FIELD OF THE INVENTION
The present invention relates to a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutical^ acceptable, salts, esters, solvates, polymorphs thereof along with one or more pharmaceutical^ acceptable excipients. It further relates to a pharmaceutical composition comprising SGLT2 inhibitor in combination with other anti-diabetics.
» ■ ■ . * '
BACKGROUND OF THE INVENTION
Oral antidiabetic drugs conventionally used in therapy (such as e.g. first- or second-line, and/or mono- or (initial or add-on) combination therapy) include, without being restricted thereto, metformin, sulphonylureas, thiazolidinedione's, glinides and a-glucosidase inhibitors.
The high incidence of therapeutic failure is a major contributor to the high
rate of long-term hyperglycaemia-associated complications or chronic damages
(including micro and macrovascular complications such as e.g. diabetic.
nephropathy, retinopathy, neuropathy, or cardioVascular complications) in patients
with type 2 diabetes. i
Type 2 diabetes is an increasingly prevalent disease that due to a high frequency of complications leads to a significant reduction of life expectancy. Because of diabetes-associated microvascular complications, type 2 diabetes is currently the most frequent cause of adult-onset loss of vision, renal failure, and amputations in the industrialized world. In addition, the presence of type 2 diabetes is associated with a two to five fold increase in cardiovascular disease risk. After long duration of disease, most patients with type 2 diabetes will eventually fail on oral therapy and become insulin dependent with the necessity for daily injections and multiple daily glucose measurements.
The UKPDS (United Kingdom Prospective, Diabetes Study) demonstrated that intensive treatment with metformin, sulfonylureas or insulin resulted in only a limited improvement of glycemic control (difference in HbAlc about 0.9%). In addition, even in patients within the intensive treatment arm glycemic control

deteriorated significantly over time and this was attributed to deteriorationof P-cell function. Importantly, intensive treatment was not associated with a significant reduction in macrovascular complications, i.e. cardiovascular events. Therefore many patients with type 2 diabetes remain inadequately treated, partly because of limitations in long term efficacy, tolerability and dosing inconvenience of existing anti-hyperglycaemic therapies.
SGLT2 inhibitors represent a novel class of agents that are being developed
for the treatment or improvement in glycemic control in patients with type 2
diabetes. Glucopyranosyl-substituted benzene derivative are described in the prior
art as SGLT2 inhibitors^ for example in WO 01/27128, WO 03/099836, WO
2005/092877, WO 2006/034489, WO 2006/064033, WO 2006/117359, WO
2006/117360, WO 2007/025943, WO 2007/028814, WO 2007/031548, WO
2007/093610, WO 2007/128749, WO 2008/049923, WO 2008/055870, WO
2008/055940. ^
Empagliflozin is a novel SGLT2 (sodium/glucose cotransporter-2) inhibitor that is described for the treatment or improvement in glycemic control in patients with type 2 diabetes mellitus. Empagliflozin is chemically known as (l.S)-l, 5-anhydro- l-C-[4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyl] oxy] phenyl] methyl] phenyl]-D-glucitol (Formula I).

OH Formula I
Empagliflozin is marketed in US, Europe and other countries under the brand name of.Jardiance®, which is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus and to reduce the risk of cardiovascular death in adult patients with type 2 diabetes mellitus and established cardiovascular disease.
There i are several references known in the literature, which describe the different polymorphic forms of empagliflozin and pharmaceutical composition of

the same, which is used in the treatment of various diseases. US Patent No. 7,713,938 discloses a stable crystalline form of empagliflozin and a pharmaceutical composition comprising said crystalline form. Additional crystalline forms of (R)-Empagliflozin are disclosed in U.S. Patent No. 7,723,309. ,
US Patent Publication No. 2016/0038524 of Boehringer relates to a method of treating prediabetes, type 1 or type 2 diabetes mellitus in patient comprising administering empagliflozin to the patient, wherein the patient has moderate renal v impairment or stage 3 chronic kidney disease.
US Patent Publication No. 2016/0038523 & US 2016/0000816 of. Boehringer relates to a method for treating and/or preventing oxidative stress, collagen deposition, vessel wall thickening, vascular stress and/or endothelial dysfunction comprising administering empagliflozin, optionally in combination with one or more other therapeutic substances, to a patient in need thereof.
US Patent Publication No. 2011/0014284 of Boehringer relates to a composition comprising empagliflozin (less than 25% by weight of the pharmaceutical composition), binder, disintegrant, wherein the ratio of disintegrantbinder is 1.5:3.5 and 1:1, wherein d90 of empagliflozin is 1-200 \im
Indian Patent Publication No. 6157/DELNP/20n covers a composition of - empagliflozin with specific pharmacokinetic parameters.
Indian Patent Publication No. 4964/CHE/2014 of Mylan covers an amorphous empagliflozin complex with a cyclodextrin.
Indian Patent Publication No. 1985/MUM/2013 of Cadila covers an amorphous form of empagliflozin and pharmaceutical composition comprising amorphous empagliflozin. It further relates to the amorphous solid dispersion of
empagliflozin and polymer.
- ■ i
Indian Patent Publication No. 2756/DELNP/2012 of Boehringer covers a crystalline form of empagliflozin characterized by purity above 99%.
As pharmaceutical excipients have various functions and contribute to the pharmaceutical formulations in many different ways. The properties that are commonly considered when formulating an active drug substance include

bioavailability, ease of manufacture, ease of administration, and stability of the
dosage form. ,
In view of the above, it is therefore, desirable to provide a pharmaceutical composition of empagliflozin which provides comparable bioavailability and stability when compared to the marketed formulation. Further, there exists a need to develop a process for the development of pharmaceutical composition which provides an efficient and more economical process.
SUMMARY OF THE INVENTION
In one aspect, the present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is free of binder.
In one embodiment, the present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is free of binder. ,
In one embodiment, the, present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically > acceptable excipients, wherein the pharmaceutically acceptable excipients are selected from the group comprising of diluents, disintegrants, glidants, lubricants, surfactants and/or combinations thereof.
In one embodiment, the present invention provides a pharmaceutical composition wherein the SGLT2 inhibitor is empagliflozin or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof.
In one embodiment, the present invention provides a pharmaceutical composition, wherein the diluent is microcrystalline cellulose.
In one embodiment, the present' invention provides a pharmaceutical composition, wherein the disintegrant is selected from the group consisting of sodium starch glycolate, croscarmellose sodium and/or combinations thereof.

In one embodiment, the present invention provides a pharmaceutical composition wherein, wherein the lubricant is sodium stearyl fumarate.
In another embodiment, the present invention provides a pharmaceutical composition wherein the pharmaceutical composition is prepared by dry granulation/compaction or direct compression.
In preferred embodiment, the present invention provides a pharmaceutical composition wherein the pharmaceutical composition is prepared by dry granulation/compaction.
In another embodiment, the present invention provides 'a method of making
a pharmaceutical composition of empagliflozin or its pharmaceutically acceptable
salts, esters, solvates, and polymorphs thereof, wherein said method comprises the
steps of: ,
1. sifting all the ingredients through appropriate sieves;
2. dry mixing the pre-sifted empagliflozin, microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium and silicon dioxide in a suitable blender; 3. lubricating the dry mixed ingredients of step b) in the blender with sodium stearyl fumarate to obtain a blend;
4. passing the blend through roller compactor to obtain compact mass/ribbons;
5. passing the compaqt mass/ribbons through appropriate mesh screen and
passing the blend through the required sieve to obtain granules;
t
6. blending the granules obtained from step e) in a suitable blender;
7. lubricating the granules of step f) with sodium stearyl fumarate in a blender;
8. compressing the blend of step g) into tablets; and optionally;
9.' performing film coating on the tablets of step h) to form coated tablets. In another embodiment, the present invention provides a pharmaceutical composition wherein the pharmaceutical composition is in the form of tablet.

■ I
In another embodiment, the present invention provides a pharmaceutical composition wherein the tablet is coated with film coating which comprises film forming polymer.
* In another embodiment, the present invention provides a pharmaceutical composition wherein the pharmaceutical composition wherein the pharmaceutical composition is used for the treatment of type 2 or type 1 diabetes mellitus in a patient with or at risk of oxidative stress, vascular stress and/or endothelial dysfunction, or diseases or conditions related or associated therewith.
In yet another preferred embodiment, the pharmaceutical composition comprises:

Ingredient Quantity % w/w
Empagliflozin 12.83
Microcrystallihe cellulose 67.36
Sodium starch glycolate '• 8.98
Croscarmellose sodium 6.41
Colloidal Silicon Dioxide 0.97
Sodium stearyl fumarate 0.97
Film Coating 2.43 '
In another aspect, the present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and other anti-diabetic agentv or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is free of binder.
In another embodiment, the present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and other anti-diabetic agent, wherein the other anti-diabetic agent is selected from the group comprising dipeptidyl peptidase-IV

inhibitor, biguanide, thiazolidindione, sulfonylurea, glinide, insulin, alpha glucosidase inhibitor, GLP-1 analogues and/or combinations thereof.
In another aspect, the present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and dipeptidyl peptidase-IV inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically acceptable excipients, wherein the pharmaceutical composition is free of binder.
In another embodiment, the present invention provides a pharmaceutical composition wherein dipeptidyl peptidase-IV inhibitor is linagliptin or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof.
DETAILED DESCRIPTION OF THE INVENTION
The present invention may be understood more readily by reference to the
following detailed description of preferred embodiments of the invention and the
? Examples included therein.
Definitions and Use of Terms. ,
As used in this specification and in the claims which follow, the singular forms "a," "an" and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "an ingredient" includes mixtures of ingredients, reference to "an active pharmaceutical agent" includes more than one active pharmaceutical agent, and the like.
Unless specified otherwise, the term "wt %" as used herein with reference to the final product, denotes the percentage-of the total dry weight contributed by the subject ingredient.
The term "SGLT2 inhibitor" in the scope of the present invention relates to
compounds, in particular to glucopyranosyl-derivatives, i.e. compounds having a glucopyfanosyl-moiety, which show an inhibitory effect on the sodium-glucose transporter 2 (SGLT2), in particular the human SGLT2. The inhibitory effect on hSGLT2 measured as IG50 is preferably below 1000 nM, even more preferably below 100 nM, most preferably below 50 nM. The inhibitory effect on hSGLT2 can

be defined by methods known in,he literature, in particular as described in the application WO 2005/092877 or WO 2007/093610 (pages 23/24), which are mcorporated herein by reference in its entirety. The term "SGLT2 inhibitor" also compnses any pharmaceuticaliy acceptable salts, esters, hydrates, solvates and polymorphs thereof.
The term "type 2 diabetes" is defined as the condition in which a subject has , a fastmg blood glucose or serum glucose concentration grea.er.than 125 mg/dL (6.94 mmol/L). The measurement of blood glucose values is a standard procedure « routme medical analysis. If a glucose tolerance test is carried ou, the blood sugar level of a diabetic will be in excess of 200 mg of glucose per dL (11,. mmol/1) of Plasma 2 hours after 75 g of glucose have been taken on an empty' stomach. In a glucose tolerance tes, 75 g of glucose are administered orally to the patient being ' tested after 10-12 hours of fasting andthe blood sugar level is recorded immediately before taking the glucose and 1 and 2 hours after taking it. In a healthy subject the blood sugar level before taking the glucose wil. be between 60 and 110 mg per dL of plasma, less than 200 mgper dL 1 hour after taking the g,UCOSe ^ less than m mg per dL after 2 hours. If after 2 hours the value is between 140'and 200 mg this . is regarded as abnormal glucose tolerance.
The term "table," comprises tablets without a coating and tablets with one or more coatings. Furthermore the "term" table, comprises tablets having one two three or even more layers and press-coated tablets, wherein each of me before ' mentioned types of tablets may be without or with one or more coatings. The term
Wbl« a.so comprises mini, melt, chewable, effervescent and orally disintegrating
tablets. • &
The pharmaceutical composition according ,„ the present invention may also comprise one or more diluents. Suitable diluents (also referred to as fillers) accordmg to the invention are for example, cellulose and derivatives, such as powdered cellulose, microcrys,al.i„e or silicified microcrystalline cellulose cellulose acetate, lactose, in particular lactose monohydrate, starches and denvat.ves.such as-pregelatinized starch, corn starch, calcium carbonate, calcium Phosphate, particularly dibasic calcium phosphate, calcium sulphate, dicalcium or

IKAJ

9

tricalcium phosphate, magnesium carbonate, magnesium oxide, sugars and derivatives such as confectioner's sugar, fructose, sucrose, dextrates, dextrin, D-sorbitol sulfobutylether .beta.-cyclodextrin, dextrose, polydextrose, trehalose, maltose, maltitol, mannitol, maltodextrin, sorbitol, inulin, xylitol, erythritol, isomalt, kaolin and lactitol. Preferred diluents are microcrystalline cellulose.
The pharmaceutical composition according to the present invention may also comprise one or more disintegrants. Suitable disintegrants according to the invention are for example crospovidone, croscarmellose sodium, docusate sodium, low-substituted hydroxypropyl cellulose, magnesium aluminum silicate, polacrilin potassium, sodium starch glycolate and corn starch. Preferred lubricants include sodium starch glycolate and croscarmellose sodium.
The pharmaceutical composition according to the present invention may also comprise one or more lubricants. Suitable lubricants includes, but not limited to, talc, calcium stearate, zinc stearate, magnesium stearate, sodium stearyl fumarate, glyceryl monostearate, particularly magnesium stearate. Preferred lubricants include sodium stearyl fumarate.
The pharmaceutical composition according to the present invention may also comprise one or more glidants. Suitable glidants according to the invention are silicon dioxide, particularly colloidal silicon dioxide (e.g. Aerosil®, Cab-Q-Sil® and talc. Preferred glidant is colloidal silicon dioxide.
The pharmaceutical composition according to the present invention may also comprise one or more surfactants. Suitable surfactants according to the invention are for example, sodium lauryl sulfate, sodium dodecyl sulfate, ammonium lauryl sulfate, benzalkonium chloride, alkyl poly (ethylene oxide),
copolymers of poly (ethylene oxide) and poly (propylene oxide) commercially
i called as poloxamers or poloxamines, fatty alcohols, polysorbates e.g., Tween 20,
Tween 80, or mixtures thereof.
The pharmaceutical composition according to the present invention
comprises SGLT2 inhibitor, wherein the SGLT2 inhibitor is selected from the
group comprising empagliflozin, canagliflozin,. dapagliflozin, ipragliflozin,

tofogliflozin, sergliflozin etabonate, remogliflozin etabonate preferably Empagliflozin.
The empagliflozin used according to the present invention can be crystalline or amorphous or mixtures thereof.
The empagliflozin used according to the present invention is haying the particle size of D90 is about ljx to 200ja (microns).
The empagliflozin used according to the present invention is having the particle size of D90 is about 200|i to 400^ (microns).
The pharmaceutical composition according to the present invention comprises about 1% w/w to about 30% w/w of empagliflozin or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof.
The pharmaceutical composition according to the present invention, comprises about lmg to about 50mg of empagliflozin or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof.
There are various anti-diabetics known in the prior art, which are given in *
combination with SGLT2 inhibitor. These are as following: N
a) DPP-4 inhibitor such as sitagliptin, vildagliptin,_saxagliptin, linagliptin,
gemigliptin, anagliptin, teneligliptin, alogliptin, trelagliptin, omarigliptin,
evogliptin or dutogliptin.
b) Biguanides such as metformin; thiazolidindiones such as Pioglitazone,
. rosiglitazone; sulfonylureas such as glipizide, glimepiride; glinides such as
repaglinide," nateglinide; alpha- glucosidase inhibitors such as acarbose, voglibose, miglitol; and GLP-1 analogues such as exenatide, liraglutide.
c) Insulins such as insulin glargine, insulin aspart, insulin degludec, Insulin
Lispro, Insulin Glulisine, Insulin detemir and other derivatives thereof.
The pharmaceutical composition according to the present invention
comprises SGLT2 inhibitor or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and/or dipeptidyl peptidase-IV inhibitor or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof optionally along with one or more pharmaceutically acceptable excipients, wherein" the -pharmaceutical composition is free of binder.

I
The pharmaceutical composition according to the present invention comprises dipeptidyl peptidase-IV inhibitor, wherein the dipeptidyl peptidase-IV inhibitor is linagliptin.
The linagliptin used according to the present invention can be crystalline or amorphous or mixtures thereof.
The linagliptin used,according to the present invention is having the particle size of D90 is about l|i to 300|a (microns).
The pharmaceutical composition according to the present invention comprises about 1% w/w to about 30% w/w of linagliptin or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof.
The pharmaceutical composition according to the present invention comprises about lmg to about 50mg of linagliptin or pharmaceutically acceptable salts, esters, solvates, polymorphs thereof
The present invention provides a pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof along with one or more pharmaceutically acceptable excipients, whetein the and one or more pharmaceutically acceptable excipients are selected from the group comprising of diluents, disintegrants, glidants, lubricants, surfactants and/or combinations thereof.
The pharmaceutical composition according to the present invention is in the form of tablets, capsules, granules, pellets, caplets or beads. Preferably, the pharmaceutical composition of the present invention is in the form of tablets/
The pharmaceutical composition according to the present invention is suitable for mucosal, buccal, sublingual, or oral administration to a patient, preferably oral.
The pharmaceutical composition-according to the present invention is in the form of immediate release, delayed release, sustained release, extended release, controlled release or modified release form.
The pharmaceutical composition according to the present invention is prepared by dry granulation/compaction, direct compression or wet granulation.

The present invention provides a dry granulation process for making a pharmaceutical composition comprising a SGLT2 inhibitors and/or dipeptidyl peptidase-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein said process comprises the steps pf: (1) mixing SGLT2 inhibitors and/or dipeptidyl peptidase-IV inliibitor with either all or a portion of the pharmaceutically acceptable excipients in a mixer; (2) compaction/slugging of the mixture of step (1); (3) reducing the ribbons/slugs obtained during step (2) to granules by suitable milling or sieving steps; (4) optionally mixing the granules of step (3) with the remaining pharmaceutically acceptable excipients in a mixer to obtain the final mixture; (5) tabletting the granules of step (3) or the final mixture of step (4) by compressing it on a suitable tablet press to produce the tablet cores; (6) optionally film-coating of the tablet cores of step (5) with a film coat.
The present invention provides a dry granulation process for making a pharmaceutical composition comprising a SGLT2 inhibitors and one or more pharmaceutically acceptable excipients, wherein said process comprises the steps of:
1. sifting all the ingredients through appropriate sieves;
2. dry mixing the pre-sifted empagliflozin, microcrystalline cellulose, sodium starch glycolate, croscarmellbse sodium and silicon dioxide in a suitable blender; ,
3. lubricating the dry mixed ingredients of step 2 in the blender with sodium stearyl fumarate to obtain a blend;
4. passing the blend through roller compactor to obtain compact mass/ribbons;
5. passing the compact mass/ribbons through appropriate mesh screen and passing the blend through the required sieve to obtain granules;
6. blending the granules obtained from step 5 in a suitable blender;
7. lubricating the granules of step 6 with sodium stearyl fumarate in a blender;
8. compressing the blend of step 7 into tablets; and optionally;
9. performing film coating on the tablets of step 8 to form coated tablets.
i

The present invention provides a direct compression process for making a pharmaceutical composition comprising a SGLT2 inhibitors and/or dipeptidyl peptidase-IV inhibitor and one or more pharmaceutically acceptable excipients, wherein said process comprises the steps of: (1) Premixingsaid SGLT2 inhibitors and/or dipeptidyl peptidase-IV inhibitor and the main portion of the pharmaceutically acceptable excipients in a mixer to obtain a pre-mixture; (2) optionally dry screening the pre-mixture through a screen in order to segregate cohesive particles and to improve content uniformity; (3) mixing the pre-mixture of step (1) or'(2) in a mixer, optionally by adding remaining pharmaceutically acceptable excipients to the mixture and continuing mixing; (4) tableting the final mixture of step (3) by compressing it on a suitable tablet press to produce the tablet cores; (5) optionally film-coating of the tablet cores of step (4) with a film coat.
The pharmaceutical composition prepared by any of the above described processes may further be coated with a film-forming polymer and one or more pharmaceutically acceptable excipients, using techniques well known in the art, e.g.^ spray coating or dip coating. The film coating may contain one or more film-forming polymers and optionally one or more pharmaceutically acceptable excipients. Suitable film- forming polymers are selected from hydroxypropylmethyl cellulose, ethyl cellulose, methyl' cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, cellulose acetate, hydroxypropylmethyl cellulose phthalate, methacrylic acid copolymers, e.g., Eudragit®, polyvinylpyrrolidone, polyvinylalcohol, polyethylene glycol, or mixtures thereof.
The pharmaceutical composition according to the present invention is in the form of film coated tablet, wherein said film coat is applied in a concentration of 1-5% and comprises hypromellose, polyethylene glycol (macrogol) and titanium oxide. .
The pharmaceutical composition according to the present invention is used for preventing, slowing the progression of, delaying or treating of an onset of type 2 diabetes mellitus in a patient. Further, the pharmaceutical composition of present invention is used for improving glycemic control and/or for reducing of fasting

plasma glucose, of postprandial plasma glucose and/or of glycosylated haemoglobin HbAl c in a patient diagnosed of being overweight or obese.
The pharmaceutical composition according to the present invention is used for treating type 1 or type 2 diabetes mellitus in a patient with or at risk of oxidative stress, vascular stress and/or endothelial dysfunction, or diseases or conditions related or associated therewith.
The present invention is further illustrated by the following examples which are provided merely to be exemplary of the invention and don't limit the scope of the invention. Certain modifications and equivalents will be apparent to those skilled in the art and are intended to be included within the scope of the present invention.

Example- 1 .: Pharmaceutical composition of Empagliflozin
S.No. Ingredient Quantity % w/w
1 Empagliflozin 12.83
- 2 Microcrystalline cellulose 67.36
3 Sodium starch glycolate 8.98
4 Croscarmellose sodium 6.41
5 Colloidal Silicon Dioxide 0.97
6. Sodium stearyl fumarate 0.97
7 Film Coating 2.43
Process:
1. All the ingredients were sifted through appropriate sieves (100% should pass through sieve).
2. The pre-sifted Empagliflozin, microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium and silicon dioxide were dry mixed in a suitable blender.
3. The dry mixed ingredients of step 2 in the blender were lubricated using sodium stearyl fumarate.

2J&2J&L

15

4. The blend was passed through roller compactor to obtain compacted
mass/ribbons.
5. The compacted mass/ribbons were passed through appropriate mesh screen and the blend was passed through the required sieve to obtain granules.
6. The granules obtained from step 5 were blended in a suitable blender and lubricated using sodium stearyl fumarate.
7. The blend of step 6 was compressed into tablets.
8. The tablets of step 7 were film coated.
Example- 2: Pharmaceutical composition of Empagliflozin

S.No. ' Ingredient Quantity % w/w
1 Empagliflozin 1-30
2 • • Microcrystalline cellulose , 1-95
3 Colloidal Silicon Dioxide 0.1-20
4 Magnesium stearate 0.01-10
5 Film Coating 0.1-10
Process:
1. Sift Empagliflozin and microcrystalline cellulose through # 40 mesh.
2. Sift blend of Step 1 with colloidal silicon dioxide through #40 mesh.
3. Mix the blend of Step 2 in a blender for 10-20 minutes.
4. Lubricate blend of Step. 3 in a blender for 3-7 minutes in a blender with
i
stearic acid and magnesium stearate.
5. Compress the final blend of step 4 on a compression machine to obtain compressed tablets.
6. Coat the tablets in a coating machine with Opadry white (weight build-up 2-4%).
Example- 3: Pharmaceutical composition of Empagliflozin

Sr.'No. Ingredient Quantity % w/w
1 Empagliflozin 1-30
2 Microcrystalline cellulose 1-95
3. Colloidal Silicon Dioxide 0.1-20
4 Magnesium stearate ,0.01-10
' 5 Film Coating 0.1-10
Process:
1. Sift Empagliflozin and microcrystalline cellulose through # 40 mesh.
2. Sift blend of Step 1- with colloidal silicon dioxide through #40 mesh.
3. Mix the blend of Step 2 in a blender for 10-20 minutes.
4. Lubricate blend of Step 3 in a blender for 3-7 minutes in a blender with magnesium stearate.
5. Compress the final blend of step 4 on a compression machine to obtain compressed tablets.
6. Coat the tablets in a coating machine with Opadry white (weight build-up 2-4%).
Example-4: Pharmaceutical composition of Empagliflozin and linagliptin

Sr. No. Ingredient Quantity % w/w
1 Empagliflozin 1-30
2 Linagliptin 1-30 , ■
3 Lactose Monohydrate " 1-95
4 Colloidal Silicon Dioxide 0.1-20
5 Magnesium stearate 0.01-10
6 Film Coating 0.1-10
Process:
1. Sift Empagliflozin, linagliptin and Lactose monohydrate through #40 mesh.
i
/

. 2. Sift blend of Step l.with colloidal silicon dioxide through #40 mesh.
3. Mix the blend of Step 2 in a blender for 10-20 minutes.
4. Lubricate blend of Step 3 in a blender for 3-7 minutes in a blender with magnesium stearate.
5. Compress the final blend of step 4 on a compression machine to obtain compressed tablets.
6. Coat the tablets in a coating machine with Opadry white (weight build-up 2-4%).
Example-5: Pharmaceutical composition of Empagliflozin

Sr. No. Ingredient Quantity % w/w
1 Empagliflozin 1-30
2 Lactose Monohydrate 1-95
3 Colloidal Silicon Dioxide 0.1-2G
4 Magnesium stearate 0.01-10
Process:
1. Sift Empagliflozin and Lactose monohydrate through # 40> mesh.
2. Sift blend of Step 1 with colloidal silicon dioxide through #40 mesh.
3. Mix the blend of Step 2 in a blender for 10-20 minutes.
4. Lubricate blend of Step 3 in a blender for 3-7 minutes in a blender with magnesium stearate.
5. Fill the blend in the capsule.
ExampIe-6: Pharmaceutical composition of Empagliflozin and linagliptin

Sr. No. Ingredient Quantity % w/w
1 Empagliflozin 1-30
2 Linagliptin 1-30

,3 Microcrystalline cellulose 1-95
• 4. Colloidal Silicon Dioxide 0.1-20 '
5 Magnesium stearate 0.01-10
Process:
1. Sift Empagliflozin, linagliptin and microcrystalline cellulose through # 40 •mesh.
2. Sift the blend of Step 1 with colloidal silicon dioxide through #40 mesh.
3. Mix the blend of Step 2 in a blender for 10^20 minutes,

4. Lubricate blend of Step 3 in a blender for 3-7 minutes in a blender with magnesium stearate.
5. Fill the blend in the capsule.
Dissolution Test Studies
The standard dissolution test is described in USP31-NF26 S2, chapter 711 (dissolution). The pharmaceutical composition prepared according to example 1 was subjected to dissolution studies. The paddle method (Apparatus 2) with an agitation speed of 75 rpm was used. The dissolution media used was 900 mL phosphate buffer pH 6.8 at a temperature of 40°C. Samples were taken after up to 60 minutes. The results are reported in table 1 (for 10 mg tablet) and in table 2 (for 25 mg tablet).
Table 1

Composition (as per Example 1) %age release of Empagliflozin
5 min 10 min 15 min 20 min 30min 45 min 60 min
Tab-1 97 98 100 105 101 102 • ••
Tab-2 95 96 99 101 102 102 102

{
Tab-3 97 95 97 95 98 98 98
Tab-4 90 94 96 97 97 98 98
Tab-5 89 95 97 101 98 99 99
Tab-6 84 95 96 97 97 97 97
Min 84 94 96 95 97 97 97
Max , 97 98 100 105 102 102 102
Mean (%) 92 96 98 99 99 99 99
Conditions: Medium pH 6.8 phosphate buffer, Volume: 900mL, RPM 75, Apparatus USP- [I
Table 2

Composition (as per Example 1) % age release of Empagliflozin
5 min 10 min 15 min 20 min 30min 45 min 60 min
Tab-1 85 94 97 98 100 100 100
Tab-2 83 91 95 96 97 97 97
Tab-3 85 94 96 98 100 100 100
Tab-4 76 88 92 94 96 97 98
Tab-5 83 92 94 96 97 97 98
Tab-6 81 91 94 96 97 97 97
Min 76 88 92 94 96 : 97 97
Max 85 94 97 98 100 100 100
Mean(%) 82 92 95 96 98 98 98
Conditions: Medium: pH 6.8 phosphate buffer, Volume: 900mL, RPM 75, Apparatus USP-II
The dissolution studies were conducted for 10 mg tablets and 25 mg tablets in comparison to JARDIANCE® 10 mg and 25 mg respectively. The paddle method (Apparatus 2) with an agitation speed of 75 rpm was used. The dissolution media used was 900 mL phosphate buffer pH 6.8 at a temperature of 40°C. Samples were taken after up to 60 minutes at initial as well as after 1 month. The data is reported in table 3 & 4 for 10 mg and 25 mg tablets respectively.

Table 3
Conditions: Medium: pH 6.8 phosphate buffer, Volume: 900mL, RPM 75, Apparatus USP-II
Table 4
Conditions: Medium: pH 6.8 phosphate buffer, Volume: 900mL, RPM 75, Apparatus USP-II
The results show that the pharmaceutical composition of the present invention are having similar dissolution profile as that of reference listed drug i.e. JARDIANCE®. , Throughout this application, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to

which this invention pertains. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. Other embodiments of the invention will be apparent to those skilled in the art from consideration of the specification and practice of the invention disclosed herein. It is intended that the specification and examples be considered as exemplary only, with a true scope and spirit of the invention being indicated by the following claims.

WE CLAIM:
1. A pharmaceutical composition comprising SGLT2 inhibitor or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and one or more pharmaceutically acceptable excipients, wherein the composition is free of binder.
2. The pharmaceutical composition as claimed in claim 1, wherein the SGLT2 inhibitor is empagliflozin,
3. The pharmaceutical composition as claimed in claim 1, wherein the one or more pharmaceutically acceptable excipients are selected from a group comprising of diluents, disintegrants, glidants, lubricants, surfactants or combinations thereof.
4. The pharmaceutical composition as claimed in claim 3, wherein the diluent is microcrystalline cellulose.
5. The pharmaceutical composition as claimed in claim ,3, wherein the disintegrant is selected from the group consisting of sodium starch glycolate, croscarmellose sodium or combinations thereof.
6. The pharmaceutical composition as claimed in claim 3, wherein the lubricant is sodium stearyl fumarate.
7. The pharmaceutical composition as claimed in claim 1, wherein said composition, is in the form of tablet.
8. The pharmaceutical composition as claimed in claim 1, wherein said composition comprises: •

9. A method of making a pharmaceutical composition of empaghflozin or its pharmaceutically acceptable salts, esters, solvates and polymorphs thereof, wherein said method comprises the steps of:
1. sifting all the ingredients through appropriate sieves;
2. dry mixing the pre-sifted empaghflozin, microcrystalline cellulose, sodium starch glycolate, croscarmellose sodium and silicon dioxide in a suitable blender;
3. lubricating the dry mixed ingredients of step 2 in the blender with sodium stearyl fumarate to obtain a blend;
4. passing the blend through roller compactor to obtain compact mass/ribbons;
v 5. passing the compact mass/ribbons' through appropriate mesh screen and passing the blend through the required sieve to obtain granules; v .6. blending the granules obtained from step 5 in a suitable blender;
7. lubricating the granules of step 6 with sodium stearyl fumarate in a blender; *
8. compressing the blend of step/7 into tablets; and optionally;
9. performing film coating on the tablets of step 8 to form coated tablets.

A pharmaceutical composition comprising empagliflozin or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and linagliptin or its pharmaceutically acceptable salts, esters, solvates, polymorphs thereof and one or more pharmaceutically acceptable excipients, wherein said composition is free of binder.