RESUMO
Developing transdermal therapeutic systems for estradiol and norethindrone acetate raised questions about the steroids penetration pathway across and retention in the skin. This paper describes the distribution of 3H-estradiol and 3H-norethindrone acetate in human stratum corneum after topical application to dermatomed skin in vitro. The study involved (a) permeation experiments to determine the steroid flux, (b) autoradiographical visualization of the steroid distribution in the same skin samples, and (c) a correlation between flux and skin distribution in time. On correlating the steroid flux with intraepidermal steroid distribution, it was concluded that both permeants were bound in the skin tissue. The steroids were preferentially located in or close to the intercellular lipids of the stratum corneum, indicating that both transport and binding occurred via this domain of the stratum corneum. This study demonstrated the importance of correlating drug flux with intraepidermal drug distribution as a function of time.
Assuntos
Epiderme/metabolismo , Estradiol/farmacocinética , Noretindrona/farmacocinética , Congêneres da Progesterona/farmacocinética , Administração Cutânea , Autorradiografia , Transporte Biológico , Estradiol/administração & dosagem , Espaço Extracelular/metabolismo , Feminino , Humanos , Metabolismo dos Lipídeos , Pessoa de Meia-Idade , Noretindrona/administração & dosagem , Noretindrona/análogos & derivados , Acetato de Noretindrona , Permeabilidade , Congêneres da Progesterona/administração & dosagem , Compostos Radiofarmacêuticos , Absorção Cutânea/efeitos dos fármacos , Fatores de Tempo , TrítioRESUMO
A study was made of the validity of freeze-drying to visualize the distribution of 3H-estradiol in human stratum corneum after topical application of a dry dose, a patch or a buffer solution. Each of these donor formulations was applied to human dermatomed skin for 24 h using Franz permeation cells. Subsequently, small pieces of skin were subjected to cryofixation, freeze-drying, osmium tetroxide vapor fixation, Spurr resin embedding and electron microscopic autoradiography. Stratum corneum from dry dose and patch application experiments was well preserved by freeze-drying, allowing an accurate localization of 3H-estradiol. In contrast, stratum corneum from buffer solution experiments suffered from cryofixation artifacts due to excessive hydration of the skin. The corresponding autoradiographs showed strong redistribution of 3H-estradiol. Thus, the visualization method under investigation has its limitations regarding the hydration level of the skin.