LIQUID PHARMACEUTICAL FORMULATIONS OF PALONOSETRON
The present invention relates to shelf-stable liquid formulations of palonosetron for reducing chemotherapy and radiotherapy induced emesis with palonosetron. The formulations are particularly useful in the preparation of intravenous and oral liquid medicaments.
1 . A pharmaceutical single-use, unit-dose formulation for intravenous administration to a human to reduce the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising a 5 mL sterile aqueous isotonic solution, said solution comprising:
palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its free base;
from 0.005 mg/mL to 1.0 mg/mL EDTA; and
from 10 mg/mL to 80 mg/mL mannitol,
wherein said formulation is stable at 24 months when stored at room temperature.
2 . The pharmaceutical formulation of claim 1 , wherein said EDTA is in an amount of 0.5 mg/mL.
3 . The pharmaceutical formulation of claim 1 , wherein said mannitol is in an amount of 41.5 mg/mL.
4 . The pharmaceutical formulation of claim 1 , wherein said solution further comprises a citrate buffer.
5 . The pharmaceutical formulation of claim 4 , wherein said citrate buffer is at a concentration of 20 millimolar.
6 . The pharmaceutical formulation of claim 1 , wherein said solution is buffered at a pH of 5.0±0.5.
7 . The pharmaceutical formulation of claim 1 , wherein said EDTA is in an amount of 0.5 mg/mL, wherein said mannitol is in an amount of 41.5 mg/mL, wherein said solution further comprises a citrate buffer at a concentration of 20 millimolar, and wherein said solution is buffered at a pH of 5.0±0.5.
8 . A pharmaceutical single-use, unit-dose formulation for intravenous administration to a human to reduce the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising a 5 mL sterile aqueous isotonic solution, said solution comprising:
palonosetron hydrochloride in an amount of 0.25 mg based on the weight of its free base;
from 0.005 mg/mL to 1.0 mg/mL EDTA; and
from 10 mg/mL to 80 mg/mL mannitol, wherein said formulation is stable at 18 months when stored at room temperature.
9 . A pharmaceutical single-use, unit-dose formulation for intravenous administration to a human to reduce the likelihood of cancer chemotherapy-induced nausea and vomiting, comprising a 50 mL sterile isotonic solution buffered at a pH of 4.8±0.5 comprising:
palonosetron hydrochloride in an amount of 0.75 mg based on the weight of its free base;
450.0 mg sodium chloride;
2.5 mg EDTA;
18.5 mg sodium citrate; and
7.8 mg citric acid monohydrate,
wherein said formulation is contained in a polyethylene multilayer film infusion bag comprising an isoprene rubber stopper.