DESC:FIELD OF THE INVENTION
The present invention generally relates to solid forms of Empagliflozin, including its co-crystals, solvates and/or their polymorphs, processes for their preparation and pharmaceutical composition containing the same.

The present invention also relates to processes for the preparation of amorphous form of empagliflozin and pharmaceutical composition containing the same.

BACKGROUND OF THE INVENTION
Empagliflozin, also known as (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol is represented by the formula,

Empagliflozin (Jardiance), a SGLT2 Inhibitor, received FDA approval for the treatment of patients with Type 2 Diabetes and is marketed by Boehringer Ingelheim as 10 mg and 25 mg, film coated tablet.

SGLT2 is a protein that absorbs glucose back from the urine into the bloodstream as the blood is filtered in the kidneys. Empagliflozin works by blocking a protein in the kidneys called sodium-glucose co-transporter 2 (SGLT2). By blocking the action of SGLT2, Jardiance causes more glucose to be removed via the urine, thereby reducing the levels of glucose in the blood.

U.S. Patent. No. 7,579,449 B2 (“the '449 patent”) discloses preparation of Glucopyranosyl-substituted benzene derivatives, specifically preparation of empagliflozin in example no. 1. The '449 patent further discloses isolation of empagliflozin by subjecting the crude empagliflozin tosilica gel chromatography using dichloromethane / methanol in 1:0->5:1 as aneluent.The '449 patent makes no reference to the existence of specific polymorphic forms of empagliflozin or its pharmaceutically acceptable salts thereof.
U.S. Patent No. 7,723,309 B2 (“the ‘309 patent”) discloses crystalline form of empagliflozin and process for preparation thereof. In particular, the said patent discloses the crystalline Form-I and Form-II and process for preparation thereof.

Indian Patent Application No. 1985/MUM/2013 (“the ‘1985 application”) discloses amorphous form of empagliflozin, which is substantially free from one or more of residual organic solvents. In particular, the said patent application discloses the amorphous form of empagliflozin and process for preparation thereof.

CN Patent No. 104788438(“the '438 Application”) discloses Empagliflozin polymorph B and process for preparation thereof.

CN Patent No. 105481843A1 (“the '843 Application”) discloses Empagliflozin amorphous form and process for preparation thereof.

CN Patent No. 105384730A (“the '730 Application”) discloses crystalline Empagliflozin and process for preparation thereof.

WO Publication No. 2016131431A1 (“the '431 Publication”) discloses complex of empagliflozin with proline and process for preparation thereof.

Discovering new polymorphic forms, solvates or co-crystals of a pharmaceutical product can provide materials having desirable processing properties, such as ease of handling, ease of processing, storage stability, and ease of purification or as desirable intermediate forms that facilitate conversion to other solid-state forms. New polymorphic forms, solvates or co-crystals of a pharmaceutically useful compound can also provide an opportunity to improve the performance characteristics of a pharmaceutical product. It enlarges the repertoire of materials that a formulation scientist has available for formulation optimization, for example by providing a product with different properties, e.g., better processing or handling characteristics, better purity, improved dissolution profile, or improved shelf-life.

In view of the foregoing, it would be desirable to provide new co-crystals and solvates of empagliflozin. Further, it would be desirable to have reliable processes for producing these co-crystals and solvates. Therefore, the present invention addresses the need in the art for pharmaceutically useful co-crystals and solvates of empagliflozin that may have improved physicochemical properties, such as a higher solubility and dissolution rate, enhanced flow properties and enhanced stability.

SUMMARY OF THE INVENTION
Accordingly the present invention provides solid forms of empagliflozin, including its co-crystals, solvates and/or their polymorphs, processes for their preparation and pharmaceutical composition containing the same.

In accordance with one embodiment, the present invention provides novel solid forms of empagliflozin.

In accordance with another embodiment, the present invention provides novelsolid forms of empagliflozin, which are characterized by one or more of analytical techniques such as powder X-Ray diffraction (XRD); XH NMR Spectrum; infrared spectrum (IR), differential scanning calorimetry (DSC) and/or thermogravimetric analysis (TGA), among others.

In accordance with another embodiment, the present invention provides solid forms of empagliflozin, exists in the form ofco-crystals, solvates and/or their polymorphsthereof.
In accordance with another embodiment, the present invention provides co-crystals of empagliflozin.

In accordance with another embodiment, the present invention provides co-crystals of empagliflozin, whereinthe co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.
In accordance with another embodiment, the present invention provides a process for the preparation of co-crystals of empagliflozin, comprising:
a) providing a solution or suspension comprising empagliflozin and a co-crystal formerin one or more solvents; and
b) Isolating the co-crystals of empagliflozin; wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.
In accordance with another embodiment, the present invention provides co-crystals of empagliflozin, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid and the like.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal monohydrate.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystalcharacterized byX-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 01.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystalcharacterized by 1H NMR Spectrum substantially in accordance with Figure 02.

In accordance with another embodiment, the present invention empagliflozin DL-pipecolic acid co-crystal characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 03.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal characterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 04.

In accordance with another embodiment, the present invention provides a process for the preparation of empagliflozin DL-pipecolic acid co-crystal, comprising:
a) providing a solution or suspension comprising empagliflozin and DL-pipecolic acid, and
b) isolating the empagliflozin DL-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides process for the preparation of an amorphous form of empagliflozin and pharmaceutical composition containing the same.

In accordance with another embodiment, the present invention provides a process for the preparation of an amorphous empagliflozin, comprising:
a) dissolving or suspending empagliflozin co-crystal in a suitable solvent;
b) optionally treating the step a) reaction mass with a suitable base or an acid;
c) extracting empagliflozin into an organic solvent; and
d) converting empagliflozin of Formula I to amorphous form of empagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous empagliflozin, comprising:
a) providing a solution of empagliflozin in a suitable solvent; and
b) removing the solvent from the solution to obtain amorphous form of empagliflozin.

In accordance with another embodiment, the present invention provides a pharmaceutical composition comprising at least one of the solid forms of empagliflozin described above and at least one or more pharmaceutically acceptable excipients.

BRIEF DESCRIPTION OF THE DRAWINGS
Figure 1 is the characteristic powder XRD pattern of empagliflozin DL-pipecolic acid co-crystal.
Figure 2 is the characteristic 1H NMR Spectrum of empagliflozin DL-pipecolic acid co-crystal.
Figure 3 is the characteristic DSC thermogram of empagliflozin DL-pipecolic acid co-crystal.
Figure 4 is the characteristic TGA curve of empagliflozin DL-pipecolic acid co-crystal.
Figure 5 is the characteristic powder XRD pattern of amorphous form of empagliflozin.

DETAILED DESCRIPTION OF THE INVENTION
The present invention providessolid forms of empagliflozin, including its co-crystals, solvates and/or their polymorphs, processes for their preparation and pharmaceutical composition containing the same.
In one embodiment, the present invention provides novel solid forms of empagliflozin.
In accordance with another embodiment, the present invention provides solid forms of empagliflozin, which are characterized by one or more of analytical techniques such as powder X-Ray diffraction (XRD); XH NMR Spectrum; infrared spectrum (IR), differential scanning calorimetry (DSC) and/or thermogravimetric analysis (TGA), among others.
In accordance with another embodiment, the present invention provides solid forms of empagliflozin, exists in the form of co-crystals, solvates and/or their polymorphs thereof.
In accordance with another embodiment, the present invention provides co-crystals of empagliflozin.

In accordance with another embodiment, the present invention provides co-crystals of empagliflozin, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.
The ratio of empagliflozin to that of the co-crystal former may be stoichiometric or non-stoichiometric according to the present invention. For example, the ratio of the empagliflozin to co-crystal former is about 1:1, 1.5:1, 2:1,1:1.5 and 1:2 ratios is acceptable.

In accordance with another embodiment, the present invention provides a process for the preparation of co-crystals of empagliflozin, comprising:
a) providing a solution or suspension comprising empagliflozin and a co-crystal former in one or more solvents; and
b) isolating the co-crystals of empagliflozin; wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

In another embodiment, the present invention provides co-crystals of empagliflozin, which are characterized by one or more of analytical techniques such as powder X-Ray diffraction (XRD); 1H NMR Spectrum; differential scanning calorimetry (DSC) and/or thermogravimetric analysis (TGA), among others.

The starting material empagliflozin used in the present invention is known in the art and can be prepared by any known methods, for example empagliflozin may be synthesized as disclosed in U.S. Patent No. 7,579,449 B2 or it may be obtained as a solution directly from a reaction mixture in which empagliflozin is formed and used as such without isolation.
The step of providing a solution or suspension includes any form of empagliflozin that may be mixed with one or more solvents and co-crystal former or includes any form of empagliflozin that may be combined with one or more solvents and then the co-crystal former may be mixed with the resulting solution or slurry. Alternatively, the mixture may be formed by adding empagliflozin and co-crystal former at the same time in to one or more solvents.

Examples of one or more solvents of step a) includes but are not limited to esters such as methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate and the like; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol and the like; ethers such as tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone and the like, hydrocarbon solvents such as hexane, heptane, cyclohexane and the like, halogenated hydrocarbon solvents such as dichloromethane, dichloroethane, chloroform and the like, nitriles such as acetonitrile, propionitrile and the like; water or mixtures thereof.

The temperature suitable for dissolving or suspending the empagliflozin in one or more solvents depends on the solvent used and the amount of empagliflozin in the reaction mass. Typically, the solution or suspension is heated at a temperature of at least about 30°C to about reflux.

The step b) of the foregoing process, the isolation of co-crystals ofempagliflozin may be carried out by concentration by subjecting the solution to heating, cooling the solution to precipitation, crystallization, solvent precipitation, spray drying, freeze drying, agitated thin film evaporator (ATFE), evaporation on rotary evaporator under vacuum and the like. Preferably the reaction solution may be cooled to less than about 10°C, preferably less than 5°C to precipitation followed by stirring the reaction mixture for sufficient period of time. Optionally, an anti-solvent may be added to improve the product precipitation prior to cooling the reaction mass. The co-crystals of empagliflozin can berecovered by any conventional technique known in the art, for example, filtration. The resultant co-crystals of empagliflozin may optionally be further purified.
In another embodiment, the present invention provides co-crystals ofempagliflozinhaving a chemical purity greater than or equal to about 97%, as measured by HPLC, preferably about 98% as measured by HPLC, and more preferably about 99.5%, as measured by HPLC.
In another embodiment, some of the co-crystals of the present invention may exist as polymorphs and as such are intended to be included in the present invention. In addition, some of the co-crystals of the present invention may form solvates with water (i.e., hydrates) or common organic solvents, and such solvates are also intended to be encompassed within the scope of this invention.

In another embodiment, the co-crystals of empagliflozin recovered using the process of the present invention described above includes empagliflozinDL-pipecolic acid co-crystal.

In another embodiment, the present invention provides co-crystal of empagliflozin DL-pipecolic acid.

In another embodiment, the present invention provides co-crystal of empagliflozin DL-pipecolic acid monohydrate.

In another embodiment, the present invention provides a process for the preparation of empagliflozin DL-pipecolic acidco-crystals, comprising:
a) providing a solution or suspension comprising empagliflozin and DL-pipecolic acid in one or more solvents; and
b) isolating the empagliflozinDL-pipecolic acidco-crystals.

The step of providing a solution or suspension comprising empagliflozin and DL-pipecolic acid in one or more solvent may include heating to dissolve. The temperature suitable for dissolving or suspending the empagliflozin in the one or more solvents depends on the solvent used and the amount of empagliflozin in the reaction mass. Typically, the solution or suspension is heated at a temperature of at least about 30°C to about reflux. Examples of one or more solvents used in step a) are same as solvents defined just as above.

The step b) of the foregoing process, isolation of the co-crystal of empagliflozin and DL-pipecolic acid obtained may be carried out by optionally allowing the reaction mass to gradually cool to a temperature of less than 30°C and the resultant empagliflozinDL-pipecolic acid co-crystals can be isolated by conventional techniques, for example by filtration. The resultant wet product may optionally be further dried. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like.

In another embodiment, empagliflozin DL-pipecolic acid co-crystalis recovered using the process as described just above is a monohydrate form.

In another embodiment, empagliflozin DL-pipecolic acid monohydrate co-crystals is recovered using the process as described just above is substantially a crystalline form.

In another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 01.

In another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystalcharacterized by X-Ray powder diffraction (XRD) pattern having one or more peaks at about 5.5, 9.8, 11.0, 12.0, 12.2, 14.7, 15.8, 16.3, 17.3, 17.7, 18.1, 18.5, 18.9, 19.6, 20.7, 21.1, 22, 22.5, 23.5, 24.5, 25.0, 26.4, 27.2, 28.1, 29, 29.8, 30.9, 31.4, 33.7, 35.3, 36.7, 39.6 ± 0.2° 2?.

In another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal characterized by a 1H NMR Spectrum substantially in accordance with Figure 02.

In another embodiment, the present invention empagliflozin DL-pipecolic acid co-crystal characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 03.

In another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystalcharacterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 04.

In another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystal characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 01, differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 03 and a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 04.

The term "co-crystal" as used herein means a crystalline material comprised of two or more unique solids at room temperature, each containing distinctive physical characteristics, such as structure, melting point and heats of fusion.

The X-Ray powder diffraction can be measured using PANalytical X’per3pro X-ray powder Diffractometer equipped with a Cu-anode ([?] =1.54 Angstrom), X-ray source operated at 45kV, 40 mA. Two-theta calibration is performed using an NIST SRM 640c Si standard. The sample was analyzed using the following instrument parameters: measuring range=3-45°2?; step size=0.01°; and Time per step=43 sec.

All DSC data reported herein were analyzed in hermitically sealed pinhole aluminium pan, with a blank hermitically sealed aluminium pan as the reference and were obtained using DSC (DSC Q200, TA instrumentation, Waters) at a scan rate of 10°C per minute with an Indium standard.

All TGA data reported herein were analyzed using TGA Q500 V 20.13 build 39 in platinum pan with a temperature rise of about 10°C/min in the range of about 30°C to about 250°C.

In another embodiment, the present invention provides process for the preparation of an amorphous form of empagliflozin and pharmaceutical composition containing the same.
In another embodiment, the present invention provides process for the preparation of an amorphous form of empagliflozin, wherein the process involves one or more solid forms of empagliflozin of the invention as intermediate(s).

In another embodiment,the present invention provides the use of one or more co-crystals of empagliflozin of the invention as intermediate(s) in the preparation of high purityamorphous empagliflozin.

In another embodiment, the present invention provides the use of one or more co-crystal(s) of empagliflozin, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like;in the preparation of high purityamorphous empagliflozin.

In another embodiment, the present invention provides the use of DL-pipecolic acid co-crystals in the preparation of high purityamorphous empagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of an amorphous empagliflozin, comprising:
a) dissolving or suspending empagliflozin co-crystal in a suitable solventat a temperature of at least about 20°C to about reflux;
b) optionally treating the step a) reaction mass with a suitable base or an acid;
c) extracting empagliflozin into an organic solvent; and
d) isolating the amorphous form of empagliflozin; wherein the co-crystal used in step a) is selected from the group consisting of DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

The empagliflozin co-crystals used in step a) includes but are not limited to DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

Preferably the empagliflozin co-crystal used herein isempagliflozin DL-pipecolic acid, which is prepared by the processes as described above.

The suitable solvent used herein for dissolution of empagliflozin co-crystalincludes but is not limited to methanol, ethanol, n-butanol, acetonitrile, dichloromethane or water or mixtures thereof. Preferably the solvent used for dissolving empagliflozin co-crystalis dichloromethane.

The temperature suitable for dissolving or suspending the empagliflozin co-crystal in the one or more organic solvents depends on the solvent used and the amount of empagliflozin co-crystals in the reaction mass. Typically, the solution or suspension is stirred at a temperature of at least about 20°C to about reflux.

Step b) of the foregoing process involvestreating the step a) reaction mass with a base or an acid before extracting the empagliflozin into an organic solvent. The base or acid may be added from about 0.5 to about 5 mole equivalents per mole of starting co-crystals of empagliflozin, preferably about 1 to about 4 moles.

Suitable base is either inorganic or organic base. The inorganic base is selected from the group comprising alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate; alkali metal bicarbonates such as sodium bicarbonate, potassium bicarbonate and the like; alkali metal hydroxides such as sodium hydroxide, potassium hydroxide and lithium hydroxide and the like. The organic base used herein is selected from the group comprising of alkyl amines such as di-isopropyl ethylamine, triethyl amine and the like; heterocyclic amines such as pyridine and the like. The suitable base can be added either as a solution in one or more solvents as herein before defined or it may be added directly to the solution of co-crystals of empagliflozin in one or more solvents.

Suitable acid is selected from the group comprising of hydrochloric acid, sulfuric acid, acetic acid or mixtures thereof.

Examples of organic solvents used for extraction herein includes but are not limited to esters such as methyl acetate, ethyl acetate, isopropyl acetate n-propyl acetate, n-butyl acetate, t-butyl acetate and the like; ethers such as dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane and the like; cyclic hydrocarbons such as hexane, heptane, pentane and the like; aromatic hydrocarbons such as toluene, xylene and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like; or mixtures thereof.

Pure empagliflozin optionally, may isolated from the reaction mass by methods known in the art, for example, the product containing organic layer may be separated followed by distillation of solvent completely under reduce pressure to obtain empagliflozin.

In another embodiment, pure empagliflozin of Formula I obtained by the process of the invention is having chemical purity of at least about 95%, as measured by HPLC, preferably at least about 98%, as measured by HPLC and more preferably at least about 99.5%, as measured by HPLC; and contains less than 0.5% of total impurities,which include Impurity 5, Impurity 6 and other non polar impurities as measured by HPLC. Impurity 5 and Impurity 6 are represented as follows:

In an embodiment,pure empagliflozin of Formula I contains less than 0.5% of total impurities,which include Impurity 5, Impurity 6 and other non polar impurities as measured by HPLC; preferably less than 0.3% as measured by HPLC, more preferably less than 0.1% as measured by HPLC.

In another embodiment, the present invention provides amorphous empagliflozin characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Fig 05.

In another embodiment, the present invention involves converting empagliflozin of Formula I to amorphous form of empagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous empagliflozin, comprising:
a) providing a solution of empagliflozin in a suitable; and
b) removing the solvent from the solution to obtain amorphous form of empagliflozin.

Step a) of the forgoing process involves the dissolution of empagliflozin in a suitable solvent, wherein the solvent includes but are not limited to esters such as methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate and the like; ethers such as methyl tertiary butyl ether, tetrahydrofuran, dimethyl ether, diisopropyl ether, 1,4-dioxane and the like; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol and the like; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone and the like; nitriles such as acetonitrile, propionitrile and the like; halogenated hydrocarbons such as dichloromethane, chloroform and the like;preferably methyl acetate, isopropyl acetate, ethyl acetate, methyl tertiary butyl ether, dichloromethaneor mixtures thereof.
The dissolution temperatures may range from about 10°C to about reflux temperature of the solvent. The step of removal of solvent may be carried out by one or more techniques of distillation, distillation under vacuum, spray drying, agitated thin film drying ("ATFD"), and freeze drying (lyophilization). The resultant wet product may optionally be further dried. Drying can be suitably carried out in a tray dryer, vacuum oven, air oven, fluidized bed drier, spin flash dryer, flash dryer and the like.

In accordance with another embodiment, the present invention provides a pharmaceutical composition comprising at least one of the solid forms of empagliflozin described above and at least one or more pharmaceutically acceptable excipients.

EXAMPLES
The present invention is further illustrated by the following examples, which are provided by way of illustration only and should not be construed to limit the scope of the invention.

EXAMPLE 1: Preparation of empagliflozin DL-pipecolic acid co-crystals.
Empagliflozin (10 gm), DL-pipecolic acid (5.75 gm) and n-butanol (100 ml) were charged into a round bottom flask and raise the temperature to 80°C. DM water (5 ml) was added and stirred the reaction mass for 30 min. The resultedclear solution was allowed to cool to 25°C and stirred for 30 min. The suspensionwas further allowed to cool to 3°C, filtered the product and washed with n-butanol (20 ml). The obtained solid was dried under vacuum for 8 hrs at 40°C to obtain empagliflozin DL-pipecolic acid co-crystals (12.8 gms).
The PXRD is set forth in Figure 01,
The 1H NMR is set forth in Figure 02,
The DSC thermogram is set forth in Figure 03,
The TGA is set forth in Figure 04.

EXAMPLE 2: Preparation of empagliflozin DL-pipecolic acid monohydrate co-crystals.
Empagliflozin (1gm), pipecolic acid (0.572 gm) and n-butanol (10 ml) were charged into a round bottom flask and raise the temperature to 80°C. DM water (0.5 ml) was added and stirred the reaction mass for 30 min. The resulted clear solution was cooled to 25°C and stirred the suspension for 30 min. The suspension was further cooled to 3°C, filtered, washed with n-butanol (2 ml) and suck dried for 30 min. The obtained solid was dried under vacuum for 8 hrs at 45°C to obtain empagliflozin DL-pipecolic acid monohydrate co-crystals (1.1 gms).

EXAMPLE 3: Preparation of empagliflozin.
Empagliflozin DL-Pipecolic acid co-crystal (100 gr) and dichloromethane (5000 ml) were taken in a round bottom flask at 25-35°C. pH of the reaction mass was adjusted to 7 to 8 using 10% Sodium carbonate solution. The reaction mass was maintained with stirring for 30-60 min. Layers were separated and the aqueous layer was extracted with dichloromethane (5000 ml). Combined organic layers and washed with 10% sodium chloride solution and dried over sodium sulphate. The reaction mass was filtered and washed with dichloromethane. Distilled off the solvent completely under vacuum to obtain pure Empagliflozin of formula I, as a residue.

EXAMPLE 4: Preparation of amorphous empagliflozin.
Methanol (105 ml) and dichloromethane (875 ml) were added to the residue of empagliflozin of formula I, obtained according to Example 3. The reaction mass temperature was raised to 45°C and stirred further for 60-90min. Filtered the reaction mass through 0.2 micron and feed the reaction mass through Spray dry instrument and dried the compound at 35-40°C under vacuum for 10-12hrs.
Yield: 28gms
PXRD of amorphous empagliflozin is shown in Fig 05
Purity by HPLC : NLT: 99.0% ,CLAIMS:1. Co-crystals of empagliflozin, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid and L-pipecolic acid.

2. Co-crystals of Empagliflozin DL-pipecolic acid.

3. Co-crystal of Empagliflozin DL-pipecolic acid of claim 2, characterized by one or more of the following: characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure1, 1H NMR Spectrum substantially in accordance with Figure 2; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 3 and/or a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 4.

4. A process for the preparation of empagliflozin DL-pipecolic acid co-crystal, comprising:
a) providing a solution or suspension comprising empagliflozin and DL-pipecolic acid in one or more solventsat a temperature of about 30°C to about reflux; and
b) cooling the solution to less than 10°C, and
c) isolating the empagliflozin DL-pipecolic acid co-crystal.

5. The process of claim 4, wherein one or more solvents used in step a) is selected from the group comprising of methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate, methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane, acetone, methyl ethyl ketone, methyl isobutyl ketone, hexane, heptane, cyclohexane, dichloromethane, dichloroethane, chloroform,acetonitrile, propionitrile, water or mixtures thereof.

6. A process for the preparation of amorphous empagliflozin, comprising:
a) dissolving or suspending empagliflozin co-crystal in a suitable solventat a temperature of at least about 20°C to about reflux;
b) optionally treating the step a) reaction mass with a suitable base or an acid;
c) extracting empagliflozin into an organic solvent; and
d) isolating the amorphous form of empagliflozin; wherein the co-crystal used in step a) is selected from the group consisting of DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

7. The process of claim 6, wherein the suitable solvent used in step a) is selected from the group comprising methanol, ethanol, n-butanol, acetonitrile, dichloromethane, water or mixtures thereof.

8. The process of claim 6, wherein the organic solvent of step c) is selected from the group consisting of methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane, hexane, heptane, pentane, toluene, xylene, dichloromethane, chloroform or mixtures thereof.

9. A process for the preparation of amorphous empagliflozin, comprising:
a) providing a solution of empagliflozinat a temperature of about 10°C to about refluxin a solvent selected from the group consisting of esters, ethers, alcohols, ketones, nitriles, halogenated hydrocarbons or mixtures thereof, and
b) removing the solvent from the solution to obtain amorphous form of empagliflozin.

10. The process of claim 9, wherein the solvent used in step a) is selected from the group consisting of methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate, methyl tertiary butyl ether, tetrahydrofuran, dimethyl ether, diisopropyl ether, 1,4-dioxane, methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, propionitrile, dichloromethane, chloroform or mixtures thereof.