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, 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.
2 . The method of claim 1 wherein the composition 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 0.01 to about 25 wt. % of at least one enhancer having a partition coefficient ranging from about 4.0 to about 7.0; (C) about 0.1 to about 10 wt. % of a thickening agent; and, (D) a mixture of solvents which include about 40 wt. % to about 80 wt. % of a lower alkanol.
3 . The method of claim 2 further comprising a crystallization inhibitor that is capable of inhibiting crystallization of testosterone.
4 . The method of claim 1 wherein the lower alkanol ranges from about 50 wt. % to about 75 wt. %.
5 . The method of claim 4 wherein the lower alkanol ranges from about 60 wt. % to about 75 wt. %.
6 . The method of claim 5 wherein the lower alkanol comprises ethanol.
7 . The method of claim 6 wherein the lower alkanol comprises isopropanol.
8 . The method of claim 6 further comprising propylene glycol.
9 . The method of claim 8 further comprising glycerin.
10 . The method of claim 2 wherein the enhancer is selected from the group of consisting of 3-methylcyclopentadecanone, 9-cycloheptadecen-1-one, cyclohexadecanone, cyclopentadecanone, oxacyclohexadecan-2-one and mixtures thereof.
11 . The method of claim 10 wherein the macrocyclic enhancer is 3-methylcyclopentadecanone.
12 . The method of claim 10 wherein the macrocyclic enhancer is 9-cycloheptadecen-1-one.
13 . The method of claim 10 wherein the macrocyclic enhancer is cyclohexadecanone.
14 . The method of claim 10 wherein the macrocyclic enhancer is cyclopentadecanone.
15 . The method of claim 10 wherein the macrocyclic enhancer is oxacyclohexadecan-2-one.
16 . The method of claim 1 wherein the composition 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 0.01 to about 25 wt. % of at least one enhancer having a partition coefficient ranging from about 2.0 to about 9.0; (C) about 0. 1 to about 10 wt. % of a thickening agent; and, (D) a mixture of solvents which include about 40 wt. % to about 80 wt. % of a lower alkanol.