AbstractBased on the results of simultaneous skin permeation and bioconversion profiles, a Transdermal Bioactivated Hormone Delivery (TBHD) System was developed from the microreservoir partition-controlled drug delivery technology for the transdermal controlled delivery of estradiol prodrugs.Using the in vitro skin permeation apparatus developed earlier, the kinetics of release and skin permeation of estradiol prodrugs from the TBHD system and the regeneration of estradiol were simultaneously studied. Results indicated that all prodrugs are totally converted by the esterase to estradiol during the course of skin permeation.The release rate of estradiol was found to be first enhanced by the esterification of the OH groups at 3- and 17-position and then decreased as the alkyl chain length increased.The rate of regeneration of estradiol from the prodrugs was found to follow the order of: diacetate>valerate>heptanoate>acetate>cypionate.