PRIORITY

This application claims the benefit under Indian Provisional Application No(s). 4903/CHE/2015 filed on 15th September 2015 entitled "Co-crystals of SGLT2 inhibitors, process for their preparation and pharmaceutical compositions thereof; 201641010442 filed on 28th March 2016 entitled "Solid forms of dapagliflozin, process for its preparation and pharmaceutical compositions thereof and 201641029280 filed on 29th August 2016 entitled "Solid forms of empagliflozin, process for its preparation and pharmaceutical compositions thereof; the content of which are incorporated by reference herein.

FIELD OF THE INVENTION

The present invention relates to solid forms of SGLT2 inhibitors, processes for their preparation and use of such solid forms in pharmaceutical compositions and to their use in therapy. In particular, the present invention relates to solid forms of SGLT2 inhibitors, including their co-crystals, solvates and/or their polymorphs, process for their preparation and a pharmaceutical composition comprising the same.

BACKGROUND OF THE INVENTION

Diabetes mellitus is a serious and chronic metabolic disease that is characterized by high blood glucose (hyperglycemia) and affects millions of people worldwide. SGLT2 is a Sodium-dependent Glucose co-Transporter protein, which affects the reabsorption of glucose in the kidney. It is estimated that 90% of renal glucose reabsorption is facilitated by SGLT2. Since glucose reabsorption is mediated predominantly by SGLT2 and because high glucose levels have been identified as a cause of disease in diabetes, SGLT2 has become a drug target for type 2 diabetes therapy. Selective inhibition of SGLT2 has the potential to reduce hyperglycemia by inhibiting glucose reabsorption in the kidney with elimination of glucose by excretion in the urine (glucosuria).

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are a new class of diabetic medications indicated only for the treatment of type 2 diabetes. In conjunction with exercise and a healthy diet, they can improve glycemic control. They have been studied alone and with other medications including metformin, sulfonylureas, pioglitazone, DPP-4 inhibitors and insulin.

Drugs in the SGLT2 inhibitors class include, but are not limited to canagliflozin, dapagliflozin, empagliflozin and the like. The structures of these SGLT2 inhibitors are represented below:

Canagliflozin Dapagliflozin

Empagliflozin

SGLT2 inhibitor compounds and their preparation process have been described in the art, for example U.S. Patent. No. 7,943,788 disclosed canagliflozin; U.S. Patent. No. 6,515,117 disclosed dapagliflozin and U.S. Patent. No. 7,579,449 disclosed empagliflozin.

Solid forms of SGLT2 inhibitor compounds in the form of crystalline forms, solvates, co-crystals, eutectic mixtures etc. have been described in the art on various occasions, e.g. US6774112, US7723309, US7919598, US7943582, US9006188, US9035044, WO 2002083066, WO2004063209, WO2007114475, WO2008002824, WO2013064909, WO2012163546, WO2013079501, WO2014178040, WO2015071761, WO2015132803, WO2015198227, WO2016018024, US2015307540, IN1985/MUM/2013, CN102167715B and CN 103965267 A.

Further, amorphous form of dapagliflozin has been described in the art, for example in U.S. Patent. No. 8,999,941; PCT Publication Nos. WO 2015/104658, WO 2015/132803 and WO 2015/040571.

Obtaining suitable solid forms of a drug is a necessary stage for many orally available drugs. Suitable solid forms possess the desired properties of a particular drug. Such suitable forms often possess more favorable pharmaceutical and pharmacological properties or may be easier to process than known forms of the drug itself or may be used as a drug product intermediate during the preparation of the drug. For example, new drug formulations comprising crystalline forms of a given drug may have superior properties, such as solubility, dissolution, hygroscopicity and storage stability over existing formulations of the drug.

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.

A co-crystal of a drug is a distinct chemical composition between the drug and the co-crystal former, and generally possesses distinct crystallographic and spectroscopic properties when compared to those of the drug and the co-crystal former individually. 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 former based on charge balance. Indeed, one can often obtain co-crystals having stoichiometric ratios of drug to the co-crystal former of greater than or less than 1 : 1. The stoichiometric ratio of an API to co -crystal former is a generally unpredictable feature of a co-crystal.

In view of the foregoing, it would be desirable to provide new solid forms of SGLT2 inhibitors. Further, it would be desirable to have reliable processes for producing these solid forms. Therefore, the present invention addresses the need in the art for pharmaceutically useful solid forms of SGLT2 inhibitor that may have improved physicochemical properties, such as a higher solubility and dissolution rate, enhanced flow properties and enhanced stability.

Although processes have been described in the art for the preparation of amorphous dapagliflozin, there still remains a need for simple, environmental -friendly, stable, economical and industrially feasible and scalable processes for the preparation of dapagliflozin amorphous form.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides solid forms of SGLT2 inhibitors, including its co-crystals, solvates and/or polymorphs, processes for their preparation, pharmaceutical compositions containing the same and to their use in therapy.

In particular, the present invention relates to solid forms of SGLT2 inhibitors, wherein the SGLT2 inhibitor can be, but is not limited to canagliflozin, dapagliflozin, empagliflozin and the like, processes for their preparation and pharmaceutical compositions.

In accordance with another embodiment, the present invention provides solid forms of SGLT2 inhibitors, 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 one embodiment, the present invention provides novel co-crystals of SGLT2 inhibitors.

In accordance with another embodiment, the present invention provides the solid forms of SGLT2 inhibitors exist in the form of co-crystals, solvates, polymorphs of co-crystals or polymorphs of solvates.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, wherein the SGLT2 inhibitor is selected from canagliflozin, dapagliflozin, empagliflozin and the like.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, wherein the SGLT2 inhibitor is selected from canagliflozin, dapagliflozin, empagliflozin and the like and co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazole, 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 SGLT2 inhibitors, comprising:

a) providing a solution or suspension comprising SGLT2 inhibitor and a co-crystal former in one or more solvents; and

b) isolating the co-crystals of SGLT2 inhibitors; wherein the SGLT2 inhibitor is selected from canagliflozin, dapagliflozin and empagliflozin and 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, pyrazole, pyrazine-2- carboxylic acid, imidazole, morpholine, proline and the like.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, wherein the SGLT2 inhibitor is Canagliflozin.

In accordance with another embodiment, the present invention provides co-crystals of canagliflozin and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine and the like.

In accordance with another embodiment, the present invention provides co-crystal of canagliflozin and a co-crystal former, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, nicotinic acid, pyrazine 2-carboxylic acid, ammonia or pyrazole.

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

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

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

In accordance with another embodiment, the present invention provides canagliflozin 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 canagliflozin 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 Canagliflozin DL-pipecolic acid co-crystal characterized by an Infrared spectroscopy (IR) spectrum substantially in accordance with Figure 05.

In accordance with another embodiment, the present invention provides Canagliflozin DL-pipecolic acid co-crystal characterized by one or more of the following: a powder X-Ray diffraction (XRD) pattern substantially in accordance with Figure 01; a XH NMR Spectrum substantially in accordance with Figure 02; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 03; a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 04 and/or an Infrared spectroscopy (IR) spectrum substantially in accordance with Figure 05.

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin DL-pipecolic acid co-crystal, comprising providing a solution or suspension comprising canagliflozin and DL-pipecolic acid in one or more organic solvents and isolating the canagliflozin DL-pipecolic acid co-crystal.

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

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin L-pipecolic acid co-crystal, comprising providing a solution or suspension comprising canagliflozin and L-pipecolic acid in one or more organic solvents and isolating the canagliflozin L-pipecolic acid co-crystal.

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

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin D-pipecolic acid co-crystal, comprising providing a solution or suspension comprising canagliflozin and D-pipecolic acid in one or more organic solvents and isolating the canagliflozin D-pipecolic acid co-crystal.

In accordance with another embodiment, the present invention provides canagliflozin nicotinic acid co-crystal.

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin nicotinic acid co-crystal, comprising providing a solution or suspension comprising canagliflozin and nicotinic acid in one or more organic solvents and isolating the canagliflozin nicotinic acid co-crystal.

In accordance with another embodiment, the present invention provides canagliflozin pyrazine-2-carboxylic acid co-crystal.

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin pyrazine-2-carboxylic acid co-crystal, comprising providing a solution or suspension comprising canagliflozin and pyrazine-2-carboxylic acid in one or more organic solvents and isolating the canagliflozin pyrazine-2-carboxylic acid co-crystal,

In accordance with another embodiment, the present invention provides canagliflozin pyrazole co-crystal.

In accordance with another embodiment, the present invention provides a process for the preparation of Canagliflozin pyrazole co-crystal, comprising providing a solution or suspension comprising canagliflozin and pyrazole in one or more organic solvents and isolating the canagliflozin pyrazole co-crystal.

In accordance with another embodiment, the solid forms of canagliflozin of the present invention may be used as an intermediate in obtaining high purity canagliflozin, preferably amorphous form of canagliflozin.

In accordance with another embodiment, the present invention provides an improved process for the preparation of canagliflozin from the co-crystals of canagliflozin of the present invention.

In accordance with another embodiment, the present invention provides an improved process for the preparation of canagliflozin, comprising:

a) preparing co-crystals of canagliflozin according to processes described as above; and b) converting the co-crystal of canagliflozin in to canagliflozin.

In accordance with another embodiment, the present invention provides an improved process for the preparation of canagliflozin; comprising:

a) preparing co-crystal of canagliflozin according to processes described as above; and b) converting the co-crystal of canagliflozin in to canagliflozin; 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, pyrazole, pyrazine- 2-carboxylic acid, imidazole, morpholine and the like.

In accordance with another embodiment, the present invention provides co-crystals of dapagliflozin.

In accordance with another embodiment, the present invention provides co-crystals of dapagliflozin and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, and the like.

In accordance with another embodiment, the present invention provides a process for the preparation of co-crystals of dapagliflozin, comprising:

a) providing a solution or suspension comprising dapagliflozin and a co-crystal former in one or more organic solvents; and

b) isolating the co-crystals of dapagliflozin; 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, and the like.

In accordance with another embodiment, the present invention provides a process for the preparation of co-crystals of dapagliflozin, wherein the co-crystals are selected from the group comprising DL-pipecolic acid, D-pipecolic acid and L-pipecolic acid; comprising:

a) providing a solution or suspension comprising dapagliflozin and a co-crystals former in one or more organic solvents; and

b) isolating the co-crystals of dapagliflozin, wherein the co-crystals former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid and L-pipecolic acid.

In accordance with another embodiment, the present invention provides co-crystals of dapagliflozin and a co-crystal former, wherein the co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

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

In accordance with another embodiment, the present invention provides dapaghflozin DL-pipecolic acid co-crystals characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 09.

In accordance with another embodiment, the present invention provides dapaghflozin DL-pipecolic acid co-crystals characterized by a ΧΗ NMR Spectrum substantially in accordance with Figure 10.

In accordance with another embodiment, the present invention provides dapaghflozin DL-pipecolic acid co-crystals characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 11.

In accordance with another embodiment, the present invention provides dapaghflozin DL-pipecolic acid co-crystals characterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 12.

In accordance with another embodiment, the present invention provides dapaghflozin DL-pipecolic acid co-crystals characterized by one or more of the following: a powder X-Ray diffraction (XRD) pattern substantially in accordance with Figure 09; a XH NMR Spectrum substantially in accordance with Figure 10; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 11; and/or a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 12.

In accordance with another embodiment, the present invention provides a process for the preparation of dapaghflozin DL-pipecolic acid co-crystals, comprising providing a solution or suspension comprising dapagliflozin and DL-pipecolic acid in one or more organic solvents and isolating the dapagliflozin DL-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides dapagliflozin D-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides dapagliflozin D-pipecolic acid co-crystals characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 13.

In accordance with another embodiment, the present invention provides a process for the preparation of dapagliflozin D-pipecolic acid co-crystals, comprising providing a solution or suspension comprising dapagliflozin and D-pipecolic acid in one or more organic solvents and isolating the dapagliflozin D-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides dapagliflozin L-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides dapagliflozin L-pipecolic acid co-crystals characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 14.

In accordance with another embodiment, the present invention provides a process for the preparation of dapaghflozin L-pipecolic acid co-crystals, comprising providing a solution or suspension comprising dapaghflozin and L-pipecolic acid in one or more organic solvents and isolating the dapaghflozin L-pipecolic acid co-crystals.

In accordance with another embodiment, the present invention provides dapaghflozin 2, 3-butanediol solvate.

In accordance with another embodiment, the present invention provides crystalline dapaghflozin 2, 3-butanediol solvate.

In accordance with another embodiment, the present invention provides crystalline dapaghflozin 2,3-butanediol solvate characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 15.

In accordance with another embodiment, the present invention provides crystalline dapaghflozin 2,3-butanediol solvate characterized by a 1H NMR Spectrum substantially in accordance with Figure 16.

In accordance with another embodiment, the present invention provides crystalline dapaghflozin 2,3-butanediol solvate characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 17.

In accordance with another embodiment, the present invention provides crystalline dapaghflozin 2,3-butanediol solvate characterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 18.

In accordance with another embodiment, the present invention provides dapaghflozin 2,3-butanediol solvate characterized by one or more of the following: a powder X-Ray diffraction (XRD) pattern substantially in accordance with Figure 15; a XH NMR Spectrum substantially in accordance with Figure 16; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 17; and/or a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 18.

In accordance with another embodiment, the present invention provides a process for the preparation of dapaghflozin 2,3-butanediol solvate, comprising:

a) dissolving dapaghflozin or a solvate or a co-crystal in an organic solvent, b) treating the above solution with 2,3-butanediol,

c) optionally adding seed crystals of dapaghflozin 2,3-butanediol solvate,

d) adding an anti-solvent to the reaction mass, and

e) isolating the dapaghflozin 2,3-butanediol solvate.

In accordance with another embodiment, the solid forms of dapaghflozin of the present invention may be used as an intermediate in obtaining high purity dapaghflozin, preferably amorphous form of dapaghflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous form of dapaghflozin, wherein the process involves one or more solid forms of dapagliflozin of the invention as an intermediate.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous dapagliflozin, comprising:

a) dissolving or suspending dapagliflozin co-crystals in a suitable solvent;

b) optionally treating the step a) reaction mass with a suitable base or an acid;

c) extracting dapagliflozin into an organic solvent; and

d) removing the solvent to obtain amorphous form of dapagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous dapagliflozin, comprising:

a) dissolving or suspending dapagliflozin co-crystals in a suitable solvent,

b) treating the step a) reaction mass with a suitable base or an acid,

c) optionally extracting dapagliflozin into an organic solvent,

d) removing the solvent to obtain a residue,

e) dissolving the residue in an organic solvent to obtain a solution,

f) adding an anti-solvent to the step e) solution or vice-versa,

g) optionally seeding with amorphous dapagliflozin, and

h) isolating the amorphous dapagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous dapagliflozin, comprising:

a) providing a solution of dapagliflozin in a solvent selected from the group consisting of esters, ethers, alcohols, ketones, nitriles or mixtures thereof, and

b) removing the solvent from the solution to obtain amorphous form of dapagliflozin.

In accordance with another embodiment, the present invention provides a process for the preparation of amorphous dapagliflozin, comprising:

a) providing a solution of dapagliflozin in a solvent selected from the group consisting of esters, ethers, alcohols, ketones, nitriles or mixtures thereof,

b) adding an anti-solvent to the solution or vice versa,

c) optionally seeding with amorphous dapagliflozin, and

d) isolating the amorphous form of dapagliflozin; wherein the anti-solvent is selected from the group consisting of water, hydrocarbons solvents, ether solvents or mixtures 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 and a co-crystal former, 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, pyrazole, 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 former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

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

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

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystals characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 21.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystals characterized by 1H NMR Spectrum substantially in accordance with Figure 22.

In accordance with another embodiment, the present invention empagliflozin DL-pipecolic acid co-crystals characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 23.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystals characterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 24.

In accordance with another embodiment, the present invention provides empagliflozin DL-pipecolic acid co-crystals characterized by one or more of the following: a powder X-Ray diffraction (XRD) pattern substantially in accordance with Figure 21; a XH NMR Spectrum substantially in accordance with Figure 22; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 23; and/or a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 24.

In accordance with another embodiment, the present invention provides a process for the preparation of empagliflozin DL-pipecolic acid co-crystals, 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 solid forms of co-crystals of empagliflozin of the present invention may be used as an intermediate in obtaining high purity empagliflozin.

In accordance with another embodiment, the present invention provides solid forms of SGLT2 inhibitors, which may have greater stability, bioavailability, and having desired pharmacological, pharmacokinetic and pharmacodynamic effects.

In accordance with another embodiment, the present invention provides a pharmaceutical composition comprising at least one of the solid forms of SGLT2 inhibitors described above and at least one or more pharmaceutically acceptable excipients.

BRIEF DESCRIPTION OF THE DRAWINGS:

The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate several embodiments of the invention and together with the description, serve to explain the principles of the invention.

Figure 1 is the characteristic powder XRD pattern of Canagliflozin DL-pipecolic acid co-crystal.

Figure 2 is the characteristic 1H NMR Spectrum of Canagliflozin DL-pipecolic acid co-crystal.

Figure 3 is the characteristic DSC thermogram of Canagliflozin DL-pipecolic acid co-crystal.

Figure 4 is the characteristic TGA curve of Canagliflozin DL-pipecolic acid co-crystal.

Figure 5 is the characteristic IR spectrum of Canagliflozin DL-pipecolic acid co-crystal.

Figure 6 is the characteristic powder XRD pattern of Canagliflozin obtained according to example 10 of the present invention.

Figure 7 is the characteristic TGA curve of Canagliflozin obtained according to example 10 of the present invention.

Figure 8 is the characteristic IR spectrum of Canagliflozin obtained according to example 10 of the present invention.

Figure 9 is the characteristic powder XRD pattern of dapagliflozin DL-pipecolic acid co-crystal.

Figure 10 is the characteristic ΧΗ NMR Spectrum of dapagliflozin DL-pipecolic acid co-crystals.

Figure 11 is the characteristic DSC thermogram of dapagliflozin DL-pipecolic acid co-crystals.

Figure 12 is the characteristic TGA curve of dapagliflozin DL-pipecolic acid co-crystal.

Figure 13 is the characteristic powder XRD pattern of dapagliflozin D-pipecolic acid co-crystals.

Figure 14 is the characteristic powder XRD pattern of dapagliflozin L-pipecolic acid co-crystals.

Figure 15 is the characteristic powder XRD pattern of dapagliflozin 2,3-butanediol solvate.

Figure 16 is the characteristic XH NMR Spectrum of dapagliflozin 2,3-butanediol solvate. Figure 17 is the characteristic DSC thermogram of dapagliflozin 2,3-butanediol solvate.

Figure 18 is the characteristic TGA curve of dapagliflozin 2,3-butanediol solvate.

Figure 19 is the characteristic powder XRD pattern of amorphous dapagliflozin.

Figure 20 is the characteristic DSC thermogram of amorphous dapagliflozin.

Figure 21 is the characteristic powder XRD pattern of empagliflozin DL-pipecolic acid co-crystals.

Figure 22 is the characteristic ΧΗ NMR Spectrum of empagliflozin DL-pipecolic acid co-crystals.

Figure 23 is the characteristic DSC thermogram of empagliflozin DL-pipecolic acid co-crystals.

Figure 24 is the characteristic TGA curve of empagliflozin DL-pipecolic acid co-crystals. DETAILED DESCRIPTION OF THE INVENTION

As used herein, the term "co-crystals" 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.

As used herein, the term "solvate" refers to a crystalline compound in which molecules of solvents are incorporated into the crystal lattice of the compound.

The starting SGLT2 inhibitors used in the present invention is known in the art and can be prepared by any known methods, for example Canagliflozin may be synthesized as disclosed in U.S. Patent Nos. 7,943,788 and 9,024,009; Dapagliflozin may be synthesized as disclosed in U.S. Patent No. 6,515,117, 7,375,213, 7,932,379 and 7,919,598; and Empagliflozin may be synthesized as disclosed in U.S. Patent No. 7,579,449, which are incorporated herein by

reference; or the SGLT2 inhibitor may be obtained as a solution directly from a reaction mixture in which it is formed and used as such without isolation.

The present invention relates to solid forms of SGLT2 inhibitors, including their co-crystals, solvates and/or their polymorphs, processes for their preparation, pharmaceutical compositions containing the same and to their use in therapy.

In accordance with another embodiment, the present invention provides the solid forms of SGLT2 inhibitors exist in the form of co-crystals, solvates, polymorphs of co-crystals or polymorphs of solvates.

In particular, the present invention relates to solid forms of SGLT2 inhibitors, wherein the SGLT2 inhibitor can be, but is not limited to Canagliflozin, Dapagliflozin, Empagliflozin and the like, processes for their preparation and pharmaceutical compositions.

In accordance with one embodiment, the present invention provides novel co-crystals of SGLT2 inhibitors.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, wherein the SGLT2 inhibitor is selected from Canagliflozin, Dapagliflozin, Empagliflozin and the like.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, wherein the SGLT2 inhibitor is selected from the group comprising Canagliflozin, Dapagliflozin, Empagliflozin and the like and co-crystal former is selected from the group comprising DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

The ratio of SGLT2 inhibitor to co-crystal former may be stoichiometric or non-stoichiometric according to the present invention. For example, 1: 1, 1.5: 1, 1 : 1.5, 2: 1 and 1:2 ratios of SGLT2 inhibitor : co-crystal former is acceptable.

In accordance with another embodiment, the present invention provides co-crystals of SGLT2 inhibitors, which are characterized by one or more of analytical techniques such as powder X-Ray diffraction (XRD); ¾ 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 a process for the preparation of co-crystals of SGLT2 inhibitors, comprising:

a) providing a solution or suspension comprising SGLT2 inhibitor and a co-crystal former in one or more solvents; and

b) isolating the co-crystals of SGLT2 inhibitors; wherein the SGLT2 inhibitor is selected from the group comprising Canagliflozin, Dapagliflozin and Empagliflozin and 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

The step of providing a solution or suspension includes any form of SGLT2 inhibitor that may be combined with one or more organic solvents at a suitable temperature, and then the co-crystal former may be mixed with the resulting solution or slurry. Alternatively, the mixture may be formed by adding both the SGLT2 inhibitor and the co-crystal former at the same time in to one or more organic solvents.

Suitable one or more solvents includes but are not limited to alcohols, esters, ethers, ketones, nitriles, halogenated hydrocarbons, aromatic hydrocarbons, aliphatic hydrocarbons, amides, nitroalkanes and the like; water and mixtures thereof.

CLAIMS:

Claim 1: Co-crystals of SGLT2 inhibitors and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine or proline.

Claim 2: Co-crystals of SGLT2 inhibitors of claim 1, wherein the SGLT2 inhibitor is selected from the group comprising Canagliflozin, Dapagliflozin and Empagliflozin.

Claim 3: Co-crystals of SGLT2 inhibitors of claim 1, wherein the SGLT2 inhibitor is selected from Canagliflozin, Dapagliflozin or Empagliflozin and 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine or proline.

Claim 4: A process for the preparation of co-crystals of SGLT2 inhibitors and a co-crystal former, comprising:

a) providing a solution or suspension comprising SGLT2 inhibitor and a co-crystal former in one or more solvents; and

c) isolating the co-crystals of SGLT2 inhibitors; wherein the SGLT2 inhibitor is selected from the group comprising canagliflozin, dapagliflozin and empagliflozin and 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, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine, proline and the like.

Claim 5: The process of claim 4, wherein the solvent is selected from the group comprising alcohols, esters, ethers, ketones, nitriles, halogenated hydrocarbons, aromatic hydrocarbons, aliphatic hydrocarbons, amides, nitroalkanes; water and mixtures thereof.

Claim 6: The process of claim 4, wherein the solvent is selected from the group comprising methanol, ethanol, isopropanol, n- propanol, n-butanol, isobutanol, methyl acetate, ethyl acetate, isopropyl acetate, tetrahydrofuran, dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane, acetone, methyl isobutyl ketone, methyl ethyl ketone, acetonitrile, propionitrile, methylene chloride, ethylene chloride, chloroform, carbon tetrachloride, toluene, xylene, n-hexane, n-heptane, cyclohexane, dimethyl formamide, dimethyl acetamide, dimethyl sulfoxide, N-methyl pyrrolidinone, nitromethane, nitroethane, water and mixtures thereof.

Claim 7: The process of claim 4, wherein the organic solvent is selected from the group consisting of ethanol, n-butanol, ethyl acetate, isopropyl acetate, heptane, water and mixtures thereof.

Claim 8: The process of claim 4, wherein the solution or suspension is formed by heating at a temperature of at least about 30°C to about reflux.

Claim 9: The process of claim 4, wherein the isolation of step b) is carried out by crystallization, solvent precipitation, concentration by subjecting the solution to heating, spray drying, freeze drying, evaporation on rotary evaporator under vacuum or agitated thin film evaporator (ATFE).

Claim 10: The process of claim 9, wherein the isolation is carried out by crystallization or solvent precipitation.

Claim 11: The process of claim 10, wherein the isolation further comprises: cooling the reaction solution to less than 35 °C, adding an anti solvent, optionally heating the solution to about 40°C to 75°C, further cooling the solution to less than 30°C and filtering the product. Claim 12: The process of claim 11, wherein the anti solvent is n-heptane.

Claim 13: Co-crystals of Canagliflozin and a co-crystal former, wherein the co-crystal former is selected from DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine.

Claim 14: Co-crystals of Canagliflozin and a co-crystal former of claim 13, wherein the co-crystal former is selected from DL-pipecolic acid, D-pipecolic acid and L-pipecolic acid.

Claim 15: Co-crystals of Canagliflozin and DL-pipecolic acid.

Claim 16: Co-crystals of Canagliflozin and DL-pipecolic acid of claim 15, characterized by n X-Ray powder diffraction (XRD) pattern having one or more peaks at about 4.00, 9.12, 9.60, 10.50, 11.34, 14.92, 17.56, 17.92, 18.92, 19.80, 20.18, 20.60, 21.74, 22.20, 22.94, 23.48 and 26.90 ±0.2° 2Θ.

Claim 17: Co-crystals of Canagliflozin and DL-pipecolic acid of claim 15, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 01.

Claim 18: Co-crystals of Canagliflozin and DL-pipecolic acid of claim 15, characterized by one or more of the following: a powder X-Ray diffraction (XRD) pattern substantially in accordance with Figure 01; a 1H NMR Spectrum substantially in accordance with Figure 02; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 03; a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 04 and/or an Infrared spectroscopy (IR) spectrum substantially in accordance with Figure 05. Claim 19: A process for the preparation of co-crystal of Canagliflozin and DL-pipecolic acid, comprising providing a solution or suspension comprising Canagliflozin and DL-pipecolic acid in one or more organic solvents and isolating the co-crystal of Canagliflozin and DL-pipecolic acid.

Claim 20: The process of claim 19, wherein the organic solvent is selected from the group consisting of methanol, ethanol, n-butanol, ethyl acetate, isopropyl acetate, hexane, heptane and mixtures thereof.

Claim 21: The process of claim 20, wherein the solvent is ethanol, n-butanol, ethyl acetate, isopropyl acetate, heptane or mixtures thereof and optionally a mixture of these solvents with water.

Claim 22: The process of claim 19, wherein the solution or suspension is formed by heating at a temperature of at least about 30°C to about reflux.

Claim 23: Co-crystals of Canagliflozin and L-pipecolic acid.

Claim 24: A process for the preparation of Co-crystals of Canagliflozin and L-pipecolic acid of claim 23, comprising providing a solution or suspension comprising canagliflozin and L-pipecolic acid in one or more organic solvents and isolating the canagliflozin L-pipecolic acid co-crystal.

Claim 25: The process of claim 24, wherein the solvent is ethanol, ethyl acetate, n-heptane or mixtures thereof.

Claim 26: Co-crystals of Canagliflozin and D-pipecolic acid.

Claim 27: A process for the preparation of Co-crystals of Canagliflozin and D-pipecolic acid of claim 26, comprising providing a solution or suspension comprising canagliflozin and D-pipecolic acid in one or more organic solvents and isolating the canagliflozin D-pipecolic acid co-crystals.

Claim 28: The process of claim 27, wherein the solvent is ethanol, ethyl acetate, n-heptane or mixtures thereof.

Claim 29: Co-crystals of Canagliflozin and nicotinic acid.

Claim 30: A process for the preparation of Co-crystals of Canagliflozin and nicotinic acid of claim 29, comprising providing a solution or suspension comprising canagliflozin and nicotinic acid in one or more organic solvents and isolating the canagliflozin nicotinic acid co-crystals.

Claim 31: The process of claim 30, wherein the solvent is ethanol.

Claim 32: Co-crystals of Canagliflozin and pyrazine-2-carboxylic acid.

Claim 33: A process for the preparation of Co-crystals of Canagliflozin and pyrazine-2-carboxylic acid of claim 32, comprising providing a solution or suspension comprising

canagliflozin and pyrazine-2-carboxylic acid in one or more organic solvents and isolating the canagliflozin pyrazine-2-carboxylic acid co-crystal.

Claim 34: The process of claim 33, wherein the solvent is ethanol.

Claim 35: Co-crystals of Canagliflozin and pyrazole.

Claim 36: A process for the preparation of Co-crystals of Canagliflozin and pyrazole, comprising providing a solution or suspension comprising canagliflozin and pyrazole in one or more organic solvents and isolating the canagliflozin pyrazole co-crystal.

Claim 37: The process of claim 36, wherein the solvent is ethanol, n-heptane or a mixture thereof.

Claim 38: A process for the preparation of canagliflozin, comprising:

a) preparing a co-crystals of canagliflozin and a co-crystal former; and

b) converting the co-crystal of canagliflozin in to canagliflozin; 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, pyrazole, pyrazine- 2-carboxylic acid, imidazole and morpholine.

Claim 39: The process of claim 38, further comprising the steps of: providing a solution of co-crystals of canagliflozin and a co-crystal former in an organic solvent at a temperature of about 25°C to about reflux; treating the solution with a suitable base, and isolating the canagliflozin.

Claim 40: The process of claim 39, wherein the organic solvent is selected from the group comprising alcohols, ketones, esters, ethers, aliphatic hydrocarbons, aromatic hydrocarbons, halogenated hydrocarbons, nitriles and mixtures thereof.

Claim 41: The process of claim 40, wherein the organic solvent is selected from the group comprising ethyl acetate, isopropyl acetate, dichloromethane, toluene, methyl tertiary butyl ether and mixtures thereof.

Claim 42: The process of claim 40, wherein the suitable base is selected from the group comprising di-isopropyl ethylamine, triethyl amine, pyridine, sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, sodium hydride or potassium hydride.

Claim 43: The process of claim 40, wherein the canagliflozin is isolated by concentrating the reaction solution under vacuum.

Claim 44: The process of claim 43, wherein the canagliflozin is isolated by treating the residue with a suitable solvent, wherein the suitable solvent is selected from the group

comprising toluene, xylene, methyl tertiary butyl ether, di-isopropyl ether, acetone, methyl ethyl ketone, heptane, hexane, cyclohexane, cycloheptane and methyl cyclohexane.

Claim 45: The process of claim 44, wherein the suitable solvent is cyclohexane or cycloheptane.

Claim 46: Co-crystals of Dapagliflozin and a co-crystal former, 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, pyrazole, pyrazine-2-carboxylic acid, imidazole and morpholine.

Claim 47: Co-crystals of Dapagliflozin and a co-crystal former of claim 46, wherein the co-crystal former is selected from DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

Claim 48: Co-crystals of Dapagliflozin and DL-pipecolic acid.

Claim 49: Co-crystals of Dapagliflozin and DL-pipecolic acid of claim 48, characterized by an X-Ray powder diffraction (XRD) pattern having one or more peaks at about 3.91, 7.83, 8.41, 9.38, 11.76, 15.38, 15.65, 16.26, 16.99, 17.62, 17.95, 18.36, 19.96, 20.28, 21.29, 21.97, 23.02, 23.65, 24.68, 26.72, 30.43 and 31.34 ±0.2° 20.

Claim 50: Co-crystals of Dapagliflozin and DL-pipecolic acid of claim 48, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 09.

Claim 51: Co-crystals of Dapagliflozin and DL-pipecolic acid of claim 48, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 09, a H NMR Spectrum substantially in accordance with Figure 10, a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 11 and a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 12.

Claim 52: A process for the preparation of Co-crystals of Dapagliflozin and DL-pipecolic acid of claim 48, comprising:

a) providing a solution or suspension comprising dapagliflozin and DL-pipecolic acid in one or more organic solvents; and

b) isolating the dapagliflozin DL-pipecolic acid co-crystals.

Claim 53: The process of claim 52, wherein the solvent is selected from the group comprising esters such as methyl acetate, ethyl acetate, isopropyl acetate; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, water or mixtures thereof;

Claim 54: The process of claim 53, wherein the solvent is isopropyl acetate.

Claim 55: The process of claim 52, wherein step a) is carried out at a temperature of about 30°C to about reflux.

Claim 56: The process of claim 52, wherein the isolation of step b) is carried out by filtration.

Claim 57: Co-crystals of Dapagliflozin and D-pipecolic acid.

Claim 58: Co-crystals of Dapagliflozin and D-pipecolic acid, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 13.

Claim 59: A process for the preparation of Co-crystals of Dapagliflozin and D-pipecolic acid, comprising:

a) providing a solution or suspension comprising Dapagliflozin and D-pipecolic acid in one or more solvents; and

b) isolating the dapagliflozin D-pipecolic acid co-crystals.

Claim 60: The process of claim 59, wherein the solvent is wherein the solvent is selected from the group comprising esters such as methyl acetate, ethyl acetate, isopropyl acetate; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, water or mixtures thereof.

Claim 61: The process of claim 60, wherein the solvent is isopropyl acetate.

Claim 62: The process of claim 60, wherein the isolation of step b) is carried out by filtration.

Claim 63: Co-crystals of Dapagliflozin and L-pipecolic acid.

Claim 64: Co-crystals Dapagliflozin and L-pipecolic acid, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 14.

Claim 65: A process for the preparation of Co-crystals Dapagliflozin and L-pipecolic acid, comprising:

a) providing a solution or suspension comprising dapagliflozin and L-pipecolic acid in one or more organic solvents; and

b) isolating the dapagliflozin L-pipecolic acid co-crystals.

Claim 66: The process of claim 65, wherein the solvent is wherein the solvent is selected from the group comprising esters such as methyl acetate, ethyl acetate, isopropyl acetate; alcohols such as methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, water or mixtures thereof.

Claim 67: The process of claim 66, wherein the solvent is isopropyl acetate.

Claim 68: The process of claim 65, wherein the isolation of step b) is carried out by filtration.

Claim 69: Dapagliflozin 2,3-butanediol solvate.

Claim 70: Dapagliflozin 2,3-butanediol solvate of claim 69, characterized by X-Ray powder diffraction (XRD) pattern having one or more peaks at about 3.69, 8.62, 9.52, 10.70, 14.63, 15.74, 16.09, 16.60, 18.33, 18.55, 19.82, 20.15, 20.56, 21.20, 21.79, 22.75, 23.39, 24.23, 24.68, 25.15, 25.76, 26.50, 27.03, 27.36, 29.48, 29.94, 30.60, 31.66, 32.56, 34.21 and 36.95±0.2°2Θ.

Claim 71: Dapagliflozin 2,3-butanediol solvate of claim 69, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 15.

Claim 72: Dapagliflozin 2,3-butanediol solvate of claim 69, characterized by a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 17.

Claim 73: Dapagliflozin 2,3-butanediol solvate of claim 69, characterized by a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 18.

Claim 74: A process for the preparation of dapagliflozin 2,3-butanediol solvate of claim 69, comprising:

a) dissolving dapagliflozin or a solvate or a co-crystal in an organic solvent at a temperature of about 20°C to reflux,

b) treating the above solution with 2,3-butanediol,

c) optionally adding seed crystals of dapagliflozin 2,3-butanediol solvate,

d) adding an anti-solvent to the reaction mass, and

e) isolating dapagliflozin 2,3-butanediol solvate.

Claim 75: The process of claim 74, wherein the organic solvent in step a) is selected from the group consisting of methyl tertiary butyl ether, tetrahydrofuran, dimethyl ether, diisopropyl ether, 1,4-dioxane, isopropyl acetate, methyl acetate, ethyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate, methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, acetone, methyl ethyl ketone, methyl isobutyl ketone, acetonitrile, propionitrile and mixtures thereof.

Claim 76: The process of claim 74, wherein the anti-solvent in step d) is selected from the group consisting of water, n-pentane, n-hexane, n-heptane, cyclohexane, methyl cyclohexane, cycloheptane and mixture thereof.

Claim 77: The process of claim 74, wherein the solvent is methyl tertiary butyl ether, ethyl acetate, isopropyl acetate and mixtures thereof and the anti solvent is heptane.

Claim 78: A process for the preparation of amorphous dapagliflozin, comprising:

a) dissolving or suspending dapagliflozin co-crystals in a suitable solvent;

b) optionally treating the step a) reaction mass with a suitable base or an acid;

c) extracting dapagliflozin into an organic solvent; and

d) removing the solvent to obtain amorphous form of dapagliflozin.

Claim 79: The process of claim 78, wherein the dapagliflozin co-crystal used in step a) is selected from the group consisting of DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

Claim 80: The process of claim 78, wherein the suitable solvent of step a) is selected from water or mixture of water and an organic solvent.

Claim 81 : The process of claim 80, wherein the organic solvent is selected from alcohols such as methanol, ethanol, 1-propanol, isopropanol, butanol, isobutanol, t-butanol or mixtures thereof; esters such as methyl acetate, ethyl acetate, isopropyl acetate.

Claim 82: The process of claim 78, wherein suitable base in step b) is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, di-isopropyl ethylamine, triethyl amine or pyridine.

Claim 83: The process of claim 78, wherein the organic solvent of step c) is selected from esters such as methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate; ethers such as dimethyl ether, diisopropyl ether, methyl tertiary butyl ether, 1,4-dioxane; aliphatic hydrocarbons such as hexane, heptane, pentane; aromatic hydrocarbons such as toluene, xylene; halogenated hydrocarbons such as dichloromethane, chloroform or mixtures thereof.

Claim 84: The process of claim 78, wherein the step of removing the solvent is carried out by distillation under vacuum.

Claim 85: A process for the preparation of amorphous dapagliflozin, comprising:

a) dissolving or suspending dapagliflozin co-crystals in a suitable solvent,

b) treating the step a) reaction mass with a suitable base or an acid,

c) optionally extracting dapagliflozin into an organic solvent,

d) removing the solvent to obtain a residue,

e) dissolving the residue in an organic solvent to obtain a solution,

f) adding an anti-solvent to the step e) solution or vice-versa,

g) optionally seeding with amorphous dapagliflozin, and

h) isolating amorphous dapagliflozin.

Claim 86: The process of claim 85, wherein the dapagliflozin co-crystal used in step a) is selected from the group consisting of DL-pipecolic acid, D-pipecolic acid or L-pipecolic acid.

Claim 87: The process of claim 85, wherein the suitable solvent of step a) is selected from water or mixture of water and an organic solvent.

Claim 88: The process of claim 85, wherein the organic solvent is selected from alcohols such as methanol, ethanol, 1-propanol, isopropanol, butanol, isobutanol, t-butanol or mixtures thereof; esters such as methyl acetate, ethyl acetate, isopropyl acetate.

Claim 89: The process of claim 85, wherein suitable base in step b) is selected from the group consisting of sodium carbonate, potassium carbonate, cesium carbonate, sodium bicarbonate, potassium bicarbonate, sodium hydroxide, potassium hydroxide, lithium hydroxide, di-isopropyl ethylamine, triethyl amine or pyridine.

Claim 90: The process of claim 85, wherein the organic solvent of step e) is selected from the group consisting of methyl tertiary butyl ether, tetrahydrofuran, dimethyl ether, diisopropyl ether, 1,4-dioxane, methyl acetate, ethyl acetate, isopropyl acetate, n-propyl acetate, n-butyl acetate, t-butyl acetate, methanol, ethanol, isopropanol, n-propanol, n-butanol, isobutanol, acetone, methyl ethyl ketone, methyl isobutyl ketone and mixtures thereof.

Claim 91: The process of claim 85, wherein the anti-solvent of step f) is selected from water, heptane or cycloheptane.

Claim 92: A process for the preparation of amorphous dapagliflozin, comprising:

a) providing a solution of dapagliflozin in a solvent selected from the group consisting of esters, ethers, alcohols, ketones, nitriles or mixtures thereof, and

b) removing the solvent from the solution to obtain amorphous form of Dapagliflozin.

Claim 93: The process of claim 92, wherein the solvent of 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 and mixtures thereof.

Claim 94: The process of claim 92, wherein step a) is carried out at a temperature of about 30°C to about reflux.

Claim 95: The process of claim 92, wherein the step of removal of solvent is carried out by distillation, distillation under vacuum, spray drying, agitated thin film drying ("ATFD"), or freeze drying (lyophilization).

Claim 96: A process for the preparation of amorphous dapagliflozin, comprising:

a) providing a solution of dapagliflozin in a solvent selected from the group consisting of esters, ethers, alcohols, ketones, nitriles or mixtures thereof,

b) adding an anti-solvent to the solution or vice versa,

c) optionally seeding with amorphous dapagliflozin, and

d) isolating amorphous form of dapagliflozin; wherein the anti-solvent is selected from the group consisting of water, hydrocarbons solvents, ether solvents or mixtures thereof.

Claim 97: The process of claim 96, wherein the solvent of 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 and mixtures thereof.

Claim 98: The process of claim 97, wherein the anti-solvent of step b) is selected from the group consisting of water, n-pentane, n-hexane, 3-methylpentane, 2,3-dimethylbutane, n-heptane, 2,3-dimethylpentane, 2,4-dimethylpentane, 3,3-dimethylpentane, 3-ethylpentane, 2,2,3-trimethylbutane, n-octane, 3-methylheptane, cyclohexane, methylcyclohexane, cycloheptane and mixtures thereof.

Claim 99: The process of claim 96, wherein the solvent of step a) is methyl acetate, isopropyl acetate, ethyl acetate, methyl tertiary butyl ether or mixtures thereof and the anti solvent of step b) is water, heptane or cycloheptane.

Claim 100: Co-crystals of Empagliflozin and a co-crystal former, wherein the co-crystal former is selected from DL-pipecolic acid, D-pipecolic acid, L-pipecolic acid, ammonia, nicotinic acid, isonicotinic acid, pyridine, pyrazole, pyrazine-2-carboxylic acid, imidazole, morpholine or proline.

Claim 101 : Co-crystals of Empagliflozin and a co-crystal former of claim 100, wherein the co-crystal former is selected from DL-pipecolic acid, D-pipecolic acid and L-pipecolic acid.

Claim 102: Co-crystals of Empagliflozin DL-pipecolic acid.

Claim 103: Co-crystals of Empagliflozin DL-pipecolic acid of claim 102, characterized 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° 2Θ.

Claim 104: Co-crystals of Empagliflozin DL-pipecolic acid of claim 102, characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 21.

Claim 105: Co-crystals of Empagliflozin DL-pipecolic acid of claim 102, characterized by one or more of the following: characterized by X-Ray powder diffraction (XRD) pattern substantially in accordance with Figure 21, a XH NMR Spectrum substantially in accordance with Figure 22; a differential scanning calorimetry (DSC) thermogram substantially in accordance with Figure 23 and a thermogravimetric analysis (TGA) curve substantially in accordance with Figure 24.

Claim 106: A process for the preparation of empagliflozin DL-pipecolic acid co-crystals, comprising:

a) providing a solution or suspension comprising empagliflozin and DL-pipecolic acid in one or more solvents; and

b) isolating the empagliflozin DL-pipecolic acid co-crystals.

Claim 107: The process of claim 106, wherein the solvents are selected from the group comprising esters, alcohols, ethers, ketones, aliphatic hydrocarbon, halogenated hydrocarbons, nitriles, water or mixtures thereof.

Claim 108: The process of claim 107, wherein the solvent is n-butanol, ethanol or acetone.

Claim 109: The process of claim 106, wherein the solution or suspension is formed by heating at a temperature of at least about 30°C to about reflux.

Claim 110: A pharmaceutical composition comprising at least one of the solid forms of SGLT2 inhibitors according to claims 1-110 and at least one or more pharmaceutically acceptable excipients.