Claims for Patent: 9,271,990

Summary for Patent: 9,271,990

Title:	Fulvestrant formulations
Abstract:	The invention provides a fulvestrant composition comprising a pharmaceutically acceptable alcohol, polysorbate 80, an antioxidant, and castor oil, which is substantially or completely free of a non-aqueous ester solvent and which demonstrates excellent storage stability. The composition may be used to treat hormone receptor positive metastatic breast cancer in a subject.
Inventor(s):	Faraj; Jabar A. (Skokie, IL)
Assignee:	Fresenius Kabi USA, LLC (Lake Zurich, IL)
Application Number:	14/181,244
Patent Claims:	1. A composition, comprising: fulvestrant, a pharmaceutically acceptable alcohol, polysorbate 80, an antioxidant, and castor oil, wherein the composition is substantially free of a non-aqueous ester solvent. 2. The composition of claim 1, wherein the composition is completely free of a non-aqueous ester solvent. 3. The composition of claim 1, wherein the antioxidant is a vitamin E compound. 4. The composition of claim 3, wherein the vitamin E compound is .alpha.-tocopherol. 5. The composition of claim 1, wherein the pharmaceutically acceptable alcohol comprises a mixture of ethanol and benzyl alcohol. 6. The composition of claim 5, wherein the ethanol and benzyl alcohol are present in approximately equivalent w/v amounts. 7. The composition of claim 6, comprising 10% w/v ethanol and 10% w/v benzyl alcohol. 8. The composition of claim 1, wherein the castor oil is characterized by a carbonyl value of 0.5 micromole/gram or less, a peroxide value of 5.0 meq O.sub.2/kg or less, an iodine value of 85 g iodine/100 g castor oil or less, and/or a Gardner 1933 value of 1.5 or less. 9. The composition of claim 1, wherein following storage of the composition at 25.degree. C. for a period of 3 months, the amount of total impurities present in the composition is not more than 1%. 10. The composition of claim 1, wherein following storage of the composition at 25.degree. C. for a period of 3 months, the amount of fulvestrant sulfone present in the composition is not more than 0.5%. 11. The composition of claim 1, comprising 5-10% w/v fulvestrant, 10-30% w/v pharmaceutically acceptable alcohol, and 0.05-0.2% w/v polysorbate 80. 12. A syringe comprising 2.5 mL-5 mL of the composition of claim 1. 13. A vial comprising 2.5 mL-5 mL of the composition of claim 1. 14. A composition, comprising: 5% w/v fulvestrant, 10% ethanol, 10% benzyl alcohol, 0.12% w/v polysorbate 80, 0.06% a-tocopherol, and castor oil, wherein the composition is substantially free of a non-aqueous ester solvent. 15. A method of stabilizing a fulvestrant composition, comprising forming a mixture comprising: 5-10% w/v fulvestrant, 10-30% w/v pharmaceutically acceptable alcohol, 0.05-0.2% w/v polysorbate 80, an antioxidant, and castor oil, thereby stabilizing a fulvestrant composition, wherein the mixture is substantially free of a non-aqueous ester solvent. 16. The method of claim 15, wherein following storage of the composition at 25.degree. C. for a period of 3 months, the amount of total impurities present in the composition is not more than 1%. 17. A method of treating hormone receptor positive metastatic breast cancer in a subject in need thereof, comprising administering a therapeutically effective amount of the composition of claim 1 to the subject, thereby treating the hormone receptor positive metastatic breast cancer in the subject.