DESC:FIELD OF THE INVENTION
This invention relates to pharmaceutical formulation of Vildagliptin, a process for the preparation thereof, to new pharmaceutical formulations, tableting comprising Vildagliptin formulations capable of being directly compressed into tablets. The invention relates further to the new formulations of Vildagliptin and Metformin and a process for the preparation thereof.

BACKGROUND OF THE INVENTION
Diabetes mellitus is a common disorder more prevalent in developed countries. It is characterized by its clinical manifestations, namely the non-insulin-dependent or maturity onset form, also known as type 2 diabetes and the insulin-dependent or juvenile onset form, also known as type 1 diabetes. It is a metabolic disease in which there is a high blood sugar level over a prolonged period. This disorder is associated with high morbidity and mortality. Dipeptidyl-peptidase-IV (DPP-IV) inhibitors are an oral drug class that was introduced in 2006 and that seems easy to use and do not require regular glucose monitoring or dose adjustments. DPP-IV inhibitors act by inhibiting DPP-IV enzyme, a multifunctional transmembrane glycoprotein enzyme that cleaves N-terminal dipeptides from polypeptides with L-proline or L- alanine at the penultimate position. Vildagliptin is an orally active inhibitor of the DPP-IV enzyme. After a meal intake, insulinotropic hormone glucagon- like peptide- 1 (GLP-1) is released which in turn induces insulin release from the pancreas. Some of the GLP-1 is inactivated by the DPP-IV present in plasma and intestinal capillary endothelium. Therefore, if the DPP-IV inhibited, more GLP-1 will be available to activate insulin release from the pancreas. The advantage of this mechanism of insulin release is that insulin is secreted only in response to a meal. Therefore, problems of hypoglycemia associated with other diabetes drugs are less likely with a DPP-IV inhibitor. Vildagliptin alone or in combination with other anti-diabetic agents is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type-2 diabetes mellitus in multiple clinical conditions. Vildagliptin is marketed by Novartis in the Europe in the form of tablets under the trademark GALVUS. The recommended daily dose of Vildagliptin is l00mg, administered as one dose of 50mg in the morning and one dose of 50mg in the evening.
U.S. Patent No. 6,166,063 discloses a DPP-IV inhibitor compound Vildagliptin, its use in treating type-2 diabetes mellitus and its pharmaceutical composition. U.S. Patent No. 6,303,661 discloses methods of using an oral inhibitor of DPP-IV or DPP IV-like enzyme activity to reduce blood glucose levels after food intake. U.S. Patent No. 8,143,217 discloses methods of using Vildagliptin in combination with insulin to treat hypoglycemic events in a patient with diabetes. European Patent Application, EP 1,537,880 Al relates to a sustained release formulation of DPP-IV inhibitor (Vildagliptin) comprising a hydrophilic polymer. European Patent No. EP 2,191,824 Bl discloses sustained release formulation of DPP-IV inhibitor (Vildagliptin) comprising hydroxypropyl methylcellulose. European Patent Application, EP 2,578,208 Al discloses solid dosage formulation obtained with briquette pressing or compression between rollers and characterized in that it comprises DPP-IV inhibitor. European patent application EP 3,023,095 relates to formulation of direct compressed Vildagliptin tablets. PCT Publication No. WO 2014/029841 Al discloses extended release compositions of an amino-C2-C6-alkyl nitrate and fixed dose combinations with Vildagliptin.
Despite recent advances, the formulation of Vildagliptin and Vildagliptin and Metformin, there is a continuing need for new and improved formulation which overcome the drawback of prior art. The instant invention addresses this problem by providing a stable and cheapest formulation of Vildagliptin and Vildagliptin and Metformin.

OBJECTIVE OF THE INVENTION
General aspect of the present invention relates to a pharmaceutical formulation of vildagliptin, comprises pharmaceutically acceptable excipients such as lactose monohydrate, microcrystalline cellulose, sodium starch glycolate, magnesium stearate pregelatinized starch, mannitol, and low substituted hydroxypropyl cellulose.
In another aspect of the present invention relates to a pharmaceutical formulation of vildagliptin in combination with metformin comprising vildagliptin metformin HCl and hydroxypropyl cellulose (Klucel EXF).
In yet another aspect of the present invention relates to a process for the preparation of pharmaceutical formulation comprising Vildagliptin and a combination of vildagliptin and metformin HCl.

DETAILED DESCRIPTION OF THE INVENTION
Present invention provides a pharmaceutical formulation of vildagliptin and its combination with metformin HCl comprising variety of pharmaceutically acceptable excipients.
In a first aspect of the present invention relates to a pharmaceutical formulation of vildagliptin comprising: vildagliptin in amount of 25 %w/w, lactose monohydrate in amount of less than 25 % w/w, microcrystalline cellulose, sodium starch glycolate, magnesium stearate and optionally pregelatinized corn starch an in amount ranging from 1-15 % w/w, mannitol in an amount ranging from 30-70 % w/w and low substituted hydroxypropyl cellulose in amount of 5-15 % w/w.
In an aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of lactose monohydrate is in amount ranging from 1-15% w/w.
In other aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein lactose monohydrate is absent.
In yet other aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of microcrystalline cellulose is more than 50 % w/w.
In another aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of microcrystalline cellulose is less than 40 % w/w.
In another aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of sodium starch glycolate ranges from 0.1-1.0 % w/w.
In yet another aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of sodium starch glycolate ranges from 3-10% w/w, more preferably it ranges from 3.0-5.0% w/w.
In a further aspect, the present invention relates to a pharmaceutical formulation of vildagliptin wherein amount of magnesium stearate is 0.5-3.5 %w/w, preferable amount of magnesium stearate is 0.7 - 3.0 % w/w.
In a preferred aspect of the present invention relates to a pharmaceutical formulation of vildagliptin comprising: vildagliptin in amount of 25 %w/w, lactose monohydrate in amount of less than 25 % w/w, microcrystalline cellulose, sodium starch glycolate, magnesium stearate and optionally pregelatinized corn starch an in amount ranging from 1-10 % w/w, mannitol in an amount ranging from 35-65 % w/w and low substituted hydroxypropyl cellulose in amount of 8-12 % w/w.
Present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25.00 % w/w, lactose monohydrate less than 25 % w/w, microcrystalline cellulose more than 50 % w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.5-3.5 % w/w.
Specifically, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25.00 % w/w, lactose monohydrate in amount of 1-15 % w/w, microcrystalline cellulose in amount of 55-65% w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.7-3.0 % w/w.
In other specific aspect, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25% w/w, pregelatinized corn starch in amount of 1.00-10.00 % w/w, microcrystalline cellulose in amount of 55-65 % w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.7-3.0 % w/w.
In another specific aspect, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 30-70 %w/w, microcrystalline cellulose in amount of 25-35 %w/w, sodium starch glycolate in amount of 3-10 % w/w, and magnesium stearate 0.5-3.5 %w/w.
In another specific aspect, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 35-65 %w/w, microcrystalline cellulose in amount of 25-35 %w/w, sodium starch glycolate in amount of 3-5 % w/w, and magnesium stearate 0.7-3.0 %w/w.
In yet another specific aspect, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 30-70 %w/w, low substituted hydroxypropyl cellulose in amount of 5-15 %w/w and magnesium stearate in amount of 0.5-3.5 % w/w.
In yet another specific aspect, the present invention relates to a pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 35-65 %w/w, low substituted hydroxypropyl cellulose in amount of 8-12 %w/w and magnesium stearate in amount of 0.7-3.0 % w/w.
In another general aspect, the invention relates also to process for the preparation of pharmaceutical formulation of vildagliptin. Specifically, the invention relates to process for the preparation of pharmaceutical formulation of vildagliptin as described in Example 1-4.
In an another aspect, the present invention provides a pharmaceutical formulation of vildagliptin in combination with metformin comprising vildagliptin in amount of 4.22 %w/w, metformin HCl in amount of 84.41 %w/w, and hydroxypropyl cellulose (Klucel EXF) in amount of 7-9%w/w.
In a yet another aspect, the invention also relates to process for the preparation of pharmaceutical formulation of vildagliptin in combination with metformin as disclosed in Example-5.
The presently described technology and its advantages will be better understood by reference to the following examples. These examples are provided to describe specific embodiments of the present technology. By providing these specific examples, it is not intended limit the scope and spirit of the present technology. It will be understood by those skilled in the art that the full scope of the presently described technology encompasses the subject matter defined by the claims appending this specification, and any alterations, modifications, or equivalents of those claims.

EXAMPLES
Example 1: Composition of Vildagliptin
Sr. No. Name of Ingredient Qty. / Tab (mg) Qty.
(% w/w)
1. Vildagliptin 50.00 25.00
2. Lactose Monohydrate, Granular 30.00 15.00
3. Microcrystalline Cellulose
PH 112 117.50 58.75
4. Sodium Starch Glycolate
Type-A 1.00 0.50
5. Magnesium Stearate (Veg Origin) 1.50 0.75
Total weight /tablet or batch 200.00 100.00

Brief manufacturing Process for Composition as disclosed in Example -1
Sifting
Step1 Sifted Vildagliptin through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Sift lactose monohydrate, microcrystalline cellulose and sodium starch glycolate Type-A was passed through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Step3 Sifted magnesium stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending Loaded the sifted Vildagliptin of Step1 and the sifted materials of Step 2 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution of Vildagliptin.
Lubrication Added sifted Magnesium Stearate of Step3 to the Blend and mixed for sufficient time to get lubricated blend.
Compression Compressed the lubricated blend on a rotary tablet press using prescribed punches and dies.
Packing Packing of tablets done in Alu-Alu Blister /PVC –Aclar – Aluminium Blister/ PVC-PVDC-Aluminium Blister/PVC –Aluminium Blister/ Aluminium Strip / Bottle of suitable size and shape with appropriate Cap / Bottle of suitable size and shape with appropriate Cap with Desiccant and/ or filler (Cotton/ Rayon/Polyester) as per the packing configuration.

Product Specification of Composition as disclosed in Example -1
Parameters Specifications
Appearance
White to off white, round, flat, bevel edged, uncoated tablet, debossed with EMV/ any other letters/symbol on one side and plain/ break line on the other side.
Identification The retention time of major peak of the sample solution corresponds to that of the standard solution.
Average weight of tablet 175mg to 225mg ? 5%
Hardness 20 N to 100 N
Friability NMT 1.0 % w/w
Disintegration time NMT 15 minutes at 37 °C ? 0.5 °C in water
Assay 90.0 to 110.0 % of label claim.
Dissolution Not less than 75% (Q) of the labelled amount of Vildagliptin is dissolved in 30 minutes.
Related Substances
Maximum Individual Impurity NMT 0.2% to 1.0 %
Total Impurities NMT 0.5% to 5.0 %

Example 1a: Composition of Vildagliptin
Sr. No. Name of Ingredient Qty. / Tab (mg) Qty.
(% w/w)
1 Vildagliptin 50.00 25.00
2 Lactose Monohydrate, Granular 50.00 25.00
3 Microcrystalline Cellulose 94.50 47.25
4 Sodium starch Glycolate 4.00 2.00
5 Magnesium Stearate 1.50 0.75
Total weight /tablet or batch 200.00 100.00

Brief manufacturing Process for Composition as disclosed in Example -1a
Sifting
Step1 Sifted Vildagliptin through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Sifted lactose monohydrate, microcrystalline cellulose and sodium starch glycolate Type-A was passed through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Step3 Sifted Magnesium Stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending The sifted Vildagliptin of Step1 was loaded along with the sifted materials of Step 2 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution of Vildagliptin.
Lubrication Added the sifted Magnesium Stearate of Step3 to the Blend and mixed for sufficient time to get lubricated blend.
Compression Compressed the lubricated blend on a rotary tablet press using prescribed punches and dies.
Packing Packing of tablets was done in Alu-Alu Blister /PVC –Aclar – Aluminium Blister/ PVC-PVDC-Aluminium Blister/PVC –Aluminium Blister/ Aluminium Strip / Bottle of suitable size and shape with appropriate Cap / Bottle of suitable size and shape with appropriate Cap with Desiccant and/ or filler (Cotton/ Rayon/Polyester) as per the packing configuration.

Product Specification of Composition as disclosed in Example -1a
Parameters Specifications
Appearance
White to off white, round, flat, bevel edged, uncoated tablet, debossed with EMV/ any other letters/symbol on one side and plain/ break line on the other side.
Identification The retention time of major peak of the sample solution corresponds to that of the standard solution.
Average weight of tablet 200mg ? 5%
Hardness 40 N to 100 N
Friability NMT 1.0 % w/w
Disintegration time NMT 15 minutes at 37 °C ? 2.0 °C in water
Assay 90.0 to 110.0 % of label claim.
Related Substances
Maximum Individual Impurity NMT 0.5 %
Total Impurities NMT 2.0 %
Example 2: Composition of Vildagliptin
Sr. No. Name of Ingredient Qty. / Tab (mg) Qty.
(% w/w)
1. Vildagliptin 50.00 25.00
2. Pregelatinized, Corn Starch 20.00 10.00
3. Microcrystalline Cellulose PH 112 127.5 63.75
4. Sodium Starch Glycolate Type-A 1.00 0.50
5. Magnesium Stearate (Veg Origin) 1.50 0.75
Total weight /tablet or batch 200.00 100.00

Brief manufacturing Process for Composition as disclosed in Example -2
Sifting
Step1 Sifted Vildagliptin through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Pregelatinized Corn Starch, microcrystalline cellulose and sodium starch glycolate Type-A was passed through S. S. sieve of suitable mesh on a vibratory sifter and collect separately.
Step3 Sifted Magnesium Stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending Loaded the sifted Vildagliptin of Step1 and the sifted materials of Step 2 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution of Vildagliptin.
Lubrication Added the sifted Magnesium Stearate of Step3 to the Blend and mixed for sufficient time to get lubricated blend.
Compression Compressed the lubricated blend on a rotary tablet press using prescribed punches and dies.
Packing Packing of tablets was done in Alu-Alu Blister /PVC –Aclar – Aluminium Blister/ PVC-PVDC-Aluminium Blister/PVC –Aluminium Blister/ Aluminium Strip / Bottle of suitable size and shape with appropriate Cap / Bottle of suitable size and shape with appropriate Cap with Desiccant and/ or filler (Cotton/ Rayon/Polyester) as per the packing configuration.

Product Specification of Composition as disclosed in Example -2
Parameters Specifications
Appearance
White to off white, round, flat, bevel edged, uncoated tablet, debossed with EMV/ any other letters/symbol on one side and plain/ break line on the other side.
Identification The retention time of major peak of the sample solution corresponds to that of the standard solution.
Average weight of tablet 175mg to 225mg ? 5%
Hardness 20 N to 100 N
Friability NMT 1.0 % w/w
Disintegration time NMT 15 minutes at 37 °C ? 0.5 °C in water
Assay 90.0 to 110.0 % of label claim.
Dissolution Not less than 75% (Q) of the labelled amount of Vildagliptin is dissolved in 30 minutes.
Related Substances
Maximum Individual Impurity NMT 0.2% to 1.0 %
Total Impurities NMT 0.5% to 5.0 %

Example 3: Composition of Vildagliptin
Sr. No. Name of Ingredient Qty. / Tab (mg) Qty.
(% w/w)
1. Vildagliptin 50.00 25.00
2. Mannitol, Spray Dried 79.00 39.50
3. Microcrystalline Cellulose PH 112 60.00 30.00
4. Sodium Starch Glycolate Type-A 6.00 3.0
5. Magnesium Stearate
(Veg Origin) 5.0 2.50

Total weight /tablet or batch 200 100

Brief manufacturing Process for Composition as disclosed in Example -3
Sifting
Step1 Sifted Vildagliptin through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Spray dried mannitol, microcrystalline cellulose and sodium starch glycolate Type-A through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Step3 Sifted Magnesium Stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending Loaded the sifted Vildagliptin of Step1 and the sifted materials of Step 2 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution of Vildagliptin.
Lubrication Added the sifted Magnesium Stearate of Step3 to the Blend and mixed for sufficient time to get lubricated blend.
Compression Compressed the lubricated blend on a rotary tablet press using prescribed punches and dies.
Packing Packing of tablets was done in Alu-Alu Blister /PVC –Aclar – Aluminium Blister/ PVC-PVDC-Aluminium Blister/PVC –Aluminium Blister/ Aluminium Strip / Bottle of suitable size and shape with appropriate Cap / Bottle of suitable size and shape with appropriate Cap with Desiccant and/ or filler (Cotton/ Rayon/Polyester) as per the packing configuration.
Product Specification of Composition as disclosed in Example -3
Parameters Specifications
Appearance
White to off white, round, flat, bevel edged, uncoated tablet, debossed with EMV/ any other letters/symbol on one side and plain/ break line on the other side.
Identification The retention time of major peak of the sample solution corresponds to that of the standard solution.
Average weight of tablet 175mg to 225mg ? 5%
Hardness 20 N to 100 N
Friability NMT 1.0 % w/w
Disintegration time NMT 15 minutes at 37 °C ? 0.5 °C in water
Assay 90.0 to 110.0 % of label claim.
Dissolution Not less than 75% (Q) of the labelled amount of Vildagliptin is dissolved in 30 minutes.
Related Substances
Maximum Individual Impurity NMT 0.2% to 1.0 %
Total Impurities NMT 0.5% to 5.0 %

Example 4: Composition of Vildagliptin
Sr. No. Name of Ingredient Qty. / Tab (mg) Qty.
(% w/w)
1. Vildagliptin 50.00 25.00
2. Mannitol, Spray Dried 125.00 62.50
3. Low Substituted Hydroxypropyl Cellulose 20.00 10.00
4. Magnesium Stearate
(Veg Origin) 5.0 2.50
Total weight /tablet or batch 200.00 100.00

Brief manufacturing Process for Composition as disclosed in Example -4
Sifting
Step1 Sifted Vildagliptin through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Spray dried mannitol and Low Substituted Hydroxypropyl Cellulose through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Step3 Sifted Magnesium Stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending Loaded sifted Vildagliptin of Step1 and the sifted materials of Step 2 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution of Vildagliptin.
Lubrication Added the sifted Magnesium Stearate of Step3 to the Blend and mixed for sufficient time to get lubricated blend.
Compression Compressed lubricated blend on a rotary tablet press using prescribed punches and dies.
Packing Packing of tablets was done in Alu-Alu Blister /PVC –Aclar – Aluminium Blister/ PVC-PVDC-Aluminium Blister/PVC –Aluminium Blister/ Aluminium Strip / Bottle of suitable size and shape with appropriate Cap / Bottle of suitable size and shape with appropriate Cap with Desiccant and/ or filler (Cotton/ Rayon/Polyester) as per the packing configuration.

Product Specification of Composition as disclosed in Example -4
Parameters Specifications
Appearance
White to off white, round, flat, bevel edged, uncoated tablet, debossed with EMV/ any other letters/symbol on one side and plain/ break line on the other side.
Identification The retention time of major peak of the sample solution corresponds to that of the standard solution.
Average weight of tablet 175mg to 225mg ? 5%
Hardness 20 N to 100 N
Friability NMT 1.0 % w/w
Disintegration time NMT 15 minutes at 37 °C ? 0.5 °C in water
Assay 90.0 to 110.0 % of label claim.
Dissolution Not less than 75% (Q) of the labelled amount of Vildagliptin is dissolved in 30 minutes.
Related Substances
Maximum Individual Impurity NMT 0.2% to 1.0 %
Total Impurities NMT 0.5% to 5.0 %

Example 5: Composition of Vildagliptin and Metformin Hydrochloride
Name of Ingredient Unit dose (mg / Tablet) Quantity (%W/W)*
Strength 50/500 50/850 50/1000 50/500 50/850 50/1000
Vildagliptin 50.00 50.00 50.00 8.09 4.93 4.22
Metformin HCl 500.00 850.00 1000.00 80.89 83.76 84.41
Hydroxypropyl cellulose (Klucel EXF) 50.00 85.00 100.00 8.09 8.38 8.44
Magnesium Stearate 6.00 9.85 11.50 0.97 0.97 0.97
Weight of Core tablet 606.00 994.85 1161.50 98.04 98.04 98.04
Opadry 05F32897 Yellow$ 12.12 19.90 23.23 1.96 1.96 1.96
Weight of Film-coated tablet 618.12 1013.75 1184.73 100.00 100.00 100.00
* Calculated considering average weight of Film-Coated Tablet
$ Opadry 05F32897 Yellow consists of Hypromellose, Polyethylene Glycol, Titanium Dioxide and Ferric Oxide Yellow.
Brief manufacturing Process of Vildagliptin and Metformin Hydrochloride composition as disclosed in Example 5
Sifting
Step1 Sifted Metformin HCl through S. S. sieve of suitable mesh on a vibratory sifter and collected in suitable container.
Step2 Sifted Hydroxypropyl Cellulose through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Wet Granulation
Step3 Loaded the sifted Metformin HCl (Step1) and Sifted Hydroxypropyl Cellulose (Step2) in a High Shear Mixer Granulator and mixed to get a homogenous powder mix.
Step4 Added adequate quantity of purified water to the powder mix of Step 3 to get wet mass of properly wet substance with required particle size. The High Shear Mixer Granulator was operated at appropriate impeller and chopper speed.
Step5 The wet granules were dried in a Fluid Bed Drier or any suitable drier to get dried granular mass with LOD less than 5%.
Step 6 Size reduction of dried granules of Step5 was done by milling or by other suitable means known in the art.
Sifting
Step7 Vildagliptin was sifted through S. S. sieve of suitable mesh on a vibratory sifter and collect separately.
Step8 Sifted Magnesium Stearate through S. S. sieve of suitable mesh on a vibratory sifter and collected separately.
Blending
Step9 Loaded the sized granules of Step 6 and sifted Vildagliptin of Step 7 in a blender of suitable capacity, mixed to get a powder blend with uniform distribution on Vildagliptin and Metformin HCl.
Lubrication
Step10 Added the sifted Magnesium Stearate of Step8 to the blend of Step 9 and mixed for sufficient time to get lubricated blend.
Compression
Step11 Compressed the lubricated blend on a rotary tablet press using prescribed punches and dies as per the core tablet specification.
Film-Coating
Step 12 Film-coating of Core Tablets of Step11 was done in a coating machine with Opadry 05F32897 Yellow dispersion in suitable liquid media.
Packing
Step13 Blister Packing/ Bottle Packing of tablets was done as per packing configuration.

Product Specification of Vildagliptin and Metformin Hydrochloride composition
FINISHED PRODUCT SPECIFICATION
Parameters Specifications
Strength of Tablets 50mg/500mg 50mg/850mg 50mg/1000mg
Appearance
Light yellow to yellow, oval, biconvex, film-coated tablet, plain / logo /letter on both sides. Light yellow to yellow, oval, biconvex, film-coated tablets, plain / logo /letter on both sides. Light yellow to yellow, capsule shape, biconvex film-coated tablet, plain / logo /letter on both sides.
Avg. wt. of tablet 618.12 mg ? 3% 1013.75 mg ? 3% 1184.73 mg ? 3%
Tablet thickness 5.8 mm ? 0.3 mm 7.5 mm ? 0.3 mm 6.9 mm ? 0.3 mm
Uniformity of Dosage Unit (by assay content of Vildagliptin and Metformin HCl)
AV = 15.0 at L1 or 25.0 at L2
Disintegration time NMT 30 minutes at 37 °C ? 0.5 °C in Water.
Assay 90.0 to 110.0 % of label claim of Vildagliptin and Metformin HCl.
Dissolution NLT 75 %(Q) in 45 Minutes of Labelled amount of Vildagliptin and Metformin HCl
Related Substances for Vildagliptin Single Max Impurity : NMT 1.0 %
Total Impurities :NMT 2.0 %
Related Substances for Metformin HCl 1-cynogunidine: NMT 0.02 %
Single Max Impurity: NMT 0.1 %
Total Impurities :NMT 0.5 %

Stability data:
Disintegration time (in minutes):
Disintegration time of the prepared examples were checked at 37.0o ± 2.0o C in water.
Example Initial 1 month 2 month 3 month
1 01:26 01:08 01:11 01:15
1a < 1 <1 <1 <1
2 01:29 <1 01:11 01:10

,CLAIMS:We claim:
1. A pharmaceutical formulation of vildagliptin comprising: vildagliptin in amount of 25 %w/w, lactose monohydrate in amount of less than 25 % w/w and further comprising of excipients selected from microcrystalline cellulose, sodium starch glycolate and magnesium stearate and which optionally further contains excipients selected from pregelatinized corn starch , mannitol and low substituted hydroxypropyl cellulose.
2. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of lactose monohydrate is in amount ranging from 1-15% w/w.
3. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of microcrystalline cellulose is more than 50 % w/w, preferably 55-75% w/w.
4. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of microcrystalline cellulose is less than 40 % w/w, preferably 25-55%.
5. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of sodium starch glycolate ranges from 0.1-1.0 % w/w.
6. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of sodium starch glycolate ranges from 3-10% w/w, more preferably it ranges from 3.0-5.0% w/w.
7. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of magnesium stearate is 0.5-3.5 %w/w, preferable amount of magnesium stearate is 0.7 - 3.0 % w/w.
8. A pharmaceutical formulation of vildagliptin as claimed in claim 1 wherein amount of pregelatinized corn starch ranges from 1-15 % w/w, mannitol in an amount ranging from 30-70 % w/w and low substituted hydroxypropyl cellulose in amount of 5-15 % w/w.
9. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25.00 % w/w, lactose monohydrate in amount of 1-15 % w/w, microcrystalline cellulose in amount of 55-65% w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.7-3.0 % w/w.
10. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25% w/w, pregelatinized corn starch in amount of 1.00-10.00 % w/w, microcrystalline cellulose in amount of 55-65 % w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.7-3.0 % w/w.
11. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 30-70 %w/w, microcrystalline cellulose in amount of 25-35 %w/w, sodium starch glycolate in amount of 3-10 % w/w, and magnesium stearate 0.5-3.5 %w/w.
12. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 35-65 %w/w, microcrystalline cellulose in amount of 25-35 %w/w, sodium starch glycolate in amount of 3-5 % w/w, and magnesium stearate 0.7-3.0 %w/w.
13. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 30-70 %w/w, low substituted hydroxypropyl cellulose in amount of 5-15 %w/w and magnesium stearate in amount of 0.5-3.5 % w/w.
14. A pharmaceutical formulation of vildagliptin as claimed in claim 1 comprising vildagliptin in amount of 25 %w/w, mannitol in amount of 35-65 %w/w, low substituted hydroxypropyl cellulose in amount of 8-12 %w/w and magnesium stearate in amount of 0.7-3.0 % w/w.
15. A process for the preparation of pharmaceutical formulation of vildagliptin as claimed in claim 1 as described in examples 1-4.
16. A pharmaceutical formulation of vildagliptin as claimed in claim 1 in combination with metformin comprising vildagliptin in amount of 4.22 %w/w, metformin HCl in amount of 84.41 %w/w, and hydroxypropyl cellulose (Klucel EXF) in amount of 7-9%w/w.
17. A process for the preparation of pharmaceutical formulation of vildagliptin as claimed in claim 1 in combination with metformin as disclosed in Example-5.
18. A pharmaceutical formulation of vildagliptin comprising vildagliptin in amount of 25% w/w, pregelatinized corn starch in amount of 1.00-10.00 % w/w, microcrystalline cellulose in amount of 55-65 % w/w, sodium starch glycolate in amount of 0.1-1.0 % w/w, magnesium stearate in amount of 0.7-3.0 % w/w.

Dated this 25th day of October 2019

ASHISH KUMAR SHARMA
[IN/PA-858]
of SUBRAMANIAM & ASSOCIATES
Attorney for the applicants