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 method of storing one or more containers in which are contained a solution of palonosetron or a pharmaceutically acceptable salt thereof comprising:
a) providing a room comprising said one or more containers;
b) adjusting or maintaining the temperature of the room at greater than ten degrees Celsius;
c) storing said containers in said room for one month or more, wherein (i) the palonosetron or pharmaceutical salt thereof is present in an intravenous formulation at a concentration of from 0.01 mg/mL to about 5.0 mg/mL, (ii) the pH of the solution is from about 4.0 to about 6.0, (iii) the solution comprises from 0.01 to about 5.0 mg/ml palonosetron or a pharmaceutically acceptable salt thereof, from about 10 to about 100 millimoles citrate buffer and from about 0.005 to about 1.0 mg/ml EDTA, (iv) the solution comprises mannitol, or (v) the solution comprises from about 10 to about 100 milliMoles of a citrate buffer.
2. A pharmaceutically stable solution for preventing or reducing emesis stored by the method of claim 1 , said solution comprising
a) from 0.01 to about 5.0 mg/ml palonosetron or a pharmaceutically acceptable salt thereof;
b) from 10 to about 100 millimoles citrate buffer;
c) from 0.005 to about 1.0 mg/ml EDTA;
d) mannitol,
and wherein the pH of said stable solution is from 4.0 to about 6.0.
3. A method of filling a container in which is contained a solution of palonosetron or a pharmaceutically acceptable salt thereof comprising:
a) providing one or more sterile open containers;
b) filling said containers with a solution of palonosetron in a non-aseptic environment
c) sealing said filled containers; and
d) sterilizing said sealed, filled containers, wherein (i) the palonosetron or pharmaceutical salt thereof is present in an intravenous formulation at a concentration of from 0.01 mg/mL to about 5.0 mg/mL, (ii) the pH of the solution is from 4.0 to about 6.0, (iii) the solution comprises from about 0.01 to about 5.0 mg/ml palonosetron or a pharmaceutically acceptable salt thereof, from 10 to about 100 millimoles citrate buffer and from 0.005 to about 1.0 mg/ml EDTA, (iv) the solution comprises mannitol, or (v) the solution comprises from 10 to about 100 milliMoles of a citrate buffer.