LOW-OIL PHARMACEUTICAL EMULSION COMPOSITIONS COMPRISING PROGESTOGEN
Described are sterile, ready-to-use, pharmaceutical oil-in-water emulsion compositions for parenteral administration comprising: 0.015 to 0.5% wt/vol progesterone; 0.5 to 10% wt/vol oil, wherein the oil comprises at least 85% wt./wt. triglyceride; 0.0425 to 4.1% wt/vol phospholipid; 80-99.4% wt/vol aqueous medium; wherein the composition has an osmolality in the range of 200-1000 mOsm/kg. Also described are methods of making such compositions and method of using such compositions in therapeutic or prophylactic treatment, such as treatments comprising intravenous administration of the pharmaceutical composition.
1 .- 20 . (canceled)
21 . A sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition for parenteral administration comprising:
an oil;
an aqueous phase;
a progestogen; and
a phospholipid;
wherein the progestogen:oil (wt./wt.) ratio is at least 1:32, and
wherein the composition contains less than 2.5% (wt./vol.) benzyl benzoate and less than 1.5% wt./wt. polyethylene glycol 15-hydroxystearate.
22 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 21 , comprising less than or equal to 0.4% (wt./vol) progestogen.
23 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 21 , wherein the progestogen is progesterone.
24 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 21 , further comprising a co-surfactant.
25 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 24 , wherein the co-surfactant is selected from the group consisting of oleate, oleic acid and combinations thereof.
26 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 24 , wherein the co-surfactant is present in an amount from 0.005% to 1.0% (wt./vol.).
27 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 21 , wherein the composition comprises an osmotic agent.
28 . The sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition of claim 21 , wherein the emulsion comprises structured triglycerides in an amount of no more than 30% (wt./wt.) of the total oil phase.
29 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the phospholipid is present in an amount from of 6.8 to 43% (wt./wt.) of the oil.
30 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the oil comprises at least 85% (wt./wt.) triglycerides, based on the total oil content of the emulsion.
31 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the composition does not contain any benzyl benzoate.
32 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the osmolality is between 200 and 1000 mOsm/kg.
33 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the composition has a PFAT 5 value of ≦0.05%.
34 . The sterile, ready-to-use, pharmaceutical oil-in-water composition of claim 21 , wherein the droplet particles of the dispersed oil phase have a volume-based mean diameter of ≦300 nm.
35 . A method of manufacturing a composition according to claim 21 , said method comprising the steps of:
a) combining water and phospholipid to produce an aqueous composition;
b) combining progestogen and oil to produce an oily composition; and
c) combining the aqueous composition and the oily composition followed by homogenization to form a homogenous oil-in-water emulsion.
36 . The method of claim 35 , wherein step (c) comprises adding the oily composition to the aqueous composition, and homogenization at greater than or equal to 350 bar.
37 . A method of administering a progestogen to a subject in need thereof, comprising administering a composition according to claim 21 .
38 . The method of claim 37 , wherein the administering is by parenteral administration.
39 . The method of claim 37 , wherein the administering is by intravenous administration.