FORMULATIONS OF BENDAMUSTINE
Methods of treatment using bendamustine formulations designed for small volume intravenous administration are disclosed. The methods conveniently allow shorter administration time without the active ingredient coming out of solution as compared to presently available formulations.
1 . A method of treating or preventing cancer or malignant disease in a subject, comprising parenterally administering a volume of about 120 ml or less of a liquid composition containing:
a) about 12.5 mg/ml or less of bendamustine or a pharmaceutically acceptable salt thereof; and
b) a solubilizer;
over a substantially continuous period of less than or equal to about 60 minutes to a subject in need thereof.
2 . The method of claim 1 , wherein the solubilizer comprises propylene glycol.
3 . The method of claim 2 , wherein propylene glycol is present in an amount of about 90% or less, by volume of the formulation.
4 . The method of claim 3 , wherein propylene glycol is present in an amount of from about 5% to about 85%, by volume of the formulation.
5 . The method of claim 4 , wherein the propylene glycol is present in an amount of from about 30% to about 70%, by volume of the formulation.
6 . The method of claim 5 , wherein the propylene glycol is present in an amount of about 34%, by volume of the formulation.
7 . The method of claim 4 , wherein the propylene glycol is present in an amount of about 5%, by volume of the formulation.
8 . The method of claim 1 , wherein the composition is administered over a time period of less than or equal to about 30 minutes.
9 . The method of claim 8 , wherein the composition is administered over a time period of less than or equal to about 15 minutes.
10 . The method of claim 9 , wherein the composition is administered over a time period of less than or equal to about 10 minutes.
11 . The method of claim 1 , wherein the volume administered is from about 15 ml to about 100 ml.
12 . The method of claim 11 , wherein the volume administered is from about 30 ml to about 50 ml.
13 . The method of claim 11 , wherein the volume administered is about 100 ml.
14 . The method of claim 12 , wherein the volume administered is about 50 ml.
15 . The method of claim 1 , wherein the concentration of bendamustine or pharmaceutically acceptable salt is from about 0.05 mg/ml to about 10 mg/ml.
16 . The method of claim 15 , wherein the concentration of bendamustine or pharmaceutically acceptable salt is from about 0.1 mg/ml to about 7.0 mg/ml.
17 . The method of claim 16 , wherein the concentration of bendamustine or pharmaceutically acceptable salt is from about 0.5 mg/ml to about 3.2 mg/ml.
18 . The method of claim 15 , wherein the concentration of bendamustine or pharmaceutically acceptable salt is about 10 mg/ml.
19 . The method of claim 16 , wherein the concentration of bendamustine or pharmaceutically acceptable salt is about 5.6 mg/ml.
20 . The method of claim 18 , wherein the composition is administered intravenously over a time period of about 30 minutes or less.
21 . The method of claim 20 , wherein the composition is administered intravenously over a time period of about 15 minutes or less.
22 . The method of claim 21 , wherein the composition is administered intravenously over a time period of about 10 minutes or less.
23 . The method of claim 19 , wherein the composition is administered intravenously over a time period of about 30 minutes or less.
24 . The method of claim 23 , wherein the composition is administered intravenously over a time period of about 15 minutes or less.
25 . The method of claim 24 , wherein the composition is administered intravenously over a time period of about 10 minutes or less.
26 . The method of claim 13 , wherein the composition is administered intravenously over a time period of about 30 minutes or less.
27 . The method of claim 26 , wherein the composition is administered intravenously over a time period of about 15 minutes or less.
28 . The method of claim 27 , wherein the composition is administered intravenously over a time period of about 10 minutes or less.
29 . The method of claim 14 , wherein the composition is administered intravenously over a time period of about 30 minutes or less.
30 . The method of claim 29 , wherein the composition is administered intravenously over a time period of about 15 minutes or less.
31 . The method of claim 30 , wherein the composition is administered intravenously over a time period of about 10 minutes or less.
32 . A method of treating or preventing cancer or malignant disease in a subject, comprising parenterally administering a volume of about 120 ml or less of a liquid composition containing:
a) about 12.5 mg/ml or less of bendamustine or a pharmaceutically acceptable salt thereof; and
b) a solubilizer comprising propylene glycol;
over a substantially continuous period of less than or equal to about 60 minutes to a subject in need thereof.