Transdermal hormone delivery system: compositions and mtehods

Abstract

A transdermal hormone delivery system (THDS) is disclosed. The THDS is useful for control of fertility and as therapy for a variety of diseases and conditions treatable by robust delivery of progestin and estrogen hormones, particularly the progestin, levonorgestrel. The THDS comprises a backing layer, an adjoining adhesive polymer matrix comprising an effective amount of at least a progestin hormone, delivery of which is enhanced by one or more skin permeation enhancing agents present in pre-determined amounts. The THDS is capable of providing effective daily doses of progestin and estrogen hormones from a small surface area in contact with the skin, e.g., less than 20 square centimeters. Methods of fertility control and various types of hormone replacement therapy utilizing the THDS are also disclosed.

What is claimed: 
     
         1 . A method of controlling fertility in a female, comprising applying to the skin of the female a transdermal hormone delivery device comprising a backing layer and an adhesive polymer matrix affixed to the backing layer, the adhesive polymer matrix comprising levonorgestrel and ethinyl estradiol, wherein application of the device to the skin of a female for one or more one-week dosing periods results in an in vivo serum concentration profile of levonorgestrel in which a maximum concentration is reached by or before about midway through the dosing period and thereafter declines to the end of the dosing period, and an average serum concentration of at least about 1,000 pg/ml levonorgestrel is achieved for the dosing period, wherein the device is applied to the skin in a four-week regimen comprising application of one device once each week for three consecutive weeks, followed by one week in which the device optionally is not applied, thereby controlling fertility in the female. 
     
     
         2 . The method of  claim 1 , wherein the C max  of levonorgestrel during a dosing period is up to about 4,500 pg/ml. 
     
     
         3 . The method of  claim 1 , wherein the average AUC for levonorgestrel for three consecutive dosing periods is between about 18,390+/−1,603 pg-day/ml and about 59,036+/−6,163 pg-day/ml. 
     
     
         4 . The method of  claim 1 , wherein the average serum concentration of levonorgestrel per dosing period increases from week to week in the three consecutive weeks of the four week dosing regimen. 
     
     
         5 . The method of  claim 1 , wherein the application of the device to the skin of the female for the one or more one-week dosing periods results in an in vivo serum concentration profile of ethinyl estradiol in which a maximum concentration is reached by or before about midway through the dosing period and thereafter declines to the end of the dosing period. 
     
     
         6 . The method of  claim 5 , wherein an average serum concentration of not more than about 64+/−4 pg/ml ethinyl estradiol is achieved for the dosing period. 
     
     
         7 . The method of  claim 5 , wherein the C max  of ethinyl estradiol during the dosing period is up to about 90 pg/ml. 
     
     
         8 . The method of  claim 5 , wherein the average AUC for ethinyl estradiol for three consecutive dosing periods is no more than about 1,456+/−101 pg-day/ml.