RESUMEN
The effect of various surfactants (sodium cholate, sodium taurocholate, Tween 80 and Poloxamer F68) on enhancing the transepithelial permeability of fexofenadine.HCl was evaluated in a human nasal epithelial cell monolayer model. The cytotoxicity of the surfactants on the human nasal epithelial cells was evaluated by the MTT assay. A dose-dependent reduction of cell viability was observed at higher than critical micelle concentration (CMC) of the surfactants, and the IC50 of non-ionic surfactants (Tween 80 and Poloxamer F68) was higher than that of ionic surfactants (sodium cholate and sodium taurocholate). The TEER values significantly decreased after 2 h incubation with the ionic surfactants, but were recovered after 24 h in the fresh culture media. Ionic surfactants significantly increased the transepithelial permeability (P(app)) of fexofenadine.HCl compared to the non-ionic surfactants. The reduction of TEER values upon exposing the cell monolayer to the surfactants for 2 h correlated well with the P(app) of fexofenadine.HCl, which suggests that the permeation-enhancing mechanism of the ionic surfactants is by altering the tight junction property of the paracellular pathway. F-actin staining showed that the effect of ionic surfactants on the tight junction is temporary and reversible, which is consistent with the TEER value recovery within 24 h. These results imply that ionic surfactants are potentially useful permeation enhancers for nasal delivery of hydrophilic compounds, such as fexofenadine.HCl. This study also indicated the usefulness of the human nasal epithelial cell monolayer model not only for evaluating the in vitro nasal drug transport but also for studying the mechanism and toxicity of enhancers.
Asunto(s)
Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacocinética , Mucosa Nasal/efectos de los fármacos , Mucosa Nasal/metabolismo , Tensoactivos/farmacología , Terfenadina/análogos & derivados , Permeabilidad de la Membrana Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Sinergismo Farmacológico , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Formazáns , Antagonistas de los Receptores Histamínicos H1 no Sedantes/farmacología , Humanos , Microscopía Confocal , Poloxámero/farmacología , Polisorbatos , Colato de Sodio/farmacología , Ácido Taurocólico/farmacología , Terfenadina/farmacocinética , Terfenadina/farmacología , Sales de TetrazolioRESUMEN
Glucosamine sulfate (GS) is known to stop the degenerative process of osteoarthritis. Because most of the GS formulation on the market is in the oral form, an alternative formulation such as a transdermal delivery system (TDS) is necessary in order to increase patient compliance. As the initial step to develop a TDS of GS, the physicochemical stability and permeation study in rat skin were examined. Evaluation of the stability of GS at different pHs showed the compound to be most stable at pH 5.0. The degradation rate constant at 25 degrees C was estimated to be 5.93 x 10(-6) hr(-1) (t90 approximately 2.03 years) in a pH 5 buffer solution. Due to its hydrophilic characteristic, low skin permeability was expected of GS. However, the skin permeation rate was determined to be 13.27 microg/cm2/hr at 5% concentration. Results of this study suggest the possibility of developing GS into a transdermal delivery system.