Pharmaceutical composition
View Patent ↗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.
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.