DESC:Field of the invention
The present invention relates to an amorphous form of Dapagliflozin 1,2-Propanediol solvate of formula-I and the process for preparing said amorphous form. The present invention also relates to Dapagliflozin 1,2-Propanediol premix comprising Dapagliflozin 1,2-Propanediol in an amorphous form and process for preparing said premix. The present invention also relates to process for the preparation of stable amorphous form of Dapagliflozin.

Formula-I

Background of the invention
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia and an increased risk of microvascular and macrovascular complications. The number of adults with T2DM is approximately 285 million globally, 55 million in Europe, and 37 million in North America, and is expected to rise to 438 million, 67 million, and 53 million, respectively, by the year 2030.
Currently available therapy includes oral agents with different mechanisms of action such as insulin sensitizing agents (metformin and thiazolidinediones), agents promoting insulin secretion (sulphonylureas, GLP-1 analogues and DPP4-antagonists), as well as insulin.
Patients with T2DM are at risk for the development of microvascular and macrovascular complications. While improved glycemic control results in reduced rates of complications, especially microvascular, at least 44% of patients continue to fall short of treatment goals.
Hypoglycemia is a clinically important barrier to optimize the treatment with insulin and sulphonylureas (SUs), both of which are preferred second-line treatment options. Efforts by patients to lose weight as part of a therapeutic lifestyle program are undermined by therapies that lead to weight gain, such as thiazolidinediones (TZDs) and insulin and SUs.
Dapagliflozin (BMS-512148) is a potent, competitive, reversible, highly selective and orally active inhibitor of the human sodium-glucose co-transporter 2 (SGLT2), the major transporter responsible for the renal glucose reabsorption. It improves glycemic control in patients with T2DM by reducing renal glucose reabsorption leading to urinary glucose excretion (glucuresis). Dapagliflozin’s mechanism of action is different and complementary to the mechanisms of currently available medicines, resulting in the direct, and insulin-independent, elimination of glucose by the kidney. SGLT2 is almost exclusively expressed in the kidney minimizing the risk of off-target (i.e. non-kidney) effects.
Dapagliflozin having the chemical name (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxy benzyl)phenyl]-6-(hydroxymethyl)tetrahydro-2H-pyran-3,4,5-triol, is disclosed in US 6515117B2. Amorphous form of solid Dapagliflozin is disclosed in US patent 6515117B2 which in its entirety is incorporated herein by reference.

US 6515117B2 describes the synthesis of dapagliflozin from the corresponding tetra acetylated ß-C-glucoside precursor. After removal of the acetate moieties, the residue was dissolved in Ethyl acetate, washed with brine containing Potassium Hydrogen Sulfate and dried. The volatile solvents were removed and the resultant oil was taken in minimum amount of dichloromethane and distilled under vacuum to give the desired title compound described as a glassy off white solid containing 0.11 mol of Ethyl acetate. The applicants of the present invention have characterized the Dapagliflozin form described in US 6515117 as being amorphous and unstable (very hygroscopic, readily forming a gel-like consistency). Accordingly, this form appears unsuitable for pharmaceutical applications.
WO2008002824A1 discloses crystalline solvates and complexes of dapagliflozin, namely (S)- propylene glycol, ((S)-PG) hydrate (Form SC-3), (R)-1,2-Propanediol ((R)-PG) hydrate (Form SD-3), Ethanol dihydrate (Form SA-I), ethylene glycol (EG) dihydrate (Form SB-I), ethylene glycol (EG) dihydrate (Form SB-2), 1 :2 L-proline complex (Form 3), 1 :1 L-proline complex (Form 6), 1 :1 L-proline hemihydrate complex (Form H.5-2), and 1 :1 L-phenylalanine complex (Form 2).
US7851502B2 and US8221786B2 disclose pharmaceutical compositions comprising crystalline Dapagliflozin propylene glycol (PG) hydrate.
All of references cited above did not mention or disclose stable amorphous form of Dapagliflozin and amorphous forms of Dapagliflozin 1,2-Propanediol solvate and process for its preparation.
The difference in many aspects of solid state properties such as solubility, dissolution and bioavailability of crystal (polymorphic) forms and amorphous forms of a given drug substance has been widely reported. The amorphous forms in a number of drugs exhibit superior dissolution characteristics and in some cases different bioavailability patterns compared to crystalline forms [Konne T., Chem Pharm Bull, 38, 2003 (1990)] were also noticed. For some therapeutic indications one bioavailability pattern may be favored over another. In addition, since the physical and chemical stability of amorphous form can be improved by making solid amorphous dispersion containing drug substance and a carrier, the amorphous forms of most drug substances are therefore suitable for preparing solid pharmaceutical dosage forms.
Present inventors have unexpectedly discovered an amorphous form of Dapagliflozin 1,2-Propanediol solvate or solid amorphous dispersion of Dapagliflozin 1,2-Propanediol solvate and stable amorphous form of Dapagliflozin and process for preparing the same.
Present inventions also describe stable amorphous Dapagliflozin 1,2-Propanediol premix, method of making and pharmaceutical composition thereof.

Object of the invention:
In one aspect, the present invention relates to an Amorphous form of Dapagliflozin 1,2-Propanediol solvate of formula-I
In another aspect, the present invention relates to a process for preparing an amorphous form of Dapagliflozin 1,2-Propanediol solvate, comprising the steps of
i) providing a solution of Dapagliflozin in a suitable organic solvent(s) or water or mixture thereof
ii) adding (S)-(+)-1,2-Propanediol or (R)-(-)-1,2-Propanediol in the solution of Dapagliflozin
iii) isolating Dapagliflozin 1,2-Propanediol solvate by conventional techniques.
In another aspect, the present invention is to provide process for the preparation of an amorphous form of Dapagliflozin 1,2-Propanediol solvate by melting Dapagliflozin 1,2-Propanediol solvate followed by cooling to obtain amorphous form of Dapagliflozin 1,2-Propanediol solvate.
In another aspect, the present invention provides an amorphous Dapagliflozin 1,2-Propanediol premix having enhanced stability and dissolution properties and process for preparation thereof.
In another aspect, the present invention provides pharmaceutical compositions comprising the aforementioned amorphous Dapagliflozin 1,2-Propanediol premix.
In another aspect, the present invention provides process for the preparation of stable amorphous form of Dapagliflozin comprising the steps of
i) providing a solution of Dapagliflozin in a suitable organic solvent(s) or water or mixture thereof
ii) adding (S)-(+)-1,2-Propanediol or (R)-(-)-1,2-Propanediol and premix in the solution of Dapagliflozin
iii) isolating stable amorphous form of Dapagliflozin by conventional techniques.

Brief description of the Drawings
Figure 1 is an illustration of a PXRD pattern of an amorphous Dapagliflozin 1,2-Propanediol solvate.
Figure 2 is an illustration of a PXRD pattern of stable amorphous Dapagliflozin.

Detailed description of the invention:
Present invention provides an amorphous form of Dapagliflozin 1,2-Propanediol solvate.
In another aspect of present invention relates to a process for preparing an amorphous form of Dapagliflozin 1,2-Propanediol solvate, comprising the steps of i) providing a solution of Dapagliflozin in a suitable organic solvent(s) or
water or mixture thereof
ii) adding (S)-(+)-1,2-Propanediol or (R)-(-)-1,2-Propanediol in the solution of Dapagliflozin
iii) isolating Dapagliflozin 1,2-Propanediol solvate by conventional techniques.
The term "conventional techniques" as used herein includes but not limited to distillation, distillation under reduced pressure or vacuum, evaporation, solvent-antisolvent, spray drying, lyophilization or freeze drying.
In another aspect of the present invention is to provide process for the preparation of an amorphous form of Dapagliflozin 1,2-Propanediol solvate by melting Dapagliflozin 1,2-Propanediol solvate followed by cooling to obtain amorphous form of Dapagliflozin 1,2-Propanediol solvate.
Amorphous Dapagliflozin or amorphous Dapagliflozin 1,2-Propanediol solvate obtained by present invention is stable and not contaminated with any crystalline form.
Another embodiment of present invention is to provide an Amorphous Dapagliflozin 1,2-Propanediol premix having enhanced stability and dissolution properties and process for preparation thereof.
Premixes are characterized by a variety of associated properties such as stability, flow, and solubility. Typical premixes represent inclusion of the above properties, as for example, an increase in stability and dissolution properties of the premix. Although there are a variety of premixes, there is a continuous search in this field of art for premixes that exhibit improved properties. Thus, the instant invention provides a premix in which Dapagliflozin 1,2-Propanediol solvate exists in stable amorphous form and process of manufacture of the premix and pharmaceutical compositions comprising said amorphous Dapagliflozin 1,2-Propanediol premix.
One of the embodiments of the present invention is to provide a process for the preparation of solid premix comprising:
(a) providing an intimate mixture comprising organic solvent, amorphous Dapagliflozin 1,2-Propanediol solvate and premixing agents, and optionally, water;
(b) optionally removing solvent from the mixture;
(c) optionally dissolving in secondary solvent;
(d) isolating premix of Amorphous Dapagliflozin 1,2-Propanediol.

As used herein, the term "intimate mixture" can denote a solution, suspension, emulsion, colloid, dispersion or the like. Generally, the term "intimate mixture" as used herein denotes a solution.
Suitable premixing agents are pharmaceutically acceptable carrier or excipients include polymers/agents used in the process for manufacturing of the premix may be selected from group of cellulose derivatives but not limited to Croscarmellose Sodium, micro crystalline cellulose, hydroxyethylcellulose(HEC), hydroxypropylcellulose(HPC), hydroxypropyl methylcellulose (HPMC), hydroxymethylethylcellulose (HEMC), ethylcellulose (EC), methylcellulose (MC), cellulose esters, cellulose glycolate, hydroxypropyl methyl cellulose phthalate, polymethylacrylate (HPMCP), hypromellose, vinylpyrrolidone monomers but not limited to polyvinylpyrrolidone and polyol but not limited to mannitol. The said polymers/agents are used to facilitate the presence of an amorphous Dapagliflozin 1,2-Propanediol solvate.
In another embodiment, the present invention provides pharmaceutical compositions comprising the aforementioned amorphous Dapagliflozin 1,2-Propanediol glycol premix.
There is further provided by the present invention a process of preparing a pharmaceutical composition of said premix which process comprises the step of mixing a solid premix substantially as hereinbefore described together with a pharmaceutically acceptable carrier. Conveniently the following combinations of carrier or excipient and co- precipitation medium can be employed in a process according to the present invention.
One of the embodiments of the present invention is to provide a process for the preparation of stable Amorphous form of Dapagliflozin of formula- XI, comprising of:
a) reacting the compound of formula-III with 4-bromo-1-chloro-2-(4- ethoxybenzyl) benzene compound of formula-II in presence of n-butyllithium in tetrahydrofuran, followed by treating the obtained compound with methane sulfonic acid in water to provide pentahydroxy Dapagliflozin compound of formula-V,
b) reacting the compound of formula-V with methane sulfonic acid in methanol to provide compound of formula-VI, reacting the compound of formula-VI in-situ with triethylsilane in presence of aluminumchloride OR borontrifluoridediethyletherate in dichloromethane to provide the compound of formula-VII, reacting the compound of formula-VII in-situ with acetic anhydride in presence of dimethylaminopyridine in dichloromethane to provide the compound of formula-IX.
c) treating the compound of formula-IX with a base preferably sodium hydroxide a mixture of water and methanol to provide the Dapagliflozin crude compound of formula- X, which further reacting with (S)-(+)-1,2-Propanediol or (R)-(-)-1,2-Propanediol in presence of suitable organic solvent followed by treatment with water and melting to provide stable amorphous Dapagliflozin (XI).

Process of present invention is schematically disclosed in below scheme.

Crystal engineering is of importance in the production of API's. During crystallisation, many physico-chemical characteristics of the API or drug substance are defined, including crystal polymorph, shape, size, particle size distribution, chemical purity and stability. These characteristics influence the stirrability, residual solvent level, drying time, agglomeration, fragmentation and attrition during the isolation process, which in turn affects the drug product manufacturing by determining particle flow, compressibility, solubility, dissolution rate and bioavailability. The specifications towards the physical properties of the API, driven by the drug product manufacturing, are very narrow concerning particle size distribution, bulk density, electrostatic charge and flowability.
One of the embodiments of the present invention is to provide an amorphous Dapagliflozin or amorphous Dapagliflozin 1,2-Propanediol solvate having particle size distributions wherein the 10th volume percentile particle size (D10) is less than about 10 µ??, the 50th volume percentile particle size (D50) is less than about 20 µ??, or the 90th volume percentile particle size (D90) is less than about 40 µ??, or any combination thereof.
The term “organic solvent” or “solvent” as used hereinabove include but not limited to substituted or unsubstantiated alcoholic solvent, halogenated hydrocarbon solvent, aromatic hydrocarbon solvent, ester solvent, ether solvent, cyclic ether solvent, ketone solvent, nitrile solvent and aqueous solvent or mixture thereof. It also includes polar or nonpolar protic solvent, polar or nonpolar aprotic solvent and the like or mixture thereof.
The following examples are provided to enable one skilled in the art to practice the invention and merely illustrate the process of this invention. However, it is not intended in any way to limit the scope of the present invention

Preparation of stable amorphous Dapagliflozin and amorphous Dapagliflozin 1,2-Propanediol solvate
Example-1 : 2,3,4,6-tetra-O-trimethylsilyl-ß-D-glucolactone (III)
To a stirred solution of gluconolactone (100 g) and Hexamethyldisilazane (271.8 g) in 500 mL of Acetonitrile under Nitrogen was added trimethylsilyl chloride (12.19 g) at 20°C-30°C. The stirred reaction was heated to 80°C-85°C for 9 hr whereupon it was allowed to cool to 20°C-30°C. The reaction was quenched by addition of water, was extracted with toluene, and the solvent was evaporated under reduced pressure to give 260 g of title compound (III).

Example-2 : Pentahydroxy Dapagliflozin (V)
To a stirred -70°C to -80°C solution of n-butyl lithium (135 mL) in 600 mL of tetrahydrofuran under N2 was added solution of 5-bromo-2-chloro-4'-ethoxydiphenyl methane (100 g) in 100 mL of tetrahydrofuran at a rate that maintained the reaction below -70°C. After completion of 60 min, solution of 2,3,4,6-tetra-O-trimethylsilyl-ß-D-glucolactone (184.73 g) in 100 mL of Methyl tert-butylether was added at a rate that maintained the reaction below -70°C. After stirring for 60 minutes, solution was quenched with water and methanesulfonic acid (88.4 g). The reaction stirred for 60 min as the temperature rose to 0°C-5°C. The reaction, once complete, was quenched by the solution of sodium bicarbonate, was extracted with Methyl tert-butylether and the solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate and n-Heptane was added. The precipitate was collected, washed by n-Heptane and dried to give 98 g of title compound (IX).

Example-3 : Preparation of tetra acetylated Dapagliflozin (IX)
To a stirred -5°C to 5°C solution of Pentahydroxy Dapagliflozin (100 g) (V) in 1 L of Methanol under N2 was added methanesulfonic acid (54.3 g) at a rate that maintained the reaction below 5°C. The reaction stirred for 3 hr as the temperature rose to 20°C-30°C. The reaction, once complete, was quenched by the solution of sodium bicarbonate, was extracted with dichloromethane and the solvent was evaporated under reduced pressure to give residue (VI). After dissolution of this residue in dichloromethane (250 mL) and acetonitrile (250 mL) was added to prior cooled solution of triethylsilane (75.4 g) and aluminum chloride (64.2 g) OR Borontrifluoridediethyletherate (66 g) in mixture of dichloromethane (250 mL) and acetonitrile (250 mL). The reaction stirred for 60 min as the temperature rose to 20°C-25°C. The reaction was quenched by addition of water, was extracted with dichloromethane, and the solvent was evaporated under reduced pressure to give residue (VII). After dissolution of this residue in dichloromethane (500 mL), 4-dimethylaminopyridine (5.7 g) was added followed by acetic anhydride (131.9 g) under cooling. The reaction stirred for 2 hr at the temperature of 25°C-30°C. The reaction was quenched by addition of water, after separating phases organic layer washed with sodium bicarbonate and the solvent was evaporated under reduced pressure to give residue, which was recrystallized from methanol (1 L) to yield 95 g of the desired tetra acetylated Dapagliflozin (IX).

Example-4 : Preparation of tetra acetylated Dapagliflozin (IX)
To a stirred -5°C to 5°C solution of Pentahydroxy Dapagliflozin (100 g) (V) in 1 L of Methanol under N2 was added methanesulfonic acid (54.3 g) at a rate that maintained the reaction below 5°C. The reaction stirred for 3 hr as the temperature rose to 20°C-30°C. The reaction, once complete, was quenched by the solution of sodium bicarbonate, was extracted with dichloromethane and the solvent was evaporated under reduced pressure to give residue (VI). After dissolution of this residue in dichloromethane (500 mL) was added to prior cooled solution of triethylsilane (75.4 g) and Borontrifluoridediethyletherate (66 g) in dichloromethane (500 mL). The reaction stirred for 60 min as the temperature rose to 20°C-25°C. The reaction was quenched by addition of water, was extracted with dichloromethane, and the solvent was evaporated under reduced pressure to give residue (VII). After dissolution of this residue in dichloromethane (500 mL), 4-dimethylaminopyridine (5.7 g) was added followed by acetic anhydride (131.9 g) under cooling. The reaction stirred for 2 hr at the temperature of 25°C-30°C. The reaction was quenched by addition of water, after separating phases organic layer washed with sodium bicarbonate and the solvent was evaporated under reduced pressure to give residue, which was recrystallized from methanol (1 L) to yield 95 g of the desired tetra acetylated Dapagliflozin (IX).

Example-5 : Preparation of stable Amorphous Dapagliflozin (XI)
To a stirred 25°C to 30°C solution of Acetylated Dapagliflozin (100 g), in 1 L 1:1 methanol / water was added sodium hydroxide (31.2 g). The reaction was heated to 50°C-55°C for 2 hr. The reaction, once complete, was quenched by the solution of hydrochloric acid, was extracted with ethyl acetate and the solvent was evaporated under reduced pressure to give Dapagliflozin crude residue (X). After dissolution of this residue in dichloromethane (350 mL), (S)-(+)-1,2-Propane diol (6.12 g) and warmed solution for 30 min. The solvent was evaporated, residue was stirred with water followed my isolation, melting and isolation by adding n-Heptane, washing and dried to give pure Amorphous Dapagliflozin (XI).

Example-6: Preparation of amorphous Dapagliflozin 1,2-Propanediol solvate (I)
(S)-(+)- 1,2-Propanediol (0.93 g) was added to a solution of crude dapagliflozin (10 g) (X) in methylene chloride (50 mL) at 25-30°C. The resulting reaction was heated to reflux 60 minutes. The obtained solution was distilled off completely under vacuum below 45°C. The obtained mass was cooled to room temperature and water (50 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and wet material was heated to 40-45°C under vacuum to get amorphous dapagliflozin 1,2-Propanediol solvate anhydrous (I).
[Content of (S)-(+)-1,2-Propanediol: 2800 ppm; Moisture content: 0.9%, HPLC purity: 98.87%]

Example-7: Preparation of amorphous dapagliflozin
(S)-(+)-1,2-Propanediol (0.93 g) was added to a solution of crude dapagliflozin (10 g) (X) in methylene chloride (50 mL) at 25-30°C. The resulting reaction was heated to reflux for 60 minutes. The obtained solution was distilled off completely under vacuum below 45°C. The obtained mass was cooled to room temperature and water (50 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and wet material was heated to 40-45°C under vacuum. The obtained product stirred with n-Heptane (30 mL) for 2 hours at 20-30°C. Product was filtered and dried at 35-40°C under vacuum to get pure amorphous Dapagliflozin (9 g, 90%) (XI).
[Content of (S)-(+)-1,2-Propanediol: 3100 ppm; Moisture content: 1.13%, HPLC purity: 98.66%]

Example-8: Preparation of amorphous dapagliflozin (XI)
(S)-(+)-1,2-Propanediol (0.93 g) was added to a solution of crude dapagliflozin (10 g) (X) in Isopropyl acetate (50 mL) at 25-30°C. The resulting reaction was heated to at 40-45°C for 60 minutes. The obtained solution was distilled off completely under vacuum below 45°C. Obtained mass was cooled at room temperature and water (50 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and wet material was heated to 40-45°C under vacuum. The obtained product stirred with n-Heptane (30 mL) for 2 hours at 20-30°C. The product was filtered and dried at 35-40°C under vacuum to get pure amorphous Dapagliflozin (9 g, 90%) (XI).
[Content of (S)-(+)-1,2-Propanediol: 5000 ppm; Moisture content: 0.9%, HPLC purity: 99.94%]

Example-9: Preparation of amorphous Dapagliflozin (XI)
(S)-(+)-1,2-Propanediol (0.93 g) was added to a solution of crude Dapagliflozin (10 g) (X) in methanol (20 mL) at 25-30°C. The resulting reaction was stirred at 25-30°C for 60 minutes. Water (100 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and wet material was heated to 40-45°C under vacuum. The obtained product was stirred with n-Heptane (30 mL) for 2 hours at 20-30°C. The product was filtered and dried at 35-40°C under vacuum to get pure amorphous Dapagliflozin (9 g, 90%) (XI).
[Content of (S)-(+)-1,2-Propanediol: 2800 ppm; Moisture content: 1.0%, HPLC purity: 98.87%]

Example-10: Preparation of amorphous Dapagliflozin (XI)
(S)-(+)- 1,2-Propanediol glycol (464 mg) was added to a solution of crude Dapagliflozin (5 g) (X) in methylenechloride or methanol (50 mL) at 25-30°C. The resulting reaction was stirred at 40-45°C for 60 minutes. Reaction mixture was spray dried to get pure amorphous Dapagliflozin (4.5 g, 90%) (XI).
Content of (S)-(+)-1,2-Propanediol : 1900 ppm; Moisture content: 1.1%, HPLC purity: 99.21%]

Example-11: Preparation of amorphous Dapagliflozin (XI)
(S)-(+)- 1,2-Propanediol (464 mg) was added to a solution of crude Dapagliflozin (5 g) (X) in methanol (50 mL) at 25-30°C. The resulting reaction was stirred at 25-30°C for 60 minutes. Reaction mixture was freeze dried to get pure amorphous Dapagliflozin (4.5 g, 90%) (XI).
[Content of (S)-(+)-1,2-Propanediol : 5900 ppm; Moisture content: 1.1%, HPLC purity: 99.15%]

Example-12: Preparation of amorphous dapagliflozin 1,2-Propanediol solvate (I)
(R)-(-)-1,2-Propanediol (0.93 g) was added to a solution of crude Dapagliflozin (10 g) (X) in methylene chloride (50 mL) at 25-30°C. The resulting reaction was heated to reflux 60 minutes. The obtained solution was distilled off completely under vacuum below 45°C. The obtained mass was cooled to room temperature and water (50 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and heat the wet material was heated to 40-45°C under vacuum to get amorphous dapagliflozin 1,2-Propanediol solvate (I).
[Content of (R)-(-)-1,2-Propanediol : 2800 ppm; Moisture content: 0.9%, HPLC purity: 98.87%]

Example-13: Preparation of amorphous dapagliflozin
(R)-(-)-1,2-Propanediol (0.93 g) was added to a solution of crude Dapagliflozin (10 g) (X) in Isopropyl acetate (50 mL) at 25-30°C. The resulting reaction was heated to at 40-45°C for 60 minutes. The obtained solution was distilled off completely under vacuum below 45°C. The obtained mass was cooled to room temperature and water (50 mL) was added to the reaction mass and stirred for solid separation at 5-100C. The separated solid was filtered and washed with water (10 mL). The obtained wet solid was charged into the bucci flask connected to rotavapor and heat the wet material was heated to 40-45°C under vacuum. The obtained product stirred with n-Heptane (30 mL) for 2 hours at 20-30°C. The product was filtered and dried at 35-40°C under vacuum to get pure amorphous Dapagliflozin (9 g, 90%) (I).
[Content of (R)-(-)-1,2-Propanediol : 5000 ppm; Moisture content: 0.9%, HPLC purity: 99.94%]

Dated this 3rd day of December 2015.

,CLAIMS:1. An amorphous form of Dapagliflozin 1,2-Propanediol solvate.

2. A method for the preparation of the dapagliflozin 1,2-Propanediol solvate according to claim 1, comprising
i) providing a solution of dapagliflozin in a suitable organic solvent(s) or
water or mixture thereof
ii) adding (S)-(+)-1,2-Propanediol or (R)-(-)-1,2-Propanediol in the solution of dapagliflozin
iv) isolating dapagliflozin 1,2-Propanediol solvate by conventional techniques.

3. A process for the preparation of stable Amorphous form of Dapagliflozin of formula- XI, comprising
a) reacting the compound of formula-III

with 4-bromo-1-chloro-2-(4- ethoxybenzyl) benzene compound of formula-II

in presence of n-butyl lithium and sulfonic acid in water that form a reaction product comprising the formula-V

b) reacting the compound of formula-V

with methane sulfonic acid in methanol that form a reaction product comprising the formula-VI

reacting the compound of formula-VI with triethylsilane in presence of aluminum chloride OR Borontrifluoridediethyletherate that form a reaction product comprising the formula-VII

reacting the compound of formula-VII acetic anhydride that form a reaction product comprising the formula-IX

c) reacting the compound of formula-IX with a base that form a reaction product comprising the formula-X

reacting the compound of formula- X with (S)-(+)-1,2-Propanediol or (R)-(-)- 1,2-Propanediol to provide stable amorphous Dapagliflozin (XI).

4. The process of claim 2, characterized in that the solvent is selected from the
Methanol, Ethanol, Isopropanol, Ethyl acetate, Isopropyl acetate, methylene chloride

5. The process of claim 3, characterized in that the base is selected from the LiOH, NaOH, KOH