AN APPLICATION OF TRANSDERMAL ANTIVIRAL DELIVERY SYSTEMS TO THE ESTABLISHMENT OF A NOVEL ANIMAL-MODEL APPROACH IN THE EFFICACY EVALUATION FOR DERMATOLOGICAL FORMULATIONS

This report described the establishment and the examination of a novel hairless mouse model in the efficacy evaluation for topical antiviral dosage forms with a focus on the relationship between the in vitro de rmal flux of the antiviral agent and the in vivo antiviral efficacy. A unique dose/flux-efficacy relationship in topical antiviral treatment was obtained by applying a series of transdermal acyclovir delivery s ystems (TADS) for the treatment of cutaneous herpes simplex virus type 1 infected hairless mouse in our earlier study. By konwing the pharma cokinetic parameters of acyclovir in hairless mouse and the flux (J) o f a suitable TADS, the skin target site concentration (C) could be ca lculated for that patch. With the corresponding C value, the in vivo permeability coefficient (P-D,P-in vivo ) of that patch could be calcu lated from P-D,P-in vivo=J/C. The difference between this in vivo per meability coefficient and the in vitro permeability coefficient (P-D,P - in vivo , obtained from in vitro diffusion experiment) was considere d due to the blood flow effect in the in vivo condition. This P-D,P-in vivo can be further applied to calculate the C value of any acyclovi r topical formulation with flux, J', from C'=J'/P(D,i)n(vivo) where t he C' represents the calculated skin target site concentration for an y acyclovir topical formulation. After knowing different C' values of different dermatological formulations of acyclovir, the efficacy of e ach formulation can be estimated from the dose/flux-efficacy relations hip. Two formulations with different fluxes were examined under this s tudy. The results showed very good correlation between the in vitro ac yclovir flux and the in vivo antiviral efficacy and the applicability of this model approach was validated.