Formulations of bendamustine
Long term storage stable bendamustine-containing compositions are disclosed. The compositions can include bendamustine or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable fluid which can include in some embodiments PEG, PG or mixtures thereof and an antioxidant or chloride ion source. The bendamustine-containing compositions have less than about 5% total impurities, on a normalized peak area response (“PAR”) basis as determined by high performance liquid chromatography (“HPLC”) at a wavelength of 223 nm, after at least about 15 months of storage at a temperature of from about 5° C. to about 25° C.
1. A sterile container containing a liquid bendamustine-containing composition comprising
bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration in the composition is about 25 mg/ml;
a pharmaceutically acceptable fluid consisting of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol; and
a stabilizing amount of an antioxidant,
wherein the total impurities resulting from the degradation of the bendamustine is less than about 5% peak area response, as determined by HPLC at a wavelength of 223 nm after at least about 15 months at a temperature of about 5° C. to about 25° C.
2. The sterile container of claim 1 , wherein the antioxidant is monothioglycerol.
3. The sterile container of claim 1 , wherein the antioxidant is monothioglycerol in a concentration of about 5 mg/mL.
4. The sterile container of claim 1 , wherein the composition is stable for at least about 15 months at 5° C. or for at least about 15 months at 25° C.
5. The sterile container of claim 1 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol.
6. The sterile container of claim 1 , wherein the liquid bendamustine-containing composition comprises about 100 mg of bendamustine, or a pharmaceutically acceptable salt thereof.
7. The sterile container of claim 1 , wherein the liquid bendamustine-containing composition comprises about 100 mg of bendamustine.
8. A liquid bendamustine-containing composition comprising
bendamustine, or a pharmaceutically acceptable salt thereof, and a stabilizing amount of an antioxidant, in a pharmaceutically acceptable fluid;
wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and optionally one or more of propylene glycol, ethanol, benzyl alcohol and glycofurol; and
wherein the bendamustine concentration in the pharmaceutically acceptable fluid is about 25 mg/mL,
wherein the total impurities resulting from the degradation of the bendamustine is less than about 5% peak area response, as determined by HPLC at a wavelength of 223 nm after at least about 15 months at a temperature of about 5° C. to about 25° C.
9. The composition of claim 8 , wherein the antioxidant is monothioglycerol.
10. The composition of claim 8 , wherein the antioxidant is monothioglycerol in a concentration of about 5 mg/mL.
11. The composition of claim 8 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and one or more of propylene glycol, ethanol, benzyl alcohol, and glycofurol.
12. The composition of claim 8 , wherein the bendamustine concentration in the composition is 25 mg/mL.
13. The sterile container of claim 5 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol.
14. The sterile container of claim 5 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and propylene glycol.
15. The sterile container of claim 5 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and ethanol.
16. The sterile container of claim 5 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and benzyl alcohol.
17. The sterile container of claim 5 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and glycofurol.
18. The composition of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol.
19. The composition of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and propylene glycol.
20. The composition of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and ethanol.
21. The composition of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and benzyl alcohol.
22. The composition of claim 11 , wherein the pharmaceutically acceptable fluid consists of polyethylene glycol and glycofurol.