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 ready to use 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 ready to use 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 ready to use 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 ready to use 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 ready to use liquid bendamustine-containing composition of claim 1 , wherein the bendamustine concentration is from about 20 mg/mL to about 60 mg/mL.
6. The ready to use liquid bendamustine-containing composition of claim 1 , wherein the bendamustine concentration is about 25 mg/mL.
7. The ready to use 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 ready to use 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 ready to use 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 ready to use 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 in the ready to use liquid bendamustine-containing composition is from about 20 mg/mL to about 60 mg/mL.
15. The method of claim 8 , wherein the bendamustine concentration in the ready to use liquid bendamustine-containing composition is about 25 mg/mL.
16. The method of claim 8 , wherein the ready to use liquid bendamustine-containing composition comprises bendamustine hydrochloride.