DESC:RELATED PATENT APPLICATION
This application claims the priority to and benefit of Indian Provisional Patent Application No. 202141016883 filed on April 10, 2021; the disclosure of which are incorporated herein by reference.

FIELD OF THE INVENTION
The present invention relates to solid forms of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient and the process for the preparation thereof. It further discloses physical mixtures of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient and L-pyroglutamic acid.

BACKGROUND OF THE INVENTION
Ertugliflozin L-pyroglutamic acid (1) is used to improve glycemic control in adults with type 2 diabetes mellitus. Ertugliflozin L-pyroglutamic acid (1) is chemically described as (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4ethoxy benzyl) phenyl)-1- (hydroxy methyl) -6,8-dioxabicyclo [3.2.1] octane -2,3,4-triol L-pyroglutamic acid salt. It is white to off-white powder. It was approved by USFDA under the brand name STEGLATRO.

The synthesis of Ertugliflozin L-pyroglutamic acid (1) has been reported in few patents the contents of which are hereby incorporated as reference in their entirety.
US10294239 patent discloses a process for the preparation of ertugliflozin-L-pyroglutamic acid (1:1) and co-crystal ertugliflozin-L-proline (1:1) co-crystal and an ertugliflozin-L-proline (1:2) co-crystal.

WO2018055496 application discloses process for the preparation of crystalline Form G 1 of Ertugliflozin and a pharmaceutical composition comprising the same.
US8080580 patent discloses processes for the preparation of Ertugliflozin and its salts as shown in scheme 1, below:

Scheme-1
WO2020026273 application discloses the crystalline form N, form S of Ertugliflozin free base and amorphous solid dispersion forms of Ertugliflozin L-pyroglutamic acid, amorphous form of Ertugliflozin L-pyroglutamic acid

Thus, there is need of preparing novel forms of Ertugliflozin (1a), Ertugliflozin L-pyroglutamic acid (1) which is commercially viable and economical having good yields with high purity and desired physiochemical property. Hence, the present inventors, hereby disclose solid dispersions Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient.

OBJECTIVE OF THE INVENTION
Accordingly, one objective of the present invention is to provide solid forms of Ertugliflozin L-pyroglutamic acid (1).

In another objective, the present invention provides solid forms comprising of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient, physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient and physical mixtures of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient.

In another objective, the present invention provides process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient.

In another objective, the present invention provides process for the preparation of physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient.
In another objective, the present invention provides a process for the preparation of physical mixtures of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient.

In another objective, the solid forms obtained by any of the described methods is having purity more than equal to 99.0 %(w/w) by HPLC.

SUMMARY OF THE INVENTION
Accordingly, in one aspect the present invention provides solid forms of Ertugliflozin L-pyroglutamic acid (1).

In another aspect, the present invention provides solid forms may be comprising of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient, physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient and physical mixtures of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient.

In another aspect, the present invention provides a process for preparing solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient, comprising:
a) suspending Ertugliflozin L-pyroglutamic acid (1) and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
b) stirring the reaction mixture at a suitable temperature;
c) filtering the reaction mixture at a suitable temperature;
d) removing the excess solvent; and
e) isolating solid dispersion (s) of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient using a suitable technique.

In another aspect, the solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient is characterized by X-ray powder diffraction pattern as shown in figure 1, figure 2, figure 3 and figure 4.

In another aspect, the present invention provides a process for preparing physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient comprising:
i. suspending Ertugliflozin free base and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
ii. stirring the reaction mixture at a suitable temperature;
iii. filtering the reaction mixture at a suitable temperature;
iv. removing the excess solvent;
v. isolating solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient using a suitable technique;
vi. adding L-Pyro glutamic acid to the solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient;
vii. stirring the reaction mixture;
viii. sieving the reaction mixture; and
ix. isolating the physical mixture of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient.

In another aspect, the physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient is characterized by X-ray powder diffraction pattern as shown in figure 5, figure 6, figure 7 and figure 8.
In another aspect, the present invention provides an alternate process for preparing physical mixture(s) of Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient, comprising:
I. mixing Ertugliflozin free base, a suitable pharmaceutically acceptable excipient and L-Pyro glutamic acid;
II. stirring the reaction mixture at a suitable temperature;
III. sieving the reaction mixture; and
IV. isolating the physical mixture of Ertugliflozin with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient using a suitable technique.

In another aspect, the physical mixture Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient, is characterized by X-ray powder diffraction pattern as shown in figure 9 and figure 10.

In another aspect, the solid dispersions, physical mixtures of Ertugliflozin L-pyroglutamic acid (1) obtained by any of the above methods having purity more than equal to 99.0 % (w/w), preferably more than equal to 99.5 % (w/w) by HPLC.

BRIEF DESCRIPTION OF DRAWINGS
Figure 1: X-Ray powder diffraction (XPRD) pattern of solid dispersion of Ertugliflozin L-pyroglutamic acid (1) prepared by example 1.
Figure 2: X-Ray powder diffraction (XPRD) pattern of solid dispersion of Ertugliflozin L-pyroglutamic acid (1) prepared by example 2.
Figure 3: X-Ray powder diffraction (XPRD) pattern of solid dispersion of Ertugliflozin L-pyroglutamic acid (1) prepared by example 3.
Figure 4: X-Ray powder diffraction (XPRD) pattern of solid dispersion of Ertugliflozin L-pyroglutamic acid (1) prepared by example 4.
Figure 5: X-Ray powder diffraction (XPRD) pattern of physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient prepared by example 5.
Figure 6: X-Ray powder diffraction (XPRD) pattern a physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient prepared by example 6.
Figure 7: X-Ray powder diffraction (XPRD) pattern of a physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient by example 7.
Figure 8: X-Ray powder diffraction (XPRD) pattern of physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient prepared by example 8.
Figure 9: X-Ray powder diffraction (XPRD) pattern of physical mixtures of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient prepared by example 9.
Figure 10: X-Ray powder diffraction (XPRD) pattern of physical mixtures of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient prepared by example 10.

DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides solid forms of Ertugliflozin L-pyroglutamic acid (1).

In another embodiment, the present invention provides solid forms may be comprising of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient, physical mixtures of solid dispersions of Ertugliflozin (1) with a suitable pharmaceutically acceptable excipient with L-pyroglutamic acid (1) and physical mixture of Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient.

In some embodiment, the present invention provides a process for preparing solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient, comprising:
a) suspending Ertugliflozin L-pyroglutamic acid (1) and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
b) stirring the reaction mixture at a suitable temperature;
c) filtering the reaction mixture at a suitable temperature;
d) removing the excess solvent; and
e) isolating solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient using a suitable technique.

In some embodiment, the present invention provides process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) by suspending Ertugliflozin L-pyroglutamic acid (1) and a suitable pharmaceutically acceptable excipient in a suitable solvent and stirring to a suitable temperature of 20-40 °C, preferably 25- 30 °C. The reaction mixture may be filtered, and the solvent of the filtrate may be removed by a suitable technique. The solid dispersions of Ertugliflozin L-pyroglutamic acid (1) and a suitable pharmaceutically acceptable excipient may be isolated using a suitable technique.

In another aspect, the present invention provides solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient is characterized by X-ray powder diffraction pattern as shown in figure 1, figure 2, figure 3 and figure 4.

In some embodiment, the present invention provides a process for preparing physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient comprising:
i. suspending Ertugliflozin free base and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
ii. stirring the reaction mixture at a suitable temperature;
iii. filtering the reaction mixture at a suitable temperature;
iv. removing the excess solvent;
v. isolating solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient using a suitable technique;
vi. adding L-Pyro glutamic acid to the solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient;
vii. stirring the reaction mixture;
viii. sieving the reaction mixture; and
ix. isolating the physical mixture of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient.

In some embodiment, the present invention provides process for preparing physical mixtures of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient. Ertugliflozin free base and a suitable pharmaceutically acceptable excipient may be suspended in a suitable solvent or mixture of solvents and stirred at a suitable temperature of 20-40 °C, preferably 25- 30 °C. The reaction mixture may be filtered, and the solvent of the filtrate may be removed by a suitable technique. The solid dispersions so obtained may be isolated and added to L-pyroglutamic acid. The reaction mixture may be stirred and sieved through a suitable sieve to yield physical mixtures of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient

In another embodiment, the present invention provides a physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient which is characterized by X-ray powder diffraction pattern as shown in figure 5, figure 6, figure 7 and figure 8.

In another embodiment, the present invention provides a process for preparing physical mixtures of Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient, comprising:
i. mixing Ertugliflozin free base, a suitable pharmaceutically acceptable excipient and L-Pyro glutamic acid;
ii. stirring the reaction mixture at a suitable temperature;
iii. sieving the reaction mixture; and
iv. isolating the physical mixture of Ertugliflozin with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient using a suitable technique.

In some embodiment, the present invention provides process for the preparation of physical mixture (s) of Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient. Ertugliflozin free base, L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient were mixed in a suitable glass container at 25-30 °C. The reaction mixture may be stirred and sieved through a sieve with suitable mesh size to yield a physical mixture of Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient.

In another embodiment, the present invention provides a physical mixture Ertugliflozin free base with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient, characterized by X-ray powder diffraction pattern as shown in figure 9 and figure 10.

In some embodiment, the suitable pharmaceutically acceptable excipients used in the present invention may be selected from a group comprising of lactose, sorbitol, mannitol, saccharose, cellulose, Soluplus, methyl cellulose, ethyl cellulose, microcrystalline cellulose (MCC), polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyvinylpyrrolidone K-30, (PVP K-30), magnesium stearate, polyvinyl acetate hydroxyethyl cellulose (HEC), hydroxy propyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy propyl methyl cellulose acetate succinate (HPMC-AS), hydroxy propyl methyl cellulose -E3, (HPMC-E3), Neusilin, Eudragit, Eudragit-EPO, Dicalcium phosphate (DCP), croscarmellose, sodium croscarmellose, a-cyclodextrin, ß-Cyclodextrin, ?-cyclodextrin, hydroxypropyl beta cyclodextrin (HPBCD), sulfobutylether-ß-cyclodextrin (SBCED) or the like. Preferably hydroxypropyl beta cyclodextrin (HPBCD), Eudragit, polyvinylpyrrolidone K-30 (PVP K-30), hydroxy propyl methyl cellulose-E3 (HPMC-E3), Eudragit-EPO, hydroxy propyl methyl cellulose -E3 (HPMC-E3), hydroxypropyl beta cyclodextrin (HPBCD), Neusilin, Dicalcium phosphate (DCP), were used in the present invention.

In another embodiment, the ratio of Ertugliflozin L-pyroglutamic acid (1) and the pharmaceutically acceptable excipients used in solid dispersion may range from 1:1 to 1:5, preferably 1:2 was used.

In another embodiment, the ratio of Ertugliflozin, L-pyroglutamic acid (1) and the pharmaceutically acceptable excipients used in the preparation of physical mixture may range from 1:1 to 1:5, preferably 1:2 was used.

The suitable solvents used herein may be selected from but not limited to a group comprising of water, methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, 2-butanol, tert-butanol, n-hexane, n-heptane, cyclohexane, pet ether, benzene, toluene, dimethyl ether, diethyl ether, di iso propyl ether, methyl tert-butyl ether, 1 ,2-dimethoxyethane, tetrahydrofuran, 1 ,4- dioxane , methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, tert-butyl acetate , dimethylformamide, dichloromethane, dichloroethane, chloroform, carbon tetrachloride , acetone, methyl ethyl ketone, acetonitrile, propionitrile, , or mixtures thereof. Preferably, methanol and dichloromethane were used in the present invention.

In another embodiment the solid forms obtained in the present invention may be isolated by a suitable technique comprising of but not limited to filtration, precipitation, cooling, re-crystallization, concentrating the mass, distillation, flash evaporation, simple evaporation, fast solvent evaporation, rotational drying, spray drying, thin-film drying, agitated thin-film drying, freeze-drying or the like, preferably distillation was used in the present invention.

The suitable techniques used for isolating the desired product may be selected from but not limited to filtration, solvent evaporation, lyophilization or freeze drying, spray drying, agitated thin film drying (ATFD), air tray drying (ATD), Vacuum tray dryer (VTDR), vacuum drying, cooling the solvent, adding anti-solvent to the reaction mixture and combination thereof. Preferably, Vacuum tray dryer (VTDR) was used in the present invention. The drying can be carried out at a suitable temperature ranging from 40 °C to about 70°C, preferably from 60 °C to about 65 °C.

The suitable mesh size may be used to sieve the physical mixture. Preferably, 40 mesh was used in the present invention.

In another embodiment, the solid dispersions of Ertugliflozin L-pyroglutamic acid (1) obtained by any of the above method was having purity more than equal to 99.0 % (w/w), preferably more than equal to 99.5 % (w/w) by HPLC.

In another embodiment, the physical mixture of Ertugliflozin free base with Dicalcium phosphate (DCP) and L-pyroglutamic acid is characterized by the XRD pattern as shown in figure 3 and having 2(?) theta values of ± 0.5o.

Two theta (2T) values Relative Intensity I/Io (%)
11.54 22.8
13.12 32.4
25.6 22
26.40 80.2
26.57 96.9
30.18 100
30.38 41.3
30.97 25.3
32.45 43.3
32.83 41.6
35.99 29.7
40.05 26.8
40.97 24.8
42.10 22.1

The following examples further illustrate the present invention, but should not be construed in anyway, as to limit its scope.

EXAMPLES
Example- 1: Process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl beta-Cyclodextrin (HPBCD)
1g of Ertugliflozin L-pyroglutamic acid (1) and 2.0g of Hydroxypropyl beta-Cyclodextrin (HPBCD) was added to 15 mL of methanol at 25-30 °C and stirred for 10-15 mins. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl beta-Cyclodextrin (HPBCD). Yield: 83% (w/w), XRD: Figure 1.
Examples 2: Process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with Eudragit
1g of Ertugliflozin L-pyroglutamic acid (1) and 2.0g of Eudragit was added to 15 mL of methanol at 25-30 °C and stirred for 10-15 mins. The reaction mass was then, filtered and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Eudragit. Yield: 83% (w/w), XRD: Figure 2.
Examples 3: Process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with Polyvinylpyrrolidone K 30 (PVP K-30)
1g of Ertugliflozin L-pyroglutamic acid (1) and 2.0g of Polyvinylpyrrolidone K 30 (PVP K-30) was added to 15 mL of methanol at 25-30 °C and stirred for 10-15 mins. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Polyvinylpyrrolidone K30 (PVP K-30). Yield: 86% (w/w),XRD: Figure 3.
Examples 4: Process for the preparation of solid dispersions of Ertugliflozin L-pyroglutamic acid (1) with hydroxy propyl methyl cellulose -E3 (HPMC-E3)
1g of Ertugliflozin L-pyroglutamic acid (1) and 2.0g of hydroxy propyl methyl cellulose -E3 (HPMC-E3) was added to 15 mL of methanol at 25-30 °C and stirred for 10-15 mins. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with hydroxy propyl methyl cellulose -E3 (HPMC-E3). Yield: 80% (w/w), XRD: Figure 4.
Examples 5: Process for the preparation of physical mixture of L-pyroglutamic acid and Ertugliflozin free base with Eudragit-EPO
1g of Ertugliflozin and 2.5g of Eudragit-EPO was added to 20 mL of methanol at 25-30 °C and stirred for 10-15 mins to form a clear solution. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Eudragit-EPO. 0.295g of L-Pyro glutamic acid and the amorphous solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Eudragit-EPO were mixed in a Buchi flask and stirred for 15-20 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh to obtain a physical mixture of L-pyroglutamic acid and Ertugliflozin free base with Eudragit-EPO. Yield: 82% (w/w), XRD: Figure 5.
Examples 6: Process for the preparation of physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Povidone K30
1g of Ertugliflozin and 2.5g of Povidone K30 was added to 20 mL of methanol at 25-30 °C and stirred for 10-15 mins to form a clear solution. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Povidone K30 .0.295g of L-Pyro glutamic acid and the amorphous solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Eudragit-EPO were mixed in a Buchi flask and stirred for 15-20 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh to obtain a physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Povidone K30. Yield: 90% (w/w), XRD: Figure 6.
Examples 7: Process for the preparation of physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Hydroxypropyl methylcellulose -E3 (HPMC-E3)
1g of Ertugliflozin and 2.5g of Hydroxypropyl methylcellulose-E3 was added to 20 mL of methanol at 25-30 °C and stirred for 10-15 mins to form a clear solution. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl methylcellulose -E3. 0.295g of L-Pyro glutamic acid and the amorphous solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl methylcellulose-E3 were mixed in a Buchi flask and stirred for 15-20 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh to obtain a physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Hydroxypropyl methylcellulose-E3. Yield: 82% (w/w), XRD: Figure 7.
Examples 8: Process for the preparation of physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Hydroxypropyl beta-Cyclodextrin (HPBCD).
1g of Ertugliflozin and 2.5g of Hydroxypropyl beta-Cyclodextrin (HPBCD) was added to 20 mL of methanol at 25-30 °C and stirred for 10-15 mins to form a clear solution. The reaction mass was then filtered, and the filtrate distilled off under vacuum below 65°C. The obtained solid was collected and dried in Vacuum Tray Dryer (VTDR) below 65°C to yield solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl beta-Cyclodextrin (HPBCD). 0.295g of L-Pyro glutamic acid and the amorphous solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with Hydroxypropyl beta-Cyclodextrin (HPBCD) were mixed in a Buchi flask and stirred for 15-20 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh to obtain a physical mixture of L-pyroglutamic acid and solid dispersion of Ertugliflozin free base with Hydroxypropyl beta-Cyclodextrin (HPBCD). Yield: 86% (w/w), XRD: Figure 8.
Examples 9: Process for the preparation of physical mixture of Ertugliflozin free base, L-pyroglutamic acid with Neusilin
2.5g of Neusilin, 1g of Ertugliflozin and 0.295 g of L-pyroglutamic acid was mixed in a Buchi flask and stirred for 10-15 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh and stored under nitrogen atmosphere to obtain a physical mixture of Ertugliflozin free base with Neusilin and L-pyroglutamic acid. Yield: 80% (w/w), XRD: Figure 9.
Examples 10: Process for the preparation of physical mixture of Ertugliflozin free base, L-pyroglutamic acid with Dicalcium phosphate (DCP)
2.5g of Dicalcium phosphate (DCP), 1g of Ertugliflozin and 0.295 g of L-pyroglutamic acid was mixed in a Buchi flask and stirred for 10-15 mins at 25-30 °C. The reaction mixture was then sieved through 40 mesh and stored under nitrogen atmosphere to obtain a physical mixture of Ertugliflozin free base with Dicalcium phosphate (DCP) and L-pyroglutamic acid. Yield: 92% (w/w), XRD: Figure 10.
,CLAIMS:1. A process for preparing solid dispersions of Ertugliflozin L-pyroglutamic acid (1), comprising:
a) suspending Ertugliflozin L-pyroglutamic acid (1) and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
b) stirring the reaction mixture at a suitable temperature;
c) filtering the reaction mixture at a suitable temperature;
d) removing the excess solvent; and
e) isolating solid dispersion of Ertugliflozin L-pyroglutamic acid (1) with a suitable pharmaceutically acceptable excipient using a suitable technique.

2. A process for preparing physical mixture (s) of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base comprising:
i. suspending Ertugliflozin free base and a suitable pharmaceutically acceptable excipient in a suitable solvent or mixture of solvents;
ii. stirring the reaction mixture at a suitable temperature;
iii. filtering the reaction mixture at a suitable temperature;
iv. removing the excess solvent;
v. isolating solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient using a suitable technique;
vi. adding L-Pyro glutamic acid to the solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient;
vii. stirring the reaction mixture;
viii. sieving the reaction mixture; and
ix. isolating the physical mixture of L-Pyro glutamic acid and solid dispersion of Ertugliflozin free base with a suitable pharmaceutically acceptable excipient.

3. A process for preparing physical mixtures of Ertugliflozin free base with L-pyroglutamic acid, comprising:
I. mixing Ertugliflozin free base, a suitable pharmaceutically acceptable excipient and L-Pyro glutamic acid;
II. stirring the reaction mixture at a suitable temperature;
III. sieving the reaction mixture; and
IV. isolating the physical mixture of Ertugliflozin with L-pyroglutamic acid and a suitable pharmaceutically acceptable excipient using a suitable technique.

4. The process as claimed in claim 1, wherein the ratio of Ertugliflozin L-pyroglutamic acid (1) and the pharmaceutically acceptable excipients used in solid dispersion may range from 1:1 to 1:5.

5. The process as claimed in claim 2 and 3, wherein the ratio of Ertugliflozin, L-pyroglutamic acid (1) and the pharmaceutically acceptable excipients used in the preparation of physical mixture may range from 1:1 to 1:5.

6. The process as claimed in claim 1, 2 and 3, wherein the pharmaceutically acceptable excipient is selected from lactose, sorbitol, mannitol, saccharose, cellulose, soluplus , methyl cellulose, ethyl cellulose, microcrystalline cellulose (MCC), polyethylene glycol (PEG), polyvinylpyrrolidone (PVP), polyvinylpyrrolidone K-30, (PVP K-30), magnesium stearate, polyvinyl acetate hydroxyethyl cellulose (HEC), hydroxy propyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), hydroxy propyl methyl cellulose acetate succinate (HPMC-AS), hydroxy propyl methyl cellulose -E3, (HPMC-E3), neusilin, Eudragit, Eudragit-EPO, Dicalcium phosphate (DCP), croscarmellose, sodium croscarmellose, a-cyclodextrin, ß-Cyclodextrin, ?-cyclodextrin, hydroxypropyl beta cyclodextrin (HPBCD), sulfobutylether-ß-cyclodextrin (SBCED) or the like.

7. The process as claimed in claim 1, 2 and 3, wherein the solvent is selected from water, methanol, ethanol, n-propanol, iso-propanol, n-butanol, iso-butanol, 2-butanol, tert-butanol, n-hexane, n-heptane, cyclohexane, pet ether, benzene, toluene, dimethyl ether, diethyl ether, di isopropyl ether, methyl tert-butyl ether, 1,2-dimethoxyethane, tetrahydrofuran, 1,4- dioxane, methyl acetate, ethyl acetate, n-propyl acetate, isopropyl acetate, n-butyl acetate, isobutyl acetate, tert-butyl acetate, dimethylformamide, dichloromethane, dichloroethane, chloroform, carbon tetrachloride, acetone, methyl ethyl ketone, acetonitrile, propionitrile, or mixtures thereof.