An Application of Transdermal Antiviral Delivery Systems to the Establishment of a Novel Animal Model Approach in the Efficacy Evaluation for Dermatological Formulations

Abstract 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 dermal 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 systems (TADS) for the treatment of cutaneous herpes simplex virus type 1 infected hairless mouse in our earlier study. By konwing the pharmacokinetic parameters of acyclovir in hairless mouse and the flux (J) of a suitable TADS, the skin target site concentration (C*) could be calculated for that patch. With the corresponding C* value, the in vivo permeability coefficient (Pd,in vivo) of that patch could be calculated from Pd,in vivo = J/C*. The difference between this in vivo permeability coefficient and the in vitro permeability coefficient (Pd,in vivo. obtained from in vitro diffusion experiment) was considered due to the blood flow effect in the in vivo condition. This Pd,in vivo can be further applied to calculate the C* value of any acyclovir topical formulation with flux, J', from C'*=J'/Pd,in vivo, where the C'* represents the calculated skin target site concentration for any acyclovir topical formulation. After knowing different C* values of different dermatological formulations of acyclovir, the efficacy of each formulation can be estimated from the dose/flux-efficacy relationship. Two formulations with different fluxes were examined under this study. The results showed very good correlation between the in vitro acyclovir flux and the in vivo antiviral efficacy and the applicability of this model approach was validated.