# US 2024/0197705 A1 · Stable Pharmaceutical Compositions of Apixaban > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2024/0197705 A1 - Document ID: US20240197705A1 - Status: Published application - Kind: A1 - Application number: 18/420,099 - Filed: 2024-01-23 - Published: 2024-06-20 - Earliest claimed: 2022-07-27 - Assignees: Slayback Pharma LLC - Applicants: Slayback Pharma LLC - Inventors: Shailendra Mandge; Venkateshwar Reddy Keesara; Harish Gunda; Naga Venkata Durga Prasad Ketha; Satheesh Balasubramanian; Sumitra Ashokkumar Pillai; Sushant Omprakash Dube; Praveen Kumar Subbappa - Web page: https://patentgrep.com/patent/US20240197705A1 ## CPC - A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone - A61K 9/4825: {Proteins, e.g. gelatin (gelatin capsule shells with substantial amounts of other macromolecular substances A61K9/4816)} - A61K 9/4858: {Organic compounds} - A61K 9/4866: {Organic macromolecular compounds} - A61K 9/4891: {Coated capsules; Multilayered drug free capsule shells (with drug coating for immediate release A61K9/4808; osmotic devices A61K9/0004)} - A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) ## Abstract The present invention relates to stable pharmaceutical compositions comprising apixaban or its pharmaceutically acceptable salts thereof. The present invention further relates to a capsule composition comprising a therapeutically effective amount of apixaban solubilized or dispersed in a pharmaceutically acceptable carrier, wherein the therapeutically effective amount of apixaban ranges from about 0.5 mg/unit dosage form to about 50 mg/unit dosage form. The present invention also provides manufacturing processes thereof and use of the said compositions for prevention, treatment or prophylaxis of disorders in human patients in need thereof. ## Claims ### Claim 1 An immediate-release pharmaceutical composition comprising a fill material encapsulated in a capsule shell, wherein the fill material comprises: a. apixaban and b. a pharmaceutically acceptable carrier system comprising at least one of a solubilizing agent, a crystallization inhibitor, a stabilizer, and a solvent; wherein fill material is in the form of a liquid; wherein apixaban is uniformly solubilized in the pharmaceutically acceptable carrier system; and wherein the capsule shell is a gelatin capsule coated with a functional coating; and wherein the composition provides an in-vitro release of not more than about 50 wt % of the apixaban, within 60 min of dissolution in 900 mL of a 0.1N HCl with 0.05% SLS, (pH 1.2) dissolution medium, measured using USP Apparatus II, at 75 RPM and 37° C. ### Claim 2 (depends on 1) The pharmaceutical composition of claim 1, wherein the composition provides an in-vitro release of not more than about 50 wt % of the apixaban, within 60 min of dissolution in 900 mL of a 0.05 M Sodium Phosphate Buffer with 0.05% SLS, (pH 6.8) dissolution medium, measured using USP Apparatus II, at 75 RPM and 37° C. ### Claim 3 (depends on 1) The pharmaceutical composition of claim 1, wherein the functional coating comprises a methacrylic acid/methylmethacrylate copolymer. ### Claim 4 (depends on 3) The pharmaceutical composition of claim 3, wherein the functional coating comprises an ammonio methacrylate copolymer type A® (Eudragit RL30D), hydroxypropyl methylcellulose, polyethylene glycol, talc, and triethyl citrate. ### Claim 5 (depends on 4) The pharmaceutical composition of claim 4, wherein the functional coating comprises an ammonio methacrylate copolymer type A® (Eudragit RL30D) in an amount of about 21.8 mg, hydroxypropyl methylcellulose in an amount of about 26.0 mg, polyethylene glycol in an amount of about 6.5 mg, talc in an amount of about 2.1 mg, and triethyl citrate in an amount of about 6.5 mg. ### Claim 6 (depends on 1) The pharmaceutical composition of claim 1, wherein the fill material comprises (a) apixaban in an amount selected from the group consisting of about 2.5 mg and about 5 mg, (b) polyethylene glycol-400 in an amount of about 500 mg, (c) propylene glycol in an amount of about 60 mg, (d) triacetin in an amount of about 25 mg, and (e) polyvinylpyrrolidone in an amount of about 10 mg. ### Claim 7 (depends on 1) The pharmaceutical composition of claim 1, wherein the capsule shell comprises gelatin in an amount of about 70% by weight of the capsule shell, sorbitol solution in an amount of about 10% by weight of the capsule shell, glycerin in an amount of about 10% by weight of the capsule shell, and water in an amount of about 10% by weight of the capsule shell. ### Claim 8 (depends on 5) The pharmaceutical composition of claim 5, wherein the fill material comprises (a) apixaban in an amount selected from the group consisting of about 2.5 mg and about 5 mg, (b) polyethylene glycol-400 in an amount of about 500 mg, (c) propylene glycol in an amount of about 60 mg, (d) triacetin in an amount of about 25 mg, (e) polyvinylpyrrolidone in an amount of about 10 mg. ### Claim 9 (depends on 8) The pharmaceutical composition of claim 8, wherein the capsule shell comprises gelatin in an amount of about 70% by weight of the capsule shell, sorbitol solution in an amount of about 10% by weight of the capsule shell, glycerin in an amount of about 10% by weight of the capsule shell, and water in an amount of about 10% by weight of the capsule shell. ### Claim 10 (depends on 1) The pharmaceutical composition of claim 1, wherein the said pharmaceutical composition provides a release of the apixaban bioequivalent to the same dose of apixaban in immediate release tablet form, wherein the said bioequivalence is established by at least one of: (i) a confidence interval for mean AUC0-t between about 80% and about 125%; (ii) a confidence interval for mean AUC0-infinity between about 80% and about 125%; (iii) a confidence interval for mean Cmax between about 80% and about 125%, following administration in human subjects under fasting condition. ### Claim 11 An immediate-release pharmaceutical composition comprising a fill material encapsulated in a capsule shell, wherein the fill material comprises: a. apixaban and b. a pharmaceutically acceptable carrier system comprising at least one of a solubilizing agent, a crystallization inhibitor, a stabilizer, and a solvent; wherein fill material is in the form of a liquid; wherein apixaban is uniformly solubilized in the pharmaceutically acceptable carrier system; and wherein the capsule shell is a gelatin capsule coated with a functional coating; and wherein the said pharmaceutical composition provides a release of the apixaban bioequivalent to the same dose of apixaban in immediate release tablet form, wherein the said bioequivalence is established by at least one of: (i) a confidence interval for mean AUC0-t between about 80% and about 125%; (ii) a confidence interval for mean AUC0-infinity between about 80% and about 125%; (iii) a confidence interval for mean Cmax between about 80% and about 125%, following administration in human subjects under fasting condition. ### Claim 12 (depends on 11) The pharmaceutical composition of claim 11, wherein the functional coating comprises a methacrylic acid/methylmethacrylate copolymer. ### Claim 13 (depends on 12) The pharmaceutical composition of claim 12, wherein the functional coating comprises an ammonio methacrylate copolymer type A® (Eudragit RL30D), hydroxypropyl methylcellulose, polyethylene glycol, talc, and triethyl citrate. ### Claim 14 (depends on 13) The pharmaceutical composition of claim 13, wherein the functional coating comprises an ammonio methacrylate copolymer type A® (Eudragit RL30D) in an amount of about 21.8 mg, hydroxypropyl methylcellulose in an amount of about 26.0 mg, polyethylene glycol in an amount of about 6.5 mg, talc in an amount of about 2.1 mg, and triethyl citrate in an amount of about 6.5 mg. ### Claim 15 (depends on 11) The pharmaceutical composition of claim 11, wherein the fill material comprises (a) apixaban in an amount selected from the group consisting of about 2.5 mg and about 5 mg, (b) polyethylene glycol-400 in an amount of about 500 mg, (c) propylene glycol in an amount of about 60 mg, (d) triacetin in an amount of about 25 mg, and (e) polyvinylpyrrolidone in an amount of about 10 mg. ### Claim 16 (depends on 11) The pharmaceutical composition of claim 11, wherein the capsule shell comprises gelatin in an amount of about 70% by weight of the capsule shell, sorbitol solution in an amount of about 10% by weight of the capsule shell, glycerin in an amount of about 10% by weight of the capsule shell, and water in an amount of about 10% by weight of the capsule shell. ### Claim 17 (depends on 13) The pharmaceutical composition of claim 13, wherein the fill material comprises (a) apixaban in an amount selected from the group consisting of about 2.5 mg and about 5 mg, (b) polyethylene glycol-400 in an amount of about 500 mg, (c) propylene glycol in an amount of about 60 mg, (d) triacetin in an amount of about 25 mg, and (e) polyvinylpyrrolidone in an amount of about 10 mg. ### Claim 18 (depends on 17) The pharmaceutical composition of claim 17, the capsule shell comprises gelatin in an amount of about 70% by weight of the capsule shell, sorbitol solution in an amount of about 10% by weight of the capsule shell, glycerin in an amount of about 10% by weight of the capsule shell, and water in an amount of about 10% by weight of the capsule shell.