DESC:According to the embodiments of The present invention relates to oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof and its combination with Metformin or its salts, one or more pharmaceutically acceptable excipients. Where in the Metformin is in the form of immediate release or extended release.

The present invention relates to oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof and its combination with Metformin or its salts, one or more pharmaceutically acceptable excipients free of magnesium stearate.

The present invention relates to a solid oral pharmaceutical composition comprising the pharmaceutically acceptable excipients, where in the lubricant is calcium stearate.

The present invention relates to a solid oral pharmaceutical composition comprising Dapagliflozin or its pharmaceutically acceptable salts thereof and its combination with Metformin or its salts, where in the lubricant is calcium stearate in an amount of 2-5%

The present invention relates to a pharmaceutical dosage form comprising Intra-granular portion containing Dapagliflozin or its pharmaceutically acceptable salt thereof and one or more pharmaceutical acceptable excipients and an extra-granular portion containing one or more pharmaceutically acceptable excipients thereof. Where in Dapagliflozin is incorporated in the formulation by dissolving in granulation fluid.

The present invention relates to pharmaceutical dosage form comprising Intra-granular portion containing Dapagliflozin or its pharmaceutically acceptable salt thereof and metformin or its salts and one or more pharmaceutical acceptable excipients.

The present invention relates to preparation of solid oral pharmaceutical composition comprising Dapagliflozin or its pharmaceutically acceptable salt thereof and metformin or its salts, wherein the Dapagliflozin is incorporated in the granulation fluid and added to the other pharmaceutical acceptable excipients.

The present invention relates to preparation of solid oral pharmaceutical composition comprising Dapagliflozin or its pharmaceutically acceptable salt thereof, wherein the Dapagliflozin is incorporated in the granulation fluid and added to the other pharmaceutical acceptable excipients.
The present invention is relates to oral pharmaceutical compositions comprising Metformin or its salts, one or more pharmaceutically acceptable excipients. Where in the Metformin is in the form of immediate release or extended release.

The present invention is relates to oral pharmaceutical compositions comprising Metformin or its salts, one or more pharmaceutically acceptable excipients free of magnesium stearate. Where in the Metformin is in the form of immediate release or extended release.

The term "pharmaceutical acceptable excipient" as used herein refers to additives useful for converting pharmacologically active compounds into pharmaceutical dosage forms which are suitable for administration to patients. Suitable excipients include diluents, binders, disintegrant, surfactants, lubricants, glidants and coloring agents. Other pharmaceutically acceptable excipients can also be included.

The term “composition” or “pharmaceutical composition” or “solid dosage forms” such as granules, multiunit particulate systems (MUPS), pellets, spheres, tablets, capsules, mini-tablets, beads, particles and the like; and liquid dosage forms such as solutions, suspensions, emulsions, colloids and the like, meant for oral administration.

The term “Dapagliflozin” as used herein means Dapagliflozin or its pharmaceutically acceptable salts. Dapagliflozin may be in amorphous form, crystalline form, a mixture thereof or co-crystals with suitable co-formers. Preferably, Dapagliflozin base is in amorphous form.

The term “Metformin” as used herein means Metformin or its pharmaceutically acceptable salts. Metformin may be in amorphous form, crystalline form, a mixture thereof or co-crystals with suitable co-formers.

The articles "a" and "an" are used in this disclosure to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, "a diluent" means one diluent or more than one diluent.
Throughout this specification and the appended claims, it is to be understood that the words "comprise", “have”, “contain” and "include" and variations such a "comprises", "comprising", “having”, “containing” "includes", "including" are to be interpreted inclusively, unless the context requires otherwise. That is, the use of these words may imply the inclusion of an element or elements not specifically recited.

According to the embodiments of the present invention diluent are selected from the group comprising of, Micro crystalline cellulose, starch, pregelatinized starch, calcium carbonate, dibasic, tribasic calcium phosphate, calcium phosphate, lactose, dextrose, calcium phosphate, fructose, lactitol, lactose, magnesium carbonate, magnesium oxide, maltitol, maltose, simethicone, sodium chloride, talc, xylitol, sorbitol, mannitol, maltodextrin and mixtures thereof.

According to the embodiment of the present invention suitable binders used according to the present invention are selected from the group comprising of hydroxypropylmethylcellulose, maize starch, povidone, hydroxypropylcellulose, pregelatinized starch and the like or combination thereof.

According to the embodiments of the present invention disintegrant are selected from the group comprising of starches, croscarmellose sodium, carmellose, sodium starch glycolate, pregelatinized starch, sodium carboxymethyl cellulose, microcrystalline cellulose, cross-linked polyvinylpyrrolidone, sodium alginate, low-substituted hydroxypropylcellulose, crospovidone and mixtures thereof.

According to the embodiments of the present invention suitable surfactants are selected from Tyloxapol®, Triton X-100®, polysorbates, polyoxyl 35 castor oil, polyoxyl 40 hydrogenated castor oil, polyoxyl 40 stearates, sorbitan monolaureates, sodium lauryl sulphate, polyethylene-propylene glycol copolymer (poloxamer), cremophor-40, propylene glycol and mixtures thereof.
According to the embodiments of the present invention lubricant selected for the group anti-tacking agent, sodium lauryl sulphate, metallic stearates such as magnesium stearate, calcium stearate, zinc stearate; stearic acid, hydrogenated vegetable oil, hydrogenated castor oil, glycerylpalmitostearate, glyceryl behenate, polyethylene glycols, corn starch, sodium stearylfumarate, sodium benzoate, mineral oil, glycerine fumarate and mixtures thereof.

According to the embodiments of the present invention suitable film coating polymers used according to the present invention are selected from polyvinyl alcohol (part hydrolyzed), titanium dioxide, macrogol (polyethylene glycol 3350), Hypromellose, Lactose, Triacetin, Talc, Titanium oxide and iron oxide and the like or mixtures thereof.

According to an embodiment of the present invention composition will provide stable product, as well as improved dissolution profile and bioavailability.

According to an embodiment of the present invention relates to oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, one or more pharmaceutically acceptable excipients free of magnesium stearate.

According to an embodiment of the present invention relates to process for preparing oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, one or more pharmaceutically acceptable excipients free of magnesium stearate.

According to an embodiment of the present invention relates to oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, where in the Metformin is in the form of immediate release or extended release.

According to an embodiment of the present invention relates to process for preparing oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, where in the Metformin is in the form of immediate release or extended release.

According to an embodiment of the present invention relates to a solid oral pharmaceutical composition comprising the pharmaceutically acceptable excipients is selected from diluents, binders, disintegrant, surfactants, lubricants, glidants and coloring agents and the like or mixture thereof and optionally a pharmaceutical acceptable excipient.

According to an embodiment of the present invention relates to process for preparing oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, where in the Metformin is in the form of immediate release or extended release, where in the lubricant is Calcium Stearate.

According to the preferred embodiment of the present invention relates to process for preparing oral pharmaceutical compositions comprising Dapagliflozin or its pharmaceutically acceptable salts thereof alone or its combination with Metformin or its salts, where in the Metformin is in the form of immediate release or extended release, where in the lubricant is Calcium Stearate in about 2-5%.

The process details of the invention are provided in the examples given below, which are provided by way of illustration only and therefore should not be construed to limit the scope of the invention.

Example-1:
S.No. Ingredients mg/Tablet
5 mg 10 mg
1. Micro Crystalline Cellulose 101 (Hicel 50M) 46.50 93.00
2. Lactose Anhydrous (Supertab 21AN) 16.00 32.00
3. Croscarmellose sodium (Pharmellose) 2.50 5.00
4. Hydroxy Propyl Methyl Cellulose (Methocel E5) 3.00 6.00
5. Dapagliflozin Propanediol Monohydrate 6.15 12.30
6. Purified Water (70) q.s q.s
7. Iso Propyl Alcohol (30) q.s q.s
8. Microcrystalline cellulose (Hicel 90M / XLM 90) 18.35 36.70
9. Croscarmellose sodium (Pharmellose) 1.50 3.00
10. Colloidal Silicon Dioxide
(Aerosil 200) 3.00 6.00
11. Calcium Stearate
(Ligamed CPR-2-V-MB) 3.00 6.00
Total weight of uncoated tablets 100.00 200.00
Film coating (3.00%w/w build up)
12. Opadry II Yellow $ 3.00 6.00
13. Purified water q.s q.s
Total weight of coated tablet 103.00 206.00
Manufacturing Process:
Sifting
i. Co-sift Microcrystalline cellulose 50M, Anhydrous lactose, Croscarmellose sodium and Hydroxypropylmethylcellulose E5 through sieve # 30 ASTM (600 µm).
Dry mixing and Granulation
ii. Load the sifted materials of step i in rapid mixer granulator and mix for 15 minutes using impeller at slow speed and chopper off.
Drug Solution Preparation
iii. Weigh the required quantities of Purified water and Isopropyl alcohol at 70:30 ratio and add in SS container with proper closure under continuous stirring.
iv. Separate 10% quantity from step iii in to SS container for rinsing purpose.
v. Dissolve Dapagliflozin Propanediol Monohydrate in remaining 90% quantity of step iii under stirring and stir until a clear solution is formed.
Granulate step ii dry mix with prepared drug solution of step no.v & rinsing solution of step iv by the following granulation parameters.
Wet milling:
vi. Unload the wet mass from RMG and mill through co-mill fitted with 8.0 mm screen at slow speed.
Drying
vii. Load the contents of step vi in FBD and dry the granules initially for 15 minutes at inlet temperature of 25°C ± 5°C and then at inlet temperature of 45°C ± 10°C until the LOD of the granules reaches 1.0 – 3.0 % w/w at 60°C.
Sizing and Milling
viii. Sift the dried granules of step vii through sieve #40 ASTM (425 µm) and collect in doubled lined polybag.
ix. Mill the retentions of step viii by using co-mill fitted with 1.0 mm screen at slow speed and sift through #40 ASTM (425 µm) and collect in doubled lined polybag.
x. Ensure that all materials of step ix passed through #40 ASTM (425 µm), if any retains present continue the step ix until all granules pass through #40 ASTM (425 µm).
Sifting of extra-granular material
xi. Co-Sift microcrystalline cellulose XLM 90, Croscarmellose sodium and Colloidal silicon dioxide through sieve # 40 ASTM (425 µm).
xii. Sift magnesium stearate through sieve #60 ASTM (250 µm).
Blending and Lubrication
xiii. Load the sifted materials of step viii, ix, x and step xi in to blender and mix for 20 minutes .
xiv. Add step xii of sifted magnesium stearate to step xiii and mix for 5 minutes and collect in doubled lined polybag.
Compression
xv. Compress the lubricated blend of step-xiv with the suitable parameters.
Film Coating:
xvi. Disperse the Opadry II colorant in purified water (15% w/w solids) under stirring and continue stirring for 45 minutes to form uniform dispersion.
xvii. Load the core tablets of step xv in coating pan and pre-warm the tablets for 10 minutes at product temperature 35°C – 45°C and coat the tablets for 3.0 % ± 1.0 % w/w with the suitable parameters.
After achieving the desired weight gain dry the coated tablets for 5 minutes at product temperature 35°C – 45°C.
Example-2
S.
No. Ingredients Qty. per Unit (mg)
5 mg / 500 mg 5 mg/850 mg 5 mg/1000 mg 10 mg/500 mg 10 mg/850 mg 10 mg/1000 mg
1 Metformin HCl 500.00 850.00 1000.00 500.00 850.00 1000.00
2 Microcrystalline cellulose PH 101 30.00 51.00 60.00 30.00 51.00 60.00
3 Copovidone 30.00 51.00 60.00 30.00 51.00 60.00
4 Croscarmellose Sodium 14.00 23.80 28.00 14.00 23.80 28.00
Binder Solution
5 Dapagliflozin Propanediol Monohydrate 6.15 6.15 6.15 12.30 12.30 12.30
6 Copovidone 10.00 17.00 20.00 10.00 17.00 20.00
7 Purified water : IPA (70:30) Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.
Extra granular
8 Microcrystalline cellulose PH 102 88.85 141.25 174.85 82.70 135.10 168.70
9 Croscarmellose Sodium 14.00 23.80 28.00 14.00 23.80 28.00
10 Calcium Stearate 22.00 36.00 43.00 22.00 36.00 43.00
Core Tablet Weight (mg) 715 1200 1420 715 1200 1420
Film Coating
11 Opadry II Orange 21.45 -- -- -- -- --
12 Opadry II Brown -- 36.00 -- -- -- --
13 Opadry II Yellow -- -- 42.6 -- -- --
14 Opadry II Pink -- -- -- 21.45 -- --
15 Opadry II Brown -- -- -- -- 36.00 --
16 Opadry II Yellow -- -- -- -- -- 42.6
17 Purified water4 Q.S. Q.S. Q.S. Q.S. Q.S. Q.S.
Coated Tablet Weight (mg) 736.45 1236.00 1462.60 736.45 1236.00 1462.60
MANUFACTURING PROCESS:
Milling:
xviii. Mill the Metformin Hydrochloride through multi-mill with 2.0 mm screen at fast speed and sift the material through sieve# 20.
xix. Co-sift Metformin Hydrochloride, Microcrystalline cellulose PH 101, Copovidone and Croscarmellose Sodium through sieve# 20.
Dry Mixing and Granulation:
xx. Load the sifted materials of step-ii in Rapid Mixer granulator and mix for 15 minutes using impeller at slow speed and chopper off.
Drug + Binder Preparation
xxi. Dissolve Dapagliflozin Propanediol Monohydrate in Purified Water + Isopropyl Alcohol (70:30) under stirring and continue stirring until it forms clear solution. Keep the solution aside to clear the foam and add Copovidone to the clear solution under stirring and continue stirring until it forms a clear solution.
xxii. Granulate step-iii dry mix by using step-iv binder solution with the following granulation parameters.
xxiii. Unload the wet mass through co-mill fitted with 6.0 mm screen at fast speed.
Drying
xxiv. Air dry the step-vi wet mass in Fluid Bed Dryer for 5 minutes. Dry the granules at an inlet temperature of 50°C ± 10°C in FBD until the LOD of the granules reaches less than 1.0 % w/w at 60°C (Auto mode) using IR moisture balance.
Sizing, Milling and blending
xxv. Sift the step-vii dried granules through sieve #24 and collect the retains and undersize granules separately.
xxvi. Mill the retentions of step-viii by using co-mill fitted with 2.0 mm screen at fast speed and sift through sieve #24.
xxvii. Mill the retentions of step-ix by using co-mill fitted with 1.0 mm screen at me fast speed and sift through sieve #24.
Sifting of extra-granular material
xxviii. Sift Microcrystalline cellulose PH 102 and Croscarmellose Sodium through sieve #24.
xxix. Sift calcium stearate through sieve #60.
Blending and Lubrication
xxx. Load the granules of step viii, step ix, step x and step xi in blender and blend for 10 minutes at slow speed.
xxxi. Load calcium stearate of step-xii to the step xiii and blend for 5 minutes at slow speed.
Compression
xxxii. Compress the lubricated blend of step-xiv.
Film Coating:
xxxiii. Weigh required quantity of purified water in a stainless steel vessel.
xxxiv. Disperse Opadry II in step xvi (12% w/w solids) under stirring and continue stirring for 45 minutes to form uniform dispersion.
xxxv. Load the core tablets of step-xv in coating pan and pre-warm for 5 minutes at Inlet temperature 45° C and check the pre warmed tablet weights.
Example-3:
S. No. Ingredients Qty. per Unit (mg)
2.5 mg / 1000 mg 5 mg / 500 mg 5 mg / 1000 mg 10 mg / 500 mg 10 mg / 1000 mg
Metformin Hydrochloride Extended Release Layer
Intra granular agents
1. Metformin HCl 1000.00 500.00 1000.00 500.00 1000.00
2. Hydroxypropylmethyl cellulose K100M CR 180.00 180.00 180.00 180.00 180.00
3. Microcrystalline cellulose 23.00 13.50 23.00 13.50 23.00
Binder solution
4. Polyvinyl pyrrolidone K-90 50.00 30.00 50.00 30.00 50.00
5. Iso Propyl Alcohol q.s. q.s. q.s. q.s. q.s.
Extra granular agents
6. Talc 8.00 4.00 8.00 4.00 8.00
7. Calcium Stearate 39.00 22.50 39.00 22.50 39.00
Metformin Hydrochloride ER Tablet weight (mg) 1300.00 750.00 1300.00 750.00 1300.00
Dapagliflozin Immediate Release layer
Intra granular agents
8. Micro Crystalline Cellulose 91.00 91.00 91.00 91.00 91.00
9. Lactose Anhydrous 30.00 30.00 30.00 30.00 30.00
10. Croscarmellose sodium 5.00 5.00 5.00 5.00 5.00
11. Hydroxy Propyl Methyl Cellulose E5 6.00 6.00 6.00 6.00 6.00
Drug solution
12. Dapagliflozin Propanediol Monohydrate 3.075 6.15 6.15 12.30 12.30
13. Purified Water (70) q.s. q.s. q.s. q.s. q.s.
14. Iso Propyl Alcohol (30) q.s. q.s. q.s. q.s. q.s.
Extra granular agents
15. Microcrystalline cellulose 49.825 46.75 46.75 40.60 40.60
16. Croscarmellose sodium 3.00 3.00 3.00 3.00 3.00
17. Colloidal Silicon Dioxide 6.00 6.00 6.00 6.00 6.00
18. Sunset Yellow 0.10 0.10 0.10 0.10 0.10
19. Calcium Stearate 6.00 6.00 6.00 6.00 6.00
Dapagliflozin IR Tablet Weight (mg) 200.00 200.00 200.00 200.00 200.00
Total tablet weight (mg) 1500.00 950.00 1500.00 950.00 1500.00
Film Coating $ (2.5% weight build up)
20. Opadry II Light brown 37.50 -- -- -- --
21. Opadry II Orange -- 23.75 -- -- --
22. Opadry II Dark Pink -- -- 37.50 -- --
23. Opadry II Pink -- -- -- 23.75 --
24. Opadry II Yellow -- -- -- -- 37.50
25. Purified water q.s. q.s. q.s. q.s. q.s.
Coated Tablet Weight (mg) 1537.50 973.75 1537.50 973.75 1537.50

MANUFACTURING PROCESS:
Metformin HCl Layer:
Milling & Sifting:
i. Mill the Metformin Hydrochloride through multi-mill with 2.0 mm screen at fast speed with impact forward and sift the material through sieve # 20 ASTM.
ii. Co-sift Metformin Hydrochloride, Hydroxypropylmethyl cellulose K100M CR and Microcrystalline cellulose through sieve # 20 ASTM and collect in double lined polybag.
iii. Again Co-sift materials of step ii through sieve # 20 ASTM and collect in double lined polybag.
Dry Mixing:
iv. Load the sifted materials of step iii in Rapid Mixer granulator and mix for 15 minutes using impeller at slow speed and chopper off.
Binder Preparation and Granulation:
v. Dissolve Polyvinyl pyrrolidone K-90 in Iso Propyl Alcohol under stirring and continue stirring until it forms clear solution.
vi. Granulate step iv dry mix by using step-v binder solution with the following granulation parameters.
vii. Unload the wet mass through co-mill fitted with 8.0 mm screen at fast speed.
Drying
viii. Load the contents of step vii in FBD and dry the granules initially for 15 minutes at inlet temperature of 25°C ± 5°C and then at inlet temperature of 50°C ± 10°C until the LOD of the granules reaches less than 1.5 % w/w at 105°C (Auto mode) using IR moisture balance.
Sizing, Milling and blending
ix. Sift the step viii dried granules through sieve #20 and collect the retains and undersize granules separately.
x. Mill the retentions (oversized granules) of step ix using co-mill fitted with 2.0 mm screen at medium speed and sift through sieve #20 ASTM.
xi. Mill the retentions of step x by using co-mill fitted with 2.0 mm screen at medium speed and sift through sieve #20 ASTM. Continue this to mill the granules with 2.0 mm screen until all the material passes through sieve #20 ASTM and collect in double lined polybag.
Sifting of extra-granular material
xii. Sift talc through sieve #40 ASTM.
xiii. Sift calcium stearate through sieve #60 ASTM.
Blending and Lubrication
xiv. Load the granules of step ix, x, xi and xii in blender and blend for 10 minutes at slow speed.
xv. Load magnesium stearate of step-xiii to the step xiv and blend for 5 minutes at slow speed and collect in doubled lined polybag.
Dapagliflozin Layer:
Milling & Sifting:
xvi. Co-sift Micro Crystalline Cellulose 101, Lactose Anhydrous, Croscarmellose sodium and Hydroxy Propyl Methyl Cellulose E5 through sieve # 30 ASTM.
Dry mixing
xvii. Load the sifted materials of step xvi in rapid mixer granulator and mix for 15 minutes using impeller at slow speed and chopper off.
Drug Solution Preparation and Granulation:
xviii. Weigh the required quantities of Purified water and Isopropyl alcohol at 70:30 ratio and add in SS container with proper closure under continuous stirring.
xix. Separate 10% quantity from step xviii in to SS container for rinsing purpose.
xx. Dissolve Dapagliflozin Propanediol Monohydrate in remaining 90% quantity of step xviii under stirring and stir until a clear solution is formed.
xxi. Granulate step xvii dry mix with prepared drug solution of step no. xx & rinsing solution of step xix by the following granulation parameters.
Wet milling:
xxii. Unload the wet mass from RMG and mill through co-mill fitted with 8.0 mm screen at slow speed.
Drying
xxiii. Load the contents of step xxii in FBD and dry the granules initially for 15 minutes at inlet temperature of 25°C ± 5°C and then at inlet temperature of 45°C ± 10°C until the LOD of the granules reaches 1.0 – 2.0 % w/w at 60°C (Auto mode) using IR moisture balance.
Sizing and Milling
xxiv. Sift the dried granules of step xxiii through sieve #30 ASTM and collect in double lined polybag.
xxv. Mill the retentions of step xxiv by using co-mill fitted with 1.0 mm screen at slow speed and sift through #30 ASTM and collect in double lined polybag.
xxvi. Mill the retentions of step-xxv by using co-mill fitted with 1.0 mm screen at medium speed and sift through sieve #30 ASTM. Continue this to mill the granules with 1.0 mm screen until all the material passes through sieve #30 ASTM and collect in double lined polybag.
Sifting of extra-granular material
xxvii. Co-Sift microcrystalline cellulose XLM 90, Croscarmellose sodium and Colloidal silicon dioxide through sieve # 30 ASTM.
xxviii. Sift calcium stearate through sieve #60 ASTM.
Blending and Lubrication
xxix. Load the sifted materials of step xxiv, step xxv, step xxvi and step xxvii in to blender and mix for 20 minutes at slow speed.
xxx. Add step xxviii of sifted calcium stearate to step xxix and mix for 5 minutes at slow speed and collect in doubled lined polybag.
Compression
xxxi. Compress the lubricated blend of step xv (Metfomin Layer) and step xxx (Dapagliflozin layer) with the suitable parameters.
Film Coating:
xxxii. Weigh required quantity of purified water in a stainless steel vessel.
xxxiii. Disperse Opadry II in step xxxii (15% w/w solids) under stirring and continue stirring for 45 minutes to form uniform dispersion.
xxxiv. Load the core tablets of step xxxi (Compressed tablets) in coating pan and pre-warm for 5 minutes at product temperature 35° - 45° C and check the pre warmed tablet weights.
,CLAIMS:1. A pharmaceutical composition comprising Dapagliflozin or its pharmaceutically acceptable salts alone or its combination with Metformin or its salts, one or more pharmaceutically acceptable excipients, where in the composition is free of magnesium stearate.

2. The pharmaceutical composition as claimed in claim 1, where in the Intra-granular portion containing Dapagliflozin or its pharmaceutically acceptable salt thereof and one or more pharmaceutical acceptable excipients and an extra-granular portion containing one or more pharmaceutically acceptable excipients.

3. The pharmaceutical composition as claimed in claim 1, where in the Dapagliflozin is incorporated in to granulation fluid.

4. The pharmaceutical composition as claimed in claim 1, where in the Dapagliflozin or its salts is combined with Metformin or its salts, the composition is in the form of tablet or capsule.

5. The pharmaceutical compositions as claimed in claim 1, the lubricant is used in this composition is calcium stearate.

6. The pharmaceutical compositions as claimed in claim 1, where in the Dapagliflozin and Metformin is in the form of crystalline or amorphous.

7. The process for the preparation of the pharmaceutical composition as claimed in claim 1, comprising the steps of shift the ingredients, granulate the sifted materials in rapid mixer granulator, prepare the drug solution with Dapagliflozin, mill the with RMG, perform the drying with FBD, perform the milling shift the extra granular material, lubricate with lubricating material, compress the lubricated blend with suitable parameters and optionally add the Metformin in to formulation process.
8. The pharmaceutical compositions as claimed in claim 1, the Metformin is in the form of immediate release or extended release dosage form.

9. The pharmaceutical compositions as claimed in claim 1, where in the pharmaceutical formulation in the form of Monolithic or bilayer tablet or capsule dosage form.

10. The pharmaceutical compositions as claimed in claim 1, where in the composition is used for the treatment of type-2 diabetes.