Pharmaceutical composition
A pharmaceutical composition comprising: (A) an androgen; (B) a cyclic enhancer of the type used in the compositions and methods claimed by U.S. Pat. No. 5,023,252 to Hsieh; and (C) a thickening agent; including, for example, a composition in which the cyclic enhancer is a macrocyclic ester or a macrocyclic ketone; the use of the composition to treat a condition, for example, male hypogonadism, in a patient by applying the composition to the membrane of the patient; and a method for making the composition.
1. A method for maintaining a therapeutically effective concentration of testosterone in the blood serum of a male for treating hypogonadism which comprises transdermally delivering to the male by applying to the skin a composition which is in the form of a topical gel, which has a viscosity of about 500 to about 20,000 cps and a pH of about 3 to about 9, and comprises: (A) about 0.1 to about 5 wt. % of testosterone; (B) about 0.5 to about 25 wt. % of a macrocyclic enhancer selected from the group consisting of 3-methylcyclopentadecanone, 9-cycloheptadecen-1-one, cyclohexadecanone, cyclopentadecanone, oxacyclohexadecan-2-one and mixtures thereof (C) about 0.1 to about 10 wt. % of a thickening agent; (D) a mixture of solvents which include about 40 wt. % to about 80% of ethanol.
2. The method of claim 1 wherein the composition further comprises polyethylene glycol.
3. The method of claim 2 wherein the polyethylene glycol is present in an amount that ranges from about 0.001 to about 5 wt. %.
4. The method of claim 1 wherein said composition is maintained on said skin for a period of time sufficient for delivery of the testosterone to the body of the male and is applied to the skin in the form of a unit dose which contains about 1 to about 300 mg of testosterone and such that, following a single application of the unit dose to the skin, the amount of circulating testosterone (AUC 0-24 ) in the blood serum of the male achieved in the 24-hour period following the application is about 100 to about 35,000 ng.h/dL greater than the amount of circulating testosterone (AUC 0-24 ) in the blood serum of the male than would have been achieved in the same 24-hour period had the dose not been administered.
5. The method of claim 1 wherein the viscosity ranges from about 1,000 cps to about 9,000 cps.
6. The method of claim 5 wherein the viscosity ranges from about 2,000 cps to about 8,000 cps.
7. The method of claim 6 wherein the viscosity ranges from about 3,000 cps to about 7,000 cps.
8. The method of claim 1 wherein the pH ranges from about 4 to about 8.
9. The method of claim 1 wherein ethanol ranges from about 50 wt. % to about 75 wt. %.
10. The method of claim 9 wherein ethanol ranges from about 60 wt. % to about 75 wt. %.
11. The method of claim 10 further comprising propylene glycol.
12. The method of claim 11 further comprising glycerin.
13. The method of claim 1 wherein the macrocyclic enhancer is 3-methylcyclopentadecanone.
14. The method of claim 1 wherein the macrocyclic enhancer is 9-cycloheptadecen-1-one.
15. The method of claim 1 wherein the macrocyclic enhancer is cyclohexadecanone.
16. The method of claim 1 wherein the macrocyclic enhancer is cyclopentadecanone.
17. The method of claim 1 wherein the macrocyclic enhancer is oxacyclohexadecan-2-one.