In vitro-in vivo correlation study for the dermatopharmacokinetics of terbinafine hydrochloride topical cream

Background: To investigate the relationship between dermatopharmacokinetic (DPK) tape stripping from in vitro and in vivo using 1% terbinafine hydrochloride topical cream as the model formulation. Methodology: In vitro and in vivo tape strippings were conducted on separated pig ear skin used as a biological membrane for franz diffusion cell testing and the non-hairy skin area at the ventral forearms of healthy volunteers, respectively. Terbinafine (1%) topical cream was applied to the skin for 0.5, 2, and 4h. The drug profiles of terbinafine across the stratum corneum were determined immediately (time 0h), and at 0.5, 1, 2, and 4h after removing the formulation. The amounts of terbinafine were analyzed by a validated high-performance liquid chromatography-ultraviolet method. The area under the curve (AUC) and the maximum amounts of terbinafine absorption (Q_max) were obtained from pharmacokinetic software. Partition coefficient (K_SC/veh) and diffusion parameter (D/L²) were derived from the Fick's second law equation. During the schedule time of 8h, the deviations of in vitro and in vivo data were 6.61 and 30.46% for AUC and Q_max, respectively. There was insignificant difference of the K_SC/veh and the D/L² between excised pig ear and human skin. In addition, K_SC/veh and D/L² at T_max of 2h were used to predict the AUC presented the value of 4.7481 %h whereas the true value calculated from pharmacokinetic software provided the value of 5.9311 %h differing from each other in approximate of 20%. Conclusions: In vitro tape stripping using the separated pig ear skin as a viable membrane of the franz diffusion cell testing demonstrates the potential to represent in vivo tape stripping in human for topical bioavailability/bioequivalence study of terbinafine hydrochloride 1% topical cream.