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. A sterile, ready-to-use, pharmaceutical oil-in-water emulsion composition 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, based on the total oil content of the emulsion;
0.0425 to 4.1% wt/vol phospholipid; and
80-99.4% wt/vol aqueous medium;
wherein the composition has an osmolality in the range of 200-1000 mOsm/kg, and wherein the emulsion contains no more than 1.2% wt/wt of polyethylene glycol 15-hydroxystearate.
2. The composition according to claim 1 , comprising 0.05 to 0.4% wt/vol progesterone
3. The composition according to claim 1 , wherein said progesterone is present in an amount greater than 1% wt/wt of the oil.
4. The composition according to claim 1 , wherein said progesterone is present in an amount greater than 1.5% wt/wt of the oil.
5. The composition according to claim 1 , comprising 0.064 to 3.4% wt/vol phospholipid.
6. The composition according to claim 1 , wherein the phospholipid is present in the range of 6.8 -43% of the oil.
7. The composition according to claim 1 , wherein said composition contains 0.005-4% wt/vol of a co-surfactant.
8. The composition of claim 7 , wherein the co-surfactant is selected from the group consisting of C 12 -C 22 fatty acids, salts thereof, and/or mixtures thereof.
9. The composition according to claim 8 , wherein the co-surfactant is selected from oleate, oleic acid and combinations thereof, and is present in the range of 0.005-0.5% wt/vol.
10. The composition according to claim 1 , wherein said composition contains glycerol as an osmotic agent.
11. The composition according to claim 1 , wherein the oil comprises at least 90% triglycerides, based on the total oil content of the emulsion.
12. The composition according to claim 1 , wherein the composition is suitable for intravenous administration.
13. The composition according to claim 1 , wherein the composition is packaged in a sealed container under a headspace of inert gas.
14. The composition according to claim 1 , comprising;
0.15-0.25% wt/vol progesterone;
5-7% wt/vol oil;
1.0-1.4% wt/vol egg lecithin; and
80-98.9% wt/vol water;
wherein the composition has a pH of 6.0-9.0.
15. The compositions according to claim 1 , wherein the composition has a PFAT 5 value of <0.05%.
16. The composition according to claim 1 , wherein the emulsion has a dispersed oil phase with droplet particles having a volume-based mean diameter of <300 nm.
17. A method of treatment, comprising administering a composition of claim 1 to a subject in need thereof.
18. The method of claim 17 , wherein said subject is a human suffering from a traumatic central nervous system injury.
19. A method of manufacturing a composition according to claim 1 , comprising:
(a) combining water, phospholipid and, optionally, an osmotic agent, to produce an aqueous composition;
(b) combining progesterone 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.
20. The method of claim 19 , wherein step (c) comprises adding the oily composition to the aqueous composition, and homogenization at greater than or equal to 350 bar.