초록

The present invention relates to solid state forms of N-2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl-1,4-dihydro-4-oxoquinoline-3-carboxamide (Compound 1), pharmaceutical compositions thereof and methods therewith.

대표청구항 ▼

1. A solid dispersion comprising amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and a polymer, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer

1. A solid dispersion comprising amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and a polymer, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA). 2. The solid dispersion of claim 1, wherein the polymer is polyvinylpyrrolidones (PVP). 3. The solid dispersion of claim 2, wherein the polymer is present in an amount of from about 10% by weight to about 80% by weight. 4. The solid dispersion of claim 3, wherein the polymer is present in an amount of less than about 70% by weight. 5. The solid dispersion of claim 1, wherein the N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide is present in an amount of from about 10% by weight to about 80% by weight. 6. The solid dispersion of claim 1, further comprising a surfactant. 7. The solid dispersion of claim 6, wherein the surfactant is sodium lauryl sulfate. 8. The solid dispersion of claim 7, wherein the surfactant is present in an amount from about 0.1 to about 5%. 9. The solid dispersion of claim 8, wherein the surfactant is present in 0.5%. 10. The solid dispersion according to claim 1, wherein the solid dispersion is obtained by spray drying. 11. A pharmaceutical composition comprising amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide and a polymer as a solid dispersion, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA). 12. The pharmaceutical composition of claim 11, wherein the polymer is polyvinylpyrrolidones (PVP). 13. A solid dispersion comprising N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide, a polymer and sodium lauryl sulfate, wherein the polymer is polyvinylpyrrolidones (PVP), polyvinyl alcohols (PVA), polymethacrylate, β-cyclodextin, or vinylpyrrolidone/vinyl acetate copolymer (PVP/VA). 14. The solid dispersion of claim 13, wherein the polymer is polyvinylpyrrolidones (PVP). 15. A pharmaceutical composition comprising the solid dispersion of claim 13. 16. Solid amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide. 17. Solid amorphous N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide comprising less than about 15% crystalline N-[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide. 18. A pharmaceutical composition comprising solid amorphous N -[2,4-bis(1,1-dimethylethyl)-5-hydroxyphenyl]-1,4-dihydro-4-oxoquinoline-3-carboxamide.