Low-oil pharmaceutical emulsion compositions comprising progestogen

Abstract

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.