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 vial containing a liquid bendamustine-containing composition comprising
about 100 mg of bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration in the composition is from 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 vial of claim 1 , wherein the antioxidant is monothioglycerol.
3. The sterile vial of claim 1 , wherein the antioxidant is monothioglycerol in a concentration of about 5 mg/mL.
4. The composition 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 vial of claim 1 , wherein the liquid bendamustine-containing composition further comprises ethanol.
6. A liquid bendamustine-containing composition comprising
100 mg of 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 from 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.
7. The composition of claim 6 , wherein the antioxidant is monothioglycerol.
8. The composition of claim 6 , wherein the antioxidant is monothioglycerol in a concentration of about 5 mg/mL.
9. The composition of claim 6 , further comprising ethanol.