Oral testosterone ester formulations and methods of treating testosterone deficiency comprising same
A pharmaceutical formulation of testosterone undecanoate is provided. Methods of treating a testosterone deficiency or its symptoms with the inventive formulations are also provided.
1. An oral pharmaceutical composition comprising:
a. 18-22 percent by weight of solubilized testosterone undecanoate;
b. 50-55 percent by weight of at least one lipophilic surfactant; and;
c. 15-17 percent by weight of at least one hydrophilic surfactant;
d. 10-15 percent by weight of a mixture of borage seed oil and peppermint oil.
2. The composition as recited in claim 1 wherein said hydrophilic surfactant is polyoxyethylene(40)hydrogenated castor oil.
3. The composition as recited in claim 2 wherein said lipophilic surfactant is oleic acid.
4. The composition as recited in claim 3 , wherein upon once- or twice-daily oral administration, provides an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL.
5. The composition as recited in claim 1 , wherein the ratio of lipophilic surfactants to hydrophilic surfactants is about 4:1.
6. An oral pharmaceutical composition comprising:
a. 19.8 percent by weight of solubilized testosterone undecanoate;
b. 51.6 percent by weight of oleic acid;
c. 16.1 percent by weight of polyoxyethylene(40)hydrogenated castor oil;
d. 10 percent by weight of borage seed oil;
e. 2.5 percent by weight of peppermint oil; and
f. 0.03 percent by weight of beta-hydroxy-toluene(BHT).
7. A method of treating testosterone deficiency or its symptoms comprising orally administering to a subject suffering from testosterone deficiency or its symptoms an effective amount of the oral pharmaceutical composition of claim 1 to provide an average serum testosterone concentration at steady state falling in the range of about 300 to about 1100 ng/dL.
8. The method of claim 7 in which the composition is administered once daily.
9. The method of claim 7 in which the composition is administered twice daily.
10. The method of claim 7 which gives rise to a Cmax value falling in the range of about 900 to 1100 ng/dL.
11. The method of claim 7 in which the composition is administered with a meal comprising at least 20 wt % fat.
12. The method of claim 7 which gives rise to substantially no diurnal testosterone pharmacokinetic variation.
13. The method of claim 7 which gives rise to an average serum T max value falling in the range of about 3 to 7 hours after oral administration.
14. The method of claim 13 in which the average serum T max value falls in the range of about 4 to 5 hours after oral administration.
15. The method of claim 7 in which substantially no significant decline in steady state serum testosterone response is observed upon repeat dosing.