Liquid pharmaceutical formulations of palonosetron

• US 8,518,981 B2
• Filed: 04/14/2011
• Issued: 08/27/2013
• 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: Calderari, Giorgio, Bonadeo, Daniele, Cannella, Roberta, Miksztal, Andrew, Malefyt, Thomas, Lee, Kathleen
• Primary Examiner(s): Gembeh, Shirley V
• Application Number:
  US13/087,012
• Publication Number:
  US 20110192493A1
• Time in Patent Office: 866 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 method of manufacturing and terminally sterilizing a finished single unit dose vial of palonosetron or a pharmaceutically acceptable salt thereof comprising:

a) providing one or more sterile open containers;

b) filling said containers with a pharmaceutically stable solution of palonosetron or a pharmaceutically acceptable salt thereof;

c) sealing said filled containers;

d) terminally sterilizing said sealed, filled containers; and

e) optionally adjusting the pH of said solution using HCl or NaOH prior to step (c), wherein the pharmaceutically stable solution has a pH of from about 4.0 to about 6.0 and comprises palonosetron hydrochloride in a concentration of from about 0.03 mg/mL to about 0.2 mg/mL based on the weight of the free base, an aqueous carrier, and a tonicity agent, and wherein the pharmaceutically stable solution optionally comprises one or a combination of mannitol, a chelating agent, and a citrate buffer.

2. The method of claim 1, wherein said solution comprises 0.05 mg/ml of palonosetron hydrochloride based on the weight of the free base.

3. The method of claim 1, wherein said solution comprises HCl or NaOH as a pH adjusting agent.

4. The method of claim 1, wherein said solution has a pH of from 4.5 to 5.5, HCl or NaOH as a pH adjusting agent, and mannitol.

5. A single unit dose of palonosetron hydrochloride made by the method of claim 4.

6. The method of claim 1, wherein said solution has a pH of from 4.5 to 5.5, HCl or NaOH as a pH adjusting agent, a chelating agent and mannitol.

7. A single unit dose of palonosetron hydrochloric made by the method of claim 6.

8. The method of claim 1, wherein said solution comprises HCl or NaOH as a pH adjusting agent, a chelating agent and mannitol.

9. The method of claim 1, wherein said solution comprises a chelating agent and mannitol.

10. The method of claim 1, wherein said solution comprises a chelating agent.

11. The method of claim 1, wherein said solution comprises mannitol.

12. A single unit dose of palonosetron hydrochloride made by the method of claim 1.