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 liquid bendamustine-containing composition comprising bendamustine, or a pharmaceutically acceptable salt thereof, wherein the bendamustine concentration in the composition is from about 10 mg/mL to about 100 mg/mL;
polyethylene glycol; and
a stabilizing amount of an antioxidant;
the composition having less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of from about 5° C. to about 25° C.
2 . The liquid bendamustine-containing composition of claim 1 , wherein the antioxidant is lipoic acid, thioglycerol, propyl gallate, methionine, cysteine, a metabisulfite, sodium formaldehyde sulfoxylate, a phenol-containing aromatic compound, a phenol-containing aliphatic compound, dihydrolipoic acid, or a mixture thereof.
3 . The liquid bendamustine-containing composition of claim 1 , having less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of about 5° C.
4 . The liquid bendamustine-containing composition of claim 1 , having less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of about 25° C.
5 . The liquid bendamustine-containing composition of claim 1 , wherein the bendamustine concentration is from about 20 mg/mL to about 60 mg/mL.
6 . The liquid bendamustine-containing composition of claim 1 , wherein the bendamustine concentration is about 25 mg/mL.
7 . The liquid bendamustine-containing composition of claim 1 , comprising bendamustine hydrochloride.
8 . A method of treating cancer in a mammal, comprising administering an effective amount of the liquid bendamustine-containing composition of claim 1 to the mammal.
9 . The method of claim 8 , wherein the cancer is leukemia.
10 . The method of claim 8 , wherein the cancer is Hodgkin's disease.
11 . The method of claim 8 , wherein the antioxidant is lipoic acid, thioglycerol, propyl gallate, methionine, cysteine, a metabisulfite, sodium formaldehyde sulfoxylate, a phenol-containing aromatic compound, a phenol-containing aliphatic compound, dihydrolipoic acid, or a mixture thereof.
12 . The method of claim 8 , wherein the liquid bendamustine-containing composition has less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of about 5° C.
13 . The method of claim 8 , wherein the liquid bendamustine-containing composition has less than about 5% peak area response of total impurities resulting from the degradation of the bendamustine, as determined by HPLC as a wavelength of 223 nm after at least 15 months at a temperature of about 25° C.
14 . The method of claim 8 , wherein the bendamustine concentration is from about 20 mg/mL to about 60 mg/mL.
15 . The method of claim 8 , wherein the bendamustine concentration is about 25 mg/mL.
16 . The method of claim 8 , wherein the liquid bendamustine-containing composition comprises bendamustine hydrochloride.