New molecules having the structure of (E)-2-(4-tert-butylbenzylidene) hydrazinecarbothioamide (QNT3-18) or 4-tert-butylphenylthiourea (QNT3-20) was synthesized and presupposed to inhibit melanogenesis through the inhibition of tyrosinase, which is involved in melanin formation. Therefore, we seek to develop these new molecules as skin whitening agents in topical formulations based on preformulation studies. QNT3-18 or QNT3-20 showed a strong single endothermic peak at 159.34°C with 10.79 μm-sized or at 150.69°C with 9.0 μm-sized aggregated particles, respectively. Both QNT3-18 and QNT3-20 did not show cytotoxicity at effective concentration range (0.4 µM) against keratinocyte cells and QNT3-18 was more retained than QNT3-20 in the skin instead of permeating through the skin. QNT3-18 or QNT3-20 was practically insoluble in water; the aqueous solubility was 3.8 ± 0.37 or 130.6 ± 2.52 μg/mL, respectively. Also, the partition coefficient value (log P) corresponding to the quotient between aqueous and octanol concentration of the molecule was 3.9 or 2.6, respectively. The skin retention amount of QNT3-18 was 1.7-fold higher than that of QNT3-20. When the optimal SLN cream (J3 formulation) containing 4 μM QNT3-18 was applied on the backs of hairless rats for 4 days after UV irradiation for 7 days and the skin color was checked by reflectance spectrophotometer, the rat skin treated with SLN cream with QNT3-18 quickly recovered to normal compared to skin treated with SLN cream without QNT3-18. Taken together, this study suggests that topical formulations such as creams including SLNs with QNT3-18 might be appropriate carriers for skin whitening agents.