A comparative study of an in situ adapted diffusion cell and an in vitro Franz diffusion cell method for transdermal absorption of doxylamine

In order to determine whether a drug shows the potential for percutaneous a bsorption. both in situ and in vitro studies an used. In vitro studies are good indicators of transdermal drug delivery, but the possibility exists th at anatomical changes in excised skin can influence drug delivery. The aim of this study was to compare the in vitro Franz diffusion cell method with an in situ adapted diffusion cell method. A saturated aqueous solution of d oxylamine succinate: was used as model drug and the receptor phase was an i sotonic Sorensen buffered solution. The in vitro permeation studies were co nducted using vertical Franz diffusion cells with nude mice skin. For in si tu studies. a diffusion cell was implanted under the dorsal skin of a nude mouse, simulating the in vitro method. Both in situ and in vitro experiment s were conducted over a period of 12 h during which samples were collected every 90 min. The mean steady-state flux from Franz diffusion cells was 0.1 63 +/-0.045 mug/cm(2)/h and flux determined by this in situ method was 0.11 3 +/-0.034 mug/cm(2)/h. A statistical significant difference existed betwee n the permeation results of the in vitro and in situ experimental methods. A subjective, semi-quantitative assessment of histological changes to excis ed nude mouse skin was done using light microscopy. This showed that excise d skin undergoes sub-lethal injury (necrosis) during in vitro experiments, which Inay lead to increased permeability of the drug. It was noticed that in vitro and in situ permeation results showed very close correlation until approximately 4.5 h after commencement of experiments, after which. the pe rmeation through excised skin increased. It was assumed that cell necrosis occurred to such an extent after approximately 4.5 h, that the barrier func tion of the stratum corneum decreased acid permeation of the drug increased . (C) 2001 Elsevier Science B.V. All rights reserved.