FORM 2
THE PATENTS ACT, 1970
(39 of 1970)
&
THE PATENTS RULES, 2003
COMPLETE SPECIFICATION
(See section 10 and rule 13]

1. Title of the invention: "VILDAGLIPTIN MODIFIED RELEASE
TABLETS" -
2. Macleods Pharmaceuticals Ltd., an Indian Company, having its
Registered Office at 304 - Atlanta Arcade, Opp. Leela Hotel, Marol
Church Road, Andheri (East), Mumbai - 400 059, Maharashtra, India.
3. The following specification describes the invention.


FIELD OF THE INVENTION
The present invention relates to a sustained release pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof with one or more hydrophobic excipients as release retarding material.
BACKGROUND OF THE INVENTION
Vildagliptin is dipeptidyl peptidase IV inhibitor (DPP-IV) useful for preventing or treating diabetes mellitus, non-insulin-dependent diabetes mellitus, obesity, arthritis, osteoporosis, and other diseases. It is typically administered twice daily as a 50 mg immediate release tablet dosage form.
Once-daily administration of Vildagliptin has advantages over twice-daily administration for both patient obedience and reduction of adverse events. Patient adherence to a drug regimen indirectly correlates with frequency of dosing i.e. greater adherence is seen with a once daily dosing regimen compared to a twice daily dosing regimen. There is a need to provide a once a daily formulation of vildagliptin which will provide ease, convenience and reduced side effects profile. Major data available for vildagliptin is derived from the studies based on the immediate release formulation of Vildagliptin. Replacing the 50 mg twice daily dose with a once daily modified release tablet will provide convenience and also improve the medication compliance by reducing the pill burden of the patients.
U.S. Patent application US2011086096A1 discloses once a day sustained release . formulations containing Vildagliptin with matrix formulation containing a pharmaceutically acceptable hydrophilic polymer which can retard diffusion of Vildagliptin. Vildagliptin is sensitive to moisture, which impacts product stability during development. Hydrolysis is the main degradation pathway for Vildagliptin. The stability of Vildagliptin is known to be affected by initial moisture content of the tablet, excipients with high intrinsic moisture and the amount of excipients

present in the tablet. Considering the water-sensitivity of Vildagliptin, most of the development was planned to focus on techniques that would not require the use of water, such as direct compression.
WO 2017/115252 Al discloses an oral osmotic pharmaceutical composition of Vildagliptin.
US8853385 discloses method for increasing plasma active GLP-1 levels using combination of DPP-IV inhibitor and SGLT-2 inhibitors.
U.S. Patent Application No. 2011/0046076 discloses combination of SGLT2 inhibitor and DPP-IV inhibitor broadly.
Prior art or patent application employs water swellable cellulosic polymers as matrix material to control the release of Vildagliptin. However, such polymers inherently contain moisture which causes Vildagliptin to degrade and result in rise in related substances. In the present invention, hydrophobic excipients are employed as release retarding materials, which do not contain moisture and thus enable production of a stable once daily tablet dosage form of Vildagliptin.
Moisture-sensitive therapeutic compounds may be difficult to formulate into pharmaeeutically acceptable oral compositions because of their chemical instability. This chemical instability may particularly manifest when the moisture sensitive therapeutic compound is used in a dosage form containing excipients with high equilibrium moisture content. Moisture can migrate from such excipients and cause the moisture-sensitive therapeutic compound to undergo hydrolytic degradation. Simultaneously, care has to be taken at the time of packaging.
Therefore, there is an existing and continual need for stable sustained release pharmaceutical composition of Vildagliptin with excipients which do not contain

moisture and thus enables production of a stable once daily formulation and also there is a need to obtain a tablet dosage form having desired physicochemical stability and a dissolution profile that enables once daily dosing of Vildagliptin.
SUMMARY OF THE INVENTION
The present invention relates to a sustained release pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof with one or more hydrophobic excipients as release retarding material, wherein hydrophobic excipients are selected from fatty acids, fatty alcohols and their esters or salts or mixture thereof. The invention further relates to sustained release pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof with one or more additional antidiabetic agent and one or more hydrophobic excipients as release retarding materials.
DETAILED DESCRIPTION OFTHE INVENTION:
The present invention relates to a stable pharmaceutical modified release composition(s) comprising dipeptidyl peptidase IV inhibitor (DPP IV) or its pharmaceutically acceptable derivative. The present invention relates to a sustained release pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof with one or more hydrophobic excipients as release retarding material, wherein hydrophobic excipients are selected from fatty acids, fatty alcohols and their esters or salts or mixture thereof.
The invention further relates to sustained release pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof with one or more additional antidiabetic agent and one or more hydrophobic excipients as release retarding materials.

In one aspect of the present invention, solid oral pharmaceutical compositions of Vildagliptin can be formulated by using hydrophobic excipients (e.g. fatty acids, fatty alcohols and their esters or salts) as release retarding materials. Examples of such release retarding materials include but not limited to low melting fats and waxes such as cetyl alcohol, stearyl alcohol, cetostearyl alcohol, stearic acid, beeswax, carnauba wax, hydroxy stearic acid, glyceryl monostearate, glyceryl behenate, hydrogenated vegetable oil, hydrogenated castor oil, or their derivatives.
In one embodiment the hydrophobic excipients are used as matrix forming release retarding material in intragranular part to formulate a stable sustained release composition for once daily use.
In another embodiment the hydrophobic excipients are used as a binder to formulate a stable sustained release composition for once daily use.
In another aspect of the present invention, solid oral pharmaceutical compositions of vildagliptin can be formulated in different oral dosage forms such as, but not limited to powders, granules, pellets, tablets (single layered tablets, multi layered tablets, mini tablets, bioadhesive tablets, caplets, matrix tablets, tablet within a tablet mucoadhesive tablets, immediate release tablets, sustained release tablet extended release tablet, modified release tablets, pulsatile release tablets, and timed release tablets), beads, granules, sustained release formulations, capsules, microcapsules, tablets in capsules, microspheres, matrix formulations, microencapsulation, or capsules.
In another aspect the composition of the present invention can be uncoated or coated form.
In another aspect, pharmaceutical composition of present inventions can be used for the treatment or prevention of diabetes.

In one embodiment a solid oral pharmaceutical composition is in the form of tablet comprising Vildagliptin and one or more pharmaceutically acceptable excipient(s) prepared by wet granulation method.
In another embodiment a solid oral pharmaceutical composition is in the form of tablet comprising Vildagliptin and one or more pharmaceutically acceptable excipient(s) prepared by dry granulation method.
In yet another embodiment a solid oral pharmaceutical composition is in the form of tablet comprising Vildagliptin and one or more pharmaceutically acceptable excipient(s) prepared by direct compression method.
In one embodiment a solid oral pharmaceutical composition is in the form of tablet comprising Vildagliptin and one or more pharmaceutically acceptable excipient(s) prepared by melt granulation method.
In another aspect, the present invention further provides pharmaceutical composition comprising Vildagliptin in combination therapy with one or more other active ingredients in a single pharmaceutical composition or separate pharmaceutical composition.
In one embodiment, the combination of Vildagliptin and one or more other active ingredients are in monolayer, bilayer or multilayer wherein one or more active ingredients are in same or separate layer. In another embodiment, one active layer can be coated over another active layer.
In yet another aspect, the one or more active ingredients which are optionally employed in combination therapy may include, but are not limited to other types of antidiabetic agents and/or other types of therapeutic agents.

The other type of antidiabetic agents which are optionally employed in combination may include, but are not limited to one or more antidiabetic agents or anti hyperglycemic agents including insulin secretagogues or insulin sensitizers, or other antidiabetic agents preferably having a mechanism of action different from DPP-4 inhibitors and may include biguanides, sulfonyl ureas, glucosidase inhibitors, sodium-glucose transporter modulators (SGLT2 inhibition), PPAR agonists such as thiazolidinediones, aP2 inhibitors, PPAR . dual agonists, glinides, glitazones and/or megl itinides, as well as insulin, glucagon-like peptide-1 (GLP-1 ), glycogen phosphorylase inhibitors and/or glucos- 6-phosphatase inhibitors.
The other types of therapeutic agents which are optionally employed in combination may include, but are not limited to anti-obesity agents, antihypertensive agents, anti platelet agents, anti atherosclerotic agents and/or lipid lowering agents.
The term pharmaceutically acceptable excipient(s) used in the pharmaceutical compositions of invention comprise but are not limited to release retarding materials, diluents, binders, disintegrants, glidants, lubricants, stabilizers, surfactants, solubility enhancers, coloring agents, flavouring agents, sweetening agents, coating agents.
The amount of excipient(s) employed will depend upon how much active agent is to be used. One excipient(s) can perform more than one function.
Suitable release retarding materials as used in the present invention comprises but are not limited to Hydrophobic materials and Hydrophilic materials. Hydrophobic materials comprises but are not limited to low melting fats and waxes such as cetyl alcohol, stearyl alcohol, cetostearyl alcohol, stearic acid, beeswax, carnauba wax, hydroxy stearic acid, glyceryl monostearate, glyceryl behenate, hydrogenated vegetable oil, hydrogenated castor oil, or their derivatives. Hydrophilic materials having hydrocarbon backbones, and combinations

comprises but are not limited to celluloses such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose ( HPMC), ethyl cellulose, sodium carboxy methyl cellulose.
Suitable diluents as used in the present invention comprises but are not limited to lactose, microcrystalline cellulose, starch, calcium phosphate, dextrin, dextrose, dextrates, mannitol, sorbitol, sucrose, and the like. Preferably, the diluents are lactose, starch and microcrystalline cellulose.
Suitable binders as used in the present invention comprises but are not limited to starches such as potato starch, wheat starch, corn starch; microcrystalline cellulose such as products known under the registered trademarks Avicel, Filtrak, Heweten or Pharmacel; celluloses such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose ( HPMC), ethyl cellulose, sodium carboxy methyl cellulose; natural gums like acacia, alginic acid, guar gum; liquid glucose, dextrin, povidone, syrup, polyethylene oxide, polyvinyl pyrrolidone, poly-N-vinyl amide, polyethylene glycol, gelatin, poly propylene glycol, tragacanth, combinations thereof and other materials known to one of ordinary skill in the art and mixtures thereof. Hydrophobic materials for use as binder comprises but are not limited to low melting fats and waxes such as cetyl alcohol, stearyl alcohol, cetostearyl alcohol, stearic acid, beeswax, carnauba wax, hydroxy stearic acid, glyceryl monostearate, glyceryl behenate, hydrogenated vegetable oil, hydrogenated castor oil or their derivatives.
Suitable disintegrants as used in the present invention comprises but are not limited to, alginic acid, calcium phosphate, tribasic, carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, colloidal silicon dioxide, croscarmellose sodium, crospovidone, docusate sodium, guar gum, low substituted hydroxypropyl cellulose, magnesium aluminum silicate, methyl cellulose, microcrystalline cellulose, povidone, sodium alginate, sodium starch

glycolate, polacrilin potassium, silicified microcrystalline cellulose, starch or pre-gelatinized starch or mixtures thereof.
Suitable lubricants as used in the invention comprises but not limited to magnesium stearate, calcium stearate, glycerine monostearate, glyceryl behenate, glyceryl palmitostearate, hydrogenated castor oil, hydrogenated vegetable oil type I, magnesium lauryl sulphate, medium-chain triglycerides, poloxamer, polyethylene glycol, sodium benzoate, sodium chloride, sodium lauryl sul phate, sodium stearyl fumarate, stearic acid, talc, sucrose stearate and zinc stearate. Suitable Glidants as used in the invention comprises but are not limited to, silicon dioxide; magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate, calcium silicate, magnesium silicate, colloidal silicon dioxide, silicon hydrogel and other materials known to one of ordinary skill in the art
Suitable stabilizers as used in the invention comprises but are not limited to, sodium bicarbonate, ammonium carbonate, anhydrous sodium carbonate, sodium carbonate monohydrate, sodium tartrate, sodium potassium tartrate, sodium citrate, sodium hydroxide, calcium acetate, sodium acetate, dibasic sodium phosphate, anhydrous dibasic sodium phosphate, diammonium hydrogen phosphate, calcium levulinate, sodium pyrophosphate, and mixtures thereof.
Suitable surfactants as used in the invention comprises but are not limited to, 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 called as poloxamers or poloxamines, polyvinyl alcohol, fatty alcohols, polyoxyethylene alkyl ether, polyoxyethylene alkylaryl ether, polyethylene glycol fatty acid ester, alkylene glycol fatty acid mono ester, sucrose fatty acid ester, sorbitan fatty acid mono ester, sorbitol monolaurate, polyoxyethylene sorbitan fatty acid ester (polysorbates), and mixtures thereof.

Suitable solubility enhancers as used in the invention comprises but are not limited to, dimethyl isosorbide, polyethylene glycol, propylene glycol, glycerol, sorbitol sodium lauryl sulfate, glycerol monostearate, glycerol behenate, triglycerides, mono- alcohols, higher alcohols, dimethyl sulfoxide, dimethylformamide, N, [N-dimethyl acetamide, N-methyl-2-pyrrolidone, N-(2-hydroxyethyl) pyrrolidone, 2- pyrrolidone, and mixtures thereof.
Suitable sweetening agents as used in the invention comprises but are not limited to, gluconate, aspartame, cyclamate, sodium saccharine, xylitol and maltitol, or mixtures thereof. Suitable flavoring agents, coloring agents are selected from any FDA approved flavors, colorants for oral use.
The pharmaceutical compositions disclosed herein can further comprise antioxidants and chelating agents. For example, the pharmaceutical compositions can comprise butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), propyl gallate ( PG), sodium metabi sulfite, ascorbyl palmitate, potassium metabi sulfite, disodium EDTA (ethylenediamine tetra acetic acid; also known as disodium edetate), EDTA, tartaric acid, citric acid, citric acid monohydrate, and sodium sulfite.
Suitable Coating agents as used in the invention comprises but are not limited to, cellulose derivatives, e.g., methyl cellulose, hydroxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl ethylcellulose, hydroxypropyl methylcellulose, sodium carboxymethyl cellulose, and ethyl cellulose; vinyl polymers, e.g., polyvinylpyrrolidones; acrylic polymers; and mixtures thereof. In certain preferred embodiments, the acrylic polymers comprises but not limited to, including acrylic acid and methacrylic acid copolymers, methyl methacrylate copolymers, ethoxyethyl methacrylates, cynaoethyl methacrylate, aminoalkyl methacrylate copolymer, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), poly(methacrylic acid anhydride), methyl methacrylate,

polymethacrylate, poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, and glycidyl methacrylate copolymers. In certain preferred embodiments, the acrylic polymer comprises one or more ammonio methacrylate copolymers. Ammonio methacrylate copolymers are well-known in the art.
The coating additives comprise one or more of plasticizers, glidants or flow regulators, lubricants, coloring agents, and opacifiers. Suitable plasticizers are selected from castor oil, diacetylated monoglycerides, dibutyl sebacate, diethyl phthalate, glycerin, polyethylene glycols, propylene glycols, triacetin, triethyl citrate, and mixtures thereof. An opacifier such as titanium dioxide may also be present in the coating.
Suitable solvents as used in the invention for preparing the coating solution comprises but are not limited to water, methyl alcohol, ethyl alcohol, isopropyl alcohol, dichloromethane, n-butyl alcohol, acetone, acetonitrile, chloroform, methylene chloride, and mixtures thereof.
All these excipient(s) can be used at levels well known to the persons skilled in the art.
The following examples are provided to describe the invention in further detail. These examples, which set forth the best mode presently contemplated for carrying out the invention, are intended to illustrate and not to limit the invention.
WORKING EXAMPLES
A. Vildagliptin Once daily formulations
Example 1: Vildagliptin Extended Release Tablets

S.No. Ingredients with mg / tablet
1. Vildagliptin 100.00
2. Lactose Anhydrous 73.60
3. Glyceryl Dibehenate 59.20
4. Cetyl Alcohol 59.20
5. Dichloromethane # 9.00
6. Isopropyl Alcohol # 9.00
7. Colloidal Silicon dioxide 1.00
8. Magnesium stearate 3.00
Core tablet weight 296.00
Coating
9. Hydroxypropyl Methylcellulose 5.125
10. Polyethylene Glycol 6000 1
11. Purified Talc 0.5
12. Titanium Dioxide 0.375
13. Dichloromethane # 161.200
14. Isopropyl Alcohol # 100.100
Weight build up 7.00
Coated tablet weight 303.00
# Removed during manufacturing process not considered in final mass.
Process for preparation:
1. Sift Vildagliptin, lactose anhydrous and glyceryl dibehenate through 30 mesh sieve
2. Mix the step 1 for 10 minutes
3. Prepare binder solution by melting cetyl alcohol and then add dichlormethane and Isopropyl alcohol
4. Granulate step 2 mixture in planetary mixer / rapid mixer granulator by adding step 3 binder solution and then mill the mass to get granules
5. Dry the granules of step 4

6. Sift and mill the dries granules of step 5
7. Lubricate the granules of step 6 with colloidal silicon dioxide and magnesium stearate
8. Compress the lubricated granules of step 7 into tablet and film coat the compressed tablets

Dissolution profile
Water, 900ml, Paddle 75 rpm
Time Specifications Initial Analysis (% drug release) 1M 40 IIS
(% drug release) 6M 40 115
(% drug release)
lhr NMT 30% 19.8 20.6 20.4
4hrs 30% - 60% 43.5 44.5 44.2
12hrs 60%-85% 77.2 78.7 78.4
24hrs NLT 80% 92.6 96.0 94.50
Related Substances
Amide impurity NMT 0.5 % 0.05 0.07 0.15
Individual
unknown
impurity NMT 0.5 % 0.09 0.11 0.17
Total impurities NMT 1.0% 0.21 0.27 0.43
B. Vildagliptin Once daily formulations with Other antidiabetic combinations
Example 2: Vildagliptin Extended Release Tablets and Dapagliflozin Tablets

Sr. no. Name of Ingredient mg /tab (100+ 5)mg mg/tab (100+10)mg
Vildagliptin Layer
1 Vildagliptin 100.00 100.00
2 Lactose Anhydrous 73.60 73.60
3 Glyceryl behenate 59.20 59.20
4 Cetyl Alcohol 59.20 59.20
5 Dichloromethane # 9.00 9.00
6 Isopropyl Alcohol # 9.00 9.00
7 Colloidal Silicon Dioxide 1.00 1,00
8 Magnesium Stearate 3.00 3.00
Vildagliptin Layer weight 296.00 296.00
Dapagliflozin Layer
9 Dapagliflozin premix 25.00 50.00
10 Microcrystalline cellulose PH 102 69.275 44.275
11 Lactose monohydrate 25.00 25.00
12 Crospovidone 6.250 6.250
13 Sodium lauryl sulphate 0.625 0.625
14 Ferric oxide yellow 0.10 —
15 Ferric oxide red — 0.10
16 Dichloromethane # 95.00 95.00
17 Colloidal silicon dioxide 1.25 1.25
18 Magnesium stearate 2.50 2.50
Dapagliflozin Layer weight 130.00 130.00
Core Tablet weight 426.00 426.00
Film coating
19 Hydroxypropyl Methylcellulose 9.00 9.00
20 Polyethylene Glycol 6000 1.00 1.00
21 Isopropyl alcohol # 72.00 72.00

22 Dichloromethane # 168.00 168.00
Film coat weight 10.00 10.00
Coated Tablet weight 436.00 436.00
# Removed during manufacturing process not considered in final mass.
Process for preparation:
1. Prepare Vildagliptin layer as per example 1.
2. Sift Dapagliflozin, Lactose, crospovidone, sodium lauryl sulphate, microcrystalline cellulose through 30 mesh sieve
3. Mix the step 3 for 10 minutes
4. Prepare wet mass granules by adding dichloromethane to the mixer of step 3 in planetary mixer / rapid mixer granulator
5. Dry the granules of step 4
6. Sift and mill the dries granules of step 5
7. Lubricate the granules of step 6 with magnesium stearate
8. Compress the lubricated granules of step 1 & 7 into tablet and apply the film coat to the compressed tablets
Example 3: Vildagliptin Extended Release Tablets and Canagliflozin Tablets

Sr. no. Name of Ingredient mg /tablet
Vildagliptin layer
1 Vildagliptin 100
2 Lactose anhydrous 73.6
3 Glyceryl behenate 59.2
4 Cetyl alcohol 59.2
5 Dichloromethane # 9.00
6 Isopropyl alcohol # 9.00
7 Colloidal silicon dioxide 1.00
8 Magnesium stearate 3.00

# Removed during manufacturing process not considered in final mass. Process for preparation:
1. Prepare Vildagliptin layer as per example 1.
2. Sift Canagliflozin, lactose, croscarmellose sodium , ferric oxide yellow, microcrystalline cellulose through 30 mesh sieve
3. Mix the step 3 for 10 minutes
Vildagliptin layer weight 296
Canagliflozin layer
9 Canagliflozin 100
10 Microcrystalline cellulose PH 101 34.00
11 Lactose monohydrate 34.00
12 Croscarmellose sodium 6.00
13 Ferric oxide yellow 0.50
14 Hydroxypropyl cellulose 3.00
15 Sodium lauryl sulphate 6
16 Isopropyl alcohol # q.s
17 Croscarmellose sodium 9.00
18 Magnesium stearate 1.5
Canagliflozin layer weight 194.00
Core tablet weight 490.00
Film coating
19 Hydroxypropyl methylcellulose 9
20 Polyethylene glycol 6000 1
21 Isopropyl alcohol # 72
22 DichJoromethane # 168
Film coat weight 10
Coated tablet weight 500

4. Prepare binder solution by adding hydroxypropyl cellulose to isopropyl alcohol and then adding sodium lauryl sulphate
5. Granulate step 3 mixture in planetary mixer / rapid mixer granulator by adding step 4 binder solution
6. Dry the granules of step 5
7. Sift and mill the dries granules of step 5
8. Lubricate the granules of step 7 with magnesium stearate
9. Compress the lubricated granules of step 1 & 8 into tablet and film coat the compressed tablet

We claim,
Claim 1- A sustained release pharmaceutical composition comprising
Vildagliptin or pharmaceutically acceptable salt thereof with one or more hydrophobic excipients as release retarding material and one or more pharmaceutically acceptable excipients.
Claim 2- The pharmaceutical composition of claim 1, comprises one or more hydrophobic excipients selected from low melting fats, waxes, fatty acids, fatty alcohols, cetyl alcohol, stearyl alcohol, cetostearyl alcohol, stearic acid, beeswax, carnauba wax, hydroxy stearic acid, glyceryl monostearate, glyceryl behenate, hydrogenated vegetable oil, hydrogenated castor oil, or their derivatives or esters or salts and combinations thereof.
Claim 3- The pharmaceutical composition of claim 1, comprises at least two hydrophobic excipients.
Claim 4- The pharmaceutical composition of claim 3, wherein at least one hydrophobic excipient is in intragranular part.
Claim 5- The pharmaceutical composition of claim 1 to 4, wherein one or more hydrophobic excipient(s) selected from cetyl alcohol, glyceryl behenate or combination thereof
Claim 6- The pharmaceutical composition of claim 1 to 5, wherein the one or more pharmaceutically acceptable excipients are selected from diluents, binders, disintegrants, glidants, lubricants, stabilizers, surfactants, solubility enhancers, coloring agents, flavouring agents, sweetening agents, coating agents or any combination thereof.

Claim 7- The pharmaceutical composition of claim 1, wherein the composition further comprises one or more additional antidiabetic agent selected from biguanides, sulfonyl ureas, glucosidase inhibitors, sodium-glucose transporter modulators (SGLT2 inhibition), PPAR agonists such as thiazolidinediones, aP2 inhibitors, PPAR . dual agonists, glinides, glitazones and/or meglitinides, as well as insulin, glucagon-like peptide-1 (GLP-1 ), glycogen phosphorylase inhibitors and/or glucos- 6-phosphatase inhibitors.
Claim 8- The pharmaceutical composition of claim 7, wherein the additional antidiabetic agent is a sodium-glucose transporter modulators.
Claim 9- A method of preparing pharmaceutical composition of claim 1, wherein the method comprises melt granulation.
Claim 10- A pharmaceutical composition comprising Vildagliptin or pharmaceutically acceptable salt thereof, Lactose, Glyceryl Dibehenate, Cetyl Alcohol, Magnesium stearate, Colloidal Silicon dioxide and optionally coating.
VILDAGLIPTIN MODIFIED RELEASE TABLETS