Bendamustine pharmaceutical compositions

• US 8,436,190 B2
• Filed: 01/12/2006
• Issued: 05/07/2013
• Est. Priority Date: 01/14/2005
• Status: Active Grant

• Current Assignee: Cephalon France (Teva Pharmaceutical Industries Limited)
• Original Assignee: Cephalon Incorporated (Teva Pharmaceutical Industries Limited)
• Inventors: Brittain, Jason Edward, Franklin, Joe Craig
• Primary Examiner(s): Soroush, Ali
• Application Number:
  US11/330,868
• Publication Number:
  US 20060159713A1
• Time in Patent Office: 2,672 Days
• Field of Search: 342/84, 548/304.7
• US Class Current: 548/304.7
• 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 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 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/02 for joint disorders, e.g. arthritis, arthrosis
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 37/00 Drugs for immunological or allergic disorders
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection

Abstract

The present invention provides pharmaceutical formulations of lyophilized bendamustine suitable for pharmaceutical use. The present invention further provides methods of producing lyophilized bendamustine. The pharmaceutical formulations can be used for any disease that is sensitive to treatment with bendamustine, such as neoplastic diseases.

Claims

1. A pharmaceutical composition comprising bendamustine or bendamustine hydrochloride, mannitol, tertiary-butyl alcohol and water.

2. The pharmaceutical composition according to claim 1, wherein said bendamustine or bendamustine hydrochloride is present at a concentration of about 12 to 17 mg/ml, said mannitol is present at a concentration of about 20-30 mg/ml, and said tertiary-butyl alcohol is present at a concentration of about 10-50% (v/v).

3. The pharmaceutical composition according to claim 2, wherein said bendamustine or bendamustine hydrochloride is present at a concentration of about 15 mg/ml, said mannitol is present at a concentration of about 25.5. mg/ml, and said tertiary-butyl alcohol is present at a concentration of about 30% (v/v).

4. A lyophilized pharmaceutical composition made from the pharmaceutical composition according to claim 1.

5. The lyophilized pharmaceutical composition according to claim 4, wherein said bendamustine or bendamustine hydrochloride is present in said pharmaceutical composition at a concentration of about 12 to 17 mg/ml, said mannitol is present in said pharmaceutical composition at a concentration of about 20-30 mg/ml, and said tertiary-butyl alcohol is present in said pharmaceutical composition at a concentration of about 10-50% (v/v).

6. The lyophilized pharmaceutical composition according to claim 5, wherein said bendamustine or bendamustine hydrochloride is present in said pharmaceutical composition at a concentration of about 15 mg/ml, said mannitol is present in said pharmaceutical composition at a concentration of about 25.5 mg/ml, and said tertiary-butyl alcohol is present in said pharmaceutical composition at a concentration of about 30% (v/v).

7. The lyophilized pharmaceutical composition according to claim 4 containing not more than about 0.5% bendamustine ethylester.

8. The lyophilized pharmaceutical composition according to claim 5 containing not more than about 0.5% bendamustine ethylester.

9. The lyophilized pharmaceutical composition according to claim 6 containing not more than about 0.5% bendamustine ethylester.