Objectives The objective is to investigate pig ear skin as a alternative for human skin in the prediction of drug concentration profiles in order to optimize the developmental formulation. Methods In vitro tape-stripping were conducted on pig ear skin. Three approved test (generic) lipophilic drugs and their corresponding reference drugs were applied to the skin for 4 h. These drug profiles across the stratum corneum (SC) were determined to compare the drug concentrations of test to that of reference In order to determine the drug concentration profile, Lulicon cream 1% was applied to the skin for 4, 12, and 24 h. The formulation of Luliconazole 1% ointment was optimized with the determined drug concentration profile of the cream and assessed cutaneous bioequivalence to the cream by human dermatopharmacokinetics (DPK) study. Results The in vitro test:reference ratios for drug concentration in SC 4 h after application of com. available topical formulations were close to one. Whether the dosage forms were same or different, these drug concentrations and test: reference ratios were in agreement with reported human DPK data. Evaluated drug concentration profile of Lulicon cream 1% showed that the average concentration of Luliconazole in the pig ear SC reached to steady state at 4 h after application. We developed Luliconazole 1% ointment optimized by the drug concentration profile of the cream. As a result of human DPK study, bioequivalence of the two Luliconazole formulation was confirmed. Conclusions These data suggested that pig ear skin DPK model has promise as a tool for topical formulation evaluation and optimization to predict the drug concentration profile In human SC. Especially among lipophilic drugs as like Luliconazole.