Progesterone formulations having a desirable PK profile
This disclosure provides progesterone formulations, methods of using these formulations, and their related pharmacokinetic parameters. In particular embodiments, the formulations disclosed herein allow for a reduction in the amount of progesterone administered to a patient in need thereof, while still providing the benefits of a larger dosage amount.
1. A pharmaceutical composition for orally administering progesterone to a subject in need thereof, the composition comprising:
progesterone;
a solubilizing agent; and
a nonionic surfactant;
wherein the solubilizing agent comprises predominantly C 6 -C 12 fatty acid tri-esters of glycerol;
wherein the progesterone is present from about 20 to about 50 weight percent of the composition; and
wherein the composition provides increased progesterone bioavailability compared to micronized progesterone suspended in peanut oil.
2. The pharmaceutical composition of claim 1 , wherein the solubilizing agent further comprises a C 6 -C 12 fatty acid mono-ester of glycerol.
3. The pharmaceutical composition of claim 2 , wherein the solubilizing agent further comprises a C 6 -C 12 fatty acid di-ester of glycerol.
4. The pharmaceutical composition of claim 1 , wherein the tri-ester of glycerol comprises predominantly esters of caprylic fatty acid (C 8 ) and capric fatty acid (C 10 ).
5. The pharmaceutical composition of claim 1 , wherein the nonionic surfactant is lauroyl polyoxyl-32 glycerides.
6. The pharmaceutical composition of claim 1 , wherein the nonionic surfactant is lauroyl macrogol-32 EP.
7. The pharmaceutical composition of claim 1 , wherein the nonionic surfactant is caprylocaproyl macrogol-8 glyceride EP.
8. The pharmaceutical composition of claim 1 , wherein the amount of progesterone is from 25 mg to 200 mg.
9. The pharmaceutical composition of claim 1 , wherein the amount of progesterone is 75 mg or 150 mg.
10. The pharmaceutical composition of claim 1 , wherein the progesterone includes solubilized progesterone and suspended progesterone.
11. The pharmaceutical composition of claim 1 , wherein the composition is provided in a gelatin capsule.
12. The pharmaceutical composition of claim 1 , wherein the composition has a total mass of less than 500 mg.
13. The pharmaceutical composition of claim 1 , wherein the composition provides a 25% increase in progesterone bioavailability compared to micronized progesterone suspended in peanut oil.
14. The pharmaceutical composition of claim 1 , wherein the amount of progesterone comprises about 33% by weight of the composition; the solubilizing agent comprises about 65% by weight of the composition, the non-ionic surfactant comprises about 1.7% by weight of the composition.
15. The pharmaceutical composition of claim 1 , wherein the amount of progesterone comprises about 33.33% by weight of the composition; the solubilizing agent comprises about 64.93% by weight of the composition, the non-ionic surfactant comprises about 1.67% by weight of the composition.
16. The pharmaceutical composition of claim 14 , further comprising an antioxidant.
17. The pharmaceutical composition of claim 16 , wherein the antioxidant is butylated hydroxy toluene.
18. The pharmaceutical composition of claim 17 , wherein the solubilizing agent is medium chain triglycerides of caprylic fatty acid (C 8 ) and capric fatty acid (C 10 ).
19. The pharmaceutical composition of claim 18 , wherein the non-ionic surfactant is lauroyl polyoxyl-32 glycerides.
20. The pharmaceutical composition of claim 19 , wherein the amount of progesterone is 200 mg.
21. The pharmaceutical composition of claim 19 , wherein the amount of progesterone is 150 mg.
22. The pharmaceutical composition of claim 19 , wherein the progesterone is ultra-micronized and has an X50 of less than or equal to 15 microns.
23. The pharmaceutical composition of claim 1 , wherein the progesterone is ultra-micronized and has an X90 of less than or equal to 25 microns.
24. The pharmaceutical composition of claim 1 , wherein the progesterone is the sole active ingredient in the composition.
25. A pharmaceutical composition for orally administering progesterone to a subject in need thereof, the composition comprising:
progesterone;
a solubilizing agent; and
a nonionic surfactant;
wherein the solubilizing agent comprises predominantly C 6 -C 12 fatty acid tri-esters of glycerol;
wherein the progesterone is present from about 20 to about 50 weight percent of the composition and wherein less than 6 percent of the progesterone is soluble in the solubilizing agent; and
wherein the composition provides increased progesterone bioavailability compared to micronized progesterone suspended in peanut oil.
26. The pharmaceutical composition of claim 25 , wherein more than 5 percent of the progesterone is soluble in the solubilizing agent.
27. A method of treating a progesterone-deficient state in a subject in need thereof, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 1 .
28. The method of claim 27 , wherein the progesterone-deficient state is endometrial hyperplasia, secondary amenorrhea, preterm birth, shortened cervix, or another disease states or condition treated with supplemental progesterone.
29. The method of claim 28 , wherein the progesterone-deficient state is secondary amenorrhea.
30. A method of treating a progesterone-deficient state in a subject in need thereof, the method comprising administering to a subject in need thereof an effective amount of the pharmaceutical composition of claim 25 .
31. The method of claim 30 , wherein the progesterone-deficient state is endometrial hyperplasia, secondary amenorrhea, preterm birth, shortened cervix, or another disease states or condition treated with supplemental progesterone.
32. The method of claim 31 , wherein the progesterone-deficient state is secondary amenorrhea.