High-strength testosterone undecanoate compositions
The present disclosure is drawn to pharmaceutical compositions and oral dosage capsules containing testosterone undecanoate, as well as related methods. The capsule includes a capsule shell and a capsule fill. The capsule fill can include a solubilizer and about 14 wt % to about 35 wt % testosterone undecanoate based on the total capsule fill. The oral dosage capsule is such that when a single oral administration to a male subject of one or more capsules with a total testosterone undecanoate daily dose of about 350 mg to about 650 mg it provides a ratio of serum testosterone C max to serum testosterone C ave of about 2.7 or less. In yet another embodiment, a method for providing a serum concentration of testosterone within a target serum testosterone concentration C ave range for a male subject is provided.
1. A method for replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone said method comprising:
(a) orally administering to said male two unit dosage forms of a pharmaceutical composition twice a day in a daily dosing regimen, said pharmaceutical composition comprising testosterone undecanoate and a pharmaceutical carrier, that provides about 450 mg testosterone undecanoate to said male per day;
(b) determining the serum level of testosterone of said male during the daily dosing regimen at from 1-12 hours after single dose administration of said pharmaceutical composition at steady state; and
(c) orally administering two unit dosage forms of the pharmaceutical composition twice a day in the daily dosing regimen to provide a serum testosterone Cave in said male in the range of from about 300-1100 ng/dL.
2. The method of claim 1 , wherein said pharmaceutical carrier comprises a solubilizer and a dispersant.
3. The method of claim 1 , wherein said pharmaceutical carrier comprises a solidifying agent.
4. The method of claim 1 , wherein said pharmaceutical carrier comprises a monoglyceride.
5. The method of claim 1 , wherein said pharmaceutical carrier comprises a diglyceride.
6. The method of claim 1 , wherein said pharmaceutical carrier comprises a triglyceride.
7. The method of claim 1 , wherein said pharmaceutical carrier comprises a fatty acid.
8. The method of claim 1 , wherein said pharmaceutical carrier comprises medium chain monoglycerides and diglycerides.
9. The method of claim 1 , wherein said pharmaceutical carrier comprises a tocopherol.
10. The method of claim 1 , wherein said pharmaceutical carrier comprises a hydrophilic surfactant.
11. The method of claim 1 , wherein said pharmaceutical composition has at least 5% of the testosterone undecanoate not dissolved and at least 35% dissolved in said pharmaceutical carrier.
12. A method for replacement therapy in a male having a condition associated with a deficiency or absence of endogenous testosterone said method comprising:
orally administering to said male two unit dosage forms of a pharmaceutical composition twice a day, said pharmaceutical composition comprising testosterone undecanoate and a pharmaceutical carrier, that provides about 450 mg to said male per day to provide a serum testosterone Cave in said male in the range of from about 300-1100 ng/dL,
wherein said pharmaceutical composition has at least 5% of the testosterone undecanoate not dissolved and at least 35% dissolved in said pharmaceutical carrier.
13. The method of claim 12 , wherein orally administering is twice a day.
14. The method of claim 12 , wherein said pharmaceutical carrier comprises one or more of the following: a fatty acid, a monoglyceride, a diglyceride, a triglyceride, and a tocopherol.
15. The method of claim 12 , wherein said pharmaceutical carrier comprises a hydrophilic surfactant.
16. The method of claim 12 , wherein said pharmaceutical carrier comprises a solidifying agent.
17. The method of claim 12 , wherein said pharmaceutical carrier comprises a monoglyceride.
18. The method of claim 12 , wherein said pharmaceutical carrier comprises a diglyceride.
19. The method of claim 12 , wherein said pharmaceutical carrier comprises a triglyceride.
20. The method of claim 12 , wherein said pharmaceutical carrier comprises a fatty acid.
21. The method of claim 12 , wherein said pharmaceutical carrier comprises medium chain monoglycerides and diglycerides.