Claims for Patent: 12,208,109

Summary for Patent: 12,208,109

Title:	Physiologically balanced injectable formulations of fosnetupitant
Abstract:	Injectable dosages and formulations of fosnetupitant and pharmaceutically acceptable salts thereof are provided that are efficacious, chemically stable and physiologically balanced for safety and efficacy.
Inventor(s):	Alessio Venturini, Roberta Cannella
Assignee:	Helsinn Healthcare SA
Application Number:	US17/986,934
Patent Claims:	1. A pharmaceutically stable intravenous liquid formulation of fosnetupitant comprising: a) an active ingredient component consisting essentially of from 2.3 to 30 mg/ml of the chloride hydrochloride salt of fosnetupitant; and b) an alkalizing agent; and c) an alkaline pH. 2. A pharmaceutically stable intravenous lyophilized formulation of fosnetupitant comprising: a) an active ingredient component consisting essentially of from 2.3 to 30 mg/ml of the chloride hydrochloride salt of fosnetupitant; and b) an alkalizing agent; at an alkaline pH, based on a suitable reconstitution volume. 3. The liquid formulation of claim 1 at a pH of from 7.5 to 10.0. 4. The liquid formulation of claim 1 comprising sodium hydroxide as the alkalizing agent at a pH of from 7.5 to 10. 5. The liquid formulation of claim 1 comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) sodium hydroxide as the alkalizing agent; at a pH of from 7.5 to 10. 6. The liquid formulation of claim 1 further comprising: a) sodium hydroxide; b) disodium edetate; and c) mannitol. 7. The liquid formulation of claim 1 further comprising from 0.05 to 2.0 mg/mL disodium edetate, from 10 to 100 mg/mL mannitol, sodium hydroxide to a pH of 7.5-10.0, and water q.s. 8. The liquid formulation of claim 1 further comprising from 0.1 to 0.9 mg/mL disodium edetate, from 10 to 100 mg/mL mannitol, sodium hydroxide and hydrochloric acid to a pH of 7.5-10.0, and water q.s. 9. The liquid formulation of claim 1 further comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; b) about 0.32 mg/mL disodium edetate; c) about 38 mg/mL mannitol; d) sodium hydroxide and hydrochloric acid to a pH of 8.5-9.5; and e) water q.s. 10. The liquid formulation of claim 1 in the absence of a phosphate. 11. The liquid formulation of claim 1 comprising netupitant and fosnetupitant at a weight ratio of from 0.01:99.99 to 2:98. 12. The lyophilized formulation of claim 2 at a pH of from 7.5 to 10.0 upon reconstitution in water. 13. The lyophilized formulation of claim 2 comprising sodium hydroxide as the alkalizing agent at a pH of from 7.5 to 10 upon reconstitution in water. 14. The lyophilized formulation of claim 2 comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; and b) sodium hydroxide as the alkalizing agent; at a pH of from 7.5 to 10 upon reconstitution in water. 15. The lyophilized formulation of claim 2 further comprising: a) sodium hydroxide; b) disodium edetate; and c) mannitol. 16. The lyophilized formulation of claim 2 further comprising from 0.05 to 2.0 mg/mL disodium edetate, from 10 to 100 mg/mL mannitol, and sodium hydroxide at a pH of 7.5-10.0 upon reconstitution in water. 17. The lyophilized formulation of claim 2 further comprising from 0.1 to 0.9 mg/mL disodium edetate, and from 10 to 100 mg/mL mannitol. 18. The lyophilized formulation of claim 2 further comprising from 0.1 to 0.9 mg/mL disodium edetate, from 10 to 100 mg/mL mannitol, and sodium chloride and hydrochloric acid q.s. to pH 7.5-10.0 upon reconstitution in water. 19. The lyophilized formulation of claim 2 further comprising: a) about 13.0 mg/mL of the chloride hydrochloride salt of fosnetupitant; b) about 0.32 mg/mL disodium edetate; and c) about 38 mg/mL mannitol; and sodium chloride and hydrochloric acid q.s. to a pH 8.5-9.5 upon reconstitution in water; based on a reconstitution in water volume of 20 mL. 20. The lyophilized formulation of claim 2 in the absence of a phosphate. 21. The lyophilized formulation of claim 2 comprising netupitant and fosnetupitant at a weight ratio of from 0.01:99.99 to 2:98. 22. A method of manufacturing a liquid intravenous or lyophilized intravenous formulation consisting of fosnetupitant as an active ingredient comprising: a) admixing fosnetupitant or a pharmaceutically acceptable salt thereof with sodium hydroxide in water at a basic pH to form a solution; b) after step (a), reducing the pH of the solution to a basic pH by the addition of one or more acidic pH adjusting agents; and c) after step (a), admixing the solution with one or more pharmaceutically acceptable excipients. 23. The method of claim 22, wherein the acidic pH adjusting agent comprises hydrochloric acid.