Liquid pharmaceutical formulations of palonosetron

• US 7,947,724 B2
• Filed: 07/21/2005
• Issued: 05/24/2011
• Est. Priority Date: 01/30/2003
• Status: Expired due to Term

• Current Assignee: Helsinn Advanced Synthesis SA (Helsinn Healthcare SA), Helsinn Therapeutics (U.S.), Inc (Helsinn Healthcare SA), Helsinn Birex Pharmaceuticals Ltd. (Helsinn Holding SA)
• Original Assignee: Helsinn Healthcare SA, Roche Palo Alto LLC (Roche Holding AG)
• Inventors: Cannella, Roberta, Braglia, Enrico, Lee, Kathleen M., Malefyt, Thomas, Miksztal, Andrew, Bonadeo, Daniele, Calderari, Giorgio, Braglia, Riccardo
• Primary Examiner(s): Fetterolf; Brandon J
• Assistant Examiner(s): Gembeh; Shirley V
• Application Number:
  US11/186,311
• Publication Number:
  US 20060069114A1
• Time in Patent Office: 2,133 Days
• Field of Search: 514/397
• US Class Current: 514/397
• CPC Class Codes: A61J 3/00 Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
• CPC Class Codes: A61K 31/4178 not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
• CPC Class Codes: A61K 31/473 ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
• CPC Class Codes: A61K 31/4747 spiro-condensed
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/16 containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
• CPC Class Codes: A61K 47/183 Amino acids, e.g. glycine, EDTA or aspartame
• CPC Class Codes: A61K 47/26 Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
• 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 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61K 9/0095 Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches A61K9/0007 takes precedence; eatable gels or foams A61K9/0056; oral mucosa adhesive forms A61K9/006
• CPC Class Codes: A61K 9/08 Solutions composition of solutions A61K47/00
• CPC Class Codes: A61P 1/08 for nausea, cinetosis or vertigo; Antiemetics
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B65B 3/04 Methods of, or means for, filling the material into the containers or receptacles
• CPC Class Codes: B65B 55/02 Sterilising, e.g. of complete packages

Abstract

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.

Claims

1. A pharmaceutically stable intravenous solution for reducing emesis or reducing the likelihood of emesis comprising:

a) from 0.03 mg/ml to 0.2 mg/ml palonosetron or a pharmaceutically acceptable salt thereof, buffered at a pH of from 4.0 to 6.0; and

b) a pharmaceutically acceptable sterile aqueous carrier including a tonicifying effective amount of mannitol and from 0.005 mg/ml to 1.0 mg/ml EDTA.

2. The solution of claim 1 wherein the palonosetron or pharmaceutically acceptable salt thereof is in concentration of about 0.05 mg/ml.

3. The solution of claim 1 comprising palonosetron hydrochloride.

4. The solution of claim 1 wherein the pH is from 4.5 to 5.5.

5. The solution of claim 1 wherein the pharmaceutically acceptable carrier comprises from 10 to 100 millimoles of a citrate buffer.

6. The solution of claim 1 comprising 0.3 to 0.7 mg/ml EDTA, and from 10 to 40 millimoles of a citrate buffer.

7. The solution of claim 1 comprising 0.3 to 0.7 mg/ml EDTA, from 10.0 to 80.0 mg/ml mannitol, and from 10 to 40 millimoles of a citrate buffer.

8. A pharmaceutically stable isotonic intravenous solution for reducing emesis or reducing the likelihood of emesis comprising:

a) from 0.01 mg/ml to 5 mg/ml palonosetron or a pharmaceutically acceptable salt thereof, at a pH of from 4.0 to 6.0; and

b) an aqueous pharmaceutically acceptable carrier including a chelating agent.

9. The solution of claim 8 wherein the palonosetron or pharmaceutically acceptable salt thereof is in concentration of about 0.05 mg/ml.

10. The solution of claim 8 comprising palonosetron hydrochloride.

11. The solution of claim 8 wherein the pH is from 4.5 to 5.5.

12. The solution of claim 8 wherein the pharmaceutically acceptable carrier comprises from 0.005 mg/ml to 1.0 mg/ml EDTA.

13. The solution of claim 8 wherein the pharmaceutically acceptable carrier comprises mannitol.

14. The solution of claim 8 adapted for intravenous administration.