DESC:However, before further describing this invention, the following terms are defined.

As used herein, the singular forms “a”, “an” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise.

The term “comprising” is not intended to limit inventions to only claiming the present invention with such comprising language. Any invention using the term comprising could be separated into one or more claims using “consisting” or “consisting of” claim language and is so intended.
The terms “including”, “includes”, “having”, “has”, “with”, or variants thereof are used in either the detailed description and/or the claims, such terms are intended to be inclusive in a manner similar to the term “comprising”. As used herein, the terms “include”, “includes”, and “including” are meant to be non-limiting.

The term “treatment” includes prophylactic and/or therapeutic treatments. The term “prophylactic or therapeutic” treatment is art-recognized and includes administration to the subject of one or more of the pharmaceutical compositions. If it is administered prior to clinical manifestation of the unwanted condition (e.g., disease or other unwanted state of the host animal) then the treatment is prophylactic (i.e., it protects the subject against developing the unwanted condition), whereas if it is administered after manifestation of the unwanted condition, the treatment is therapeutic, (i.e., it is intended to diminish, ameliorate, or stabilize the existing unwanted condition or side effects thereof).

The term “cardiovascular disease(s)” refers to a disorder of the heart and blood vessels, and includes disorders of the arteries, veins, arterioles, venules, and capillaries. Non-limiting examples of cardiovascular diseases include cardiac hypertrophy, myocardial infarction, stroke, arteriosclerosis, and heart failure. Additional examples of cardiovascular diseases are known in the art. One of the uses of the present invention compositions is to reduce the risk of cardiovascular death and hospitalization for heart failure in patients with chronic heart failure (NYHA Class II-IV) and reduced ejection fraction.

The term “administration” or “administering” refers to a method of giving a dosage of a pharmaceutical composition to a subject. The preferred method of administration may depend on a variety of factors, e.g., the components of the pharmaceutical composition or condition, and severity of the disease, disorder, or condition.

The term “patient”, “subject” or “individual “is used interchangeably and refers to a vertebrate, preferably a mammal. Non-limiting examples include mice, dogs, rabbits, farm animals, sport animals, pets, and humans.

The term “bioavailability” can denote the degree to which a drug or other substance becomes available to the target tissue after administration.
The term “pharmaceutically acceptable excipient(s)” or “excipient(s)” refers to those substances that are well accepted by the industry and regulatory agencies such as those listed in monographs published in compendia such as USP-NF, Food Chemicals Codex, Code of Federal Regulations (CFR), FDA Inactive Ingredients Guide and in 21 CFR parts 182 and 184 that lists substances that are generally regarded as safe (GRAS) food ingredients.

The term “pharmaceutical composition” refers to a pharmaceutical preparation that contains a compound of the present disclosure, or a pharmaceutically acceptable salt thereof, and is suitable for administration to a patient for therapeutic purposes.

To provide a more concise description, some of the quantitative expressions given herein are not qualified with the term "about". It is understood that whether the term "about" is used explicitly or not, every quantity given herein is meant to refer to the actual given value, and it is also meant to refer to the approximation to such given value that would reasonably be inferred based on the ordinary skill in the art, including approximations due to the experimental and/or measurement conditions for such given value.

The term “% by weight” is based on the weight of the total composition.

An aspect of the present invention relates to a pharmaceutical composition comprising trisodium [3-((1S, 3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl) propionate-(S)-3'-methyl-2'-(pentanoyl {2''-(tetrazol-5-ylate) biphenyl-4'-ylmeth-yl} amino) butyrate].

In an embodiment of the present invention relates to a pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and at least one pharmaceutically acceptable carrier, wherein the composition comprising solid dispersion of Sacubitril; Valsartan trisodium complex with pharmaceutically acceptable excipients selected from the group of diluents, binders, disintegrants, glidants, lubricants, wetting agents and others. The Sacubitril; Valsartan trisodium complex in the pharmaceutical composition of the present invention can be either a crystalline or an amorphous form.

In an embodiment of the present invention relates to a solid dispersion of Valsartan trisodium complex wherein the solid dispersion comprising of Valsartan trisodium complex and a carrier selected from the group of colloidal silicon dioxide, microcrystalline cellulose, copovidone and hydroxy ethyl cellulose or combination thereof. Where in the ration of Sacubitril; Valsartan trisodium complex and excipients for the solid dispersion is 60:40 to 95:5. More specifically 65:35, 75:25, 70:30, 80:20.

In an embodiment of the present invention relates to a pharmaceutical composition comprising an amorphous or anhydrous solid dispersion of Sacubitril; Valsartan trisodium complex and carrier for the solid dispersion are selected from the group of Colloidal silicon dioxide, co-povidone, microcrystalline cellulose and hydroxy ethyl cellulose or combination thereof. Where in the Sacubitril; Valsartan trisodium complex is above 60% in the composition.

In an embodiment of the present invention relates to a pharmaceutical composition comprising solid dispersion of amorphous Sacubitril; Valsartan trisodium complex and excipients like microcrystalline cellulose, low substituted hydroxypropyl cellulose (L-HPC), crospovidone, talc, colloidal silicon dioxide and magnesium stearate.

In an embodiment of the present invention relates to a process for preparing the pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and at least one pharmaceutically acceptable excipients wherein the Sacubitril; valsartan trisodium complex is in amorphous form (or) solid dispersion

In an embodiment of the present invention, relates to a pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and at least one pharmaceutically acceptable excipients and use of such compositions for the treatment of cardiovascular diseases.

In an embodiment, the present invention relates to a pharmaceutical composition comprising a therapeutic agent, a supramolecular complex.

In an embodiment, the present invention relates to featured supramolecular complex is a dual acting compound. A dual-acting compound or combination features a supramolecular complex of two active agents with different mechanisms of action, or linked pro-drug or in particular a supramolecular complex of two active agents with different mechanisms of action, namely an angiotensin receptor antagonist and a neutral endopeptidase inhibitor.

In an embodiment, the present invention relates to a pharmaceutical composition comprising trisodium [3-((1S, 3R)-1-biphenyl-4-ylmethyl-3-ethoxycarbonyl-1-butylcarbamoyl) propionate-(S)-3'-methyl-2'- (pentanoyl {2''-(tetrazol-5-ylate) biphenyl-4'-ylmeth- yl} amino) butyrate]. The Sacubitril; Valsartan trisodium complex in the pharmaceutical composition of the present invention can be either a crystalline or an amorphous form. The active ingredients Sacubitril and Valsartan may be present in the form of free base(s), its salt(s), polymorph(s), hydrate(s), solvate(s), conjugate(s), complex(s), prodrug(s), and derivative as alone or in combination thereof which may be present in the form of a complex, a premix, an amorphous powder, a solid dispersion, an anhydrous solid dispersion a solid solution, a physical mixture and the like. In certain embodiments, the present invention provides a pharmaceutical composition comprising amorphous Sacubitril; Valsartan trisodium complex in about 45 % by weight to about 70 % by weight of the total composition.

In an embodiment, the present invention relates to a pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and at least one pharmaceutically acceptable excipients selected from the group consisting of diluents, binders, disintegrants, glidants, lubricants, wetting agents and others. The Sacubitril; valsartan trisodium complex in the pharmaceutical composition of the present invention can be either a crystalline or an amorphous form.

In an embodiment, the present invention relates to a pharmaceutical composition comprising an amorphous/anhydrous solid dispersion of Sacubitril; valsartan trisodium complex and at least one pharmaceutically acceptable excipient(s). The excipient used in the present invention is selected from the group of polymeric compounds like colloidal silicon dioxide, Microcrystalline cellulose and Hydroxy ethyl cellulose or combination thereof.
In an embodiment, the present invention relates to a pharmaceutical composition comprising an amorphous Sacubitril; Valsartan trisodium premix, which is prepared by removing the solvent from the solution containing Sacubitril; valsartan a base and colloidal silicon dioxide, microcrystalline cellulose and hydroxy ethyl cellulose or combination thereof in a suitable solvent.

Examples of the diluent(s) or filler(s) include but not limited to cellulose derivatives, such as microcrystalline cellulose or silicified microcrystalline cellulose or wood cellulose, lactose, sucrose, starch, pregelatinized starch, dextrose, mannitol, fructose, xylitol, sorbitol, corn starch, modified corn starch, inorganic salts such as calcium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, dextrin/dextrates, maltodextrin, and compressible sugars. In the present invention diluents are added in an amount from about 10% to about 90% by weight of the total composition. In certain embodiments, the present invention provides a pharmaceutical composition comprising Sacubitril; valsartan trisodium complex and microcrystalline cellulose as a diluent.

Examples of binder(s) for use in accordance with the present invention include but not limited to cellulose and its derivatives including hydroxypropylmethyl cellulose (hypromellose), hydroxypropyl cellulose, hydroxypropyl cellulose (HPC), cellulose acetate, ethylcellulose, methylcellouse, and hydroxyethyl cellulose; starch and its derivatives; pregelatinized starch, hydrocolloids; sugar; polyvinyl pyrrolidone, copovidone, methacryclic acid copolymers and combinations thereof, and the like. In the present invention binders in an amount from about 1% to about 10% by weight of the total composition.

Examples of disintegrant(s) suitable for use herein include but not limited to croscarmellose sodium, crospovidone, starch, potato starch, pregelatinized starch, corn starch, sodium starch glycolate, low substituted hydroxypropyl cellulose (L-HPC) and other known disintegrant(s). In the present invention disintegrants in an amount from about 1% to about 15% by weight of the total composition. In certain embodiments, the present invention provides a pharmaceutical composition comprising Sacubitril; valsartan trisodium complex and disintegrants selected from crospovidone, low substituted hydroxypropyl cellulose or mixtures thereof.
Examples of wetting agent(s) suitable for use herein include but not limited to poloxamer, polyoxyethylene ethers, polyoxyethylene sorbitan fatty acid esters, polyoxymethylene stearate, sodium lauryl sulfate, sorbitan fatty acid esters, benzalkonium chloride, polyethoxylated castor oil, and docusate sodium. In the present invention wetting agents in an amount from about 1% to about 10% by weight of the total composition. In certain embodiments, the present invention provides a pharmaceutical composition comprising sacubitril valsartan trisodium complex and poloxamer as a wetting agent.

Examples of lubricant(s) suitable for use herein include but not limited to sodium stearyl fumarate, magnesium stearate, zinc stearate, calcium stearate, talc, carnauba wax, stearic acid, palmitic acid, sodium stearyl fumarate, sodium laurel sulfate, glyceryl palmitostearate, palmitic acid, myristic acid and hydrogenated vegetable oils and fats. In the present invention lubricants in an amount from about 1% to about 5% by weight of the total composition. In certain embodiments, the present invention provides a pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and magnesium stearate as lubricant.

Examples of glidant(s) suitable for use herein include talc, colloidal silicon dioxide, silicic acid, cornstarch, calcium silicate, magnesium carbonate, magnesium oxide, magnesium silicate, starch, castor wax. In the present invention lubricants in an amount from about 1% to about 5% by weight of the total composition. In certain embodiments, the present invention provides a pharmaceutical composition comprising Sacubitril; Valsartan trisodium complex and colloidal silicon dioxide as glidant.

In certain embodiments, pharmaceutical composition(s) of the present invention may be provided in any pharmaceutically acceptable oral solid dosage form(s). Preferably, the oral solid dosage form is selected from the group consisting of tablets, mini-tablets, multilayer tablets, inlaid tablets, tablet in tablet, granules, multi-unit particulate systems (MUPS), pellets, beads, pellets presented in a sachet, capsules such as soft and hard gelatin capsules or lozenges and the like. In certain embodiments, of the present invention provides a tablet comprising amorphous Sacubitril; valsartan trisodium complex, microcrystalline cellulose, low substituted hydroxypropyl cellulose, crospovidone, talc, colloidal silicon dioxide and magnesium stearate.
The process of preparation of dosage forms in accordance with the embodiments are designed by considering the couple of problems of Sacubitril; Valsartan trisodium complex, especially it is strictly ensured that there is no exposure of the therapeutic agent to moisture, no exposure of excessive heat and/or high shear forces as these possess a number of formulation incompatibilities and difficulties during the formulation process, which may lead to degradation or dissociation of the therapeutic agent and/or increased amorphism of the components of the dual acting compound selected for this invention. According to the literature Sacubitril; valsartan supramolecular complex is a BCS class IV compound which resembles a low solubility and low permeability. Also formulation scientists have encountered a problem of non-uniform distribution of wetting agent, for eg. Poloxamer during granulation and/or blending the formulation development of Sacubitril; Valsartan supramolecular complex.

In certain embodiments, the present invention relates to a process for preparing a pharmaceutical composition comprising amorphous Sacubitril; valsartan trisodium complex premix of: i) sifting microcrystalline cellulose; ii) preparing granulating fluid comprising L-HPC and water; iii) granulating the microcrystalline cellulose with granulating fluid of step (ii) followed by drying; iv) blending the dried granules of step (iii) with extragranular components comprising of amorphous Sacubitril; Valsartan trisodium complex premix, L-HPC, crospovidone, talc, colloidal silicon dioxide and magnesium stearate; v) compressing or filling the blend of step (iv) into an oral solid dosage form; vi) optionally coating the oral solid dosage form of step v.

Surprisingly, the inventors of the present invention have overcome the aforementioned problems and developed a novel process for preparing a pharmaceutical composition comprising Sacubitril; Valsartan complex, wherein the process comprises: i) sifting intragranular excipient(s) selected from the group consisting of diluent(s), binder(s), disintegrant(s) and lubricant(s); ii) preparing granulating fluid comprising wetting agent and water; iii) granulating the intragranular excipient(s) with granulating fluid of step (ii) in rapid mixer granulator (RMG) and drying and milling; iii) blending the milled material with extra-granular components comprising Sacubitril-Valsartan complex and excipient(s) selected from the group consisting of disintegrant(s), glidant(s), and lubricant(s); iv) compacting the lubricated blend by roller compaction and milling; v) sifting milled material with extra-granular excipient(s) selected from the group consisting of disintegrant(s), glidant(s) and lubricant(s); vi) compressing or filling the blend of step (v) into the desired oral solid dosage form; and vii) optionally coating the oral solid dosage form.

In certain embodiments, the present invention relates to a solid dispersion of Valsartan trisodium complex wherein the solid dispersion comprising of Valsartan trisodium complex and a carrier selected from the group of colloidal silicon dioxide, microcrystalline cellulose, copovidone and hydroxy ethyl cellulose or combination thereof. Where in the ration of Sacubitril; Valsartan trisodium complex and excipients for the solid dispersion is 60:40 to 95:5. More specifically 65:35, 75:25, 70:30, 80:20.

In a certain embodiment, the present invention relates to a pharmaceutical composition comprising Sacubitril-Valsartan complex, wherein the process comprises: i) Sifting microcrystalline cellulose; ii) preparing granulating fluid comprising poloxamer and water; iii) granulating the microcrystalline cellulose with granulating fluid of step (ii) in rapid mixer granulator and drying; iv) blending the dried granules of step (iii) for 10 minutes with extra-granular components comprising Solid dispersion of Sacubitril and Valsartan with low-substituted hydroxypropyl cellulose, crospovidone, talc, colloidal silicon dioxide and magnesium stearate; iv) slugging the blend of step (iii) in roller compactor followed by milling; v) blending the milled material with crospovidone for 10 minutes and lubricating with magnesium stearate for 3 minutes; vi) The final blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

In certain embodiments, the tablets of the invention have an optional protective outer layer i.e. tablet coating. The protective outer layer of the tablet is based on the weight of the pharmaceutical formulation. The formulation can contain at least one coating layer polymer and a non-aqueous coating solvent(s), for example, isopropyl alcohol which is used for processing and removed by drying. Suitable examples of polymer(s) for the coating layer include but not limited to hydroxypropyl methylcellulose, polyvinyl alcohol (PVA), ethyl cellulose, methacrylic polymers, hydroxypropyl cellulose, and starch.

In one of the particular embodiments of the present invention the film coat composition comprises plasticizer(s). Suitable plasticizer(s) include but not limited to glycerol monocaprylocaprate, triacetin, diethyl phthalate, tributyl sebacate, polyethylene glycol (PEG)/macrogol, glycerin, and triethyl citrate. The film coating composition may optionally comprise ant adherent(s) or opacifying agent(s) or dye(s) or combinations thereof including but not limited to talc, aluminum lakes, iron oxides, titanium dioxide and natural colors.

In one of the particular embodiments, the film coating composition comprises hypromellose, titanium dioxide, polyethylene glycol (PEG)/macrogol, talc, iron oxide black, iron oxide red and iron oxide yellow.

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:
Sacubitril-Valsartan Tablet microcrystalline cellulose

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan with micro crystalline cellulose (80:20) 62.513 -- -- --
Solid dispersion of Sacubitril and Valsartan with micro crystalline cellulose (70:30) -- 62.513 -- --
Solid dispersion of Sacubitril and Valsartan with micro crystalline cellulose (75:25) -- -- 62.513 --
Solid dispersion of Sacubitril and Valsartan with micro crystalline cellulose (65:35) -- -- -- 62.513
Microcrystalline cellulose 19.780 19.780 19.780 19.780
Low substituted hydroxypropyl cellulose 3.467 3.467 3.467 3.467
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.462 0.462 0.462 0.462
Colloidal silicon dioxide 0.462 0.462 0.462 0.462
Magnesium stearate 0.462 0.462 0.462 0.462
Extra granular
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.231 0.231 0.231 0.231
Magnesium stearate 0.462 0.462 0.462 0.462
Core tablet weight 97.085 97.085 97.085 97.085
Film coating
Opadry Pink 03F540294 2.915 2.915 2.915 2.915
IPA: water (70:30) ,(for 8% solid content) -- -- -- --
Total weight (Coated tablets) 100.00 100.00 100.00 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with microcrystalline cellulose was sifted with Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate. The sifted materials were blended in octagonal blender for 10 minutes. The blended material was then compacted in roller compactor and milled. The milled material was sifted and blended with Crospovidone and Talc for 10 minutes and lubricated with the previously sifted Magnesium stearate for 5 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

Example 2:
Sacubitril-Valsartan Tablet Colloidal silicon dioxide.

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan with colloidal silicon dioxide (80:20) 62.513 -- -- --
Solid dispersion of Sacubitril and Valsartan with colloidal silicon dioxide (70:30) -- 62.513 -- --
Solid dispersion of Sacubitril and Valsartan with colloidal silicon dioxide (75:25) -- -- 62.513 --
Solid dispersion of Sacubitril and Valsartan with colloidal silicon dioxide (65:35) -- -- -- 62.513
Microcrystalline cellulose 19.780 19.780 19.780 19.780
Low substituted hydroxypropyl cellulose 3.467 3.467 3.467 3.467
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.462 0.462 0.462 0.462
Colloidal silicon dioxide 0.462 0.462 0.462 0.462
Magnesium stearate 0.462 0.462 0.462 0.462
Extra granular
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.231 0.231 0.231 0.231
Magnesium stearate 0.462 0.462 0.462 0.462
Core tablet weight 97.085 97.085 97.085 97.085
Film coating
Opadry Pink 03F540294 2.915 2.915 2.915 2.915
IPA: water (70:30) ,(for 8% solid content) -- -- -- --
Total weight (Coated tablets) 100.00 100.00 100.00 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with Colloidal silicon dioxide was sifted with Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate. The sifted materials were blended in octagonal blender for 10 minutes. The blended material was then compacted in roller compactor and milled. The milled material was sifted and blended with Crospovidone and Talc for 10 minutes and lubricated with the previously sifted Magnesium stearate for 5 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

Example 3:
Sacubitril-Valsartan Tablet Colloidal silicon dioxide-aqueous granulation.

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan with Colloidal silicon dioxide (80:20) 62.513
microcrystalline Cellulose 19.780
Low substituted hydroxypropyl cellulose 3.467
Water QS
Crospovidone 4.623
Talc 0.462
Colloidal silicon dioxide 0.462
Magnesium stearate 0.462
Extra granular
Crospovidone 4.623
Talc 0.231
Magnesium stearate 0.462
Core tablet weight 97.085
Film coating
Opadry Pink 03F540294 2.915
IPA: water (70:30) ,(for 8% solid content) --
Total weight (Coated tablets) 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with Colloidal silicon dioxide was sifted with Microcrystalline Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate and blended. The above blend is granulated with solution of Low Substituted Hydroxypropyl Cellulose in water. The granulated mixture is sieved to get a suitable size of granules and dried, the dried granules are mixed with extra-granular portion of crospovidone and Talc and lubricated with the previously sifted Magnesium stearate for 5 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

Example 4:
Sacubitril-Valsartan Tablet Colloidal silicon dioxide- Direct compression.

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan with Colloidal silicon dioxide (80:20) 62.513
Microcrystalline cellulose 19.780
Low substituted hydroxypropyl cellulose 3.467
Crospovidone 4.623
Talc 0.462
Colloidal silicon dioxide 0.462
Magnesium stearate 0.462
Extra granular
Crospovidone 4.623
Talc 0.231
Magnesium stearate 0.462
Core tablet weight 97.085
Film coating
Opadry Pink 03F540294 2.915
IPA: water (70:30) ,(for 8% solid content) --
Total weight (Coated tablets) 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with Colloidal silicon dioxide was sifted with Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate. The sifted materials were blended in octagonal blender for 10 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

Example 5:
Sacubitril-Valsartan Tablet with Hydroxy ethyl cellulose

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan with Hydroxy ethyl cellulose (80:20) 62.513 -- -- --
Solid dispersion of Sacubitril and Valsartan with Hydroxy ethyl cellulose (70:30) -- 62.513 -- --
Solid dispersion of Sacubitril and Valsartan with Hydroxy ethyl cellulose (75:25) -- -- 62.513 --
Solid dispersion of Sacubitril and Valsartan with Hydroxy ethyl cellulose (65:35) -- -- -- 62.513
Microcrystalline cellulose 19.780 19.780 19.780 19.780
Low Substituted hydroxypropyl cellulose 3.467 3.467 3.467 3.467
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.462 0.462 0.462 0.462
Colloidal silicon dioxide 0.462 0.462 0.462 0.462
Magnesium stearate 0.462 0.462 0.462 0.462
Extra granular
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.231 0.231 0.231 0.231
Magnesium stearate 0.462 0.462 0.462 0.462
Core tablet weight 97.085 97.085 97.085 97.085
Film coating
Opadry Pink 03F540294 2.915 2.915 2.915 2.915
IPA: water (70:30) ,(for 8% solid content) -- -- -- --
Total weight (Coated tablets) 100.00 100.00 100.00 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with Hydroxy ethyl cellulose was sifted with Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate. The sifted materials were blended in octagonal blender for 10 minutes. The blended material was then compacted in roller compactor and milled. The milled material was sifted and blended with Crospovidone and Talc for 10 minutes and lubricated with the previously sifted Magnesium stearate for 5 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.

Example 6:
Sacubitril-Valsartan Tablet with copovidone

Ingredients % w/w
Intra granular
Solid dispersion of Sacubitril and Valsartan Copovidone (80:20) 62.513 -- -- --
Solid dispersion of Sacubitril and Valsartan with Copovidone (70:30) -- 62.513 -- --
Solid dispersion of Sacubitril and Valsartan with Copovidone (75:25) -- -- 62.513 --
Solid dispersion of Sacubitril and Valsartan with Copovidone (65:35) -- -- -- 62.513
Microcrystalline cellulose 19.780 19.780 19.780 19.780
Low substituted hydroxypropyl cellulose 3.467 3.467 3.467 3.467
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.462 0.462 0.462 0.462
Colloidal silicon dioxide 0.462 0.462 0.462 0.462
Magnesium stearate 0.462 0.462 0.462 0.462
Extra granular
Crospovidone 4.623 4.623 4.623 4.623
Talc 0.231 0.231 0.231 0.231
Magnesium stearate 0.462 0.462 0.462 0.462
Core tablet weight 97.085 97.085 97.085 97.085
Film coating
Opadry Pink 03F540294 2.915 2.915 2.915 2.915
IPA: water (70:30) ,(for 8% solid content) -- -- -- --
Total weight (Coated tablets) 100.00 100.00 100.00 100.00

Manufacturing Procedure:
Amorphous Solid dispersion of Sacubitril and Valsartan with Copovidone was sifted with Microcrystalline Cellulose, Low Substituted Hydroxypropyl Cellulose, Crospovidone, Talc, Colloidal silicon dioxide and Magnesium stearate. The sifted materials were blended in octagonal blender for 10 minutes. The blended material was then compacted in roller compactor and milled. The milled material was sifted and blended with Crospovidone and Talc for 10 minutes and lubricated with the previously sifted Magnesium stearate for 5 minutes. The lubricated blend was compressed into a tablet with a suitable tablet tooling and film-coated in a pan coater.
,CLAIMS:1) A pharmaceutical composition comprising solid dispersion of Sacubitril; Valsartan or its pharmaceutically acceptable salts with one or more pharmaceutically acceptable excipients micro crystalline cellulose, colloidal silicon dioxide, hydroxy ethyl cellulose and copovidone.

2) A pharmaceutical composition as claimed in claim 1, solid dispersion of Sacubitril; Valsartan trisodium complex with micro crystalline cellulose, the ratio between the Sacubitril; Valsartan with micro crystalline cellulose is 80:20, 70:30, 75:25, 65:35.

3) A pharmaceutical composition as claimed in claim 1, solid dispersion of Sacubitril; Valsartan with colloidal silicon dioxide, the ratio between the Sacubitril; Valsartan with colloidal silicon dioxide is 80:20, 70:30, 75:25, 65:35.

4) A pharmaceutical composition as claimed in claim 1, solid dispersion of Sacubitril; Valsartan with hydroxy ethyl cellulose, the ratio between the Sacubitril; Valsartan with hydroxy ethyl cellulose is 80:20, 70:30, 75:25, 65:35.

5) A pharmaceutical composition as claimed in claim 1, solid dispersion of Sacubitril; Valsartan with copovidone, the ratio between the Sacubitril; Valsartan with copovidone is 80:20, 70:30, 75:25, 65:35.

6) A pharmaceutical composition as claimed in claim 1, where in the composition contain excipients selected from the group of diluents, binders, disintegrants, glidants, lubricants, wetting agents and combinations thereof.

7) A pharmaceutical composition as claimed in claim 1, where in the composition contain excipients are microcrystalline cellulose, low substituted hydroxypropyl cellulose, crospovidone, talc, colloidal silicon dioxide, magnesium stearate.

8) A pharmaceutical composition as claimed in claim 1, where in the composition is used for the treatment of cardiovascular diseases.