Ready-to-use Carfilzomib compositions
The present invention provides a stable, non-aqueous, ready-to-use parenteral composition comprising: carfilzomib or pharmaceutically acceptable salt thereof, acidifying agent, optionally a surfactant, one or more solvents or co-solvents.
1. A liquid composition comprising:
carfilzomib in an amount of about 1 mg/mL to about 20 mg/mL or a pharmaceutically acceptable salt thereof;
ethanoic acid, wherein a ratio of the ethanoic acid to the carfilzomib is 1.5:1 to 10:1;
at least one solvent;
at least one surfactant selected from the group consisting of a polyoxyethylene sorbitan ester, a polyoxyethylene polyoxypropylene copolymer, a sorbitan ester, lecithin, cremophor, and mixtures thereof, wherein the at least one surfactant is included in an amount of at least about 300 mg/mL; and
an anti-oxidant,
wherein the liquid composition is stable, ready to dilute, and non-aqueous.
2. The liquid composition according to claim 1 , wherein the at least one solvent comprises at least one of an alcohol, a glycol, glycerol or a derivative thereof, and mixtures thereof.
3. The liquid composition according to claim 2 , wherein the glycol is at least one of propylene glycol, polyethylene glycol, and mixtures thereof and the alcohol is at least one of ethanol, butanol, t-butanol, and mixtures thereof.
4. The liquid composition according to claim 1 , wherein the anti-oxidant is at least one of monothioglycerol, alpha-tocopherol, L-cysteine, thioglycolic acid, sodium metabisulfite, ascorbic acid, sodium formaldehyde sulfoxylate, sodium bisulfate, butylated hydroxy toluene, butylated hydroxy anisole, and mixtures thereof.
5. The liquid composition of claim 1 , wherein the antioxidant is alpha-tocopherol; the surfactant is a polyoxyethylene sorbitan ester; and the solvent is glycerol, propylene glycol, polyethylene glycol, ethanol, butanol, t-butanol, and mixtures thereof.
6. The liquid composition according to claim 5 , wherein the liquid composition is ready to dilute; is stable when stored at 25° C., 60% relative humidity for at least 1 month, is clear upon dilution with a physiological solution and is stable when diluted for at least about 24 hours.
7. The liquid composition of claim 1 , wherein the composition is free of non-volatile sugar acid.
8. A liquid composition comprising:
carfilzomib in an amount of about 1 mg/mL to about 20 mg/mL or a pharmaceutically acceptable salt thereof;
ethanoic acid, wherein the ratio of the ethanoic acid to the carfilzomib is about 1.5:1 to about 10:1;
at least one solvent;
at least one surfactant selected from the group consisting of a polyoxyethylene sorbitan ester, a polyoxyethylene polyoxypropylene copolymer, a sorbitan ester, lecithin, cremophor, and mixtures thereof, wherein the at least one surfactant is included in an amount of at least about 300 mg/mL; and
an antioxidant,
wherein the liquid composition is non-aqueous,
wherein the liquid composition is ready to dilute and the liquid composition is clear upon dilution with physiological solution and stable for at least about 24 hours, and has a pH is from about 2 to about 9.
9. The liquid composition according to claim 8 , wherein the composition is stable when stored at 25° C., 60% relative humidity for at least 1 month.
10. A composition comprising:
carfilzomib or a pharmaceutically acceptable salt thereof present in an amount of about 10 mg/mL,
ethanoic acid present in an amount of about 30 mg/mL,
at least one solvent,
polysorbate 80 present in an amount of about 300 mg/mL, and
alpha-tocopherol present in an amount of about 0.2 mg/mL,
and
wherein the composition is stable, ready to use, and non-aqueous.
11. A method for treating multiple myeloma comprising administering the composition according to claim 1 in a parenteral dosage form.