FORM 2
THE PATENTS ACT, 1070
(39 OF 1970) PATENTS RULES, 2006
PROVISIONAL SPECIFICATION
(SECTION 10; RULE 13)
•'STABLE ORAL PHARMACEUTICAL COMPOSITION OF AMORPHOUS
EMPAGLIFLOZIN AND PROCESS FOR PREPARING THEREOF"

FIELD OF THE INVENTION
The invention relates to a stable oral pharmaceutical composition of Amorphous Empagliflozin
and process for preparing thereof
BACKGROUND OF THE INVENTION
Hrnpagliflozin is an inhibitor of the sodium glucose co-transporter-2. (SGLT-2). Empagliflozin is known chemically as (1S)-1, 5-anhydro-l-(4-chloro-3-{4-f(3S) - tetrahydrofuran-3-yloxy] benzyl} phenyJ)-D-glucitol, also known as D-Glucitol, 1, 5-anhydro-l-C-. [4-chloro-3-[[4-[[(3S)-tetrahydro-3-furanyll oxy] phenyl] methyl] phenyl]- (IS). Us empirical formula is C23H27C107 and the molecular weight is 450,91,
EmpagJiilozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor indicated as an adjunct to diet and exercise to improve glycemic control in adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for reabsorption of glucose from the glomerular filtrate in the kidney. The glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, therefore resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglycaemia and also assists weight loss and blood pressure reduction.
Following oral administration, peak plasma concentrations were reached at 1.5 hours post-dose and then declined in a biphasic manner with a rapid distribution phase and a relatively slow terminal phase. Administration following a high-fat and high-calorie meal results in a slightly lower exposure with AUC decreasing by approximately 16% and Cmax decreasing by approximately 37% compared to fasted condition.
After oral administration, empaglifozin was 41.2% eliminated in feces and 54.4% eliminated in urine. Apparent oral clearance was found to be 10.6 L/h based on population pharmacokinetic analysis. In vitro studies suggest that empaglifozin is primarily metabolized by glucuronidation by 5'-diphospho-glucuronosyltransfcrases UG2B7, UGT1A3, UGT1A8, and UGT1A9. The most abundant metabolites are three glucuronide metabolites; 2-0-, 3-0-, and 6-0-glucuronide. Empaglifiozin does not inhibit, inactivate, or induce CYP450 isoforms. It is a substrate for p-glyeoprotein (p-gp), however in vitro studies suggest that it is unlikely to cause

interactions with drugs that are p-gp substrates. Terminal elimination half-life was found to be
12.4 h based on population pharmacokinetic analysis.
Empagliilozin is a sodium glucose co-transporter-2 (SGLT-2) inhibitor. SGLT2 co-transporters
are responsible lor reabsorption of glucose from the glomerular filtrate in the kidney. The
glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and lowers the renal threshold for glucose, resulting in increased glucose excretion. Additionally, it contributes to reduced hyperglyeaemia, assists weight loss, and reduces blood pressure,
Empagliflozin is available in the United States of America as JARDIANCE® (empagliflozin) oral tablets and 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. It is available in various strengths i.e. 10 and 25 mg strengths for oral administration.
US 7,579,449 B2 discloses glucopyranosyl-substituted phenyl derivatives, medicaments containing such compounds, their use and process for their manufacture.
US 7713938 B2 discloses crystalline form of l-chloro-4~(β-D-glucopyranos-l-yl)-2-[4-((S)-
tctrahydrofuran-3-yloxy)-benzyl]-benzene, a method for its preparation and the use thereof for preparing medicaments.
US 8551957 B2 discloses a pharmaceutical composition comprising a glucopyranosyl-substituted benzene derivative in combination with a DPP IV inhibitor which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia.
US 20110014284 Al discloses pharmaceutical compositions comprising a SGLT-2 inhibitor, pharmaceutical dosage forms, their preparation, their use and methods for treating metabolic disorders.

US 20140256624 A1 discloses a pharmaceutical composition comprising an SGLT2 inhibitor and an insulin which is suitable in the treatment or prevention of one or more conditions selected from
if
type 1diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia.
US 7723309 β 32 discloses crystalline forms of l-chloro-4-(P-D-glucopyranos-l-yl)-2-[4-((R)-tetrahydrofuran-3-yJoxy)-benzyl]-benzene, a method for the preparation thereof, as well as, the use thereof for preparing medicaments.
WO 2016169534 Al discloses novel forms of amorphous empagliflozin, processes for preparing the same and the use thereof in dosage forms. These solid forms of amorphous empagliflozin can be advantageously used to increase the chemical and polymorphic stability of amorphous empagliflozin.
WO 2016051368 Al discloses a solid dispersion of a complex of amorphous empagliflozin and a eyclodcxtrin.
There is no disclosure in the above prior arts about stable immediate-release pharmaceutical composition for oral administration of an amorphous form of empagliflozin with enhanced dissolution.
The different physical properties exhibited by polymorphs affect important pharmaceutical parameters such as storage, stability, compressibility, density and dissolution rates (important in determining bioavailability). Stability differences may result from changes in chemical reactivity (e.g., differential hydrolysis or oxidation, such that a dosage form discolors more rapidly when comprised of one polymorph than when comprised of another polymorph), mechanical changes (e.g., tablets crumble on storage as a kinetically favored crystalline form converts to thermodynamically more stable crystalline form) or both (e.g., tablets of one polymorph are more susceptible to breakdown at high humidity).
An amorphous form generally provides better solubility and bioavailability than the crystalline form and may be useful for formulations which can have better stability, solubility and compressibility etc. which are important for formulation and product manufacturing.

There fore, it is desirable to have a stable amorphous form of drug with high purity to meet the needs of regulatory agencies and highly reproducible processes for its preparation,
In view of the above, it is therefore, desirable to provide an efficient, more economical, less hazardous and eco-friendly process for the preparation of oral solid dosage form of amorphous form of empagliilozin. The amorphous form provided herein in the composition of the present
invention is stable under ordinary stability conditions with respect to purity and storage.
Despite the above mentioned prior arts on solid pharmaceutical formulations of Empagliilozin there still exists a need for an oral pharmaceutical composition of amorphous Empagliilozin with enhanced dissolution and adequate chemical and physical characteristics. It has now been surprisingly found that a stable oral pharmaceutical composition of amorphous empagliflozin prepared by a simple granulation process comprising higher percentage of disintegrant has shown better dissolution rate (important in determining bioavailability) as compared to the composition having conventional amount of disintegrant.
OBJECT OF 'THE INVENTION
it is an object of the present invention to provide an oral pharmaceutical composition of
Amorphous Empagliflozin and processes for preparing thereof.
It is another object of the present invention to provide a stable oral pharmaceutical composition comprising:
(a) an amorphous form of Empagliflozin, as an active ingredient,
(b) from about 45% to about 55% by weight of croscarmellose sodium as disintegrant,
(c) at least one diluent,
(d) at least one binding agent,
(e) at least one lubricant, and
a coaling, wherein the percentage by weight is relative to the total weight of the composition and wherein about 95 to 98% of Empagliilozin is released from the composition

in about 20 minutes in an aqueous buffer solution of about pH 6.8 with a paddle speed of 75 rpm,
It is another object of the present invention to provide a stable oral pharmaceutical composition
comprising;
(a) from about 10% to about 15% by weight of an amorphous form of Empagliflozin, as an
active ingredient,
(b) from about 45% to about 55% by weight of croscarmellose sodium as disintegrant,
(c) from about 14% to about 30% by weight of a mixture of Microcrystalline Cellulose and maize starch as a diluent,
(d) from about 7% to about 15% by weight of hydroxypropyl methylcellulose as binding
agent,
(e) from about 0,5% to about 1.5% by weight of colloidal silicon dioxide and magnesium
stearate as lubricants, and
a coating, wherein the percentage by weight is relative to the total weight of the composition and wherein about 95 to 98% of Empagliflozin is released from the composition in about 20 minutes in an aqueous buffer solution of about pH 6,8 with a paddle speed of 75 rpm.
It is yet another object of the present invention to provide an oral solid stable pharmaceutical
composition of Amorphous Empagliflozin and processes for preparing thereof, which uses a new
and different beneficial formulation but is still bioequivalent to the commercially available
compositions in the United States of America i.e. JARDIANCE® oral tablets.
It is yet another object of the present invention to provide a stable oral pharmaceutical composition of amorphous empagliflozin comprising higher percentage of disintegrant which surprisingly shows better dissolution rate as compared to the composition having conventional amount of
disintegrant.
SUMMARY OF THE INVENTION

I he present invention relates to a stable oral pharmaceutical composition of Amorphous Empagliflozin and process for preparing thereof
More particularly it relates to:
A) A stable oral pharmaceutical composition comprising:
(a) an amorphous form of Empagliflozin, as an active ingredient,
(b) from about 45% to about 55% by weight of croscarmeUose sodium as disintegrant,
(c) at least one diluent,
(d) at least one binding agent,
(e) at least one lubricant, and
a coating, wherein the percentage by weight is relative to the total weight of the composition and wherein about 95 to 98% of Empagliflozin is released from the composition in about 20 minutes in an aqueous buffer solution of about pH 6,8 with a paddle speed of 75 rpm.
B) A stable oral pharmaceutical composition comprising;
(a) from about 10% to about 15% by weight of an amorphous form of Empagliflozin, as an active ingredient,
(b) from about 45% to about 55% by weight of croscarmeUose sodium as disintegrant,
(c) from about 14% to about 30% by weight of a mixture of Microcrystalline Cellulose and maize starch as a diluent,
(d) from about 7% to about 15% by weight of hydroxypropyl methylcellulose as binding agent,
(e) from about 0.5% to about 1.5% by weight of colloidal silicon dioxide and magnesium stcarate as lubricants, and
a coating, wherein the percentage by weight is relative to the total weight of the composition and wherein about 95 to 98% of Empagliflozin is released from the composition in about 20 minutes in an aqueous buffer solution of about pH 6.8 with a paddle speed of 75 rpm.

C) A process of* preparing the stable oral pharmaceutical composition as B above, wherein the process comprises;
a) Dissolving empagliflozin in a mixture of Isopropyl alcohol and methylene chloride and adding hydroxy-propyl methyl cellulose to the above solution.
b) Spraying the solution of a) into mixture of microcrystalline cellulose, maize starch and
croscarmellose sodium, then adding required amount of colloidal silicon dioxide & Magnesium
stearate.
c) Compressing the lubricated blend of b) into tablets, followed by film coating of the tablets.
d) The pharmaceutical compositions as in A & B above, wherein the said pharmaceutical composition is as physically stable as the commercially available compositions in the United States of America i.e. JARD1ANCE® oral tablets.
e) The pharmaceutical compositions as in A & B above, wherein the said pharmaceutical composition is bioequivalent to the commercially available compositions in the United States of America i.e. JARDIANCE® oral tablets.
In summary, the present invention relates to a stable oral pharmaceutical composition of amorphous empagliflozin comprising higher percentage of disintegrant which surprisingly shows better dissolution rate as compared to the composition having conventional amount of disintegrant.
DETAILED DESCRIPTION OF THE INVENTION
Before the present process and methods are described, it is to be understood that this invention is not limited to particular compounds, formulas or steps described, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be limited only by the appended claims.
Where a range of values is provided, it: is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limit of that range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of these smaller ranges may independently be included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both

of the limits, ranges excluding either both of those included limits are also included in the
invention,
Although any methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present invention, the preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and/or materials in connection with which the publications are cited.
It must be noted thai as used herein and in the appended claims, the singular forms "a", "and", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a compound" includes a plurality of such compounds and reference to "the step" includes reference to one or more step and equivalents thereof known to those skilled in the art, and so forth.
The publications discussed herein are provided solely for their availability to the applicant prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention. Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed
The term "stable" as used herein refers to chemical stability of amorphous form of Empagliflozin in solid dosage forms wherein there is no change in assay values and dissolution and/or the total impurity remains less than 1%, when the dosage form is kept at 40°C/75% RH for 6 months.
The term "composition" as used herein is intended to encompass a product comprising the specified ingredients (and in the specified amounts, if indicated), as well as any product which results, directly or indirectly, from combination of the specified ingredients in the specified amounts. By "pharmaecutically acceptable" it is meant that the diluent, excipient or carrier must be compatible with the other ingredients of the formulation and not deleterious to the recipient thereof

As used herein, the term "polymorph" refers to polymorph form of Empagliflozin which, when
present as solid,exists as different Crystalline forms, Desirably, polymorph includes solid forms
of a compound such as crystals, microcrystals, foams, and powders, among others. Polymorphs typically differ in their physical properties due to the order of the molecules in the lattice of the polymorph. In addition, the physical properties of the polymorph can differ due to the presence of solvates or other molecules incorporated into the lattice of the polymorph. Typically, polymorphs are readily distinguished using techniques such as melting point, rate of dissolution, Infrared (1R) and Raman spectroscopy, and X-ray diffraction such as crystal and powder techniques,
The term "amorphous" as used herein refers to a compound having no definite crystal structure or form. In the present application, the term amorphous refers to amorphous Empagliflozin that can be present in the amorphous form as a solid or in a solution.
According to this invention, and the teachings contained in this patent application, the dosage form can be formulated as oral formulation by any suitable granulation process, dry or wet in the form of tablet, coated tablet or multiparticulate formulation known to those skilled in the art.
According to this invention, and the teachings contained in this patent application, the dosage form can be formulated as oral tablets formulation and dissolution of formulated oral tablets is evaluated by Drug Dissolution Apparatus 11 DSP (Paddle), known to those skilled in the art.
'The pharmaceutical composition of the present invention may further comprise conventional pharmaceutically acceptable excipients. Conventional pharmaceutical excipients include those which function in a dosage form, for example, as fillers or diluents, binders, disintegrants,
lubricants, glidants, and film forming material.
Disintegrants include, but are not limited to crospovidone, croscarmellose sodium, sodium starch glycolate, combinations thereof and the like. In the present invention disintegrant can be present in an amount ranging from about 45% to about 55%, preferably from about 48% to about 53%, or from about 50% to about 52% by weight relative to the total weight of the composition,

Fillers or diluents for use in the formulations of the present invention include fillers Of diluents
typically used in the formulation of pharmaceuticals. Examples of fillers or diluents for use in accordance with the present invention include but are not limited to lactose, dextrose, glucose, sucrose, microcrystalline cellulose, maize starch, pregelatinized starch, modified corn starch, cellulose, dextratcs, maltodextrin, mannitol, xylitol, sorbitol, cyclodextrin, calcium carbonates,
magnesium carbonates, combinations thereof, and the like. Several types of lactose are suitable for use in the formulations described herein, for example, lactose selected from the group consisting of anhydrous lactose, lactose monohydrate, directly compressible anhydrous lactose, and modified lactose monohydrate. In the present invention one or more diluents can be present in an amount ranging from about 10% to about 40%, preferably from about 15% to about 35%, or from about 20% to about 30% by weight relative to the total weight of the composition.
Binders for use in the formulations of the present invention include binders commonly used in the formulation of pharmaceuticals. Examples of binders for use in accordance with the present invention include but are not limited to hydroxypropyl cellulose, hydroxypropyl mcthylcellulose,
methylcellulosc, sodium carboxymethyl cellulose, glycol, sucrose, dextrose, corn syrup, acacia, targacanth, guar, alginates, maize starch, corn starch, pregelatinized starch, modified corn starch, polyvinylpyrrolidone, polyethylene, polyethylene glycol, combinations thereof and the like. In the present invention binder can be present in an amount ranging from about 5% to about 15%, for example, from about 8%> to about 13%, or from about 10% to about 12% by weight relative to the total weight of the composition
Lubricants for use in the formulations of the present invention include lubricants commonly used in the formulation of pharmaceuticals. Examples of lubricants for use in accordance with the present invention include but are not limited to magnesium carbonate, magnesium lauryl sulphate, calcium silicate, talc, fumed silicon dioxide, magnesium stearate, calcium stearate, stearic acid, sodium slearyl fumarate, polyethylene glycol, sodium lauryl sulphate, magnesium lauryl sulphate, sodium benzoate, colloidal silicon dioxide, magnesium oxide, microcrystalline cellulose, starches, mineral oil, waxes, glyceryl behenate, polyethylene glycol, sodium acetate, sodium chloride, combinations thereof. In the present invention one or more lubricants can be present in

an amount ranging from about 0.5% to about 2%, preferably from about 0.75% to about 1.5 or from about 1% to about 1.2% by weight relative to the total weight of the composition.
Coats include, but are not limited to Opadry. In one embodiment, the coat is Opadry yellow. In another embodiment, the coal is Opadry II. In the present invention coat can be present in an amount ranging from about 1% to about 3%, preferably from about 0.7% to about 0.9 % by weight relative to the total weight of the composition
The pharmaceutical compositions of the present invention may be prepared by the conventional
processes such as wet granulation, dry granulation or direct compression as known to those skilled in the art.
The following examples are intended to illustrate the scope of the present invention in all its aspects but not to limit it thereto.
Example 1 The composition of the present invention was prepared as given in table 1.

Sr, No
A' "'
1. Ingredients Weight in composition

Intra granular

Microcrystailine Cellulose 20.0 mg
2,
B.
4. Maize Starch 22.0 mg

Croscarmellosc Sodium 110.0 mg

Granulation

Am o rpho u s Em pa gl i f 1 o z i n 25.0 mg
5. 1 lydroxypropy 1 Methyleellulose 20.0 mg
6.
c.
8 lsopropyl alcohol Q.S.

Methylene Chloride Q.S.

Pre Lubrication

Colloidal Silicon dioxide 1.0 mg
D. Lubrication

7 Magnesium Stearate 2.0mg
8
9. Coating

Opadry Yellow 6.0 mg

Purified Water Q.S.
M anufacturing Procedure:
Co-Sifted Microcrystalline Cellulose, Maize Starch and Croscarmel lose Sodium through required sieve. Empagliflo/.in API (drug) and Hydroxypropyl Methylcellulose were dissolved in mixture of I so propyl alcohol and Methylene diehloride to form drug + binder solution. Loaded the inlragranular co-sifted materials in to fluidised bed processor and preheat with definite cubic feet per minute. Soon after, drug + binder solution was sprayed by top spray technology. Dried the wet materials of fluidised bed processor until desired loss on drying is achieved followed by Milling and sifting of the dried materials carried out through required screen and sieves. Prelubrication was carried out with Colloidal silicon dioxide and mixed for 15 minutes in blender & Lubrication was carried out with Magnesium stearate for 5 minutes. Compressed the lubricated Blond in to tablets with suitable punch size and shape. Finally film coating of compressed tablets carried out with suitable coating material.
Example 2 The composition of the present invention was prepared as given in table 2.

Sr. No
A,
1.
2. Ingredients Weight in composition

Intra granular

Microcryslalline Cellulose 35.0 mg

Maize Starch 20.0 mg
Croscarmel lose Sodium 85.0 mg

Granulation
4. Amorphous Empagliflozin 25.0 mg

5
¥ I. Hydroxypropyl Methylce ulose 18.0 mg
6. Hthanol absolute Q.S.
7. Methylene Chloride Q.S.
c. Pre Lubrication
Croscarmellose Sodium 20.0 mg
8. Colloidal Silicon dioxide 1.0mg
Microcrystalline Cellulose 7.0 mg
D. Lubrication
7. Magnesium Stearate 2,0 trig
E Coating
Opadry Yellow
8.
6.0 mg
9. Purified Water Q.S.
Manufacturing Procedure;
Co-Sifted Microcrystalline Cellulose, Maize Starch and Croscarmellose Sodium through required sieve. Hmpaglifiozin API (drug) and 1 lydroxypropyl Methylcellulose were dissolved in mixture of efhanol absolute and Methylene dichloride to form drug + binder solution. Loaded the intragranular co-sifted materials in to fluidised bed processor and preheat with definite cubic feet per minute. Soon after, drug-binder solution was sprayed by top spray technology. Dried the wet materials of fluidised bed processor until desired loss on drying is achieved followed by milling and sifting of the dried materials carried out through required screen and sieves. Prelubrication was carried out with Croscarmellose sodium. Colloidal silicon dioxide & Microcrystalline Cellulose and mixed for 15 minutes in blender. Lubrication was carried out with Magnesium stearate for 5 minutes. Compressed the lubricated blend in to tablets with suitable punch size and shape, finally film coating of compressed tablets carried out with suitable coating material.
Example 3 (Comparative Batch) The composition of the comparative Batch was prepared as given in table 3.


sr No Ingredients Weight in composition
A, Intra granular
1.
■j Microcrystalline Cellulose 115.0 mg

Maize Starch 15.0 mg
3, Croscarmellose Sodium 20.0 mg
B. (Granulation
4« Amorphous Empaglitlozin 25.0 mg
6. Hydroxypropyl Methylcellulosc 22.0 mg ———

Isopropyl alcohol Q.8.

7, Methyl enc Ch l oride Q.S.
C, Pre Lubrication
8. Colloidal Silicon dioxide 1.0 mg
D). Lubrication

Magncsium Stearate 2.0 mg
E Coating
8, 9. Opadrv Yellow 6.0 mg

Purified Water Q.S
Manufacturing Procedure:
Co-Sifted Microerysialline Cellulose, Maize Starch and Croscarmellose Sodium through required sieve. bmpagliflozin API (Drug) and Hypromellose were dissolved in mixture of Isopropyl alcohol and Methylene dichloride to form drug +binder solution. Loaded the intragranular co-sifted materials in to fluidised bed processor and preheat with definite cubic feet per minute. Soon after, drug + binder solution was sprayed by top spray technology. Dried the wet materials of fluidised bed processor until desired loss on drying is achieved followed by milling and sifting of the dried materials carried out through required screen and sieves. Prelubrication was carried out with Colloidal silicon dioxide and mixed for 15 minutes in blender. Lubrication was carried out with Magnesium stearate for 5 minutes. Compressed the lubricated blend in to tablets with suitable punch size and shape. Finally film coating of compressed tablets carried out with suitable coating material.

Dissolution Profile study:
The comparative dissolution study between the Empagliflozin Tablets 25 mg of JARDIANCE®
Oral tablets as reference product and Example 1 & Example 2 of the present invention as Test products are presented in table-4 & table-5 respectively and which showed about 95 to 98% of Empagli Ho/in is released in about 20 minutes in an aqueous buffer solution of about pH 6.8 with a paddle speed of 75 rpm wherein the an aqueous buffer solution is 0.05 M Phosphate Buffer in Dissolution Apparatus 11 USP (Paddle).
Amorphous Empaglifiozin Tablets 25 mg of Example !
Table; 4

s.
No. 1.
3
5. Time (min) (% of JARDIANCE release from dosage form) Composition of example-1
(% of release from dosage form)

5 81.1 44.00

10 95.5 81.40

15 97.9 96.60

20 30 98.4 98.40

98.6 99.20
Amorphous Empagliflozin Tablets 25 mg of Example 2

5. 30 98.6 97.6
The comparative dissolution study between Example 1 & Example 2 of the present invention with example 3 (the comparative batch) are shown in table-6. From the given data, it can be see that about 95 to 98 % of Empagliflozin is released in about 20 minutes in an aqueous buffer solution of about pH 6.8 with a paddle speed of 75 rpm wherein the an aqueous buffer solution is 0.05 M Phosphate Buffer in Dissolution Apparatus II USP (Paddle) of Example 1 & Example 2 (in both cases from about 45%-55% disintcgrant is used) of the present invention. However, only about 55 to 60% of Empagliflozin is released in about 30 minutes in an aqueous buffer solution of about pHl 6.8 with a paddle speed of 75 rpm wherein the an aqueous buffer solution is 0.05 M Phosphate Buffer in Dissolution Apparatus II USP (Paddle) of Example 3 (from about 7%-15% disintegrant is used).
Amorphous Empagliflozin Tablets 25 mg of Example 3(Comparative Batch)
Table: 6

s. Time Composition of Composition oi Example 3
No. (min) example-1 example-2 (Comparative Batch)
(% of release from (% of release (% of release from
1' dosage form) from dosage form) dosage form)

5 44.00 55.40 11.00
2.
1
4. 10 81.40 84.30 28,60

15 96.60 94.00 43.00

20 98.40 95.90 50.30
5. 30 99.20 97,6 60.00
Prom the above data, it can be seen that the composition comprising higher percentage of disintegrant has shown belter dissolution rate contrast to the composition having conventional amount of disintegrant.
Bioequivalence Study:

The comparative Study between the Empagliflozin Tablets 25 rag of JARDIANCE@ Oral tablets as
reference product and Example 1 of the present invention as 'Test product showed that the two formulations were bioequivalent. (Within 90% confidence interval for the ratios).The results are as shown in tables 5 and 6.
Fasting Bioequivalence result;
Table: 5

Fasting Result Dependent
LCmax

LSMref-R LSMtest -Tl Ratio Tl/R Lower Upper Power

279 13 303.29 108.66 94.34 120.30 96.37
LAUCt 3108.27 3178.66 102.26 95.70 112.28 97.88
LAUCinf 3243.38 3282.53 101.21 94.39 108.52 98.82
Fed Biocquivalence result:
Table:6

Fed result
Dependent LSMref-R LSMtest -Tl Ratio Tl/R Lower Upper Power
LCmax 247.57 272.88 110.22 91.61 123.08 86.64
LAUCt 3101 26 3408.71 109.91 100.92 139.53 97.73
LAUCinf 3244.31 3498.86 107.85 98.58 112.50 98.97
Cmax'- Maximum plasma concentration
AUJ00.,,--- Area under the plasma concentration time curve from time 0 to t
AUCVinf):: Area under the plasma concentration time curve from time 0 to inf

All pharmacokinetic parameters of Amo rplious Empagliflozin were within the acceptable limit in
pilot level bio equivalency study of fed and fasted stage,
Although the invention has been described in terms of particular embodiments and applications, one of ordinary skill in the art, in light of this teaching, can generate additional embodiments and modifications without departing from the spirit of or exceeding the scope of the claimed invention. It should be emphasized that the above-described embodiments of the present invention, particularly any "preferred" embodiments, are merely possible examples of the invention of implementations, merely set forth for a clear understanding of the principles of the invention. Accordingly, it is to be understood that the drawings and descriptions herein are preferred by way of example to facilitate comprehension of the invention and should not be construed to limit the scope thereof.

We Claim:
1. A stable oral pharmaceutical composition comprising:
a) empagliflozin or pharmaceutical ly acceptable salt thereof
b) at atleast a disintcgrant
c) one or more pharmaceutically acceptable excipients

2. The pharmaceutical composition of claim 1, wherein disintegrate is croscarmellose sodium
3. The pharmaceutical composition of claim 1, wherein one or more pharmaceutically acceptable
excipients is selected from the group comprising diluent, binding agent, lubricant or combination thereof.
4. The pharmaceutical composition of claim 1, wherein empagliflozin is present in amorphous form.
5. The pharmaceutical composition of claim I, wherein 95-98% of empagliflozin is released from the composition in about 20 minutes in an aqueous buffer solution of about pH 6,8 with a paddle speed of 75 rpm.
6. The pharmaceutical composition of claim 1, wherein disintcgrant is present in a concentration range of about 45% to 55% by weight.
7. The pharmaceutical composition of claim 1, wherein the composition is in the form of a tablet or capsule.
8. A stable oral pharmaceutical composition comprising;

a) from about 10% to about 15% by weight of amorphous empagliflozin
b) from about 45% to about 55% croscarmellose sodium as disintcgrant
c) from about 14% to about 30% by weight of microcrystalline cellulose and maize starch as diluent
d) from about 7% to about 15% of hydroxypropyl methylcellulose as binding agent
e) from about 0.5% to about 1.5% by weight of colloidal silicon dioxide and magnesium stearate as lubricant
9. The pharmaceutical composition of claim 8, wherein 95-98% of empagliflozin is released from
the composition in about 20 minutes in an aqueous buffer solution of about pH 6.8 with a paddle
speed of 75 rpm.
10. The pharmaceutical composition of claim 8, wherein the composition is in the form of a tablet
or capsule.