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 15 wt. % of oxacyclohexadecan-2-one; (C) about 0.1 to about 10 wt. % of a thickening agent; (D) a mixture of solvents which include: (i) about 60 to about 75 wt. % of ethanol or isopropanol; and (ii) propylene glycol and glycerin as co-solvents.
2. The method of claim 1 further comprising polyethylene glycol.
3. The method of claim 2 wherein the polyethylene glycol ranges from about 0.001 to about 5 wt. %.
4. The method of claim 1 wherein the thickening agent ranges from about 1 to about 6 wt. %.
5. 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 ngh/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.
6. The method of claim 1 wherein the viscosity ranges from about 1,000 cps to about 9,000 cps.
7. The method of claim 6 wherein the viscosity ranges from about 2,000 cps to about 8,000 cps.
8. The method of claim 7 wherein the viscosity ranges from about 3,000 cps to about 7,000 cps.
9. The method of claim 1 wherein the pH ranges from about 4 to about 8.
10. 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 15 wt. % of oxacyclohexadecan-2-one; (C) about 0.1 to about 10 wt. % of a thickening agent; (D) a mixture of solvents which include: (i) about 60 to about 75 wt. % of ethanol or isopropanol; and (ii) propylene glycol and glycerin as co-solvents; and (E) about 0.001 to about 5 wt. % of polyethylene glycol as a crystallization inhibitor; 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 ngh/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.
11. The method of claim 10 wherein the viscosity ranges from about 1,000 cps to about 9,000 cps.
12. The method of claim 11 wherein the viscosity ranges from about 2,000 cps to about 8,000 cps.
13. The method of claim 12 wherein the viscosity ranges from about 3,000 cps to about 7,000 cps.
14. The method of claim 10 wherein the pH ranges from about 4 to about 8.
15. The method of claim 10 wherein the thickening agent ranges from 1 to about 6 wt. %.