LOW-OIL PHARMACEUTICAL EMULSION COMPOSITIONS COMPRISING PROGESTOGEN

• US 20110262494A1
• Filed: 04/25/2011
• Published: 10/27/2011
• Est. Priority Date: 04/26/2010
• Status: Active Grant

• Current Assignee: Besins Healthcare Luxemborg SARL (Besins Healthcare, Inc.)
• Original Assignee: Besins Healthcare Luxemborg SARL (Besins Healthcare, Inc.)
• Inventors: Hoiser, Eva-Maria, Achleitner, Georg, Pickersgill, Laura
• Granted Patent: US 8,765,149 B2
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/12 Carboxylic acids; Salts or anhydrides thereof
• CPC Class Codes: A61K 47/24 containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
• CPC Class Codes: A61K 47/44 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 Class Codes: A61K 9/0019 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 Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system

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.

Claims

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;

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.

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 C₁₂-C₂₂ 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.

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 PFAT₅ 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.