DESC:RELATED PATENT APPLICATION(S)

This application claims the priority to and benefit of Indian Patent Application No. 201941025255 filed on June 25, 2019; the disclosures of which are incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to a premix of Ertugliflozin with one or more pharmaceutically acceptable excipients. The present invention further relates to a process for preparing a premix of Ertugliflozin with one or more pharmaceutically acceptable excipients.

BACKGROUND OF THE INVENTION

Ertugliflozin is a selective sodium glucose cotransporter 2 inhibitor used for the treatment of type 2 diabetes mellitus.

Ertugliflozin is chemically known as (1S,2S,3S,4R,5S)-5-(4-chloro-3-(4­ethoxybenzyl)phenyl)-1-(hydroxymethyl)-6,8- dioxabicyclo [3.2.1] octane-2,3,4-triol, represented by the Formula I.

Ertugliflozin was first disclosed in the US Patent No. 8080580 assigned to Pfizer Inc. This patent discloses a process for the preparation of Ertugliflozin. The prepared amorphous Ertugliflozin is hygroscopic and unstable, that could create complications during formulation. Hence, Ertugliflozin was converted to a Ertugliflozin L-pyroglutamic acid for easy handling of the product during formulation.

Additional and improved ways of preparing new forms of product may provide an opportunity to improve the physical characteristics. Hence, there exists a need for the development of new stable form of Ertugliflozin that is commercially viable with better and consistent quality parameter.

OBJECTIVE OF THE INVENTION

The main objective of the invention is to provide a premix of Ertugliflozin with one or more pharmaceutical acceptable excipients.

Yet another objective of the invention is to provide a process for the preparation of premix of Ertugliflozin with one or more pharmaceutical acceptable excipients.

SUMMARY OF THE INVENTION

The present invention aims to provide a premix of Ertugliflozin with one or more pharmaceutically acceptable excipients.

In one aspect of the invention, there is provided a premix of Ertugliflozin comprising Ertugliflozin or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipients.

In an aspect the present invention provides a process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
i. Dissolving or suspending one or more pharmaceutically acceptable excipients in solvent or its mixtures thereof;
ii. Adding Ertugliflozin to the solution or the suspension obtained in step (i); and
iii. Isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

In another aspect the present invention provides a process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
i. Dissolving or suspending Ertugliflozin in solvent or its mixtures thereof;
ii. Adding one or more pharmaceutically acceptable excipients to the solution or the suspension obtained in step (i); and
iii. Isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

In some embodiment, the premix is isolated by removing the solvent or by addition of anti-solvent. In some other embodiment, the solvent is removed by evaporating the solvent, distilling, spray drying, rotational drying, thin film drying, agitated thin-film drying, freeze drying, lyophilisation, or a combination thereof. In yet another embodiment, the anti-solvent is selected from the group consisting of water, alcohols, ethers, esters, aliphatic hydrocarbon liquids, alicyclic hydrocarbon liquids, aromatic hydrocarbon liquids and mixture thereof.

In some embodiment, the premix of Ertugliflozin with one or more pharmaceutically acceptable excipient according to invention and the process for preparation thereof employs the ratio of Ertugliflozin to the pharmaceutically acceptable excipient in range from about 1:0.1 to about 1:10, preferably from about 1:0.5 to about 1:4.0.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 is an illustration of a powder X-ray diffractogram (PXRD) Ertugliflozin premix prepared according to Example 1.
Figure 2 is an illustration of a powder X-ray diffractogram (PXRD) Ertugliflozin premix prepared according to Example 4.

DETAILED DESCRIPTION OF THE INVENTION

Listed below are definitions of various terms used to describe this invention. These definitions apply to the terms as they are used throughout this specification, unless otherwise limited in specific instances.

As used herein, the term “premix” refers to combination of Ertugliflozin or a salt thereof and at least one pharmaceutically acceptable excipient.

As used herein, the term “pharmaceutically acceptable excipient” means a component of a pharmaceutical product that is not an active ingredient, and includes but not limited to filler, diluent, disintegrants, glidants, stabilizers, surface active agents etc. The excipients that are useful in preparing a pharmaceutical composition are generally safe and non-toxic and are acceptable for veterinary use as well as human pharmaceutical use. One excipient can perform more than one function.

The term “stability” as used in the description includes both physical and chemical stability. The term “physical stability” refers to maintaining the polymorphic form of Ertugliflozin such as crystalline, amorphous, or mixtures thereof, and “chemical stability” refers to maintaining acceptable concentrations of Ertugliflozin related impurities.

In one aspect of the invention, there is provided a premix of Ertugliflozin comprising Ertugliflozin or a pharmaceutically acceptable salt thereof and one or more pharmaceutically acceptable excipient.

In an embodiment the present invention provides a process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
i. Dissolving or suspending one or more pharmaceutically acceptable excipients in solvents or its mixtures thereof;
ii. Adding Ertugliflozin to the solution or the suspension obtained in step (i); and
iii. isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

Crude Ertugliflozin may be used as input for the process of the invention that may be obtained by any process including the process described in the art.

Ertugliflozin as in step (ii) of the present invention includes direct use of reaction mixture that is obtained during its synthesis; or purified solid of Ertugliflozin; or dissolving Ertugliflozin in suitable solvent thereof.

In embodiments of step (i) suitable solvent useful for providing a solution or suspension include, but are not limited to water; alcohols, such as methanol, ethanol, 1-propanol, 2-propanol, 1-butanol and 2-butanol; ethers, such as diethyl ether, diisopropyl ether, methyl tertiary-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, cyclopropylmethyl ether, dioxane and dimethoxyethane; esters, such as methyl acetate, ethyl formate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate and isobutyl acetate; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone and diethyl ketone; nitriles, such as acetonitrile and propionitrile; amides such as formamide, ?,?-dimethylformamide and N,N- dimethylacetamide; sulfoxides, such as dimethylsulfoxide; aliphatic and aromatic hydrocarbons such as n-pentane, isopentane, neopentane, n-hexane, isohexane, n-heptane, cyclohexane, methylcyclohexane, cycloheptane, petroleum ethers, benzene, toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, indane, naphthalene, tetralin, trimethylbenzene; halogenated hydrocarbons such as dichloromethane, 1,2- dichloroethane, trichloroethylene, chloroform, carbon tetrachloride; or mixtures of two or more thereof.

In embodiments of step (i) dissolving or suspending one or more pharmaceutically acceptable excipients may be carried out at a suitable temperature, ranging from about 0°C to about the reflux temperature of the solvent, or less than about 100°C, less than about 80°C, less than about 60°C, less than about 40°C, less than about 10°C, or any other suitable temperatures.

In embodiments of step (ii) adding Ertugliflozin to the solution or the suspension obtained in step (i) may be carried out at a suitable temperature, ranging from about 0°C to about the reflux temperature of the solvent, or less than about 100°C, less than about 80°C, less than about 60°C, less than about 40°C, less than about 10°C, or any other suitable temperatures.

In embodiments of step (iii), isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients may be done by removal of the solvent by using suitable techniques that include, but are not limited to evaporation of the solvent, using a rotational distillation device such as a Buchi Rotavapor®, spray drying, thin film drying, freeze drying, lyophilisation, methods as mentioned herein, and the like, or any other suitable techniques. In some embodiments, the removing the solvent comprises evaporating the solvent, distilling, spray drying, thin film drying, agitated thin-film drying, freeze drying, lyophilisation, or a combination thereof. The solvent may be removed, optionally under reduced pressures, at temperatures less than about 100° C., less than about 75° C., less than about 60°C., less than about 50°C., or any other suitable temperature.

In embodiments of step iii), isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients may be effected by removing the solvent by techniques mentioned herein above, or by any other precipitation technique. Suitable methods include, but are not limited to, concentration, removal of solvent by evaporation, distillation, crash cooling, flash evaporation, rotational drying, spray drying, thin film drying, freeze drying, and lyophilization.

In embodiments of step iii), isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients may be effected by addition of non-solvent i.e. anti-solvent.

As used herein, the term “anti-solvent” refers to a solvent that, when combined with a solution or suspension of Ertugliflozin with one or more pharmaceutically acceptable excipients obtained in step (ii), reduces solubility, causing crystallization or precipitation in some instances spontaneously, and in other instances with additional steps, such as seeding, cooling, scratching, and/or concentrating.

The choice of solvents and anti-solvents for the process is customary to one skilled in the art. Suitable anti-solvents that may be used in embodiments of step iii) are selected from the group consisting of water, alcohols, ethers, esters, aliphatic hydrocarbon liquids, alicyclic hydrocarbon liquids, aromatic hydrocarbon liquids, and mixtures of at least two thereof.

The solid obtained from step (iii) may be collected using techniques such as for example, scraping, shaking the container, or other techniques that are suited to the equipment used. Optionally, the isolated solid may be further dried.

In certain embodiments, optionally, the solution obtained at various stages may be treated to remove any insoluble particles. The insoluble particles may be removed suitably by filtration, centrifugation, decantation, or any other suitable techniques, under pressure or under reduced pressure. The solution may be filtered by passing through paper, glass fiber, cloth or other membrane material, or a bed of a clarifying agent such as Celite® or Hyflo. Depending upon the concentration and temperature of the solution and the equipment used, the filtration apparatus may optionally be preheated to avoid premature crystallization.

In embodiments of the present invention, the premix of Ertugliflozin after optional drying, may be optionally further subjected to a particle size reduction procedure to produce desired particle sizes and distributions. Milling or micronization may be performed before drying, or after the completion of drying of the product. Equipment that may be used for particle size reduction include, without limitation thereto, ball mills, roller mills, hammer mills, and jet mills.

Drying may be suitably carried out using any of an air tray dryer, vacuum tray dryer, fluidized bed dryer, spin flash dryer, flash dryer, and the like. The drying may be carried out at atmospheric pressure or above, or under reduced pressures, at temperatures less than about 100°C, less than about 60°C, less than about 50°C, less than about 20°C, less than about 0°C, less than about -20°C, or any other suitable temperatures. The drying may be carried out for any time period suitable for obtaining a desired product quality, such as from about 15 minutes to 24 hours, or longer.

The pharmaceutically acceptable excipients useful in step i) include, but are not limited to mannitol, lactose, fructose, sorbitol, xylitol, maltodextrin, dextrates, dextrins, lactitol, inositol, trehalose, maltose, raffinose, a, ß and ?-cyclodextrins, gum arabic, sodium alginate, propylene glycol alginate, agar, gelatin, tragacanth, xanthan gum, starch, lectins, urea, chitosan, chitosan glutamate, hydroxypropyl ß-cyclodextrin chitosan, hydroxypropyl methylcellulose (HPMC), Hydroxypropyl cellulose (HPC), methylcellulose (MC), cellulose acetate phthalate (CAP), Hydroxypropyl Methylcellulose Phthalate (HPMCP), hydroxypropyl methylcellulose acetate succinate (HPMC-AS), carboxymethyl ethyl cellulose (CMEC), carboxymethyl cellulose, sodium carboxymethyl cellulose, cellulose acetate butyrate, hydroxyethyl cellulose, ethyl cellulose, co- (lactic/glycolic)copolymers, poly(orthoester), polyvinyl chloride, polyvinyl acetate, ethylene vinyl acetate, carbopols, silicon elastomers, polyacrylic polymers, polyvinylacetal diethylaminoacetate, amino alkyl methacrylate copolymers, methacrylic acid copolymers, and carboxyl vinyl polymer, polyvinylpyrrolidones (such as Polyvinylpyrrolidone K 30/PVP K-30), polyethylene glycols, polyethylene-/polypropylene-/polyethylene-oxide block copolymers, polymethacrylates, polyvinylalcohol (PVA) and co-polymers thereof with PVP or with other polymers, polyacrylates, polyhydric alcohols, polyoxyethylene derivatives, organic amines such as alkyl amines (primary, secondary, and tertiary), aromatic amines, alicyclic amines, cyclic amines, aralkyl amines, hydroxylamine or its derivatives, hydrazine or its derivatives, and guanidine or its derivatives; diluents such as starches and derivative thereof, e.g. dextrin, pullulan, corn starch and potato starch pregelatinized starches; lactose, sucrose, glucose, reduced maltose, mannitol, sorbitol, xylitol, trehalose, powdered cellulose, microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, crystalline cellulose/carmellose sodium, hydroxypropyl cellulose, magnesium aluminometasilicate, silica excipients like silicon dioxide, syloid, light anhydrous silicic acid or the like; binders such as acacia, guar gum, tragacanth, gelatin, polyvinylpyrrolidones, hydroxypropyl celluloses, hydroxypropyl methylcelluloses, pregelatinized starches or the like; disintegrants such as hydroxypropyl cellulose, low- substituted hydroxypropyl cellulose, croscarmellose sodium, a starch, methylcellulose, sodium alginate, sodium carboxymethyl starch, carmellose calcium, carmellose sodium, crystalline cellulose and crystalline cellulose/carmellose sodium, sodium starch glycolate, pregelatinized starches, crospovidones, colloidal silicon dioxide or the like; lubricants such as stearic acid, magnesium stearate, talc, light anhydrous silicic acid, calcium stearate, zinc stearate, magnesium oxide, sodium lauryl sulfate, sodium stearyl fumarate, magnesium aluminometasilicate or the like; flavoring agents such as sucrose, aspartame, mannitol, dextran, saccharin, menthol, citric acid, tartaric acid, malic acid, ascorbic acid, sweet hydrangea leaves, fennel, ethanol, fructose, xylitol, glycyrrhizinic acid, purified sucrose, L-glutamine, cyclodextrin, peppermint, methyl salicylate or the like; surfactants such as sodium lauryl sulfate, polysolvate 80, sucrose fatty acid ester, polyoxyl 40 stearate, polyoxyethylene 60 hydrogenated castor oil, sorbitan monostearate, sorbitan monopalmitate or the like; complex forming agents such as various grades of cyclodextrins and resins; release rate controlling agents such as hydroxypropyl celluloses, hydroxymethyl celluloses, hydroxypropyl methylcelluloses, ethylcelluloses, methylcelluloses, various grades of methyl methacrylates, waxes or the like. Other pharmaceutically acceptable carriers that can be used include, but are not limited to, film formers, plasticizers, colorants, viscosity enhancers, preservatives, antioxidants, or the like. The scope of the present invention without limitation includes, the use of mixtures of more than one of the pharmaceutical excipients to provide desired release profiles or for the enhancement of stability and also includes all viscosity grades, molecular weights, commercially available products, their copolymers and mixtures.

In another embodiment the present invention provides a process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
i. Dissolving or suspending Ertugliflozin in solvent or its mixtures thereof;
ii. Adding one or more pharmaceutically acceptable excipients to the solution or the suspension obtained in step (i); and
iii. Isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

Crude Ertugliflozin may be used as input for the process of the invention that may be obtained by any process including the process described in the art.

Ertugliflozin in step (i) of the present invention includes direct use of reaction mixture that is obtained during its synthesis; or purified solid of Ertugliflozin; or dissolving Ertugliflozin in suitable solvent thereof.

In embodiments of step (i) suitable solvent useful for providing a solution or suspension include, but are not limited to; water; alcohols, such as methanol, ethanol, 1 -propanol, 2- propanol, 1-butanol, and 2-butanol; ethers, such as diethyl ether, diisopropyl ether, methyl tertiary-butyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, cyclopropylmethyl ether, dioxane, and dimethoxyethane; esters, such as methyl acetate, ethyl formate, ethyl acetate, propyl acetate, isopropyl acetate, butyl acetate, and isobutyl acetate; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, and diethyl ketone; nitriles, such as acetonitrile and propionitrile; amides, such as formamide, ?,?-dimethylformamide, and N,N- dimethylacetamide; sulfoxides, such as dimethylsulfoxide; aliphatic and aromatic hydrocarbons such as n-pentane, isopentane, neopentane, n-hexane, isohexane, n-heptane, cyclohexane, methylcyclohexane, cycloheptane, petroleum ethers, benzene, toluene, ethylbenzene, m-xylene, o-xylene, p-xylene, indane, naphthalene, tetralin, trimethylbenzene; halogenated hydrocarbons such as dichloromethane, 1, 2-dichloroethane, trichloroethylene, chloroform, carbon tetrachloride; or mixtures of two or more thereof.

In aspects of the present invention, the amount of Ertugliflozin thereof relative to the amount of pharmaceutically acceptable excipients, carriers, polymers or diluents present in the solid dispersions or premixes depends on the pharmaceutically acceptable excipients, carriers or diluents. Preferably, the ratio of Ertugliflozin to the pharmaceutically acceptable excipients, carriers, polymers or diluents ranges from about 1:0.1 to about 1:10, preferably from about 1:0.5 to about 1:4.0. In some embodiment, there is provided a premix of Ertugliflozin with one or more pharmaceutically acceptable excipient wherein the ratio of Ertugliflozin to the pharmaceutically acceptable excipients ranges from about 1:0.1 to about 1:10, preferably from about 1:0.5 to about 1:4.0.

In certain embodiments, the premixes of the present invention encompass all physical forms of Ertugliflozin. The premix comprises Ertugliflozin in amorphous, crystalline form or mixtures thereof, with one or more pharmaceutically acceptable excipients.

Non-limiting examples of solid dispersions or premixes of Ertugliflozin with one or more pharmaceutically acceptable excipients prepared according the processes described herein are characterized by a PXRD as illustrated in Figures 1 to 2.

Certain specific aspects and embodiments of the present invention will be better understood in connection with the following examples, which are provided only for purposes of illustration and should not be construed as limiting the scope of the application in any manner.

EXAMPLES

Example-1: Ertugliflozin and Polyvinylpyrrolidone K-30 (1:1) premix:
Polyvinylpyrrolidone K-30 (2.5 g) was dissolved in dichloromethane (25 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.5 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 4.8 g. The Figure 1 illustrates the PXRD of the obtained Ertugliflozin premix.

Example-2: Ertugliflozin and Polyvinylpyrrolidone K-30 (1:0.5) premix:
Polyvinylpyrrolidone K-30 (1.0 g) was dissolved in dichloromethane (20 mL) at 30±5°C to get a clear solution. Ertugliflozin (2 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 2.8 g

Example-3: Ertugliflozin and Polyvinylpyrrolidone K-30 (1:1) premix:
Polyvinylpyrrolidone K-30 (2.5 g) was dissolved in methanol (25 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.5 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 4.8 g

Example-4: Ertugliflozin and copovidone (1:1) premix:
Copovidone (2.5 g) was dissolved in dichloromethane (25 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.5 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 4.8 g. The Figure 4 illustrates the PXRD of the obtained Ertugliflozin premix.

Example-5: Ertugliflozin and copovidone (1:0.5) premix:
Copovidone (1.0 g) was dissolved in dichloromethane (20 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.0 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 2.8 g

Example-6: Ertugliflozin and copovidone (1:0.25) premix:
Copovidone (0.5 g) was dissolved in dichloromethane (20 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.0 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 2.4 g

Example-7: Ertugliflozin and copovidone (1:1) premix:
Copovidone (2.5 g) was dissolved in methanol (25 mL) at 30±5°C to get a clear solution. Ertugliflozin (2.5 g) was then added to the obtained solution and stirred for 1 hour at 30±5°C. The resultant mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 2.4 g

Example-8: Ertugliflozin and microcrystalline cellulose (1:1) premix:
Ertugliflozin (2.5 g) was dissolved in a mixture of isopropyl alcohol and water (1:1; 20 mL) at 30±5°C to obtain a clear solution. Microcrystalline cellulose (2.5 g) was added to the obtained solution at 55±5°C and stirred for 10 minutes at the same temperature. The resultant mass was cooled to 30±5°C and maintained at the same temperature for 30 minutes. The cooled reaction mass was concentrated under vacuum at 45°C to get off white solid material. Yield: 4.8 g

Example-9: Ertugliflozin and lactose monohydrate (1:1) premix:
Ertugliflozin (2.5 g) was dissolved in a mixture of isopropyl alcohol (10 mL) at 30±5°C to obtain a clear solution. Lactose monohydrate (2.5 g) was added to the obtained solution at 55±5°C and stirred for 10 minutes at the same temperature. The resultant mass was cooled to 30±5°C and maintained at the same temperature for 30 minutes. The cooled reaction mass was concentrated under vacuum at 40°C to get off white solid material. Yield: 4.8 g.
,CLAIMS:
1. A process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
(i) dissolving or suspending one or more pharmaceutically acceptable excipients in solvent or its mixtures thereof;
(ii) adding Ertugliflozin to the solution or the suspension obtained in step (i); and
(iii) isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

2. A process for preparing a premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients, the process comprising:
(i) dissolving or suspending Ertugliflozin in solvent or its mixtures thereof;
(ii) adding one or more pharmaceutically acceptable excipients to the solution or the suspension obtained in step (i); and
(iii) isolating the premix comprising Ertugliflozin with one or more pharmaceutically acceptable excipients from the solution or suspension obtained in step (ii).

3. The process as claimed in the claim 1 or 2, wherein the ratio of Ertugliflozin to the pharmaceutically acceptable excipients ranges from about 1:0.1 to about 1:10, preferably from about 1:0.5 to about 1:4.0.

4. The process as claimed in the claim 1 or 2, wherein the premix is isolated by removing the solvent or by addition of anti-solvent.

5. The process as claimed in the claim 4, wherein the solvent is removed by evaporating the solvent, distilling, spray drying, rotational drying, thin film drying, agitated thin-film drying, freeze drying, lyophilisation or a combination thereof.

6. The process as claimed in the claim 4, wherein the anti-solvent is selected from the group consisting of water, alcohols, ethers, esters, aliphatic hydrocarbon liquids, alicyclic hydrocarbon liquids, aromatic hydrocarbon liquids and mixture thereof.

7. A premix of Ertugliflozin comprising Ertugliflozin or a pharmaceutical acceptable salt thereof, and one or more pharmaceutically acceptable excipient.

8. The premix as claimed in claim 7, wherein the ratio of Ertugliflozin to the pharmaceutically acceptable excipient ranges from about 1:0.1 to about 1:10, preferably from about 1:0.5 to about 1:4.0.