FULVESTRANT COMPOSITIONS
The inventive subject matter provides ready to inject fulvestrant compositions with improved solubility and stability, and methods for preparing the same. Contemplated compositions include fulvestrant at a concentration of greater than 100 mg/ml, and maintain degradation of the fulvestrant at a level of less than 5 wt % when stored over at least three months at 25° C.
1 . A ready to inject fulvestrant composition, comprising:
fulvestrant present in the composition at a concentration of greater than 100 mg/ml;
diethylene glycol monoethyl ether or an alkyl derivative thereof as a solvent;
between 1-5 v/v % of a co-solvent; and
wherein the composition maintains a degradation of fulvestrant at a level of less than 5 wt % when stored over at least three months at 25° C.
2 . The composition of claim 1 , wherein the co-solvent is benzyl alcohol.
3 . The composition of claim 1 , wherein fulvestrant is present at a concentration of at least 125 mg/ml.
4 . The composition of claim 3 , wherein fulvestrant is present at a concentration of at least 150 mg/ml.
5 . The composition of claim 1 , further comprising a second co-solvent present in the composition at no more than 50 v/v %.
6 . The composition of claim 5 , wherein the second co-solvent comprises castor oil and acts as a release rate modifier.
7 . The composition of claim 1 , wherein the composition is formulated to maintain degradation of fulvestrant at a level of less than 2 wt % when stored over at least three months at 25° C.
8 . The composition of claim 1 , wherein the composition is formulated to maintain degradation of fulvestrant at a level of less than 5 wt % when stored over at least three months at 2-8° C.
9 . The composition of claim 1 , wherein the composition is provided in a multi-use container.
10 . The composition of claim 1 , wherein the diethylene glycol monoethyl ether or the alkyl derivative thereof is present in the composition at more than 40 v/v %.
11 . A method of manufacturing a ready to inject fulvestrant composition containing article, comprising:
formulating a liquid composition including fulvestrant such that the formulation exhibits less than 5 wt % degradation of the fulvestrant when stored over at least three months at 25° C.;
wherein the liquid composition comprises diethylene glycol monoethyl ether or an alkyl derivative thereof as a solvent, fulvestrant at a concentration greater than 100 mg/ml, and between 1-5 v/v % of a co-solvent; and
packaging the liquid formulation in the article.
12 . The method of claim 11 , wherein the co-solvent is benzyl alcohol.
13 . The method of claim 11 , wherein fulvestrant is present at a concentration of at least 125 mg/ml.
14 . The method of claim 13 , wherein fulvestrant is present at a concentration of at least 150 mg/ml.
15 . The method of claim 11 , wherein the liquid composition further comprises a second co-solvent present in the composition at no more than 50 v/v %.
16 . The method of claim 15 , wherein the second co-solvent comprises castor oil and acts as a release rate modifier.
17 . The method of claim 11 , wherein formulating comprises formulating the liquid composition such that the formulation exhibits less than 2 wt % degradation when stored over at least three months at 25° C.
18 . The method of claim 11 , wherein formulating comprises formulating the liquid composition such that the formulation remains clear and colorless when stored over at least three months at 25° C.
19 . The method of claim 11 , wherein the article is a multi-use container, and wherein packaging comprises packaging the liquid formulation in an amount that includes at least 500 mg fulvestrant.
20 . The method of claim 11 , wherein diethylene glycol monoethyl ether or the alkyl derivative thereof is present in the composition at more than 40 v/v %.
21 . A ready to inject fulvestrant composition, comprising:
fulvestrant present in the composition at a concentration of greater than 100 mg/ml;
diethylene glycol monoethyl ether or an alkyl derivative thereof as a solvent;
wherein the composition has a viscosity of less than 80 centipoise; and
wherein the composition maintains a degradation of the fulvestrant at a level of less than 5 wt % when stored over at least three months at 25° C.
22 . The composition of claim 21 , further comprising between 1-5 v/v % of a co-solvent.
23 . The composition of claim 21 , wherein the co-solvent is benzyl alcohol.