Liquid formulations of bendamustine

• US 8,344,006 B2
• Filed: 01/31/2012
• Issued: 01/01/2013
• Est. Priority Date: 09/25/2008
• Status: Active Grant

• Current Assignee: Cephalon France (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Drager, Anthony S., Patel, Piyush R., Labell, Rachel Y.
• Primary Examiner(s): Padmanabhan, Sreeni
• Assistant Examiner(s): KANTAMNENI, SHOBHA
• Application Number:
  US13/362,430
• Publication Number:
  US 20120129904A1
• Time in Patent Office: 336 Days
• Field of Search: 514/359, 514/715, 514/724, 514/563
• US Class Current: 514/359
• CPC Class Codes: A61K 31/4184 condensed with carbocyclic rings, e.g. benzimidazoles
• 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 47/18 Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
• 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 47/40 Cyclodextrins; Derivatives thereof
• 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: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia

Abstract

Stable liquid formulations of bendamustine, and pharmaceutically acceptable salts thereof, and polar aprotic solvents, are described.

Claims

1. A stable, non-aqueous liquid, pharmaceutical formulation comprising from about 5 mg/ml to about 120 mg/mL of bendamustine, or a pharmaceutically acceptable salt thereof, solubilized in about 66% (v/v) of dimethylacetamide and about 34% (v/v) of propylene glycol, wherein said formulation, following dilution with a pharmaceutically acceptable diluent, is suitable for injection into a patient without lyophilization.

2. The formulation of claim 1, comprising about 100 mg/mL of bendamustine, or a pharmaceutically acceptable salt thereof.

3. The formulation of claim 1, wherein the bendamustine is bendamustine hydrochloride.

4. The formulation of claim 1, further comprising at least one pharmaceutically acceptable excipient or diluent.

5. The formulation of claim 1, further comprising an antioxidant, a surfactant, a lipid, a filler, an organic acid, a hydrophilic polymer, a complexing agent, a preservative, or a combination thereof.

6. A method of treating chronic lymphocytic leukemia or non-Hodgkin'"'"'s lymphoma comprising

providing a liquid, pharmaceutical formulation of claim 1;

diluting the liquid pharmaceutical formulation with a pharmaceutically acceptable injectable diluent to form an injectable pharmaceutical preparation;

administering the injectable pharmaceutical preparation to a patient in need of treatment thereof.

7. The method of claim 6, wherein the liquid pharmaceutical formulation comprises about 100 mg/mL of bendamustine, or a pharmaceutically acceptable salt thereof.

8. The method of claim 6, wherein the pharmaceutically acceptable injectable diluent is 0.9% sodium chloride.

9. The formulation of claim 2, comprising 90 mg/mL of bendamustine hydrochloride.

10. The method of claim 7, comprising 90 mg/mL of bendamustine hydrochloride.