Formulations of bendamustine

• US 9,597,398 B2
• Filed: 01/28/2016
• Issued: 03/21/2017
• Est. Priority Date: 03/20/2012
• Status: Active Grant

• Current Assignee: Eagle Pharmaceuticals Incorporated
• Original Assignee: Eagle Pharmaceuticals Incorporated
• Inventors: Sundaram, Srikanth
• Primary Examiner(s): Ivanova, Svetlana M
• Application Number:
  US15/008,819
• Publication Number:
  US 20160144034A1
• Time in Patent Office: 418 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia

Abstract

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.

Claims

1. A method of treating cancer or malignant disease in a subject, comprising parenterally administering a volume of about 100 ml or less of a liquid composition comprising:

a) from about 0.05 to about 12.5 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof;

b) a solubilizer comprising propylene glycol in an amount of from about 0.03 to about 5% by volume of the liquid composition and polyethylene glycol;

c) a parenterally acceptable diluent; and

optionally

d) an antioxidant;

over a period of less than or equal to about 10 minutes to a subject in need thereof.

2. The method of claim 1, wherein the volume administered is from about 50 ml to about 65 ml.

3. The method of claim 1, wherein the volume administered is about 50 ml.

4. The method of claim 1, wherein the concentration of bendamustine or pharmaceutically acceptable salt thereof is from about 0.05 mg/ml to about 10 mg/ml.

5. The method of claim 1, wherein the concentration of bendamustine or pharmaceutically acceptable salt thereof is from about 0.1 mg/ml to about 7.0 mg/ml.

6. The method of claim 1, wherein the concentration of bendamustine or pharmaceutically acceptable salt thereof is from about 0.5 mg/ml to about 3.2 mg/ml.

7. The method of claim 1, wherein the concentration of bendamustine or pharmaceutically acceptable salt thereof is about 10 mg/ml.

8. The method of claim 1, wherein the concentration of bendamustine or pharmaceutically acceptable salt thereof is about 5.6 mg/ml.

9. A method of treating cancer or malignant disease in a subject, comprising parenterally administering a volume of about 100 ml or less of a liquid composition comprising:

a) from about 0.05 to about 12.5 mg/ml of bendamustine or a pharmaceutically acceptable salt thereof;

b) a solubilizer comprising propylene glycol in an amount of from about 0.03 to about 5% by volume of the liquid composition and polyethylene glycol;

c) a parenterally acceptable diluent; and

optionally

d) an antioxidant;

over a period of less than or equal to about 20 minutes to a subject in need thereof.

10. The method of claim 9, wherein the composition is administered over a time period of less than or equal to about 15 minutes.