Abstract
The aim of this study was to investigate the feasibility of transdermal fluoxetine (FX) delivery. The effects of chemical forms (base or salt) and permeation enhancers on in vitro skin permeation of FX were assessed using hairless mouse, rat and human cadaver skin. The optimized formulations from the in vitro studies were then evaluated in an in vivo pharmacokinetic study in rats. The in vitro skin permeation studies suggested that the FX base (FXB) and isopropyl myristate (IPM)-limonene mixture could be suitable for transdermal delivery of FX. The permeation parameters of FX through human cadaver skin were well correlated with that through hairless mouse and rat skin, suggesting that these animal models can be used for predicting the permeability of FX through human skin. After transdermal administration of FX with IPM or the IPM-limonene mixture to rats, the mean steady-state plasma concentration (Css) was 66.20 or 77.55 ng/mL, respectively, which was maintained over 36 h and had a good correlation with the predicted Css from the in vitro data. These in vitro and in vivo data demonstrated that permeation enhancers could be a potential strategy for transdermal delivery of FX.
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