DESC:The present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients Furthermore the invention is directed to said pharmaceutical combination for use in the prevention delay or treatment of cardiovascular disorders.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the Sacubitril; Valsartan having 30-70% w/w of the composition.

Present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients having comparable dissolution properties, content uniformity, stability and equivalent bioavailability w.r.t commercialized valsartan Sacubitril complex dosage form.

Present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients like diluent, binder, glidants, lubricant, solubilizer, antacid, disintegrant and colorant.

Present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the Sacubitril; Valsartan is in the form of trisodium salt with X hydrate, where in X is water of crystallization which can range from 0-3.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the SGLT2 inhibitor is specifically referred to Canagliflozin, Dapagliflozin, and Empagliflozin.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the SGLT2 inhibitor is specifically referred to Dapagliflozin, and Empagliflozin.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the SGLT2 inhibitor is more specifically referred to Dapagliflozin.

The term "Sacubitril" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term "Valsartan" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term "Dapagliflozin" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term "Empagliflozin" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term "Canagliflozin" as used herein includes the base, pharmaceutically acceptable salts, polymorphs, stereoisomers and mixtures thereof, the term "pharmaceutically acceptable salt" means a salt which is acceptable for administration to a patient, such as a mammal (e.g., salts having acceptable mammalian safety for a given dosage regime). Such salts can be derived from pharmaceutically acceptable inorganic or organic bases and from pharmaceutically acceptable inorganic or organic acids.

The term, "pharmaceutically acceptable excipients" as used herein refers to diluents, disintegrants, binders, lubricants, glidants, coating agents, solvents, co-solvents, preservatives, wetting agents, thickening agents, antifoaming agents, sweetening agents, flavouring agents, antioxidants, solubilizer, plasticizers or dispersing agents and the like. The pharmaceutical compositions of the present invention may be formulated in a conventional manner using one or more pharmaceutically acceptable excipients.

The term "binder" employed in a composition of the present invention is capable for holding the ingredients together and forming the granules with required mechanical strength. The binders of instant invention include, but are not limited to, but are not limited to, polyvinylpyrrolidone (povidone), polyethlylene glycol (PEG), saccharides, gelatins, pregelatinized starches, microcrystalline cellulose, hydroxypropylcellulose, hydroxypropyl methylcellulose (HPMC) and cellulose ethers.

The term "lubricant" employed in a composition of the present invention is capable of preventing the ingredients from clumping together and from sticking to the apparatus on which it is formed, for example, preventing adherence to the face of the upper punch (picking) or lower punch (sticking) of a compression machine. Preferred lubricants of instant invention includes, but are not limited to fatty acids or fatty acid derivatives such as calcium stearate, glyceryl monostearate, glyceryl palmitostearate, talc, magnesium stearate, sodium lauryl sulfate, sodium stearyl fumarate, zinc stearate, stearic acid or hydrogenated vegetable oil; polyalkylene glycols such as polyethylene glycol (PEG) or sodium benzoate and the like.

The term " Glidant" employed in a composition of the present invention is capable for providing bulkiness to obtain a desired pharmaceutical composition. The Glidant of instant invention includes, but are not limited to inorganic phosphates such as dibasic calcium phosphate, Colloidal Silicon dioxide (fumed silica), hydrophilic silica, calcium sulphate or dicalcium phosphate dihydrate; sugars such as lactose, lactose hydrate, lactose monohydrate, lactose anhydrate, sucrose, dextrose, erythritol, lactilol, xylitol, sorbitol, mannitol or malitol; cellulose or cellulose derivatives such as microcrystalline cellulose; Avicel, Avicel PH 101, Avicel PH 102 or Avicel PH 103, maize starch, Starcap-1500, Starlac and galenIQ-721.

The term "diluent" employed in a composition of the present invention is capable for providing bulkiness to obtain a desired pharmaceutical composition. The diluents of instant invention includes, but are not limited to inorganic phosphates such as dibasic calcium phosphate, calcium sulphate or dicalcium phosphate dihydrate; sugars such as lactose, lactose hydrate, lactose monohydrate, lactose anhydrate, sucrose, dextrose, erythritol, lactilol, xylitol, sorbitol, mannitol or malitol; cellulose or cellulose derivatives such as microcrystalline cellulose; Avicel, Avicel PH 101, Avicel PH 102 or Avicel PH 103, maize starch, Starcap-1500, Starlac and galenIQ-721.

The term "disintegrant" employed in a composition of the present invention is capable of facilitating the breakup of a pharmaceutical composition prepared from the composition when placed in contact with an aqueous medium. The disintegrants of instant invention includes, but are not limited to alginic acid or sodium alginate; cellulose or cellulose derivatives such as carboxymethylcellulose sodium, microcrystalline cellulose, croscarmellose sodium, powdered cellulose or croscarmellose; iron exchange resin such as amberlite, gums such as agar, locust bean, karaya, pectin and tragacanth, crospovidone (cross-linked homopolymer of N-vinyl-2-pyrrolidinone, i.e., cross-linked l-ethenyl-2-pyrrolidinone); Pregelatinized starch, sodium starch glycolate or starch.

The term "composition" or "pharmaceutical composition" or “dosage form” as used herein synonymously include 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 "stable" as used herein refers to formulations that substantially retain the label amount of the therapeutically active ingredient during storage for commercially relevant times, and the drug-related impurity contents in the formulations remain within acceptable limits.

The term "about" as used herein refers to a defined range of the value by + 10 %. For example, about 2 % means 1.8 % to 2.2 %, about 5 % means 4.5 % to 5.5 %, about 10 % means 9 % to 11 % and about 40 % means 36 % to 44 %.

The term "oral dosage forms" includes all conventional oral solid dosage forms like a tablet, capsule, syrups, suspension, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet, or any other orally ingestible dosage form comprising active ingredient and its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

The terms “prevent” and “preventing” as used herein refers the prevention of the recurrence, spread or onset. It is not intended that the present disclosure be limited to complete prevention. In some embodiments, the onset is delayed, or the severity of the disease is reduced.

The terms “treat” and “treating” as used herein refers are not limited to the case where the subject (e.g., patient) is cured and the disease is eradicated. Rather, embodiments, of the present disclosure also contemplate treatment that merely reduces symptoms, and/or delays disease progression.

The term "oral dosage forms" includes all conventional oral solid dosage forms like a Tablet, capsule, Syrups, Suspension, granules, a pill, a tablet, a caplet, pellets, a powder or a sachet, or any other orally ingestible dosage form comprising active ingredient or its salts as an active ingredient mixed with other pharmaceutically acceptable excipients.

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.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the Sacubitril & Valsartan complex can be anhydrate, hemi hydrate, mono-hydrate, sesquihydrate, di hydrate, hemi penta hydrate, tri hydrate.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the Dapagliflozin is Dapagliflozin free base, salts or solvates which can be in crystalline or Amorphous form.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the Empagliflozin is Empagliflozin free base, salts or solvates which can be in crystalline or Amorphous form.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the Canagliflozin is Canagliflozin free base, salts or solvates which can be in crystalline or Amorphous form.
Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the pharmaceutical composition is the form of tablets, capsule, mini tablets, tablets in capsule.

Present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients wherein the pharmaceutical composition is the form of immediate release, extended release, delayed release, bilayer tablet dosage form.

In one of the embodiments of the present invention relates to the pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients and processes for the preparation of formulation.

In one of the embodiments of the present invention is to provide a pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients and processes for the preparation of formulation by direct compression or wet granulation and combination thereof.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the pharmaceutical composition is multilayer tablet dosage form preferably bilayer tablet dosage form.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the pharmaceutical composition having two components tablet or capsule and final composition can be tablet in tablet, capsule in capsule, tablet in capsule, mini-tablet filled in capsule.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients, where in the said formulation has no or minimum drug-drug interaction, maximum stability along with optimal bioavailability.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, disintegrant and colorant.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the Sacubitril; Valsartan is in the form of trisodium salt with X hydrate, where in X is water of crystallization which can range from 0-3.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril, Valsartan and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the pharmaceutical composition is multilayer tablet dosage form preferably bilayer or tri-layer tablet dosage form.

In one of the embodiments of the present invention is to provide a stable pharmaceutical dosage form of Sacubitril, Valsartan and SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients where in the pharmaceutical composition having two components tablet or capsule and final composition can be tablet in tablet, capsule in capsule, tablet in capsule, mini-tablet filled in capsule.

In one of the embodiments of the present invention is to provide a method for treatment of a cardiovascular diseases by administering a pharmaceutical formulation comprising Sacubitril & Valsartan complex and SGLT2 inhibitor or its pharmaceutically acceptable salts.
Examples
The following examples are for the purpose of illustration of the invention only and are not intended in any way to limit the scope of the present invention.
Example 1:

S. No Ingredients Category Qty/ Tablet (mg)
24/26 mg 49+51 mg 97+103 mg
Intra granular Part
1. Microcrystalline cellulose PH 101 Diluent 2.50 5.00 10.00
2. Syloid XDP 3150 Glidant 20.00 40.00 80.00
Binder Solution
3. Sacubitril and Valsartan Active Ingredient 56.55
113.10 226.20
4. Polysorbate 80 Solubilizer 5.00 10.00 20.00
5. Methanol Solvent q.s. q.s. q.s.
Extragranular
6. Dapagliflozin Active Ingredient 5 5 5
7. Microcrystalline cellulose PH 102 Diluent 9.17 23.34 51.58
8. Precipitated Calcium Carbonate Antacid 5.00 10.00 20.00
9. Crospovidone Xl 10 Disintegrant 5.00 10.00 20.00
10. Colloidal silicon dioxide (Aerosil 200 Pharma) Glidant 0.90 1.79 3.58
11. Magnesium stearate ( Ligamed MF 2V) Lubricant 0.90 1.79 3.58
Total weight of uncoated tablet 110.00 220.00 440.00
Coating Materials

Manufacturing process:
1.0 Pre Warming: Load Syloid XDP 3150 in Fluid Bed Processor (Top Spray Bowl) and pre warm the material for 10 minutes.
2. Binder Solution preparation: Take required amount of Methanol and add Sacubitril/Valsartan API complex under stirring and continue stirring until to get the clear solution. Add Polysorbate 80 to above solution and mix for 10 minutes.
3. Granulation: Spray the step No. 2 solution onto the step no.1 with Top spray approach with suitable in Process Parameters.
4. Drying: After completion of the coating Dry the materials until to get the LOD between 2 – 4% w/w (Target 3% w/w)
5. Sifting and Milling: Sift the Dried Granules through #30 mesh and collect the #30 mesh retained granules and mill the retained granules through Quadro co mill with 24 R Screen with slow speed.
6. Pre-lubrication: Dapagliflozin and Sift Microcrystalline cellulose PH 102, Precipitated Calcium Carbonate, Crospovidone XL 10, Colloidal silicon Di oxide through 30 # mesh. Add this to step 6 Blend to step 5 and blend in a suitable blender up to 15 minutes.
7. Lubrication: Add ste6 blend to step 5 Blend and Blend for 5 mins.
8. Compression: Compress the above blend by using suitable punches.
9. Film Coating: Film Coating Prepare the coating dispersion by dispersing Colorozy Pink, Yellow and Pink in purified water under stirring and coat the compressed tablets of step 8 with the coating dispersion.

Example 2:

S. No Ingredients Category Qty/ Tablet (mg)
24/26 mg 49+51 mg 97+103 mg
Intra granular Part
1. Microcrystalline cellulose PH 101 Diluent 2.50 5.00 10.00
2. Syloid XDP 3150 Glidant 20.00 40.00 80.00
Binder Solution
3. Sacubitril and Valsartan Active Ingredient 56.55
113.10 226.20
4. Polysorbate 80 Solubilizer 5.00 10.00 20.00
5. Methanol Solvent q.s. q.s. q.s.
Extragranular
6. Empagliflozin Active Ingredient 5 5 5
7. Microcrystalline cellulose PH 102 Diluent 9.17 23.34 51.58
8. Precipitated Calcium Carbonate Antacid 5.00 10.00 20.00
9. Crospovidone Xl 10 Disintegrant 5.00 10.00 20.00
10. Colloidal silicon dioxide (Aerosil 200 Pharma) Glidant 0.90 1.79 3.58
11. Magnesium stearate ( Ligamed MF 2V) Lubricant 0.90 1.79 3.58
Total weight of uncoated tablet 110.00 220.00 440.00
Coating Materials

Manufacturing process:
1.0 Pre Warming: Load Syloid XDP 3150 in Fluid Bed Processor (Top Spray Bowl) and pre warm the material for 10 minutes.
2. Binder Solution preparation: Take required amount of Methanol and add Sacubitril/Valsartan API complex under stirring and continue stirring until to get the clear solution. Add Polysorbate 80 to above solution and mix for 10 minutes.
3. Granulation: Spray the step No. 2 solution onto the step no.1 with Top spray approach with suitable in Process Parameters.
4. Drying: After completion of the coating Dry the materials until to get the LOD between 2 – 4% w/w (Target 3% w/w)
5. Sifting and Milling: Sift the Dried Granules through #30 mesh and collect the #30 mesh retained granules and mill the retained granules through Quadro co mill with 24 R Screen with slow speed.
6. Pre-lubrication: Empagliflozin and Sift Microcrystalline cellulose PH 102, Precipitated Calcium Carbonate, Crospovidone XL 10, Colloidal silicon Di oxide through 30 # mesh. Add this to step 6 Blend to step 5 and blend in a suitable blender up to 15 minutes.
7. Lubrication: Add ste6 blend to step 5 Blend and Blend for 5 mins.
8. Compression: Compress the above blend by using suitable punches.
9. Film Coating: Film Coating Prepare the coating dispersion by dispersing Colorozy Pink, Yellow and Pink in purified water under stirring and coat the compressed tablets of step 8 with the coating dispersion.

Manufacturing Formula:
S. No. Ingredients Category Qty/ Tablet (mg) % w/w
24/26 mg 49+51 mg 97+103 mg
Intra granular Part
1. Sacubitril and Valsartan tri sodium hydrate (Form P) Active Ingredient 57.082 114.165 228.33 63.42
2. Microcrystalline cellulose (Hicel XLM 90) Diluent 14.418 28.835 57.67 16.02
3. Low substituted Hydroxy Propyl cellulose (L-HPC 11) Dry Binder 7.50 15.00 30.00 8.33
4. Colloidal silicon dioxide (Aerosil 200 Pharma) Glidant 1.00 2.00 4.00 1.11
5. Magnesium Stearate (Ligamed MF 2V) Lubricant 0.50 1.00 2.00 0.56
Extragranular Part
6. Microcrystalline cellulose (Hicel XLM 90) Diluent 5.00 10.00 20.00 5.56
7. Dapagliflozin API 5.00 5.00 5.00 5.00
8. Talc (Luzenac Pharma) Glidant 1.00 2.00 4.00 1.11
9. Crospovidone Xl 10 Disintegrant 2.25 4.50 9.00 2.50
10. Colloidal silicon dioxide (Aerosil 200 Pharma) Glidant 0.75 1.50 3.00 0.83
11. Magnesium stearate ( Ligamed MF 2V) Lubricant 0.50 1.00 2.00 0.56
Total weight of uncoated tablet 90.00 180.00 360.00 100.00
Coating Materials
12. Colorozy pink 17F540247$ Film coating agents 2.70 -- -- 3.00
13. Colorozy Yellow 17F520349€ -- 5.40 -- 3.00
14. Colorozy pink 17F540248p -- -- 10.80 3.00
15. Iso Propyl Alcohol Solvent q.s. q.s. q.s. q.s.
16. Di Chloro Methane Solvent q.s. q.s. q.s. q.s.
Total weight of coated Tablet 92.70 185.40 370.80

Manufacturing Process:
1. Sifting: Co sift Sacubitril and Valsartan API Complex, Microcrystalline cellulose (Hicel XLM 90), Low substituted Hydroxy propyl cellulose, Colloidal silicon Di oxide through #40 mesh.
2.Sifting: Sift Magnesium stearate through #60 mesh
3.Blending: Add step 2 blend to step 1 and blend in a suitable blender upto 15 minutes.
4.Roll compaction: Compact the step 3 with roll compactor and milled with 1.00 mm screen in multi mill to attain desired granules and continued compaction and milling process until all the granules passes through 30# mesh.
5.Prelubrication: Sift Dapagliflozin, Microcrystalline cellulose (Hicel XLM 90), Talc, Crosspovidone XL 10, Colloidal silicon Di oxide through 30 # mesh.Add this to step 4 Blend and blend in a suitable blender upto 15 minutes.
6.Sift Magnesium stearate through 60# mesh.
7.Lubrication: Add ste6 blend to step 5 Blend and Blend for 5 mins.
8.Compression: Compress the above blend by using suitable punches.
9.Film Coating: Prepare the coating dispersion by dispersing Colorozy Pink, Yellow and Pink in purified water under stirring and coat the compressed tablets of step 8 with the coating dispersion.

Example 3:
S.no Ingredient Qty./Tablet (mg)
1 Sacubitril 97.00
2 Lactose monohydrate 30.00
3 Microcrystalline cellulose 48.00
4 Hydroxypropyl cellulose 12.00
5 Purified water q.s.
6 Sodium starch glycolate 15.00
7 Colloidal silicon dioxide 3.00
8 Talc 12.00
9 Valsartan 103.00
10 Lactose monohydrate 58.00
11 Microcrystalline cellulose 20.00
12 Calcium hydrogen phosphate 7.00
13 Crospovidone 5.00
14 Magnesium stearate 1.25
15 Dapagliflozin 5.00
16 Lactose monohydrate 50.00
17 Microcrystalline cellulose 20.00
18 Sodium starch glycolate 5.00
19 Povidone 3.00
20 Sodium lauryl sulphate 2.00
21 Purified water q.s.
22 Film Coating
23 Opadry 9.000

Example 4:
1 Ingredient Qty./Tablet (mg)
2 Sacubitril 97.00
3 Valsartan 103.00
4 Dapagliflozin 5.00
5 Lactose monohydrate 30.00
6 Microcrystalline cellulose 60.00
7 Sodium starch glycolate 9.00
8 Povidone / Hydroxypropyl cellulose 15.00
9 Talc / Calcium stearate / Stearic acid 3.00
10 Film Coating
11 Opadry 9.00
12 Purified Water q.s.
,CLAIMS:1) A pharmaceutical composition comprising of Sacubitril; Valsartan complex combination with SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

2) The pharmaceutical composition as claimed in claim 1, wherein the SGLT2 inhibitor is Dapagliflozin or Empagliflozin or Canagliflozin its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients.

3) The pharmaceutical composition as claimed in claim 1, wherein the SGLT2 inhibitor is specifically Dapagliflozin or its pharmaceutically acceptable salts and one or more pharmaceutically acceptable excipients.

4) The pharmaceutical composition as claimed in claim 1, wherein the Sacubitril; Valsartan complex is an anhydrate or hydrate selected from hemi hydrate, mono-hydrate, sesquihydrate, di hydrate, hemi penta hydrate, tri hydrate, tri sodium hydrate (Form P).

5) A Bilayer tablet composition comprising Sacubitril; Valsartan complex combination with SGLT2 inhibitor or its pharmaceutically acceptable salts thereof and one or more pharmaceutically acceptable excipients.

6) The Bilayer tablet composition as claimed in claim 5, wherein the formulation is prepared by direct compression or wet granulation and combination thereof.

7) The Bilayer tablet composition as claimed in claim 5, wherein the where in the pharmaceutical composition having two components tablet or capsule and final composition can be tablet in tablet, capsule in capsule, tablet in capsule, mini-tablet filled in capsule.

8) The Bilayer tablet composition as claimed in claim 5, wherein the composition contains Sacubitril & Valsartan complex and SGLT2 inhibitor and one or more pharmaceutically acceptable excipients like diluent, binder, glidant, lubricant, solubilizer, disintegrant and colorant.

9) The Bilayer tablet composition as claimed in claim 5, wherein the composition contains Sacubitril & Valsartan complex and SGLT2 inhibitor and one or more pharmaceutically acceptable excipients like microcrystalline cellulose, syloid, polysorbate, methanol, microcrystalline cellulose, calcium carbonate, crospovidone, colloidal silicon dioxide, magnesium stearate.

10) The Pharmaceutical composition as claimed in claim 1, wherein the composition for use in the prevention, delay or treatment of cardiovascular disorders.