Details for Patent: 9,763,880

Title:	Non-aqueous taxane formulations and methods of using the same
Abstract:	Non-aqueous, ethanol-free taxane formulations are provided. Formulations of embodiments of the invention include a taxane, an oil, a non-ionic surfactant, a non-aqueous solvent, and an organic acid component, wherein the organic acid component is soluble in the non-aqueous solvent and the amount by weight of non-ionic surfactant is equal to or greater than the amount by weight of non-aqueous solvent. Also provided are methods of using the formulations, as well as kits that include the formulations. Non-aqueous, ethanol-free docetaxel formulations are provided. Formulations of embodiments of the invention include docetaxel, an oil, a non-ionic surfactant, a non-aqueous solvent, and an organic acid which is soluble in the non-aqueous solvent and is substantially free of any conjugate base. Also provided are methods of using the formulations, as well as kits that include the formulations.
Inventor(s):	Nabeta; Kiichiro (Tokyo, JP)
Assignee:	Teikoku Pharma USA, Inc. (San Jose, CA)
Filing Date:	Mar 10, 2016
Application Number:	15/066,087
Claims:	1. A method of treating a cellular proliferative disease, comprising administering to a subject in need thereof a non-aqueous, ethanol-free docetaxel liquid formulation comprising: docetaxel in an amount ranging from about 0.5 to about 5 wt %; an oil in an amount ranging from about 1 to about 5 wt %; a non-ionic surfactant; a non-aqueous solvent, which is polyethylene glycol having an average molecular weight of less than about 1000, in an amount ranging from about 20 to about 60 wt %; and an organic acid component; wherein the organic acid component is soluble in the non-aqueous solvent and the amount by weight of non-ionic surfactant is equal to or greater than the amount by weight of non-aqueous solvent. 2. The method according to claim 1, wherein the docetaxel is present in about 2 wt %. 3. The method according to claim 2, wherein the docetaxel is anhydrous docetaxel. 4. The method according to claim 2, wherein the docetaxel is docetaxel trihydrate. 5. The method according to claim 1, wherein the oil is selected from the group consisting of synthetic oils, vegetable oils, tocopherols and combinations thereof. 6. The method according to claim 5, wherein the oil is selected from the group consisting of soybean oil, olive oil, sesame oil, corn oil, a medium chain triglyceride, a tocopherol or derivative thereof and combinations thereof. 7. The method according to claim 6, wherein the oil is soybean oil. 8. The method according to claim 1, wherein the non-ionic surfactant is present in an amount ranging from about 40 to about 75 wt %. 9. The method according to claim 8, wherein the non-ionic surfactant is present in an amount ranging from about 50 to about 60 wt %. 10. The method according to claim 1, wherein the non-ionic surfactant is polysorbate 80. 11. The method according to claim 1, wherein the non-aqueous solvent is present in an amount ranging from about 35 to about 45 wt %. 12. The method according to claim 1, wherein the organic acid component is present in an amount ranging from 0.5 to 1 wt %. 13. The method according to claim 12, wherein the organic acid component is an organic acid selected from the group consisting of lactic acid and acetic acid. 14. The method according to claim 13, wherein the organic acid is lactic acid. 15. The method according to claim 1, wherein the amount by weight of oil is equal to or less than about 2.5 times the amount of taxane. 16. The method according to claim 1, wherein in the non-aqueous, ethanol-free docetaxel liquid formulation: the docetaxel is docetaxel trihydrate; the oil is soybean oil the non-ionic surfactant is polysorbate 80 in an amount ranging from about 50 to about 60 wt %; the non-aqueous solvent is polyethylene glycol in an amount ranging from about 35 to about 45 wt %; and the organic acid component is present in an amount ranging from 0.3 to 1 wt %. 17. The method according to claim 1, wherein the ethanol-free docetaxel liquid formulation has a pH of less than about 3.5. 18. The method according to claim 1, wherein the formulation is stable for more than 6 months at 40.degree. C. 19. The method according to claim 1, wherein the formulation exhibits a docetaxel recovery rate of greater than 95% after 6 months at 40.degree. C. 20. The method according to claim 1, wherein the formulation forms particles of less than about 20 nm when combined with an aqueous medium. 21. The method according to claim 1, wherein the ethanol-free docetaxel liquid formulation is administered to the subject by: (a) combining the ethanol-free docetaxel formulation with an aqueous medium to provide an ethanol-free docetaxel diluted solution; and (b) administering the ethanol-free docetaxel diluted solution to the subject.