Physical chemical properties and percutaneous absorption of dehydroepiandrosterone (DHEA).

Abstract

Dehydroepiandrosterone (DHEA, DEA) is a major adrenalcortical synthesized hormone in human and other mammals. Its blood level peaks at about 600 ng/dl between the ages of 25 to 30 and then slowly declines throughout the remainder of life. At about 10 ng/dl, there is little DHEA left circulating in men age 80 and above. Because of its association with immune function, there are some who believe that many of the afflictions of elderly men are at least partially due to inadequate levels of this compound in the body. Much the same is true for individuals whose DHEA's levels have fallen as the result of severe physical or mental stress. The drug is absorbed orally, but not without suffering substantial first-pass losses as the result of liver metabolism. Consequently, developing a topical or transdermal delivery system for this compound would be of interest. The physicochemical properties of DHEA most determinative of the ease of delivering it across a diffusionally resistant biological barrier as the skin have been investigated. The compound melts at 150$\sp\circ$C with an enthalpy of fusion of 5.83 kcal/mole. With a log $\rm(K\sb{octanol/water})$ of 1.6, it is clearly lipophilic. Its aqueous solubility is low, ${\sim}12\ \mu$g/ml. The mass transfer coefficient for its permeation through hairless mouse skin was $1.44\times10\sp{-2}$ cm/hr. Skin permeability from solvents which might be used to formulate the compound (e.g., propylene glycol, mineral oil, isopropyl myristate and Transcutol$\sp\circler)$ has been assessed. Enhancement of its skin permeability by DMSO and oleyl alcohol has also been studied. In some instances fluxes exceeding 20 $\mu$g/cm$\sp2$/h were obtained. Using this and a pharmacokinetic model which has been developed suggests that a 20 cm$\sp2$ patch delivering DHEA at 20 $\mu$g/cm$\sp2$/h would maintain a DHEA plasma level of 600 ng/dl in humans. The data indicate that this steady state level could be approached about four hours following application of such a patch.