DESC:CROSS-REFERENCE TO RELATED APPLICATIONS FIELD OF THE INVENTION

This application claims priority to the filing dates of Indian provisional patent application No. 201841041856, filed on November 05, 2018, Indian provisional patent application No. 201941001229, filed on January 10, 2019 and Indian provisional patent application No. 201941006688, filed on February 20, 2019; each of the preceding are hereby incorporated by reference in their entireties.

FIELD OF THE INVENTION
The present invention provides co-crystal of sotagliflozin proline and its preparation thereof also process for the preparation of an amorphous sotagliflozin as well as an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers and its preparation thereof.

DESCRIPTION OF THE RELATED ART
Sotagliflozin is an orally bioavailable inhibitor of the sodium-glucose co-transporter subtype 1 (SGLT1) and 2 (SGLT2), with potential antihyperglycemic activity. Upon oral administration, Sotagliflozin binds to and blocks both SGLT1 in the gastrointestinal (GI) tract and SGLT2 in the kidneys, thereby suppressing the absorption of glucose from the GI tract and the reabsorption of glucose by the proximal tubule into the bloodstream, respectively. This decreases glucose uptake and enhances the urinary excretion of glucose, which lowers and/or normalizes blood glucose levels. SGLT1 is the primary transporter responsible for glucose absorption from the GI tract. SGLT2, a transport protein exclusively expressed in the proximal renal tubules, mediates approximately 90% of renal glucose reabsorption from tubular fluid.
Sotagliflozin is chemically known as (2S,3R,4R,5S,6R)-2-[4-chloro-3-(4-ethoxyphenyl) methyl pheny1]-6-methylsulfanyloxane-3,4,5-triol, having the structure below:

Formula 1

US patent No. 7781577 discloses the sotagliflozin and process for its preparation.

US Patent No. 8217156 discloses an amorphous form of sotagliflozin and sotagliflozin crystalline form 1 and form 2.

PCT publication No. WO2018067805A1 discloses an amorphous form of sotagliflozin and sotagliflozin crystalline forms A, B, C, D, E, F, G, H and K.

US publication No. 2019169219 discloses sotagliflozin crystalline forms I, II, III, V, VI, VII and VIII.

The inventors of the present disclosure have developed novel co-crystal of sotagliflozin and a process for the preparation of an amorphous sotagliflozin.

SUMMARY OF THE DISCLOSURE

The main aspect of the present invention provides co-crystal of sotagliflozin L-proline.

In one aspect of the present invention provides a co-crystal of sotagliflozin L-proline is characterized by powder x-ray diffraction pattern having peaks at 2? angle positions of 5.67, 7.48, 9.75, 11.26, 12.29, 14.90, 15.64, 15.96, 16.69, 17.60, 18.43, 18.73, 19.60, 20.26, 21.66, 22.17, 22.65, 23.15, 23.65, 24.53, 25.20, 25.72, 27.53, 28.26, 28.76, 29.74, 30.36, 31.58, 32.11, 33.37, 34.06, 35.24, 36.12, 39.18, 40.57, 42.75, 44.87, 45.57± 0.2°.

Another aspect of the present invention provides a co-crystal of sotagliflozin L-proline may be characterized by powder x-ray diffraction pattern shown in figure 1.

Another aspect of the present invention provides a process for the preparation of co-crystal of sotagliflozin L-proline comprising the steps of;
a) forming a suspension of sotagliflozin and L-proline in an organic solvent,
b) heating the suspension to a temperature between about 55 °C and about 75 °C,
c) cooling the suspension to a temperature between about 20 °C and 30 °C; and
d) isolating the co-crystal of sotagliflozin L-proline

Another aspect of the present invention provides a co-crystal of sotagliflozin D-proline is characterized by powder x-ray diffraction pattern having peaks at 2? angle positions of 4.15, 10.70, 12.52, 13.59, 13.88, 14.35, 15.09, 16.41, 16.77, 17.06, 17.46, 17.96, 18.34, 18.64, 18.91, 19.40, 20.62, 21.75, 21.99, 22.30, 22.73, 23.18, 23.48, 23.85, 24.71, 25.69, 25.86, 26.73, 27.02, 27.71, 28.44, 28.91, 29.41, 29.86, 30.15, 30.51, 30.89, 31.51, 32.08, 32.77, 33.94, 34.46, 34.73, 35.42, 35.96, 36.82, 37.90, 38.35, 41.04, 41.55, 43.42, 46.03, 47.38, 48.23 ± 0.2°.

Another aspect of the present invention provides a co-crystal of sotagliflozin D-proline may be characterized by powder x-ray diffraction pattern shown in figure 2.

Another aspect of the present invention provides a process for the preparation of co-crystal of sotagliflozin D-proline comprising the steps of;
a) forming a suspension of sotagliflozin and D-proline in an organic solvent,
b) heating the suspension to a temperature between about 50 °C and about 70 °C,
c) cooling the suspension to a temperature between about 20 °C and 30 °C; and
d) isolating the co-crystal of sotagliflozin D-proline

Another aspect of the present invention provides a process for the preparation of an amorphous sotagliflozin comprising the steps of;
a) dissolving sotagliflozin in a mixture of an organic solvent and water to
a temperature between about 40 °C and about 60 °C,
b) isolating an amorphous sotagliflozin.

Another aspect of the present invention provides a process for the preparation of an amorphous sotagliflozin comprising the steps of;
a) dissolving sotagliflozin in an organic solvent to a temperature between about 20 °C and about 30 °C; and
b) isolating an amorphous sotagliflozin

Another aspect of the present invention provides an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers.

Yet another aspect of the present invention provides a process for the preparation of an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers comprising the steps of;
a) dissolving sotagliflozin in a mixture of an organic solvent and water to a temperature between about 40 °C and about 60 °C,
b) cooling the solution to a temperature between about 20 °C and 30 °C,
c) adding pharmaceutically acceptable carrier; and
d) isolating an amorphous solid dispersion of sotagliflozin

BRIEF DESCRIPTION OF THE FIGURES
Further aspects of the present disclosure together with additional features contributing thereto and advantages accruing there from will be apparent from the following description of embodiments of the disclosure which are shown in the accompanying drawing figures wherein:

Figure 1 depicts x-ray powder diffractogram of co-crystal of sotagliflozin L-proline (1:2)
Figure 2 depicts x-ray powder diffractogram of co-crystal of sotagliflozin D-proline (1:1.5).
Figure. 3 depicts x-ray powder diffractogram of an amorphous sotagliflozin
Figure. 4 depicts x-ray powder diffractogram of an amorphous solid dispersion of sotagliflozin

DETAILED DESCRIPTION OF THE DISCLOSURE
It is to be understood that the description of the present invention has been simplified to illustrate elements that are relevant for a clear understanding of the invention, while eliminating, for purposes of clarity, other elements that may be well known.

The polymorph of the present disclosure is characterized by its X-ray powder diffraction pattern. Thus, the X-ray diffraction patterns of amorphous sotagliflozin solid dispersion Figures 3-4 were measured on BRUKER D-8 Discover powder diffractometer equipped with goniometer of ?/2? configuration and Lynx Eye detector. The Cu-anode X-ray tube was operated at 40kV and 30mA. The experiments were conducted over the 2? range of 2.0°-50.0°, 0.030° step size and 0.4 seconds step time. The X-ray diffraction patterns of the co-crystal of Figures 1-2 provided herein were measured on PANalytical, X'Pert PRO powder diffractometer equipped with goniometer of ?/? configuration and X'Celerator detector. The Cu- anode X-ray tube is operated at 40kV and 30mA. The experiments were conducted over the 2? range of 2.0º-50.0°, 0.030° step size and 50 seconds step time.

In one embodiment of the present invention provides a co-crystal of sotagliflozin L-proline.

Another embodiment of the present invention provides a co-crystal of sotagliflozin L-proline is characterized by powder x-ray diffraction pattern having peaks at 2? angle positions of 5.67, 7.48, 9.75, 11.26, 12.29, 14.90, 15.64, 15.96, 16.69, 17.60, 18.43, 18.73, 19.60, 20.26, 21.66, 22.17, 22.65, 23.15, 23.65, 24.53, 25.20, 25.72, 27.53, 28.26, 28.76, 29.74, 30.36, 31.58, 32.11, 33.37, 34.06, 35.24, 36.12, 39.18, 40.57, 42.75, 44.87, 45.57± 0.2°.

Another embodiment of the present invention provides a co-crystal of sotagliflozin L-proline may be characterized by powder x-ray diffraction pattern shown in figure 1.

Another embodiment of the present invention provides a process for the preparation of co-crystal of sotagliflozin L-proline comprising the steps of;
a) forming a suspension of sotagliflozin and L-proline in an organic solvent,
b) heating the suspension to a temperature between about 55 °C and about 75 °C,
c) cooling the suspension to a temperature between about 20 °C and 30 °C; and
d) isolating the co-crystal of sotagliflozin L-proline

Within the context of the present invention, sotagliflozin and L-proline may be contacted in an alcohol solvent, the suspension is heated to a temperature between about 55 °C and about 75 °C under agitation, the reaction mixture is slowly cooled to 20 °C to 30 °C and filtered the obtained solid to get co-crystal of sotagliflozin L-proline.

Within the context of this embodiment of the present invention, an organic solvent may be alcohols, ketones. The alcohols include, but are not limited to methanol, ethanol, isopropanol, n-propanol or t-butanol; ketonic solvents include, but are not limited to acetone, methyl isobutyl ketone or methyl ethyl ketone and mixtures thereof; The preferred embodiment of the present invention ethanol is the solvent used.

Another embodiment of the present invention, the sotagliflozin and L-proline may be combined in the solution at a molar ratio about 1:2.

Another embodiment of the present invention provides a co-crystal of sotagliflozin D-proline is characterized by powder x-ray diffraction pattern having peaks at 2? angle positions of 4.15, 10.70, 12.52, 13.59, 13.88, 14.35, 15.09, 16.41, 16.77, 17.06, 17.46, 17.96, 18.34, 18.64, 18.91, 19.40, 20.62, 21.75, 21.99, 22.30, 22.73, 23.18, 23.48, 23.85, 24.71, 25.69, 25.86, 26.73, 27.02, 27.71, 28.44, 28.91, 29.41, 29.86, 30.15, 30.51, 30.89, 31.51, 32.08, 32.77, 33.94, 34.46, 34.73, 35.42, 35.96, 36.82, 37.90, 38.35, 41.04, 41.55, 43.42, 46.03, 47.38, 48.23 ± 0.2°.

Another embodiment of the present invention provides a co-crystal of sotagliflozin D-proline may be characterized by powder x-ray diffraction pattern shown in figure 2.

Another embodiment of the present invention provides a process for the preparation of co-crystal of sotagliflozin D-proline comprising the steps of;
a) forming a suspension of sotagliflozin and D-proline in an organic solvent,
b) heating the suspension to a temperature between about 50 °C and about 70 °C,
c) cooling the suspension to a temperature between about 20 °C and 30 °C; and
d) isolating the co-crystal of sotagliflozin D-proline

Within the context of the present invention, sotagliflozin and D-proline may be contacted in an alcohol solvent, the suspension is heated to a temperature between about 50 °C and about 70 °C under agitation, the reaction mixture is slowly cooled to 20 °C to 30 °C and filtered the obtained solid to get co-crystal of sotagliflozin D-proline.

Within the context of this embodiment of the present invention, an organic solvent may be alcohols, ketones. The alcohols include, but are not limited to methanol, ethanol, isopropanol, n-propanol or t-butanol; ketonic solvents include, but are not limited to acetone, methyl isobutyl ketone or methyl ethyl ketone and mixtures thereof; The preferred embodiment of the present invention ethanol is the solvent used.

Another embodiment of the present invention, the sotagliflozin and D-proline may be combined in the solution at a molar ratio about 1: 1.5

Another embodiment of the present invention provides a process for the preparation of an amorphous sotagliflozin comprising the steps of;
a) dissolving sotagliflozin in a mixture of an organic solvent and water to
a temperature between about 40 °C and about 60 °C, and
b) isolating an amorphous sotagliflozin

Within the context of this embodiment of the present invention, sotagliflozin is dissolved in a mixture of organic solvent and water.

Within the context of this embodiment of the present invention, sotagliflozin may be dissolved to a temperature between about 50 °C to about 75 °C. In preferred embodiments of the present invention sotagliflozin dissolved in mixture of organic solvent and water at temperature about 55°C.

Within the context of this embodiment of the present invention, an organic solvent is water miscible solvent may be ether solvents, nitrile solvents, ketonic solvents and alcohols. The ether solvents include, but are not limited to 1,4-dioxane and tetrahydrofuran (THF) and mixtures thereof; nitrile solvents include, but are not limited to acetonitrile and propionitrile and mixtures thereof; ketone solvents include, but are not limited to acetone, methyl isobutyl ketone or methyl ethyl ketone and mixtures thereof; The alcohols include, but are not limited to methanol, ethanol, isopropanol, n-propanol or t-butanol and mixtures thereof.

Within the context of this embodiment of the present invention, isolation can be done using any techniques in the art such as, lyophilization, decantation, filtration by gravity or suction, centrifugation, slow evaporation, distillation, agitated thin film drier (ATFD) and spray-drying. In preferred embodiments of the present invention the solvent is removed by filtration, lyophilization and distillation.

Another embodiment of the present invention provides a process for the preparation of an amorphous sotagliflozin comprising the steps of;
a) dissolving sotagliflozin in an organic solvent to a temperature between about 20 °C and about 30 °C; and
b) isolating an amorphous sotagliflozin

Within the context of this embodiment of the present invention, sotagliflozin is dissolved in an organic solvent.
Within the context of this embodiment of the present invention, sotagliflozin may be dissolved at temperature between about 20 °C to about 30 °C.

Within the context of this embodiment of the present invention, an organic solvent may be ketonic solvents. The ketonic solvents include but are not limited to methyl isobutyl ketone (MIBK), methyl ethyl ketone (MEK), acetone. In preferred embodiment of the present invention sotagliflozin may be dissolved in acetone.

Another embodiment of the present invention is to provide an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers.

Yet embodiment of the present invention provides a process for the preparation of an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers comprising the steps of;
a) dissolving sotagliflozin in a mixture of an organic solvent and water to a temperature between about 40 °C and about 60 °C,
b) cooling the solution to a temperature between about 20 °C and 30 °C,
c) adding pharmaceutically acceptable carrier; and
d) isolating an amorphous solid dispersion of sotagliflozin

Within the context of this embodiment of the present invention, sotagliflozin may be dissolved in a mixture of an organic solvent and water.

Within the context of this embodiment of the present invention, an organic solvent is water miscible solvent may be ether solvents. The ether solvents include but are not limited to tetrahydrofuran (THF) and 1,4-dioxane. In preferred embodiment of the present invention solvent employed is mixture of 1,4-dioxane and water.

Within the context of this embodiment of the present invention, sotagliflozin may be dissolved in mixture of 1,4-dioxane and water to a temperature between about 50°C to about 75°C. In a preferred embodiments of the present invention sotagliflozin may be dissolved in mixture of 1,4-dioxane and water about 55°C.

Within the context of this embodiment of the present invention, “About” as used herein means +/- 10% of the referenced value. In certain embodiments, “about” means +/- 9%, or +/- 8%, or +/- 7%, or +/- 6%, or +/- 5%, or +/- 4%, or +/- 3%, or +/-2 +/- or +/- 1% of the referenced value.

Within the context of this embodiment of the present invention, removing of solvent can be done using any techniques in the art such as, decantation, filtration by gravity or suction, centrifugation, slow evaporation, distillation, ATFD, lyophilization and spray-drying. In preferred embodiment of the present invention the solvent is removed by lyophilization.

Within the context of this embodiment of the present invention, pharmaceutically acceptable carrier employed may include, PLASDONETM S-630, polyvinyl pyrrolidine K-30 (PVP-K30), povidone K-30, silicon dioxide, microcrystalline cellulose, lactose monohydrate, Hydroxy propyl methyl cellulose (HPMC) or mixtures thereof. In preferred embodiment of the present invention pharmaceutically acceptable carrier selected is silicon dioxide or Hydroxy propyl methyl cellulose or povidone K-30 or microcrystalline cellulose or PLASDONETM S-630.

Within the context of this embodiment of the present invention, sotagliflozin with pharmaceutically acceptable carrier employed in the ratio of 1:99 to 99:1, preferably 1:1 ratio.

Indicative stability:
In yet another embodiment, the physical stability of 1:2 co-crystal of sotagliflozin L-proline was determined by storing the samples at 40°C and 75% relative humidity (RH) and at 25°C and 60% relative humidity (RH) conditions for six months and the samples were analyzed by PXRD. The results are shown in below Table 1. The 1:2 co-crystal of sotagliflozin L-proline was found to be physically stable at 40°C and 75% relative humidity (RH) and at 25°C and 60% relative humidity (RH) conditions up to six months.

Table 1
Conditions/ Polymorph 1:2 Co-crystal of
sotagliflozin L-proline
PXRD
at 40°C/75% RH
Initial co-crystal
1 month Stable
2 months Stable
3 months Stable
6 months Stable
at 25°C/60% RH
Initial co-crystal
1 month Stable
2 months Stable
3 months Stable
6 months Stable

Solubility
The solubility of 1:2 co-crystal sotagliflozin L-proline, literature form 1 and form 2 were determined in water and different aqueous buffers of different pH at 37°C. The results are shown in the following Table 2. 1:2 co-crystal of sotagliflozin L-proline is shows ~1.5 to 2 folds increase in buffer and aqueous solubility in comparison with Literature form 1 and form 2.

Table 2:
S. No Buffer pH (USP) Solubility at 37°C (mg/mL)
sotagliflozin
(form 1) sotagliflozin
(form 2) 1:2 Co-crystal of sotagliflozin L-proline
1 pH 1.2 0.045 0.048 0.072
2 pH 4.5 0.049 0.070 0.069
3 pH 6.0 0.041 0.045 0.064
4 pH 6.8 0.036 0.040 0.065
5 pH 8.0 0.042 0.045 0.064
6 Water 0.044 0.066 0.081

In view of the above description and the examples below, one of ordinary skill in the art will be able to practice the invention as claimed without undue experimentation. The foregoing will be better understood with reference to the following examples that detail certain procedures for the preparation of molecules, compositions and Formulations according to the present invention. All references made to these examples are for the purposes of illustration. The following examples should not be considered exhaustive, but merely illustrative of only a few of the many aspects and embodiments contemplated by the present disclosure.

EXAMPLES
Example 1: Preparation of co-crystal sotagliflozin L-proline (1:2)
sotagliflozin (0.5g), L-proline (0.14g) was taken in ethanol (14mL) at 25±5°C. Heated the contents to 65°C -70°C and stirred for 20-30 minutes at same temperature. The reaction mass was slowly cooled to 25±5°C and maintained under stirring at same temperature for 16hours. The product obtained was filtered, washed with ethanol (2mL) and dried under vacuum for 1hour at 40?C. The product obtained was checked by PXRD and identified as co-crystal sotagliflozin L-proline (1:2)

Example 2: Preparation of co-crystal sotagliflozin L-proline (1:2)
sotagliflozin (2g), L-proline (0.54g) was taken in ethanol (20mL) at 25±5°C. Heated the contents to 65°C -70°C and stirred for 20-30 minutes at 65-70°C. The reaction mass was slowly cooled to 25±5°C and maintained under stirring at same temperature for 16hours. The product was filtered, washed with ethanol (4mL) and dried under vacuum for 16hours at 40?C. The product obtained was checked by PXRD and identified as co-crystal sotagliflozin L-proline (1:2)

Example 3: Preparation of co-crystal sotagliflozin L-proline (1:2)
sotagliflozin (0.5g), L-proline (0.27g) was taken in ethanol (10mL) at 25±5°C. Heated the contents to 65°C -70°C and stirred for 20-30 minutes at same temperature. The reaction mass was slowly cooled to 25±5°C and maintained under stirring at same temperature for 48hours. The reaction mass was cooled 10±5°C and maintained under stirring for 1hour. The product obtained was filtered, washed with pre-chilled ethanol (1mL) and dried under vacuum for 16hours at 40?C. The product obtained was checked by PXRD and identified as co-crystal sotagliflozin L-proline (1:2)

Example 4: Preparation of co-crystal sotagliflozin D-proline (1:15)
sotagliflozin (0.5g), D-proline (0.27g) was taken in ethanol (5mL) at 25±5°C. Heated the contents to 60-65°C and stirred for 30-40 minutes at 60-65°C. The reaction mass was slowly cooled to 25±5°C and maintained under stirring at 25±5°C for 16hours. The product obtained was filtered, washed with pre-chilled ethanol (2mL) and dried under vacuum for 16hours at 40?C. The product obtained was checked by PXRD and identified as co-crystal sotagliflozin D-proline (1:15)

Example 5: Preparation of an amorphous sotagliflozin
sotagliflozin (100mg) was dissolved in a mixture of acetonitrile (1.2mL) and water (1mL) at 50±5°C. The resulting clear solution was subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous sotagliflozin.

Example 6: Preparation of an amorphous sotagliflozin
sotagliflozin (100mg) was dissolved in a mixture of tetrahydrofuran (1.2mL) and water (1mL) at 50±5°C. The resulting clear solution was subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous sotagliflozin.

Example 7: Preparation of an amorphous sotagliflozin
sotagliflozin (100mg) was dissolved in a mixture of t-butanol (1.2mL) and water (1mL) at 50±5°C. The resulting clear solution was subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous sotagliflozin.

Example 8: Preparation of an amorphous sotagliflozin
sotagliflozin (100mg) was dissolved in a mixture of acetone (1.2mL) and water (1mL) at 50±5°C. The resulting clear solution was subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous sotagliflozin.

Example 9: Preparation of an amorphous sotagliflozin
sotagliflozin (100mg) was dissolved in a mixture of 1,4-dioxane (1.2mL) and water (1mL) at 50±5°C. The resulting clear solution was subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous sotagliflozin.

Example 10: Preparation of an amorphous sotagliflozin
sotagliflozin (50mg) was dissolved in acetone (1ml) at 25±5ºC. The clear solution was distilled out completely in a rotary evaporator under vacuum at 35ºC and maintained under drying at same temperature for 1-2hours. The foamy solid obtained and identified as an amorphous sotagliflozin.

Example 11: Preparation of an amorphous solid dispersion of sotagliflozin
sotagliflozin (50mg) was dissolved in a mixture of 1,4-dioxane (2ml) and water (1ml) at 50±5ºC and cooled to 25±5ºC. In another RBF dissolved hydroxy propyl methyl cellulose (HPMC, 50mg) in water (1ml) at 25±5ºC. Combined the clear solutions of Sotagliflozin and HPMC at 25±5ºC and subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous solid dispersion of sotagliflozin with hydroxy propyl methyl cellulose (1:1).

Example 12: Preparation of an amorphous solid dispersion of sotagliflozin
sotagliflozin (50mg) was dissolved in a mixture of 1,4-dioxane (2ml) and water (1ml) at 50±5ºC and cooled to 25±5ºC. In another RBF dissolved Plasdone S-630 (50mg) in water (1ml) at 25±5ºC. Combined the clear solutions of sotagliflozin and Plasdone S-630 at 25±5ºC and subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous solid dispersion of sotagliflozin with plasdone S-630 (1:1).

Example 13: Preparation of an amorphous solid dispersion of sotagliflozin
sotagliflozin (50mg) was dissolved in a mixture of 1,4-dioxane (2ml) and water (1ml) at 50±5ºC and cooled to 25±5ºC. In another RBF dissolved povidone K-30 (50mg) in water (1ml) at 25±5ºC. Combined the clear solutions of sotagliflozin and povidone K-30 at 25±5ºC and subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous solid dispersion of sotagliflozin with povidone K-30 (1:1).

Example 14: Preparation of an amorphous solid dispersion of sotagliflozin
sotagliflozin (50mg) was dissolved in a mixture of 1,4-dioxane (2ml) and water (2ml) at 50±5ºC and cooled to 25±5ºC. Then charged microcrystalline cellulose (MCC, 50mg) at 25±5ºC and subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous solid dispersion of sotagliflozin with microcrystalline cellulose (1:1)

Example 15: Preparation of an amorphous solid dispersion of sotagliflozin
sotagliflozin (50mg) was dissolved in a mixture of 1,4-dioxane (2ml) and water (2ml) at 50±5ºC and cooled to 25±5ºC. Then charged silicone dioxide (SiO2, 50mg) at 25±5ºC and subjected to lyophilization using Labocon lyophilizer (Model: LFD-BT-104). The product obtained and identified as an amorphous solid dispersion of sotagliflozin with silicon dioxide in the ration of (1:1).

Example 16: Preparation of sotagliflozin form B
sotagliflozin (5g) was dissolved in tetrahydrofuran (35mL) at 50±5°C. The resulting clear solution was filtered through hyflo to remove any undissolved particulates. To the clear solution added n-heptane(125mL) at 25±5°C for 30minutes and stirred for 12hours at 25±5°C. Filtered the reaction mass and washed with n-heptane(5mL) and dried under vacuum at 40°C for 12hours, the product obtained and identified as sotagliflozin form B.

Example 17: Preparation of sotagliflozin form B
sotagliflozin (5g) was dissolved in tetrahydrofuran (35mL) at 50±5°C. The resulting clear solution was filtered through hyflo to remove any undissolved particulates. To the clear solution added water(125mL) at 25±5°C for 30min. and stirred for 12hours at 25±5°C. Then added water (50mL) and stirred for 5h at 25±5°C. Filtered the reaction mass and washed with water (5mL) and dried under vacuum at 40°C for 12hours, the product obtained and identified as sotagliflozin form B.

Example 18: Preparation of sotagliflozin form F
sotagliflozin (10g) was dissolved in ethanol (110mL) at 60±5°C. Stirred for 1hour at 60±5°C, cooled to 25±5°C, stirred for 16hours at 25±5°C, then cooled to 10-15°C and stirred for 2hours at 10-15°C. Filtered the reaction mass and washed with chilled ethanol (10mL) and dried under vacuum at 40°C for 12hours, the product obtained and identified as sotagliflozin form F.
,CLAIMS:1. Co-crystal of sotagliflozin L-proline.

2. The Co-crystal of sotagliflozin L-proline claimed in claim 1, powder X-ray diffraction pattern having significant peaks at 2? angle positions of 5.67, 9.75, 14.90, 15.96, 18.43, 20.26, 25.72 ± 0.2°.

3. The Co-crystal of sotagliflozin L-proline claimed in claim 1, powder X-ray diffraction pattern as shown in figure 1.

4. The process for the preparation of co-crystal of sotagliflozin L-proline comprising the steps of

a) forming a suspension of sotagliflozin and L-proline in an organic solvent,
b) heating the suspension to a temperature between about 55 °C and about 75 °C,
c) cooling the suspension to a temperature between about 20 °C and 30 °C; and
d) isolating the co-crystal of sotagliflozin L-proline

5. The process as claimed in claim 4, wherein an organic solvent is selected from the group consisting of alcohol solvents such as methanol, ethanol, isopropanol, n-propanol, t-butanol and mixture thereof, ketonic solvents such as acetone, methyl isobutyl ketone, methyl ethyl ketone and mixtures thereof
6. An amorphous solid dispersion of sotagliflozin.
7. The process for the preparation of an amorphous solid dispersion of sotagliflozin with pharmaceutically acceptable carriers comprising the steps of;

a) dissolving sotagliflozin in a mixture of an organic solvent and water to a temperature between about 40 °C and about 60 °C,
b) cooling the solution to a temperature between about 20 °C and 30 °C,
c) adding pharmaceutically acceptable carrier; and
d) isolating an amorphous solid dispersion of sotagliflozin

8. The process as claimed in claim 7, wherein the organic solvent is selected form the group consisting of ether solvents such as tetrahydrofuran and 1,4-dioxane

9. The process as claimed in claim 7, wherein the pharmaceutically acceptable carrier is selected from group consisting of PLASDONETM S-630, polyvinyl pyrrolidine K-30 (PVP-K30), povidone K-30, silicon dioxide, microcrystalline cellulose, lactose monohydrate, hydroxy propyl methyl cellulose (HPMC) or mixtures thereof.

10. The process as claimed in claim 7, the isolation techniques such as, lyophilization, decantation, filtration by gravity or suction, centrifugation, slow evaporation, distillation, agitated thin film drier (ATFD) and spray-drying.