Fulvestrant formulations

Patent metadata

Field	Value
Publication number	US-2016129014-A1
Application number	US-201614996489-A
Country	US
Kind code	A1
Filing date	Jan 15, 2016
Priority date	Feb 14, 2014
Publication date	May 12, 2016
Grant date	—

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.

First claim

1 . A composition, comprising:
fulvestrant, a pharmaceutically acceptable alcohol, a nonioinic surfactant, an antioxidant, and a ricinoleate vehicle, 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 nonionic surfactant is polysorbate 80.

4 . The composition of claim 1 , wherein the ricinoleate vehicle is castor oil.

5 . The composition of claim 1 , wherein the antioxidant is a vitamin E compound.

6 . The composition of claim 5 , wherein the vitamin E compound is α-tocopherol.

7 . The composition of claim 1 , wherein the pharmaceutically acceptable alcohol comprises a mixture of ethanol and benzyl alcohol.

8 . The composition of claim 7 , wherein the ethanol and benzyl alcohol are present in approximately equivalent w/v amounts.

9 . The composition of claim 8 , comprising 10% w/v ethanol and 10% w/v benzyl alcohol.

10 . The composition of claim 4 , 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 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.

11 . The composition of claim 1 , wherein following storage of the composition at 25° C. for a period of 3 months, the amount of total impurities present in the composition is not more than 1%.

12 . The composition of claim 1 , wherein following storage of the composition at 25° C. for a period of 3 months, the amount of fulvestrant sulfone present in the composition is not more than 0.5%.

13 . A syringe comprising 2.5 mL-5 mL of the composition of claim 1 .

14 . A vial comprising 2.5 mL-5 mL of the composition of claim 1 .

15 . 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.

Assignees

• Fresenius Kabi Usa Llc

Inventors

• Faraj Jabar A

Classifications

• A61K47/44

  Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14) · CPC title

• A61K31/565 Primary

  not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol · CPC title

• A61K9/0019

  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 title

• A61K47/26

  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 title

• A61K47/22

  Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones · CPC title