In this study, beclomethasone dipropionate nanocrystals were formulated using an antisolvent sonoprecipitation technique. The aim of this study was to assess the ability of these nanocrystals to actively accumulate in skin layers for the treatment of atopic dermatitis with minimal systemic levels. A three-factor, three-level central composite design was employed to optimize the formulation parameters. The following formulation variables were adopted: stabilizer concentration, antisolvent volume, and stabilizer type. The nanocrystals were assessed for particle size, zeta potential and polydispersity index. Saturation solubility and ex vivostudies were carried out on the optimized formula (PN1). The saturation solubility of PN1 was approximately 745.5 times that of raw BDP in water. Ex vivostudies showed that the calculated Local Accumulation Efficiency (LAC) in the case of PN1 was 6.20, which was significantly higher (p < 0.05) than that of the brand formula, with a LAC ratio of 0.25. Our results confirmed the enhancement of drug deposition, ascertaining the successful use of nanocrystals for the topical delivery of poorly soluble drugs.