-soluble.

In another embodiment, the coformer is a molecule that is solid at ambient temperature (15 °C - 25 °C) and normal pressure.

In the present specification, the term "organic acid" is not particularly limited as long as it is an organic compound exhibiting acidity that can form a co-crystal with Saroglitazar, and includes, for example, carboxylic acids and phenols.

"Carboxylic acid" is not particularly limited as long as it is an organic compound having at least one carboxyl group (-COOH) that can form a co-crystal with Saroglitazar, but examples include chain carboxylic acid, aromatic carboxylic acids and heterocyclic carboxylic acids.

In this specification, "non-volatile organic acid" is not particularly limited as long as it is an organic acid that can form a co-crystal with Saroglitazar; Examples include organic acids.

In certain embodiments, the non-volatile organic acid is a water-soluble organic acid. Preferably it is a carboxylic acid. More preferred is a benzoic acid compound which may be substituted at least one of the o-, m- or p-positions with a group selected from the group consisting of hydroxy, amino and carboxyl. More preferred are 2, 5-dihydroxybenzoic acid or salicylic acid.

As used herein, "amino acid" is not particularly limited as long as it is an organic compound having both amino and carboxyl functional groups, and includes natural amino acids and unnatural amino acids.

In this specification, "amine" is not particularly limited as long as it is a compound in which the hydrogen atom of ammonia is replaced with a hydrocarbon group or an aryl group, and includes aliphatic amines and aromatic amines.

In the present specification, "amide" is not particularly limited as long as it is a compound obtained by dehydration condensation of an oxoacid and ammonia or a primary or secondary amine, and examples thereof include carboxylic acid amide.

Suitable specific coformers used in the invention are selected from L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L- pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5 -nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3 -hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-Lbutyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3-, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide and combination thereof. Suitable solvent is selected from polar protic solvent used selected from methanol, ethanol, n- propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used are selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Nonpolar solvents used are selected from dichloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof.

In one embodiment of the present invention, there is provided Saroglitazar co-crystal which are in amorphous form.

In one embodiment of the present invention, there is provided Saroglitazar co-crystal which are in crystalline form.

In one embodiment of the present invention, there is provided Saroglitazar co-crystals which are in at least partially crystalline form.

In an embodiments invention is further relates to Saroglitazar isonicotinamide co-crystal. The Saroglitazar isonicotinamide co-crystal vary in ratio from 1 :1 to 1: 15 Saroglitazar to isonicotinamide or isonicotinamide to Saroglitazar.

In particular, the invention relates to a Saroglitazar isonicotinamide co-crystals in ratio (1.5:1), a Saroglitazar isonicotinamide co-crystals in ratio (1 :2) and a Saroglitazar isonicotinamide cocrystals in ratio (1:3).

In an embodiment, invention is further relates to Saroglitazar L-proline co-crystal. The Saroglitazar L-proline co-crystal vary in ratio from 1 :1 to 1: 15 Saroglitazar to L-proline or L- proline to Saroglitazar.

In particular, the invention relates to a Saroglitazar L-proline co-crystals in ratio (1: 1), a Saroglitazar L-proline co-crystals in ratio (1:2), Saroglitazar L-proline co-crystals in ratio (1 :3), a Saroglitazar L-proline co-crystals in ratio (1:4), Saroglitazar L-proline co-crystals in ratio (1 :5), a Saroglitazar L-proline co-crystals in ratio (1:6), Saroglitazar L-proline co-crystals in ratio (1 :7), and a Saroglitazar L-proline co-crystals in ratio (1:8).

These Saroglitazar L-proline co-crystal or Saroglitazar Isonicotinamide co-crystal of the invention, their preparation and their characterization are described in the examples below and shown in the figures. The invention relates to pharmaceutical compositions containing a therapeutically effective amount of a Saroglitazar L-proline co-crystal or Isonicotinamide cocrystal of the invention and a pharmaceutically acceptable carrier. The invention also relates to methods of treatment for the diseases, disorders and conditions described herein and the use of a therapeutically effective amount of Saroglitazar L-proline co-crystals or Isonicotinamide cocrystal of the invention, or a pharmaceutical composition containing it, for that treatment. The invention further provides the use of Saroglitazar L-proline co-crystals or Isonicotinamide cocrystal.

In one embodiment of the present invention, there is provided Saroglitazar L-proline co-crystal or Isonicotinamide co-crystal which are in amorphous form.

In one embodiment of the present invention, there is provided Saroglitazar L-proline co-crystal or Isonicotinamide co-crystal which are in crystalline form.

In one embodiment of the present invention, there is provided Saroglitazar L-proline co-crystals or Isonicotinamide co-crystal which are in at least partially crystalline form.

L-proline co-crystal or Isonicotinamide co-crystal of Saroglitazar of the invention in the manufacture of a medicament for use in the treatment of the diseases, disorders, and conditions described herein.

In a further embodiment of the invention disclosed Saroglitazar Isonicotinamide co-crystal (1.5: 1) which has the following characteristics: i) The differential scanning calorimetry (DSC) trace, Figure 1, shows a single endotherm with an onset temperature of 295.99 °C and a peak maximum of 302.01 °C.

In a further embodiment of the invention disclosed Saroglitazar L-proline co-crystal (1: 1) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 3; ii) A powder X-ray diffraction having amorphous pattern; iii) Saroglitazar L-proline co-crystal characterized by a melting point 53 °C ± 2 °C; iv) The differential scanning calorimetry (DSC) trace as per Figure 2; v) IR frequency having peaks at about 2972, 2920, 2877, 1720, 1610, 1510, 1408, 1311, 1238, 1111, 1043, 821, 758, 669, 542 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar L-proline co-crystals (1:2) which has the following characteristics: i) IR frequency substantially in accordance with Figure 4; ii) IR frequency having peaks at about 3053, 2976, 2920, 2873, 1720, 1610, 1560, 1510, 1406, 1377, 1311, 1296, 1238, 1112, 1095, 1035, 821, 759, 638, 542 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:3) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 6; ii) A powder X-ray diffraction pattern having peaks at about 14.953, 17.843, 18.199, 19.327, 22.472, 24.540, 33.772 ± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 12.168, 20.683, 25.673, 26.768, 30.091, 30.287, 31.920, 34.562, 35.229, 36.263, 37.319, 38.521, 39.499 ± 0.2 degrees 2-theta; iv) Saroglitazar L-proline co-crystal characterized by a melting point 194.8 °C ± 2 °C; v) The differential scanning calorimetry (DSC) trace, Figure 5, shows a single endotherm with an onset temperature of 187.90 °C and a peak maximum of 198.37 °C; vi) IR frequency having peaks at about 3049, 2980, 2922, 2875, 1720, 1610, 1556, 1510, 1406, 1377, 1313, 1294, 1238, 1112, 1095, 1033, 821, 759, 640 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:4) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 8; ii) A powder X-ray diffraction pattern having peaks at about 15.000, 17.886, 18.230, 19.382,

22.530, 24.598, 33.832 ± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 20.725, 25.731, 26.848, 30.370, 31.987, 34.617, 36.323, 37.376, 39.557± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace, Figure 7, shows a single endotherm with an onset temperature of 198.71 °C and a peak maximum of 206.35 °C; v) IR frequency having peaks at about 3053, 2981, 1718, 1610, 1556, 1510, 1448, 1357 1294, 1240, 1170, 1112, 1033, 825, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:5) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 10; ii) A powder X-ray diffraction pattern having peaks at about 15.005, 17.990, 18.299, 19.398, 22.550, 24.618, 33.839 ± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 20.753, 25.752, 26.878, 30.408, 32.013, 24.634, 26.365, 39.606± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace, Figure 9, shows a single endotherm with an onset temperature of 200.82 °C and a peak maximum of 208.73 °C; v) IR frequency having peaks at about 3055, 2981, 1720, 1610, 1556, 1510, 1448, 1357

1292, 1240, 1170, 1112, 1033, 825, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:6) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 12; ii) A powder X-ray diffraction pattern having peaks at about 14.986, 17.876, 18.264, 19.374, 22.515, 24.584, 33.813± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 20.715, 25.719, 26.844, 30.056, 30.375, 31.978, 34.593, 36.344, 37.410, 39.571± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace, Figure 11, shows a single endotherm with an onset temperature of 203.13 °C and a peak maximum of 212.33 °C; v) IR frequency having peaks at about 3051, 2981, 1720, 1610, 1556, 1375, 1292, 1240,

1033, 825, 759 cm'¹; In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:7) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 14; ii) A powder X-ray diffraction pattern having peaks at about 14.973, 17.856, 18.182, 19.352,

22.493, 24.560, 33.768± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 20.707, 25.694, 26.813, 30.333, 31.958, 34.575, 36.279, 37.362, 39.546± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace, Figure 13, shows a single endotherm with an onset temperature of 212.21 °C and a peak maximum of 216.67 °C; v) IR frequency having peaks at about 3049, 2981, 1718, 1610, 1556, 1510, 1404, 1575,

1292, 1240, 1170, 1112, 1033, 825, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar co-crystals (1:8) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 16; ii) A powder X-ray diffraction pattern having peaks at about 14.963, 17.847, 18.237, 19.349,

22.494, 24.560, 33.794± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 25.695, 26.810, 30.347, 31.952, 34.583, 36.317, 37.378, 39.554± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace, Figure 15, shows a single endotherm with an onset temperature of 209.45 °C. and a peak maximum of 215.34 °C; v) IR frequency having peaks at about 3049, 2981, 1710, 1610, 1556, 1404, 1556, 1448,

1375, 1290, 1253, 1168, 1033, 846, 786cm’¹.

The invention also provides a method for preparing the co-crystal, including:

Method: 1 a) Prepared the homogenous solution of Saroglitazar and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-/-butyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from di chloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof. b) The solvent was allowed to evaporate slowly under grinding at ambient temperature. c) The co-crystal is dried under reduced pressure for 3 days.

Method 2: a) Prepared the homogenous solution of Saroglitazar and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-/-butyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from di chloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof. b) The solvent from the homogenous solution was evaporated at elevated temperature and/or under reduced pressure. c) The co-crystals are dried under reduced pressure.

The present invention also provides another method for preparing the co-crystal, including:

Method 3:

Griding the Saroglitazar and suitable coformers such as L-proline, L-proline monohydrate, L- proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4-hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3 -/-butyl -4-hy dr oxyanisole, propyl-4-hy dr oxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide without solvents manually or mechanically for a fixed period of time.

Method 4:

Grinding the Saroglitazar and suitable coformers such as L-proline, L-proline monohydrate, L- proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4-hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3 -/-butyl -4-hy dr oxyanisole, propyl-4-hy dr oxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from dichloromethane, chloroform, tetrahydrofuran, 1, 4 dioxane or suitable mixtures thereof manually or mechanically, for a fixed period of time.

Method 5:

Heat the Saroglitazar and suitable coformers such as L-proline, L-proline monohydrate, L- proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4-hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3 -t-butyl-4-hy dr oxyanisole, propyl-4-hy dr oxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide to until melt. b) Cool at ambient temperature

Therapeutic Uses of Saroglitazar Co-crystals

As discussed above, Saroglitazar is known in the art to be useful in the treatment of various diseases, disorders, and conditions. The Saroglitazar co-crystals of the invention, specifically, 1.5: 1 Saroglitazar Isonicotinamide co-crystal, 1:1 Saroglitazar L-proline co-crystal, and 1:2 Saroglitazar L-proline co-crystal and 1 :3 Saroglitazar L-proline co-crystal and pharmaceutical compositions containing them may then also be used to treat such diseases, disorders, and conditions. The diseases, disorders, or conditions which may treated with an Saroglitazar cocrystal of the invention include, but are not limited to: treatment of dyslipidemia and hypercholesterolemia, nonalcoholic steatohepatitis (NASH), Non-alcoholic fatty liver disease (NAFLD), Primary Biliary Cholangitis (PBC), Fibrosis, Polycystic ovary syndrome (PCOS), Lipodystrophy, Diabetic retinopathy, Insulin-sensitizing and metabolic related disorders, anti-inflammatory, atherogenesis, renal dysfunction, autoimmune diseases, inflammatory bowel disease (IBD), autoimmune myocarditis, autoimmune encephalomyelitis, multiple sclerosis. Accordingly, the invention relates to the method of treating such a disease, disorder, or condition comprising the step of administering to a patient in need thereof a therapeutically effective amount of a Saroglitazar co-crystal of the invention or of administering to a patient in need thereof a therapeutic composition containing an Saroglitazar co-crystal of the invention.

The term "treatment" or "treating" used anywhere in the specification means any treatment of a disease, disorder, or condition in a mammal, including: preventing or protecting against the disease, disorder, or condition, that is, causing the clinical symptoms not to develop; inhibiting the disease, disorder, or condition, that is, arresting or suppressing the development of clinical symptoms; and/or relieving the disease, disorder, or condition (including the relief of discomfort associated with the condition or disorder), that is, causing the regression of clinical symptoms. It will be understood by those skilled in the art that in human medicine, it is not always possible to distinguish between "preventing" and "suppressing" since the ultimate inductive event or events may be unknown, latent, or the patient is not ascertained until well after the occurrence of the event or events. Therefore, as used herein the term "prophylaxis" is intended as an element of "treatment" to encompass both "preventing" and "suppressing" the disease, disorder, or condition. The term "protection" is meant to include "prophylaxis." Another aspect of the invention relates to the use of a Saroglitazar co-crystal of the invention in the treatment of diseases, disorders, and conditions discussed above. Accordingly, the invention further relates to the manufacture of a medicament for use in the treatment of such diseases, disorders, and conditions.

Pharmaceutical Compositions Containing Saroglitazar co-crystals

The present invention also provides a pharmaceutical composition, which contains the co-crystal and one or more pharmaceutically acceptable carrier or excipient.

The co-crystal of Saroglitazar of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known.

The pharmaceutical compositions according to this invention can exist in various forms. In some embodiments, the pharmaceutical composition is in the form of a powder or solution. In some other embodiments, the pharmaceutical compositions according to the invention are in the form of a powder that can be reconstituted by addition of a compatible reconstitution diluent prior to parenteral administration. Non-limiting example of such a compatible reconstitution diluents include water.

The pharmaceutical compositions are prepared and formulated according to conventional methods, such as those disclosed in standard reference texts and are well within the scope of a skilled person. For example, the solid oral compositions may be prepared by conventional methods of blending, filling or tableting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing variable quantities of fillers, binding agent, lubricants, glidants, disintegrants, etc. Such operations are of course conventional in the art. The tablets may be coated according to methods well known in normal pharmaceutical practice.

Examples of binding agents include acacia, alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, dextrates, dextrin, dextrose, ethylcellulose, gelatin, liquid glucose, guar gum, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, magnesium aluminium silicate, maltodextrin, methyl cellulose, polymethacrylates, polyvinylpyrrolidone, pregelatinised starch, sodium alginate, sorbitol, starch, syrup, tragacanth.

Examples of fillers include calcium carbonate, calcium phosphate, calcium sulphate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, fructose, glyceryl palmitostearate, glycine, hydrogenated vegetable oil-type 1, kaolin, lactose, maize starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylates, potassium chloride, powdered cellulose, pregelatinised starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, tribasic calcium phosphate, xylitol. Examples of lubricants include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulphate, stearic acid, sodium stearyl fumarate, talc, zinc stearate.

Examples of glidants include colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide, talc.

Examples of disintegrants include alginic acid, carboxymethylcellulose calcium, carboxymethylcellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, guar gum, magnesium aluminium silicate, microcrystalline cellulose, methyl cellulose, polyvinylpyrrolidone, polacrilin potassium, Pregelatinized starch, sodium alginate, sodium lauryl sulphate, sodium starch glycollate.

Use of Saroglitazar co-crystal, for the treatment of dyslipidemia or hyperglycemia.

Compared with Saroglitazar, the Saroglitazar co-crystal prepared by the invention has better stability, is convenient for storage and use, can be directly used in the preparation of solid preparations, and has good powder properties.

Following characterization methods were used to confirm synthesis of novel co-crystal.

Analytical methods:

The complete x-ray powder spectrum, was recorded with a Rigaku D/Max 2200 VPC X-ray powder diffractometer model using copper radiation. The X-ray diffraction pattern was recorded by keeping the instrument parameters as below:

X-ray: Cu/40kv/30mA, Diverging slit: lo, Scattering slit: lo, Receiving slit: 0.15 mm, Monochromator RS: 0.8 mm, Counter: Scintillation counter.

Scan mode: Continuous, Scan speed: 3.000o/min., Sampling width: 0.020o, Scan axes: 2 theta vs CPS, Scan range: 2o to 40. Oo, Theta offset: 0.000

Differential scanning calorimetric analysis was carried out in a DSC-60 model from Shimadzu (S/W: TA-60WS Acquisition version 2.1.0.0) by keeping following parameters, Sample Size: Approx. l-2mg, Sample Pans: Hermetic/Crimping Pans,

Start Temperature: 50°C, End Temperature: 300°C, Rate of Heating: 10 °C/min., Purge Gas: Nitrogen, Flowrate: 20 ml/min

The infrared (IR) spectrum has been recorded on a Shimadzu FTIR-8400 model spectrophotometer, between 450 cm-1 and 4000 cm-1, with a resolution of 4 cm-1 in a KBr pellet.

The invention is further exemplified by the following non-limiting examples, which are illustrative representing the preferred modes of carrying out the invention. The invention’s scope is not limited to these specific embodiments only but should be read in conjunction with what is disclosed anywhere else in the specification together with those information and knowledge which are within the general understanding of a person skilled in the art.

Pharmacological data:

Comparative efficacy study (Triglyceride lowering effects) of Saroglitazar (Compound-I) free acid, Saroglitazar Magnesium salt (Compound la) and Compound (I): L-proline Cocrystal in Swiss albino mice model.

The in-vivo efficacy of test compound was evaluated in Swiss albino mice. Anti-dyslipidemic drugs have been reported to lower circulating levels of triglyceride in mice through their effect on genes involved in the peroxisomal fatty acid beta oxidation via PPAR alpha agonism. Therefore, this species is preferred for evaluation of their efficacy in lowering circulating triglyceride (TG) levels.

In this experiment, seven to eight weeks old male Swiss albino mice were used after acclimatization. Near the end of the acclimatization period, animals judged to be suitable for testing were bled under light anesthesia and serum samples were analyzed for serum triglyceride levels. Animals were selected according to triglyceride levels in the range of 59 to 152 mg/dl and divided into various treatment groups (Table no.1) of 6 animals each such that the average TG levels of animals in each group were not significantly different from the others and each group. Table no.l- Treatment groups and dose levels

Test compounds were formulated at specified doses in vehicle (MiliQ Water). The animals were dosed orally, once daily in the morning during six days, starting from next day of grouping, with vehicle or test compound. The animals were weighed prior to dosing and based on these weights; the volume of administration was calculated. The volume of formulation administered orally to each mouse was 10 ml/kg body weight.

On day 6, one hour after the dose administration, blood (0.25 ml) was collected from retro- orbital sinus of the anaesthetized animals. Serum was separated by centrifugation. Analysis for serum triglyceride levels was performed by Mindray BS-240 biochemical analyzer using Mindray TG estimation kit. Calculations for determination of % change and % reduction in serum TG levels (Table 2) were performed using MS Excels sheet.

Result:

Six days oral administration of Compound (I) as free acid at 1 mg/kg, p.o. resulted in 33 % reduction in serum triglyceride level, whereas its co-crystal form with L-proline and its Magnesium salt form showed 68% and 57% reduction in serum triglyceride levels respectively as compared to vehicle treated group as depicted in Table no.2. Table no.2- Effect on serum triglyceride levels

** Significantly different from the vehicle control group at p< 0.01 using nonparametric t- test.

**** Significantly different from the vehicle control group at p< 0.0001 using nonparametric t-test.

# Significantly different from the Compound 1(a) as free acid group at p< 0.01 using nonparametric t-test.

Conclusion:

In conclusion, L-proline co-crystal form showed greater efficacy than Magnesium salt form of

Compound (I) and free acid form of Compound (I) in Swiss albino mice model.

PK data:

Oral exposure of Saroglitazar magnesium salt and Saroglitazar L-proline co-crystal was evaluated in male Wistar rats at 3 mg/kg dose:

Table No. 3:

Based on data as given in Table no. 3, Cmax and AUCO-inf of Saroglitazar -L proline co-crystal and Saroglitazar magnesium were 46.6% and 34.6% respectively.

Saroglitazar Magnesium L-proline co-crystal

As herein used the term Saroglitazar or Saroglitazar free acid or (S) 2-Ethoxy-3-(4-{2-[2-methyl- 5-(4-methylthiophenyl)-pyrrol-l-yl] -ethoxy} -phenyl)-propionic acid or formula (I) in acid form is the compound having the following formula

and Saroglitazar magnesium as shown in formula (la)

The present invention provides novel co-crystal of Saroglitazar magnesium.

Co-crystal of Saroglitazar magnesium comprising; a) Saroglitazar magnesium and; b) Suitable one or more coformers.

Specific examples include organic acids, amino acids, amines, and amides, with nonvolatile organic acids or amino acids being preferred.

The molar ratio of Saroglitazar to coformer can take any value depending on the coformer, for example, 1 to 2 : 1 to 15.

The molar ratio of Saroglitazar magnesium to coformer can take any value depending on the coformer, for example, 1 :0.5 to 1: 15, 1.5: 1 to 1.5: 15, 1 :1.5 to 1:5, 1:3 to 1 :8 preferably 1 :3.

The molar ratio of Saroglitazar magnesium to conformer is selected from 1: 1, 1 :2, 1:3, 1 :4, 1:5, 1:6, 1:7, 1 :8, 1:9, 1:10, 1.5:1, l.:2, 1.5:3, 1.5:4, 1.5:5.

The molar ratio of coformer to Saroglitazar magnesium can take any value depending on the coformer, for example, 1 :0.5 to 1: 15, 1.5: 1 to 1.5: 15, 1 :1.5 to 1:5, 1:3 to 1 :8 preferably 1 :3.

The molar ratio of conformer to Saroglitazar magnesium is selected from 1: 1, 1 :2, 1:3, 1:4, 1:5, 1:6, 1:7, 1 :8, 1:9, 1:10, 1.5:1, 1.5:2, 1.5:3, 1.5:4, 1.5:5. In some embodiments, the coformer may elute from the crystal lattice of the co-crystal under certain conditions, thereby rendering Saroglitazar magnesium supersaturated and increasing its solubility.

In this case, the coformer is preferably water-soluble.

Suitable specific coformers used in the invention are selected from L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L- pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, (E)-3-(4-hy dr oxy-3 - methoxyphenyl)acrylic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-Z-butyl-4-hydroxyanisole, propyl-4-hy dr oxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3-, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4- amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide and combination thereof.

Suitable solvent is selected from polar protic solvent used selected from methanol, ethanol, n- propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvent used is selected from dichloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof. In one embodiment of the present invention, there is provided Saroglitazar magnesium co-crystal which are in amorphous form.

In one embodiment of the present invention, there is provided Saroglitazar magnesium co-crystal which are in crystalline form.

In one embodiment of the present invention, there is provided Saroglitazar magnesium cocrystals which are in at least partially crystalline form.

In an embodiments invention is further relates to Saroglitazar magnesium L-proline co-crystal. The Saroglitazar magnesium L-proline co-crystal vary in ratio from 1:1 to 1 :15 Saroglitazar magnesium to L-proline or L-proline to Saroglitazar magnesium.

In an embodiments invention is further relates to Saroglitazar magnesium Isonicotinamide cocrystal. The Saroglitazar magnesium Isonicotinamide co-crystal vary in ratio from 1: 1 to 1:15 Saroglitazar magnesium to Isonicotinamide or Isonicotinamide to Saroglitazar magnesium.

In an embodiments invention is further relates to Saroglitazar magnesium Nicotinamide cocrystal. The Saroglitazar magnesium Nicotinamide co-crystal vary in ratio from 1 :1 to 1 :15 Saroglitazar magnesium to Nicotinamide or nicotinamide to Saroglitazar magnesium.

These Saroglitazar magnesium L-proline co-crystal, Saroglitazar magnesium nicotinamide or Saroglitazar magnesium Isonicotinamide co-crystal of the invention, their preparation and their characterization are described in the examples below and shown in the figures. The invention relates to pharmaceutical compositions containing a therapeutically effective amount of a Saroglitazar magnesium L-proline co-crystal, nicotinamide co-crystal or Isonicotinamide cocrystal of the invention and a pharmaceutically acceptable carrier. The invention also relates to methods of treatment for the diseases, disorders and conditions described herein and the use of a therapeutically effective amount of Saroglitazar magnesium L-proline co-crystals, nicotinamide co-crystal or Isonicotinamide co-crystal of the invention, or a pharmaceutical composition containing it, for that treatment. The invention further provides the use of Saroglitazar magnesium L-proline co-crystals, nicotinamide co-crystal or Isonicotinamide co-crystal. In one embodiment of the present invention, there are provided Saroglitazar magnesium L- proline co-crystals, nicotinamide co-crystal or Isonicotinamide co-crystals which are in amorphous form.

In one embodiment of the present invention, there is provided Saroglitazar magnesium L-proline co-crystals, nicotinamide co-crystals or Isonicotinamide co-crystal which are in crystalline form.

In one embodiment of the present invention, there is provided Saroglitazar magnesium L-proline co-crystals, nicotinamide co-crystals or Isonicotinamide co-crystals which are in at least partially crystalline form.

L-proline co-crystal, nicotinamide co-crystal or Isonicotinamide co-crystal of Saroglitazar magnesium of the invention in the manufacture of a medicament for use in the treatment of the diseases, disorders, and conditions described herein.

In a further embodiment of the invention disclosed Saroglitazar magnesium L-proline (1 :1) cocrystals which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 17; ii. A powder X-ray diffraction pattern having amorphous pattern; iii. Saroglitazar magnesium L-proline (1: 1) co-crystal characterized by a melting point 68.7 °C ± 2 °C; iv. The differential scanning calorimetry (DSC) trace of 1 :1 Saroglitazar magnesium L- Proline co-crystal, Figure 18 shows a single endotherm with an onset temperature of 106.71 °C and a peak maximum of 117.19 °C; v. IR frequency of 1 : 1 Saroglitazar magnesium L-Proline co-crystal having peaks at about 2972, 2920, 1602, 1510, 1408, 1311, 1238, 1176, 1095, 1043, 821, 758 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium L-proline co-crystals (1:2) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 19; ii. A powder X-ray diffraction pattern having amorphous pattern; iii. DSC of the 1:2 Saroglitazar magnesium L-Proline co-crystal, The differential scanning calorimetry (DSC) trace, Figure 20 shows a single endotherm with an onset temperature of 110.33° C. and a peak maximum of 121.82° C; iv. IR frequency of the 1 :2 Saroglitazar magnesium L-Proline co-crystal, having peaks at about 2968, 2922, 1606, 1510, 1406, 1311, 1238, 1176, 1093, 1043, 821, 759 cm ;

In a further embodiment of the invention disclosed Saroglitazar magnesium L-proline co-crystals (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 21; ii. A powder X-ray diffraction pattern having peaks at about 15.064, 17.996, 18.387, 19.465, 22.626, 24.690, 33.952 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 17.454, 29.821, 30.470, 32.075 ± 0.2 degrees 2-theta; iv. DSC of the 1:3 Saroglitazar magnesium L-Proline co-crystal, The differential scanning calorimetry (DSC) trace, Figure 22 shows a single endotherm with an onset temperature of 187.21 °C and a peak maximum of 202.11 °C; v. IR frequency of the 1 :3 Saroglitazar magnesium L-Proline co-crystal, having peaks at about 3057, 2966, 1602, 1510, 1377, 1238, 1176, 1093, 1037, 821, 758 cm⁴.

In a further embodiment of the invention disclosed Saroglitazar magnesium L-proline co-crystals (1:4) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 23; ii. A powder X-ray diffraction pattern having peaks at about 15.122, 18.018, 18.429, 19.513, 22.676, 33.983 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 20.878, 25.873, 26.991, 30.533, 32.132, 34.676 ± 0.2 degrees 2-theta; iv. DSC of the 1:4 Saroglitazar magnesium L-Proline co-crystal, The differential scanning calorimetry (DSC) trace, Figure 24 shows a single endotherm with an onset temperature of 199.38 °C and a peak maximum of 207.22 °C; V. IR frequency of the 1 :4 Saroglitazar magnesium L-Proline co-crystal, having peaks at about 3049, 2980, 1610, 1558, 1436, 1377, 1240, 1170, 1093, 1035, 821, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar magnesium L-proline co-crystals (1:5) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 25; ii. A powder X-ray diffraction pattern having peaks at about 15.091, 17.989, 18.402, 19.487, 22.647, 24.715, 33.958 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 20.846, 26.970, 30.506, 32.112, 34.741, 36.478 ± 0.2 degrees 2-theta; iv. DSC of the 1:5 Saroglitazar magnesium L-Proline co-crystal, The differential scanning calorimetry (DSC) trace, Figure 26, shows a single endotherm with an onset temperature of 202.84 °C and a peak maximum of 212.03 °C. v. IR frequency of the 1 :5 Saroglitazar magnesium L-Proline co-crystal, having peaks at about 3047, 2983, 1614, 1556, 1406, 1377, 1242, 1170, 1085, 1035, 821, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar magnesium Isonicotinamide cocrystal (1: 1) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 27; ii) A powder X-ray diffraction pattern having peaks at about 4.351, 7.688, 8.834, 14.051, 15.771, 16.344, 17.618, 18.676, 19.426, 19.766, 20.486, 21.030, 22.077, 22.728, 22.909, 23.292, 28.335 ± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 24.851, 26.805, 30.463, 32.322, 34.691, 35.673 ± 0.2 degrees 2-theta; iv) Saroglitazar magnesium Isonicotinamide co-crystal (1: 1) characterized by a melting point 198.2 °C ± 2 °C; v) The differential scanning calorimetry (DSC) trace of the 1 :1 Saroglitazar magnesium Isonicotinamide Co-crystal as per Figure 28 and shows a single endotherm with an onset temperature of 143.84 °C and a peak maximum of 150.48 °C; vi) IR frequency of the 1 : 1 Saroglitazar magnesium Isonicotinamide co-crystal having peaks at about 3327, 3062, 2972, 2920, 1678, 1608, 1554, 1510, 1409, 1311, 1240, 1112, 1093, 1062, 1045, 1002, 819, 758, 557 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium Isonicotinamide cocrystal (1:2) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 29; ii. A powder X-ray diffraction pattern having peaks at about 14.499, 18.459, 22.120 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 4.449, 18.603, 18.871, 21.617, 24.240, 25.402, 32.105 ± 0.2 degrees 2-theta; iv. DSC of the 1:2 Saroglitazar magnesium Isonicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 30, shows a single endotherm with an onset temperature of 142.01 °C and a peak maximum of 148.22 °C; v. IR frequency of the 1 :2 Saroglitazar magnesium Isonicotinamide co-crystal, having peaks at about 3327, 3057, 1676, 1610, 1554, 1508, 1394, 1238, 1002, 821, 758 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar magnesium Isonicotinamide cocrystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 31 ; ii. A powder X-ray diffraction pattern having peaks at about 14.497, 18.439, 22.117, 22.931, 23.347 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 4.392, 14.139, 18.643, 18.875, 19.807, 20.727, 21.627, 24.222, 24.863, 28.471, 32.113 ± 0.2 degrees 2- theta; iv. DSC of the 1:3 Saroglitazar magnesium Isonicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 32, shows a single endotherm with an onset temperature of 150.54 °C and a peak maximum of 154.10 °C; v. IR frequency of the 1 :3 Saroglitazar magnesium Isonicotinamide co-crystal, having peaks at about 3321, 3051, 1678, 1614, 1552, 1510, 1396, 1224, 1062, 1002, 819, 759 cm’¹; In a further embodiment of the invention disclosed Saroglitazar magnesium Isonicotinamide cocrystal (1:4) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 33; ii. A powder X-ray diffraction pattern having peaks at 18.536, 18.699, 22.197, 23.007, 22.425 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 14.200, 18.910, 19.887, 21.696, 24.312, 24.905, 25.459, 28.511, 32.179 ± 0.2 degrees 2-theta; iv. DSC of the 1:4 Saroglitazar magnesium Isonicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 34, shows a single endotherm with an onset temperature of 151.58 °C and a peak maximum of 154.81 °C; v. IR frequency of the 1 :4 Saroglitazar magnesium Isonicotinamide co-crystal, having peaks at about 3327, 3059, 1680, 1614, 1552, 1510, 1394, 1002, 819, 758 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium Isonicotinamide cocrystal (1:5) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 35; ii. A powder X-ray diffraction pattern having peaks at 14.536, 18.488, 22.166, 22.976, 23.392, 24.269 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 4.441, 1.165, 18.696, 19.853, 20.779, 21.669, 24.942, 25.434, 28.483, 32.154 ± 0.2 degrees 2-theta; iv. DSC of the 1:5 Saroglitazar magnesium Isonicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 36, shows a single endotherm with an onset temperature of 152.01 °C. and a peak maximum of 154.56 °C. v. IR frequency of the 1:5 Saroglitazar magnesium Isonicotinamide Co-crystal, having peaks at about 3325, 3057, 1678, 1614, 1552, 1508, 1394, 1224, 1002, 819, 758 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar magnesium nicotinamide cocrystal (1: 1) which has at least one of the following characteristics: i) A powder X-ray diffraction pattern substantially in accordance with Figure 37; ii) A powder X-ray diffraction pattern having peaks at about 4.372, 7.723, 8.841, 14.620,

16.921, 19.299, 22.022, 23.143, 25.202, 25.611, 26.036, 27.094 ± 0.2 degrees 2-theta; iii) A powder X-ray diffraction pattern having additional peaks at about 11.157, 23.878,

29.892, 32.362, 34.241, 36.767, 38.494 ± 0.2 degrees 2-theta; iv) The differential scanning calorimetry (DSC) trace of the 1 :1 Saroglitazar magnesium nicotinamide co-crystal as per Figure 38 and shows a single endotherm with an onset temperature of 117.64 °C and a peak maximum of 123.22 °C; v) IR frequency of the 1 : 1 Saroglitazar magnesium nicotinamide co-crystal having peaks at about 3363, 2972, 2916, 1676, 1608, 1510, 1421, 1404, 1311, 1238, 1174, 1093, 1070, 1028, 819, 758 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium nicotinamide cocrystal (1:2) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 39; ii. A powder X-ray diffraction pattern having peaks at about 4.491, 14.707, 17.111, 17.401, 19.419, 23.264, 24.487, 25.287, 25.745, 27.214 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 7.824, 9.016, 16.191, 17.966, 19.797, 23.656, 26.486, 32.497 ± 0.2 degrees 2-theta; iv. DSC of the 1:2 Saroglitazar magnesium nicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 40, shows a single endotherm with an onset temperature of 121.64 °C and a peak maximum of 125.77 °C; v. IR frequency of the 1:2 Saroglitazar magnesium nicotinamide co-crystal, having peaks at about 3367, 3155, 1678, 1614, 1510, 1402, 1238, 1028, 821, 759 cm’¹;

In a further embodiment of the invention disclosed Saroglitazar magnesium nicotinamide cocrystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 41; ii. A powder X-ray diffraction pattern having peaks at about 14.738, 22.161, 23.297, 25.319, 29.779, 27.247 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 4.507, 11.272, 19.455, 19.836 ± 0.2 degrees 2-theta; iv. DSC of the 1:2 Saroglitazar magnesium nicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 42, shows a single endotherm with an onset temperature of 123.31 °C and a peak maximum of 126.76 °C; v. IR frequency of the 1:3 Saroglitazar magnesium nicotinamide co-crystal, having peaks at about 3363, 3159, 1676, 1612, 1421, 1394, 1238, 1028, 827, 759 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium nicotinamide cocrystal (1:4) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 43; ii. A powder X-ray diffraction pattern having peaks at about 14.706, 22.123, 23.272, 25.299, 25.753, 27.226 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 11.240, 19.418, 22.613 ± 0.2 degrees 2-theta; iv. DSC of the 1:4 Saroglitazar magnesium nicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 44, shows a single endotherm with an onset temperature of 124.15 °C and a peak maximum of 128.19 °C; v. IR frequency of the 1:4 Saroglitazar magnesium nicotinamide co-crystal, having peaks at about 3361, 3147, 1674, 1614, 1510, 1394, 1240, 1028, 827, 765 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium nicotinamide cocrystal (1:5) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 45; ii. A powder X-ray diffraction pattern having peaks at about 14.704, 22.119, 23.241, 25.273, 25.728, 27.202 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 11.237, 19.418, 22.604, 30.871 ± 0.2 degrees 2-theta. iv. DSC of the 1:5 Saroglitazar magnesium nicotinamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 46, shows a single endotherm with an onset temperature of 124.57 °C and a peak maximum of 127.70 °C; v. IR frequency of the 1 : 5 Saroglitazar magnesium nicotinamide co-crystal, having peaks at about 3360, 3151,1676, 1612, 1394, 1242, 1028, 827, 763 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium Benzamide cocrystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 47; ii. A powder X-ray diffraction pattern having peaks at about 7.747, 15.627, 16.402, 17.927, 19.831, 20.790, 22.408, 26.358, 28.356, 28.605 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 4.390, 19.202, 23.723, 23.920, 25.391, 30.708, 33.274, 35.682 ± 0.2 degrees 2-theta; iv. Saroglitazar magnesium benzamide co-crystal characterized by a melting point 113.7 °C ± 2 °C; v. DSC of the 1 :3 Saroglitazar magnesium benzamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 48, shows a single endotherm with an onset temperature of 104.60 °C and a peak maximum of 116.27 °C; vi. IR frequency of the 1:3 Saroglitazar magnesium benzamide co-crystal, having peaks at about 3365, 3169, 1654, 1614, 1577, 1508, 1402, 1242, 1120, 810, 765 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium Acetamide cocrystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 49; ii. A powder X-ray diffraction pattern having peaks at about 4.453, 7.779, 8.957± 0.2 degrees 2-theta; iii. Saroglitazar magnesium Acetamide co-crystal characterized by a melting point 131.3 °C ± 2 °C; iv. DSC of the 1 :3 Saroglitazar magnesium Acetamide co-crystal, The differential scanning calorimetry (DSC) trace, Figure 50, shows a single endotherm with an onset temperature of 54.68 °C and a peak maximum of 58.31 °C; v. IR frequency of the 1:3 Saroglitazar magnesium Acetamide co-crystal, having peaks at about 3356, 3386, 1660, 1608, 1510, 1392, 1240, 1112, 821, 758 cm’¹. In a further embodiment of the invention disclosed Saroglitazar magnesium Nicotinic acid cocrystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 51; ii. A powder X-ray diffraction pattern having peaks at about 15.189, 20.062, 20.919, 24.481, 25.649, 26.566, 27.645 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 28.930, 33.827, 33.445, 35.445, 38.015, 39.608 ± 0.2 degrees 2-theta; iv. Saroglitazar magnesium Nicotinic acid co-crystal characterized by a melting point >300° C ± 2 °C; v. DSC of the 1 :3 Saroglitazar magnesium Nicotinic acid co-crystal, substantially in accordance with Figure 52; vi. IR frequency of the 1:3 Saroglitazar magnesium Nicotinic acid co-crystal, having peaks at about 2972, 2918, 1707, 1608, 1510, 1413, 1321, 1298, 1240, 1176, 1039, 812 cm’¹.

In a further embodiment of the invention disclosed Saroglitazar magnesium (E)-3-(4-hydroxy-3- methoxyphenyl)acrylic acid co-crystal (1:3) which has at least one of the following characteristics: i. A powder X-ray diffraction pattern substantially in accordance with Figure 53; ii. A powder X-ray diffraction pattern having peaks at about 8.874, 10.332, 12.661, 15.474, 17.255, 17.960, 20.297, 20.974, 21.472, 22.893, 24.482, 25.792, 26.280, 27.317, 29.302 ± 0.2 degrees 2-theta; iii. A powder X-ray diffraction pattern having additional peaks at about 22.177, 28.928, 29.675, 31.124, 31.435, 35.933, 28.883 ± 0.2 degrees 2-theta; iv. Saroglitazar magnesium (E)-3 -(4-hy dr oxy-3 -methoxyphenyl)acrylic acid co-crystal characterized by a melting point 154.5° C ± 2 ° C; v. DSC of the 1 :3 Saroglitazar magnesium (E)-3 -(4-hy dr oxy-3 -methoxyphenyl)acrylic acid co-crystal, The differential scanning calorimetry (DSC) trace, Figure 54 shows a single endotherm with an onset temperature of 139.18 °C and a peak maximum of 139.67 °C; vi. IR frequency of the 1:3 Saroglitazar magnesium (E)-3 -(4-hy dr oxy-3 - methoxyphenyl)acrylic acid co-crystal, having peaks at about 3345, 1689, 1618, 1598, 1510, 1431, 1267, 1201, 1033, 945, 850, 802 cm’¹.

The invention also provides a method for preparing the co-crystal, including:

Method: 1 a) Prepared the homogenous solution of Saroglitazar magnesium and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-/-butyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from di chloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof. b) The solvent was allowed to evaporate slowly under grinding at ambient temperature. c) The co-crystal are dried under reduced pressure for 3 days. Method 2: a) Prepared the homogenous solution of Saroglitazar magnesium and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-/-butyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from di chloromethane, chloroform, tetrahydrofuran, 1, 4 -dioxane or suitable mixtures thereof. b) The solvent from the homogenous solution was evaporated at elevated temperature and/or under reduced pressure. c) The co-crystals are dried under reduced pressure.

Method 3:

Griding the Saroglitazar magnesium and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L- pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-Lbutyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide without solvents manually or mechanically for a fixed period of time.

Method 4:

Grinding the Saroglitazar magnesium and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L- pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-Lbutyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide in the suitable solvent; Suitable solvent is polar protic solvent and selected from methanol, ethanol, n-propanol, n-butanol, acetic acid and mixture thereof. Dipolar aprotic solvents used is selected from acetone, ethyl acetate, dimethyl sulfoxide, acetonitrile, dimethyl formamide and mixture thereof. Non polar solvents used is selected from di chloromethane, chloroform, tetrahydrofuran, 1, 4 dioxane or suitable mixtures thereof manually or mechanically, for a fixed period of time.

Method 5:

Heat the Saroglitazar magnesium and suitable coformers such as L-proline, L-proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L- pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2-naphthoic acid, nicotinic acid, p-aminobenzoic acid, 4- hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4-dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-t-butyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide to until melt. b) Cool at ambient temperature Therapeutic Uses of Saroglitazar Magnesium co-crystals

As discussed above Saroglitazar magnesium is known in the art to be useful in the treatment of various diseases, disorders, and conditions. The Saroglitazar magnesium co-crystals of the invention, specifically, Saroglitazar magnesium Isonicotinamide co-crystal, Saroglitazar magnesium L-proline co-crystal, and 1:2 Saroglitazar magnesium nicotinamide co-crystal and pharmaceutical compositions containing them may then also be used to treat such diseases, disorders, and conditions. The diseases, disorders, or conditions which may treated with an Saroglitazar magnesium co-crystal of the invention include, but are not limited to: treatment of dyslipidemia and hypercholesterolemia, nonalcoholic steatohepatitis (NASH), Non-alcoholic fatty liver disease (NAFLD), Primary Biliary Cholangitis (PBC), Fibrosis, Polycystic ovary syndrome (PCOS), Lipodystrophy, Diabetic retinopathy, Insulin-sensitizing and metabolic related disorders, anti-inflammatory, atherogenesis, renal dysfunction, autoimmune diseases, inflammatory bowel disease (IBD), autoimmune myocarditis, autoimmune encephalomyelitis, multiple sclerosis.

Accordingly, the invention relates to the method of treating such a disease, disorder, or condition comprising the step of administering to a patient in need thereof a therapeutically effective amount of a Saroglitazar magnesium co-crystal of the invention or of administering to a patient in need thereof a therapeutic composition containing an Saroglitazar magnesium co-crystal of the invention.

Pharmaceutical Compositions Containing Saroglitazar magnesium co-crystals

The present invention also provides a pharmaceutical composition, which contains the co-crystal and a pharmaceutically acceptable carrier or excipient.

The co-crystal of Saroglitazar magnesium of the present invention can be formulated into suitable pharmaceutically acceptable compositions by combining with suitable excipients by techniques and processes and concentrations as are well known.

The pharmaceutical compositions according to this invention can exist in various forms. In some embodiments, the pharmaceutical composition is in the form of a powder or solution. In some other embodiments, the pharmaceutical compositions according to the invention are in the form of a powder that can be reconstituted by addition of a compatible reconstitution diluent prior to parenteral administration. Non-limiting examples of such compatible reconstitution diluents include water.

Pharmaceutical compositions are prepared and formulated according to conventional methods, such as those disclosed in standard reference texts and are well within the scope of a skilled person. For example, solid oral compositions may be prepared by conventional methods of blending, filling or tableting. Repeated blending operations may be used to distribute the active agent throughout those compositions employing variable quantities of fillers, binding agent, lubricants, glidants, disintegrants, etc. Such operations are of course conventional in the art. The tablets may be coated according to methods well known in normal pharmaceutical practice.

Examples of fillers include calcium carbonate, calcium phosphate, calcium sulphate, carboxymethylcellulose calcium, carboxymethylcellulose sodium, compressible sugar, confectioner's sugar, dextrates, dextrin, dextrose, dibasic calcium phosphate dihydrate, dibasic calcium phosphate, fructose, glyceryl palmitostearate, glycine, hydrogenated vegetable oil-type 1, kaolin, lactose, maize starch, magnesium carbonate, magnesium oxide, maltodextrin, mannitol, microcrystalline cellulose, polymethacrylates, potassium chloride, powdered cellulose, pregelatinised starch, sodium chloride, sorbitol, starch, sucrose, sugar spheres, talc, tribasic calcium phosphate, xylitol.

Examples of lubricants include calcium stearate, glyceryl monostearate, glyceryl palmitostearate, magnesium stearate, microcrystalline cellulose, sodium benzoate, sodium chloride, sodium lauryl sulphate, stearic acid, sodium stearyl fumarate, talc, zinc stearate. Examples of glidants include colloidal silicon dioxide, powdered cellulose, magnesium trisilicate, silicon dioxide, talc.

Use of Saroglitazar magnesium co-crystal, for the treatment of dyslipidemia or hyperglycemia.

Compared with Saroglitazar or Saroglitazar magnesium, the Saroglitazar magnesium co-crystal prepared by the invention has better stability, is convenient for storage and use, can be directly used in the preparation of solid preparations, and has good powder properties.

Analytical methods:

Differential scanning calorimetric analysis was carried out in a DSC-60 model from Shimadzu (S/W: TA-60WS Acquisition version 2.1.0.0) by keeping following parameters,

Sample Size: Approx. l-2mg, Sample Pans: Hermetic/Crimping Pans,

Start Temperature: 50°C, End Temperature: 300°C, Rate of Heating: 10 °C/min., Purge Gas: Nitrogen, Flowrate: 20 ml/min The infrared (IR) spectrum has been recorded on a Shimadzu FTIR-8400 model spectrophotometer, between 450 cm'¹ and 4000 cm'¹, with a resolution of 4 cm'¹ in a KBr pellet.

EXAMPLES

Example 1

Co-crystal of Saroglitazar and isonicotinamide (1.5:1)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and isonicotinamide (0.185 g, 1.515 mmol), Methanol (5.0 ml) was added. The homogenous solution was allowed to evaporate slowly under grinding at ambient temperature. The sticky solid obtained was dried under vacuum for 3 days. (Yield: 1.150 gm). The differential scanning calorimetry (DSC) trace, Figure 1, shows a single endotherm with an onset temperature of 295.99 °C and a peak maximum of 302.01 °C.

Example 2

Co-crystal of Saroglitazar and L-proline (1:1)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-Proline (0.262 g, 2.275 mmol), Methanol (20 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a Light brown solid. (Yield: 1.252 gm); Melting Point: 53 °C. XRD shows that solid compound obtained is an amorphous in nature (Figure 4). The differential scanning calorimetry (DSC) trace as per Figure 2 and IR frequency substantially in accordance with Figure 3.

Example 3

Co-crystal of Saroglitazar and L-proline (1:2)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (0.524 g, 4.55 mmol), methanol (20 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 1.500 gm). IR frequency of solid compound obtained substantially in accordance with Figure 5.

Example 4

Co-crystal of Saroglitazar and L-proline (1:3)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (0.786 g, 6.82 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 1.700 gm); Melting Point: 194.8 °C. XRD shows that solid compound obtained is a crystaline in nature (Figure 8). The differential scanning calorimetry (DSC) trace as per Figure 6 and IR frequency substantially in accordance with Figure 7.

Example 5

Co-crystal of Saroglitazar and L-proline (1:4)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (1.048 g, 9.10 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 1.950 gm). XRD shows that solid compound obtained is a crystaline in nature (Figure 11). The differential scanning calorimetry (DSC) trace as per Figure 9 and IR frequency substantially in accordance with Figure 10.

Example 6

Co-crystal of Saroglitazar and L-proline (1:5)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (1.310 g, 11.37 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 2.300 gm). XRD shows that solid compound obtained is a crystaline in nature (Figure 14). The differential scanning calorimetry (DSC) trace as per Figure 12 and IR frequency substantially in accordance with Figure 13.

Example 7

Co-crystal of Saroglitazar and L-proline (1:6)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (1.572 g, 13.65 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 2.500 gm) XRD shows that solid compound obtained is a crystaline in nature (Figure 17). The differential scanning calorimetry (DSC) trace as per Figure 15 and IR frequency substantially in accordance with Figure 16.

Example 8

Co-crystal of Saroglitazar and L-proline (1:7)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (1.833 g, 15.92 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 2.800 gm). XRD shows that solid compound obtained is a crystaline in nature (Figure 20). The differential scanning calorimetry (DSC) trace as per Figure 18 and IR frequency substantially in accordance with Figure 19.

Example 9

Co-crystal of Saroglitazar and L-proline (1:8)

To a mixture of Saroglitazar (1.0 g, 2.275 mmol) and L-proline (2.095 g, 18.20 mmol), methanol was added (20 ml). The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield off white solid. (Yield: 4.200 gm). XRD shows that solid compound obtained is a crystalline in nature (Figure 23). The differential scanning calorimetry (DSC) trace as per Figure 21 and IR frequency substantially in accordance with Figure 22.

Example 10

Co-crystal of magnesium salt of Saroglitazar and L-Proline (1:1)

To a mixture of magnesium salt of Saroglitazar (1.0 g, 2.160 mmol) and L-Proline (0.249 g, 2.160 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under a vacuum to yield a yellow solid. (Yield: 1.224 gm); Melting Point: 68.7 °C.

Example 11

Co-crystal of magnesium salt of Saroglitazar and L-Proline (1:2)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and L-Proline (0.373 g, 3.240 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under a vacuum to yield a yellow solid. (Yield: 1.1 gm). Example 12

Co-crystal of magnesium salt of Saroglitazar and L-Proline (1:3)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and L-Proline (0.560 g, 4.86 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under a vacuum to yield a yellow solid. (Yield: 1.3 gm).

Example 13

Co-crystal of magnesium salt of Saroglitazar and L-Proline (1:4)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and L-Proline (0.746 g, 6.48 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under a vacuum to yield a yellow solid. (Yield: 1.496 gm).

Example 14

Co-crystal of magnesium salt Saroglitazar and L-Proline (1:5)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and L-Proline (0.933 g, 8.10 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under a vacuum to yield a yellow solid. (Yield: 1.65 gm).

Example 15

Co-crystal of magnesium salt of Saroglitazar and Isonicotinamide (1:1)

To a mixture of magnesium salt of Saroglitazar (1.0 g, 2.160 mmol) and Isonicotinamide (0.264 g, 2.160 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.239 gm); Melting Point: 198.2 °C.

Example 16

Co-crystal of magnesium salt of Saroglitazar and Isonicotinamide (1:2)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and Isonicotinamide (0.396 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.1 gm). Example 17

Co-crystal of magnesium salt of Saroglitazar and Isonicotinamide (1:3)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and Isonicotinamide (0.594 g, 4.86 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.3 gm).

Example 18

Co-crystal of magnesium salt of Saroglitazar and Isonicotinamide (1:4)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and Isonicotinamide (0.792 g, 6.48 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.5 gm).

Example 19

Co-crystal of magnesium salt of Saroglitazar and Isonicotinamide (1:5)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and Isonicotinamide (0.989 g, 8.10 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.7 gm).

Example 20

Co-crystal of magnesium salt of Saroglitazar and nicotinamide (1:1)

To a mixture of magnesium salt of Saroglitazar (1.0 g, 2.160 mmol) and nicotinamide (0.264 g, 2.160 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.239 gm).

Example 21

Co-crystal of magnesium salt of Saroglitazar and nicotinamide (1:2)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and nicotinamide (0.396 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.1 gm). Example 22

Co-crystal of magnesium salt of Saroglitazar and nicotinamide (1:3)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and nicotinamide (0.594 g, 4.86 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.3 gm).

Example 23

Co-crystal of magnesium salt of Saroglitazar and nicotinamide (1:4)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and nicotinamide (0.792 g, 6.48 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.5 gm).

Example 24

Co-crystal of magnesium salt of Saroglitazar and nicotinamide (1:5)

To a mixture of magnesium salt of Saroglitazar (0.750 g, 1.620 mmol) and nicotinamide (0.989 g, 8.10 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 1.70 gm).

Example 25

Co-crystal of magnesium salt of Saroglitazar and benzamide (1:3)

To a mixture of magnesium salt of Saroglitazar (0.500 g, 1.080 mmol) and benzamide (0.393 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 0.850 gm). Melting Point: 113.7 °C.

Example 26

Co-crystal of magnesium salt of Saroglitazar and Acetamide (1:3)

To a mixture of magnesium salt of Saroglitazar (0.500 g, 1.080 mmol) and Acetamide (0.191 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 0.670 gm). Melting Point: 131.3 °C. Example 27

Co-crystal of magnesium salt of Saroglitazar and Nicotinic acid (1:3)

To a mixture of magnesium salt of Saroglitazar (0.500 g, 1.080 mmol) and Nicotinic acid (0.399 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 0.870 gm). Melting Point: >300 °C.

Example 28

Co-crystal of magnesium salt of Saroglitazar and (E)-3-(4-hydroxy-3- methoxyphenyl)acrylic acid(l:3)

To a mixture of magnesium salt of Saroglitazar (0.500 g, 1.080 mmol) and (E)-3 -(4-hy dr oxy-3 - methoxyphenyl)acrylic acid (0.629 g, 3.24 mmol), another mixture of methanol (10.0 ml) and tetrahydrofuran (10.0 ml) was added. The homogenous solution was concentrated under reduced pressure and dried under vacuum to yield a yellow solid. (Yield: 0.970 gm). Melting Point: 154.5

Claims

We claim:

1. A co-crystal of Saroglitazar of formula (I),

Formula (I)

2. A co-crystal as claimed in claim 1 is formed by coformer selected from L-proline, L- proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2 -naphthoic acid, nicotinic acid, p- aminobenzoic acid, 4-hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5 -nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4- dihydroxybenzoic acid, 3-hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3-Lbutyl-4-hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3-, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide and combination thereof.

3. A co-crystal as claimed in claim 1 wherein the molar ratio of Saroglitazar and coformer is 1 to 2 : 1 to 15.

4. A co-crystal as claimed in claim 3 wherein the molar ratio of Saroglitazar and coformer is 1: 1, 1:2, 1 :3, 1:4, 1:5, 1:6, 1:7, 1 :8, 1:9, 1: 10, 1.5: 1, 1.5:2, 1.5:3, 1.5:4 and 1.5:5.

5. A co-crystal as claimed in claim 4 wherein molar ratio of Saroglitazar and coformer is 1: 1, 1:2, 1 :3, 1:4, 1:5, 1:6, 1:7, 1 :8, 1.5: 1.

6. A co-crystal as claimed in claim 1 wherein coformer is L-proline or Isonicotinamide.

7. A co-crystal as claimed in claim 1 is in amorphous form or in crystalline form or in partially crystalline form.

8. A co-crystal of Saroglitazar of formula (I) and L-proline.

9. A co-crystal of as claimed in claim 8 wherein molar ratio of Saroglitazar and L-proline is 1: 1, 1:2, 1 :3, 1:4, 1:5, 1:6, 1:7 and 1 :8.

10. A co-crystal as claimed in claim 8 wherein,

(i) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:3) having peaks at about 14.953, 17.843, 18.199, 19.327, 22.472, 24.540, 33.772 ± 0.2 degrees 2-theta as per figure 6; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:3) shows a single endotherm with an onset temperature of 187.90 °C and a peak maximum of 198.37 °C as per figure 5;

(ii) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:4) having peaks at about 15.000, 17.886, 18.230, 19.382, 22.530, 24.598, 33.832 ± 0.2 degrees 2-theta as per figure 8; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:4) shows a single endotherm with an onset temperature of 198.71 °C and a peak maximum of 206.35 °C as per figure 7;

(iii) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:5) having peaks at about 15.005, 17.990, 18.299, 19.398, 22.550, 24.618, 33.839 ± 0.2 degrees 2-theta as per figure 10; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:5) shows a single endotherm with an onset temperature of 200.82 °C and a peak maximum of 208.73 °C as per figure 9; (iv) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:6) having peaks at about 14.986, 17.876, 18.264, 19.374, 22.515, 24.584, 33.813± 0.2 degrees 2-theta as per figure 12; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:6) shows a single endotherm with an onset temperature of 203.13 °C and a peak maximum of

212.33 °C as per figure 11;

(v) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:7) having peaks at about 14.973, 17.856, 18.182, 19.352, 22.493, 24.560, 33.768± 0.2 degrees 2-theta as per figure 14; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:7) shows a single endotherm with an onset temperature of 212.21 °C and a peak maximum of 216.67 °C as per figure 13;

(vi) a powder X-ray diffraction pattern of Saroglitazar L-proline co-crystals in ratio (1:8) having peaks at about 14.963, 17.847, 18.237, 19.349, 22.494, 24.560, 33.794± 0.2 degrees 2-theta as per figure 16; the differential scanning calorimetry (DSC) trace of Saroglitazar L-proline co-crystals in ratio (1:8) shows a single endotherm with an onset temperature of 209.45 °C. and a peak maximum of

215.34 °C as per figure 15.

I L A co-crystal of Saroglitazar of formula (I) and Isonicotinamide.

12. A co-crystal of as claimed in claim 11 wherein molar ratio of Saroglitazar and Isonicotinamide is 1.5: 1.

13. A co-crystal as claimed in claim 11 wherein, the differential scanning calorimetry (DSC) trace of Saroglitazar Isonicotinamide co-crystals in ratio (1.5:1) shows a single endotherm with an onset temperature of 295.99 °C and a peak maximum of 302.01 °C as per figure 1.

14. A co-crystal of Saroglitazar magnesium of formula (la),

15. A co-crystal as claimed in claim 14 is formed by coformer selected from L-proline, L- proline monohydrate, L-proline tetrahydrate, DL-proline, D-proline, D-alanine, histidine, threonine, glutamic acid, arginine, valine, cysteine, leucine, lysine, tyrosine, isoleucine, asparagine, phenylalanine, glutamine, tryptophan, methionine, serine, glycine, trimethyl glycine, L-pyroglutamic acid, Isonicotinamide, nicotinamide, acetamide, pyrazinamide, malonamide, picolinamide, anthranilamide, benzamide, succinamide, caprolactum, salicylic acid, cinnamic acid, ferulic acid, hydroxy-2 -naphthoic acid, nicotinic acid, p- aminobenzoic acid, 4-hydroxybenzoic acid, oxalic acid, pyridine, succinic acid, hippuric acid, glutaric acid, fumaric acid, malonic acid, taratric acid, aspartic acid, adipic acid, sebacic acid, trans aconitic acid, citric acid, vanillic acid, 5-nitroisophthalic acid, oxolate salt, 4-aminosalicylic acid, stearic acid, maleic acid, caffeic acid, adipic acid, 2, 4- dihydroxybenzoic acid, (E)-3-(4-hydroxy-3-methoxyphenyl)acrylic acid, 3- hydroxybenzoic acid, cinnamic acid, gallic acid, mandalic acid, resorcinol, catechol, phloroglucinol, oricinol, vaniline, metacetamol, pyridoxine, methyl gallate, 3 -/-butyl -4- hydroxyanisole, propyl-4-hydroxybenzoate, propyl gallate, saccharin, piperazine, methaneamine, pyrazine, 2, 3-, 5, 6-tetramethyl pyrazine, pyrimidine, pyridazine, phenazine, 4-amino pyridine, betaine, adenine, theophylline, caffeine, metformin, urea and isoniazide and combination thereof.

16. A co-crystal as claimed in claim 14 wherein the molar ratio of Saroglitazar and coformer is 1 to 2 : 1 to 15.

17. A co-crystal as claimed in claim 14 wherein the molar ratio of Saroglitazar and coformer is 1: 1, 1 :2, 1:3, 1:4, 1 :5, 1:6, 1:7, 1 :8, 1:9, 1 :10, 1.5:1, 1.5:2, 1.5:3, 1.5:4 and 1.5:5.

18. A co-crystal as claimed in claim 14 wherein molar ratio of Saroglitazar and coformer is 1: 1, 1:2, 1 :3, l:4 and 1:5.

19. A co-crystal as claimed in claim 14 wherein coformer is L-proline or Isonicotinamide or Nicotinamide or Benzamide or Acetamide or Nicotinic acid or (E)-3-(4-hy dr oxy-3 - methoxyphenyl)acrylic acid.

20. A co-crystal as claimed in claim 14 is in amorphous form or in crystalline form or in partially crystalline form.

21. A co-crystal of Saroglitazar magnesium of formula (la) and L-proline.

22. A co-crystal as claimed in claim 21 wherein molar ratio of Saroglitazar and L-proline is 1: 1, 1:2, 1 :3, l:4 and 1:5.

23. A co-crystal as claimed in claim 21 wherein,

(i) a powder X-ray diffraction pattern of Saroglitazar magnesium L-proline cocrystals in ratio (1:3) having peaks at about 15.064, 17.996, 18.387, 19.465, 22.626, 24.690, 33.952 ± 0.2 degrees 2-theta as per figure 21; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium L-proline cocrystals in ratio (1:3) shows a single endotherm with an onset temperature of 187.21 °C and a peak maximum of 202.11 °C as per figure 22;

(ii) a powder X-ray diffraction pattern of Saroglitazar magnesium L-proline cocrystals in ratio (1:4) having peaks at about 15.122, 18.018, 18.429, 19.513, 22.676, 33.983 ± 0.2 degrees 2-theta as per figure 23; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium L-proline co-crystals in ratio (1:4) shows a single endotherm with an onset temperature of 199.38 °C and a peak maximum of 207.22 °C as per figure 24;

(iii) a powder X-ray diffraction pattern of Saroglitazar magnesium L-proline cocrystals in ratio (1 :5) having peaks at about 15.091, 17.989, 18.402, 19.487, 22.647, 24.715, 33.958 ± 0.2 degrees 2-theta as per figure 25; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium L-proline cocrystals in ratio (1:5) shows a single endotherm with an onset temperature of 202.84 °C and a peak maximum of 212.03 °C as per figure 26.

24. A co-crystal of Saroglitazar magnesium of formula (la) and Isonicotinamide.

25. A co-crystal as claimed in claim 24 wherein molar ratio of Saroglitazar and Isonicotinamide is 1: 1, 1 :2, 1:3, 1:4 and 1 :5.

26. A co-crystal as claimed in claim 24 wherein,

(i) a powder X-ray diffraction pattern of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1 :1) having peaks at about 4.351, 7.688, 8.834, 14.051, 15.771, 16.344, 17.618, 18.676, 19.426, 19.766, 20.486, 21.030, 22.077, 22.728, 22.909, 23.292, 28.335 ± 0.2 degrees 2-theta as per figure 27; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Isonicotinamide co- crystals in ratio (1:1) shows a single endotherm with an onset temperature of 143.84 °C and a peak maximum of 150.48 °C as per figure 28;

(ii) a powder X-ray diffraction pattern of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1 :2) having peaks at about 14.499, 18.459, 22.120 ± 0.2 degrees 2-theta as per figure 29; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1 :2) shows a single endotherm with an onset temperature of 142.01 °C and a peak maximum of 148.22 °C as per figure 30;

(iii) a powder X-ray diffraction pattern of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1:3) having peaks at about 14.497, 18.439, 22.117, 22.931, 23.347 ± 0.2 degrees 2-theta as per figure 31; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1 :3) shows a single endotherm with an onset temperature of 150.54 °C and a peak maximum of 154.10 °C as per figure 32;

(iv) a powder X-ray diffraction pattern of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1:4) having peaks at about 18.536, 18.699, 22.197, 23.007, 22.425 ± 0.2 degrees 2-theta as per figure 33; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1 :4) shows a single endotherm with an onset temperature of 151.58 °C and a peak maximum of 154.81 °C as per figure 34;

(v) powder X-ray diffraction pattern of Saroglitazar magnesium Isonicotinamide cocrystals in ratio (1:5) having peaks at about 14.536, 18.488, 22.166, 22.976, 23.392, 24.269 ± 0.2 degrees 2-theta as per figure 35; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Isonicotinamide co-crystals in ratio (1:5) shows a single endotherm with an onset temperature of 152.01 °C. and a peak maximum of 154.56 °C as per figure 36.

27. A co-crystal of Saroglitazar magnesium of formula (la) and Nicotinamide.

28. A co-crystal as claimed in claim 27 wherein molar ratio of Saroglitazar and Nicotinamide is 1: 1, 1 :2, 1:3, 1:4 and 1:5.

29. A co-crystal as claimed in claim 27 wherein, (i) a powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinamide cocrystals in ratio (1: 1) having peaks at about 4.372, 7.723, 8.841, 14.620, 16.921, 19.299, 22.022, 23.143, 25.202, 25.611, 26.036, 27.094 ± 0.2 degrees 2-theta as per figure 37; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1: 1) shows a single endotherm with an onset temperature of 117.64 °C and a peak maximum of 123.22 °C as per figure 38;

(ii) a powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinamide cocrystals in ratio (1:2) having peaks at about 4.491, 14.707, 17.111, 17.401, 19.419, 23.264, 24.487, 25.287, 25.745, 27.214 ± 0.2 degrees 2-theta as per figure 39; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:2) shows a single endotherm with an onset temperature of 121.64 °C and a peak maximum of 125.77 °C as per figure 40;

(iii) a powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinamide cocrystals in ratio (1:3) having peaks at about 14.738, 22.161, 23.297, 25.319, 29.779, 27.247 ± 0.2 degrees 2-theta as per figure 41; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:3) shows a single endotherm with an onset temperature of 123.31 °C and a peak maximum of 126.76 °C as per figure 42;

(iv) a powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinamide cocrystals in ratio (1:4) having peaks at about 14.706, 22.123, 23.272, 25.299, 25.753, 27.226 ± 0.2 degrees 2-theta as per figure 43; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:4) shows a single endotherm with an onset temperature of 124.15 °C and a peak maximum of 128.19 °C as per figure 44;

(v) powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinamide cocrystals in ratio (1:5) having peaks at about 14.704, 22.119, 23.241, 25.273, 25.728, 27.202 ± 0.2 degrees 2-theta as per figure 45; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:5) shows a single endotherm with an onset temperature of 124.57 °C and a peak maximum of 127.70 °C as per figure 46.

30. A co-crystal of Saroglitazar magnesium of formula (la) and Benzamide.

31. A co-crystal as claimed in claim 30 wherein molar ratio of Saroglitazar and Benzamide is 1:3.

32. A co-crystal as claimed in claim 30 wherein, a powder X-ray diffraction pattern of Saroglitazar magnesium Benzamide co-crystals in ratio (1:3) having peaks at about 7.747, 15.627, 16.402, 17.927, 19.831, 20.790, 22.408, 26.358, 28.356, 28.605 ± 0.2 degrees 2-theta as per figure 47; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:3) shows a single endotherm with an onset temperature of 104.60 °C and a peak maximum of 116.27 °C as per figure 48.

33. A co-crystal of Saroglitazar magnesium of formula (la) and Acetamide.

34. A co-crystal as claimed in claim 33 wherein molar ratio of Saroglitazar and Acetamide is 1:3.

35. A co-crystal as claimed in claim 33 wherein, a powder X-ray diffraction pattern of Saroglitazar magnesium Acetamide co-crystals in ratio (1:3) having peaks at about 4.453, 7.779, 8.957± 0.2 degrees 2-theta as per figure 49; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:3) shows a single endotherm with an onset temperature of 54.68 °C and a peak maximum of 58.31 °C as per figure 50.

36. A co-crystal of Saroglitazar magnesium of formula (la) and Nicotinic acid.

37. A co-crystal as claimed in claim 36 wherein molar ratio of Saroglitazar and Nicotinic acid is 1 :3.

38. A co-crystal as claimed in claim 36 wherein, a powder X-ray diffraction pattern of Saroglitazar magnesium Nicotinic acid co-crystals in ratio (1:3) having peaks at about 15.189, 20.062, 20.919, 24.481, 25.649, 26.566, 27.645 ± 0.2 degrees 2-theta as per figure 51.

39. A co-crystal of Saroglitazar magnesium of formula (la) and (E)-3 -(4-hy dr oxy-3 - methoxyphenyl)acrylic acid co-crystal.

40. A co-crystal as claimed in claim 39 wherein molar ratio of Saroglitazar and (E)-3-(4- hy dr oxy-3 -methoxyphenyl)acrylic acid is 1:3.

41. A co-crystal as claimed in claim 39 wherein, a powder X-ray diffraction pattern of Saroglitazar magnesium (E)-3-(4-hy dr oxy-3 - methoxyphenyl)acrylic acid co-crystals in ratio (1:3) having peaks at about 8.874, 10.332, 12.661, 15.474, 17.255, 17.960, 20.297, 20.974, 21.472, 22.893, 24.482, 25.792, 26.280, 27.317, 29.302 ± 0.2 degrees 2-theta as per figure 53; the differential scanning calorimetry (DSC) trace of Saroglitazar magnesium Nicotinamide co-crystals in ratio (1:3) shows a single endotherm with an onset temperature of 139.18 °C and a peak maximum of 139.67 °C as per figure 54.

42. A pharmaceutical composition of co-crystal as claimed in claim 1 and 14 comprises one or more suitable pharmaceutically acceptable carrier or excipient.

43. A use of pharmaceutical composition of co-crystal as claimed in claim 1 and 14 for the treatment of dyslipidemia or hyperglycemia

44. A process for the preparation of co-crystal of Saroglitazar or co-crystal of Saroglitazar magnesium comprising following steps: a) Prepare the homogenous solution of Saroglitazar or Saroglitazar magnesium and suitable coformers in the suitable solvent or suitable solvents mixtures thereof. b) The solvent was allowed to evaporate slowly under grinding at ambient temperature manually or mechanically, for a fixed period of time. c) The co-crystal is dried under reduced pressure.