Development of patches for the controlled release of dehydroepiandrosterone

Dehydroepiandrosterone (DHEA) and its sulfate conjugate (DHEAS) are the maj or secretory steroidal products of the adrenal gland. Some epidemiologic st udies have found an association between low DHEA serum levels in patients a nd many important diseases. To prevent all such pathological conditions and , in any case, in aging, a DHEA supplementation has been proposed. DHEA sho ws a low oral bioavailability; taking the bioavailability obtained by the s ubcutaneous route as 100%, it was estimated that the potencies of DHEA by t he percutaneous and oral routes were approximately 33% and 3%, respectively . Thus, transdermal patches could be considered a promising formulation as a continuous and controlled delivery of DHEA in replacement therapy is desi red. With the aim of evaluating the effect of the matrix composition in ter ms of polymers and enhancers on the DHEA skin permeation flux, 10 types of monolayer self-adhesive patches containing 0.25 mg/cm(2) of active ingredie nt were designed. The matrices were based on three different acrylic copoly mers: an acrylate-vinylacetate copolymer, a polyaminomethylmethaerylate (PA MA), and a polymethylmethaerylate. Transcutol (TR), mint essential oil, Lau roglycol, Brij 58, and propylene glycol (PG) were evaluated as DHEA skin pe rmeation enhancers. All prepared patches were characterized by drug content , light microscopy, and in vitro skin Permeation, performed using a modifie d Franz-type diffusion cell and human stratum corneum and epidermis as a me mbrane. The in vitro skin permeation studies are particularly significant i n the development studies of DHEA patches as the in vivo determination of D HEA is affected by the fact that the endogen substance in the plasma is not constant over time. Among the tested patches, highest DHEA fluxes were obt ained using the formulation based on PAMA. Moreover, the introduction in th e matrix of binary mixtures of TR and PG, used also for their plasticizer p roperties, permitted enhancing DHEA skin permeation. On the basis of these studies, the transdermal administration of DHEA using patches seems feasibl e.