Claims for Patent: 8,052,994

Summary for Patent: 8,052,994

Title:	3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-y- lidene] hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine)
Abstract:	Disclosed are novel pharmaceutical compositions containing 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine) (eltrombopag olamine) and processes for preparing the same.
Inventor(s):	Muller; Francis X. (King of Prussia, PA), Kapsi; Shivakumar G. (King of Prussia, PA)
Assignee:	GlaxoSmithKline LLC (Philadelphia, PA)
Application Number:	12/607,305
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 8,052,994
Patent Claims:	1. A pharmaceutical tablet consisting essentially of: a) about 63.8 mg of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine); wherein, b) about 90% of the compound particles have a particle size of greater than 10 micron but less than 90 micron; 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 excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; e) the tablet is film coated; f) the tablet contains a disintegrant in an amount from 4% to about 12% by weight; g) the tablet optionally contains a binder in an amount up to about 8% by weight; and h) the tablet optionally contains a lubricant in an amount up to about 2% by weight. 2. A pharmaceutical tablet according to claim 1 wherein: the tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose and mannitol. 3. A process for preparing pharmaceutical tablets containing about 63.8 mg of 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyra- zol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine), which process comprises the steps of; a) admixing: the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine), wherein about 90% of the compound particles have a particle size of greater than 10 micron but less than 90 micron; one or more excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; and further excipients; to form a mixture; b) compressing the mixture into tablets; and c) applying a film coating to the tablets; provided: the process is carried out on a scale suitable to prepare at least about 50,000 tablets; each tablet contains about 63.8 mg of 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine); each tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; each tablet contains a disintegrant in an amount from 4% to about 12% by weight; each tablet optionally contains a binder in an amount up to about 8% by weight; and each tablet optionally contains a lubricant in an amount up to about 2% by weight. 4. A process according to claim 3 wherein: each tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose and mannitol. 5. A pharmaceutical tablet consisting essentially of: a) about 63.8 mg of the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1 ,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine); wherein, b) about 90% of the compound particles have a particle size of greater than 10 micron but less than 90 micron; c) the tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; d) the tablet is film coated; e) the tablet contains a disintegrant in an amount from 4% to about 12% by weight; f) the tablet optionally contains a binder in an amount up to about 8% by weight; and g) the tablet optionally contains a lubricant in an amount up to about 2% by weight. 6. A pharmaceutical tablet according to claim 5 wherein: the tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose and mannitol. 7. A process for preparing pharmaceutical tablets containing about 63.8 mg of 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyra- zol-4-ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine), which process comprises the steps of; a) admixing: the compound 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine), wherein about 90% of the compound particles have a particle size of greater than 10 micron but less than 90 micron; one or more excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; and further excipients; to form a mixture; b) compressing the mixture into tablets; and c) applying a film coating to the tablets; provided: each tablet contains about 63.8 mg of 3'-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-- ylidene]hydrazino]-2'-hydroxy-[1,1'-biphenyl]-3-carboxylic acid bis-(monoethanolamine); and each tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose, powdered cellulose, pregelatinized starch, starch, lactitol, mannitol, sorbitol and maltodextrin; each tablet contains a disintegrant in an amount from 4% to about 12% by weight; each tablet optionally contains a binder in an amount up to about 8% by weight; and each tablet optionally contains a lubricant in an amount up to about 2% by weight. 8. A process according to claim 7 wherein: each tablet contains from about 25% to about 89% by weight of one or more excipients selected from the group consisting of microcrystalline cellulose and mannitol. 9. A method of treating thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of a pharmaceutical tablet according to claim 1. 10. A method of treating thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of a pharmaceutical tablet according to claim 2. 11. A method of treating thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of a pharmaceutical tablet according to claim 5. 12. A method of treating thrombocytopenia in a human in need thereof which comprises administering to such human a therapeutically effective amount of a pharmaceutical tablet according to claim 6.