# US 2014/0154316 A1 · Novel pharmaceutical composition > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2014/0154316 A1 - Document ID: US20140154316A1 - Status: Published application - Kind: A1 - Application number: 14/103,092 - Filed: 2013-12-11 - Published: 2014-06-05 - Earliest claimed: 2010-12-20 - Assignees: Glaxosmithkline Intellectual Property (No.2) Limited - Applicants: GlaxoSmithKline Intellectual Property (No.2) Limited - Inventors: Douglas J. DeMARINI; Francisco Henriquez; Ngocdiep T. Le; Lihong Wang - Web page: https://patentgrep.com/patent/US20140154316A1 ## CPC - A61K 9/2059: {Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin} - A61J 3/06: into the form of pills, lozenges or dragees - A61J 3/10: into the form of compressed tablets (tablet presses B30B11/00) - A61K 9/2009: {Inorganic compounds} - A61K 9/2018: {Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates} - A61K 9/2054: {Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose} - A61K 9/2095: {Tabletting processes} - A61K 9/2813: {Inorganic compounds} - A61K 31/519: ortho- or peri-condensed with heterocyclic rings - A61P 35/00: Antineoplastic agents - C07D 471/04: Ortho-condensed systems - 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) - A61J: CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract Disclosed are novel pharmaceutical compositions containing N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, methods of using the compositions in therapy and processes for preparing the same. ## Claims ### Claim 1 A pharmaceutical tablet comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized. ### Claim 2 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; and c) the tablet contains from about 25% to about 89% by weight of one or more diluents, where the diluents are substantially free of water. ### Claim 3 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; and c) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water. ### Claim 4 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; c) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and d) the tablet is film coated. ### Claim 5 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and e) the tablet is film coated. ### Claim 6 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and e) the tablet is film coated and wherein the film coating contains a colorant. ### Claim 7 (depends on 1) The pharmaceutical tablet, according to claim 1, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) the drug particles are micronized; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; e) the tablet is film coated and wherein the film coating contains a colorant that contains iron oxide; and f) amount of unsolvated drug does not exceed about 20%. ### Claim 8 The pharmaceutical tablet comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less. ### Claim 9 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; and c) the tablet contains from about 25% to about 89% by weight of one or more diluents, where the diluents are substantially free of water. ### Claim 10 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; c) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water. ### Claim 11 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; c) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and d) the tablet is film coated. ### Claim 12 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and e) the tablet is film coated. ### Claim 13 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; and e) the tablet is film coated and wherein the film coating contains a colorant. ### Claim 14 (depends on 8) The pharmaceutical tablet, according to claim 8, comprising: a) an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; wherein, b) at least 50% of the drug particles have a particle size of 30 micron or less; c) the tablet is produced on a scale suitable to prepare at least about 50,000 tablets; d) the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactose, Di-calcium phosphate, lactitol, mannitol, sorbitol and maltodextrin, where the diluents are substantially free of water; e) the tablet is film coated and wherein the film coating contains a colorant that contains iron oxide; and f) amount of unsolvated drug does not exceed about 20%. ### Claim 15 (depends on 2) The pharmaceutical tablet according to claim 2 wherein: the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose and mannitol. ### Claim 16 (depends on 9) The pharmaceutical tablet according to claim 9 wherein: the tablet contains from about 25% to about 89% by weight of one or more diluents selected from: microcrystalline cellulose and mannitol. ### Claim 17 A process for preparing pharmaceutical tablets containing an amount of a drug, which is N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, in an amount selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg, which process comprises the steps of; admixing: N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxide solvate, one or more excipients, where the excipients are substantially free of water, and further excipients, to form a mixture; and compressing the mixture into tablets; provided: each tablet contains N-{3-[3-cyclopropyl-5-(2-fluoro-4-iodo-phenylamino)-6,8-dimethyl-2,4,7-trioxo-3,4,6,7-tetrahydro-2H-pyrido[4,3-d]pyrimidin-1-yl]phenyl}acetamide dimethyl sulfoxidein solvate in an amount selected from: about 0.5635 mg, about 1.127 mg, and about 2.254 mg; and at least 50% of the drug particles have a particle size of 30 micron or less.