Claims for Patent: 9,155,706

Summary for Patent: 9,155,706

Title:	Pharmaceutical composition
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.
Inventor(s):	DeMarini; Douglas J. (Collegeville, PA), Henriquez; Francisco (Collegeville, PA), Le; Ngocdiep T. (Collegeville, PA), Wang; Lihong (Collegeville, PA)
Assignee:	Novartis AG (Basel, CH)
Application Number:	14/103,193
Patent Claims:	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-2 H-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. 2. 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-tetra hydro-2 H-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. 3. 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-tetra hydro-2 H-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. 4. 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-2 H-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. 5. 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-2 H-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. 6. 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-2 H-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. 7. 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-2 H-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%. 8. 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-2 H-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. 9. 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-2 H-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. 10. 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-2 H-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. 11. 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-2 H-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. 12. 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-2 H-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. 13. 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-2 H-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. 14. 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-2 H-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%. 15. 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. 16. 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-2 H-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, 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-2 H-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-2 H-pyrido[4,3d]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; and at least 50% of the drug particles have a particle size of 30 micron or less.